Cost-effectiveness analysis of PET-CT positron emission ... - AOTM

Cost-effectiveness analysis of PET-CT positron emission
tomography and the diagnostic technologies financed from public
sources in oncological diagnostics in Poland. Clinical and
epidemiological aspects
Health Technology Assessment Report
commissioned by
Agency for Health Technology Assessment in Poland
prepared by
Public Health and Social Insurance Institute
WyŜsza Szkoła Biznesu
National-Louis University
Warszawa – Nowy Sącz 2006
1

PRINCIPAL
AGENCY FOR HEALTH TECHNOLOGY ASSESSMENT IN POLAND
22 Lotników Av., 02-668 Warsaw
tel. +48 22 56 67 200
fax +48 22 56 67 202
www.aotm.gov.pl
CONTRACTOR
Public Health and Social Insurance Institute
WYśSZA SZKOŁA BIZNESU
NATIONAL-LOUIS UNIVERISTY
27 Zielona Str., 33-300 Nowy Sącz
tel. +48 18 44 99 120
fax +48 18 44 99 121
e-mail. wsb-nlu@wsb-nlu.edu.pl
www.wsb-nlu.edu.pl
2

THIS REPORT WAS ASSISTED BY SPECIALISTS FROM
MARIA SKLODOWSKA-CURIE MEMORIAL CANCER CENTRE AND INSTITUTE OF
ONCOLOGY
prof. dr hab. med. Marek Nowacki
prof. dr hab. med. Witold Bartnik
doc. dr hab. med. Mariusz Bidziński
doc. dr hab. med. Andrzej Kawecki
doc. dr hab. med. Włodzimierz Ruka
doc. dr hab. med. Jan Walewski
dr med. Wiesław Lasota
dr med. Janusz Meder
dr med. Andrzej Pietraszek
dr med. Piotr Siedlecki
dr med. Piotr Rutkowski
INSTITUTE OF PULMONARY DISEASES AND TUBERCULOSIS IN WARSAW
prof. dr hab. med. Kazimierz Roszkowski-ŚliŜ
3

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
LIST OF CONTENTS
1. SUMMARY.............................................................................................................................. 15
2. INDEX OF ABBREVIATIONS.................................................................................................... 27
3. DESCRIPTION OF HEALTH PROBLEM...................................................................................... 29
3.1. Epidemiology of cancers...................................................................................................................... 29
3.2. Lung cancer............................................................................................................................................ 34
3.2.1. Epidemiology............................................................................................................................................34
3.1.1. Risk factors.................................................................................................................................................36
3.1.2. Symptoms ..................................................................................................................................................36
3.1.3. Histopathological picture.......................................................................................................................38
3.1.4. Staging.......................................................................................................................................................40
4
3.1.4.1. Non-small cell cancer staging ............................................................................................................. 41
3.1.4.2. Small cell cancer staging ..................................................................................................................... 41
3.1.5. Diagnostics and treatment ....................................................................................................................41
3.1.5.1. Case history ............................................................................................................................................. 41
3.1.5.2. Physical examination............................................................................................................................. 41
3.1.5.3. Diagnostic imaging................................................................................................................................ 42
3.1.5.4. Microscopic diagnosis........................................................................................................................... 42
3.1.5.5. Other tests................................................................................................................................................ 43
3.1.5.6. General principles in small cell lung cancer diagnosis ................................................................... 43
3.1.5.7. General principles of treatment .......................................................................................................... 43
3.1.5.8. Non-small cell cancer ........................................................................................................................... 44
3.1.5.9. Small cell carcinoma ............................................................................................................................. 45
3.1.6. Prognosis ....................................................................................................................................................45
3.3. Lymphomas ............................................................................................................................................ 46
3.3.1. Epidemiology............................................................................................................................................46
3.3.1.1 Non-Hodgkin’s lymphomas .................................................................................................................. 46
3.3.1.2 Hodgkin’s disease .................................................................................................................................. 46
3.3.2. Risk factors.................................................................................................................................................46
3.3.3. Symptoms ..................................................................................................................................................47
3.3.4. Histopathological picture.......................................................................................................................47
3.3.4.1 Hodgkin’s disease .................................................................................................................................. 47
3.3.4.2 Non-Hodgkin’s lymphomas .................................................................................................................. 48
3.3.5. Staging.......................................................................................................................................................48
3.3.6. Diagnostics and treatment ....................................................................................................................50
3.3.6.1 Additional tests ....................................................................................................................................... 50
3.3.6.2 Diagnostic imaging................................................................................................................................ 50

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.3.6.3 Cytological and histopathological study .......................................................................................... 50
3.3.6.4 Molecular tests........................................................................................................................................ 50
3.3.6.5 Treatment of Hodgkin’s disease .......................................................................................................... 51
3.3.6.6 Treatment of non-Hodgkin’s lymphomas........................................................................................... 52
3.3.7. Prognosis ....................................................................................................................................................52
3.4. Esophageal cancer ............................................................................................................................... 53
3.4.1. Epidemiology............................................................................................................................................53
3.4.2. Risk factors.................................................................................................................................................54
3.4.3. Symptoms ..................................................................................................................................................54
3.4.4. Histopathological picture.......................................................................................................................54
3.4.5. Staging.......................................................................................................................................................55
3.4.6. Diagnostics and treatment ....................................................................................................................56
3.4.6.1 Physical examination............................................................................................................................. 56
3.4.6.2 Diagnostic imaging................................................................................................................................ 56
3.4.6.3 Endoscopy............................................................................................................................................... 56
3.4.6.4 Cancer markers...................................................................................................................................... 56
3.4.6.5 Histopathological study......................................................................................................................... 56
3.4.6.6 Radical treatment.................................................................................................................................. 56
3.4.6.7 Palliative treatment................................................................................................................................ 57
3.4.7. Prognosis ....................................................................................................................................................57
3.5. Cancer of the female genitals ............................................................................................................. 57
3.5.1. Endometrial cancer.................................................................................................................................57
3.5.1.1 Epidemiology .......................................................................................................................................... 57
3.5.1.2 Risk factors ............................................................................................................................................... 58
3.5.1.3 Symptoms ................................................................................................................................................ 58
3.5.1.4 Histopathological picture ..................................................................................................................... 58
3.5.1.5 Staging ..................................................................................................................................................... 58
3.5.1.6 Diagnostics and treatment................................................................................................................... 59
3.5.1.7 Prognosis .................................................................................................................................................. 60
3.5.2. Cervical cancer .......................................................................................................................................60
3.5.2.1 Epidemiology .......................................................................................................................................... 60
3.5.2.2 Risk factors ............................................................................................................................................... 60
3.5.2.3 Symptoms ................................................................................................................................................ 61
3.5.2.4 Histopathological picture ..................................................................................................................... 61
3.5.2.5 Staging ..................................................................................................................................................... 61
3.5.2.6 Diagnostics and treatment................................................................................................................... 62
3.5.2.7 Prognosis .................................................................................................................................................. 63
3.5.3. Ovarian cancer........................................................................................................................................63
3.5.3.1 Epidemiology .......................................................................................................................................... 63
3.5.3.2 Risk factors ............................................................................................................................................... 64
5

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
6
3.5.3.3 Symptoms ................................................................................................................................................ 64
3.5.3.4 Histopathological picture ..................................................................................................................... 64
3.5.3.5 Staging ..................................................................................................................................................... 65
3.5.3.6 Diagnostics and treatment................................................................................................................... 66
3.5.3.7 Prognosis .................................................................................................................................................. 66
3.6. Thyroid gland cancer ............................................................................................................................ 67
3.6.1. Epidemiology............................................................................................................................................67
3.6.2. Risk factors.................................................................................................................................................67
3.6.3. Symptoms ..................................................................................................................................................67
3.6.4. Histopathological picture.......................................................................................................................68
3.6.5. Staging.......................................................................................................................................................68
3.6.6. Diagnostics and treatment ....................................................................................................................69
3.6.7. Prognosis ....................................................................................................................................................70
3.7. Head and neck cancer ........................................................................................................................ 70
3.7.1. Classification .............................................................................................................................................70
3.7.2. Epidemiology............................................................................................................................................70
3.7.3. Risk factors.................................................................................................................................................71
3.7.4. Symptoms ..................................................................................................................................................71
3.7.5. Histopathological picture.......................................................................................................................71
3.7.6. Staging.......................................................................................................................................................71
3.7.7. Diagnostics and treatment ....................................................................................................................72
3.7.8. Prognosis ....................................................................................................................................................73
3.8. Pancreatic cancer................................................................................................................................. 73
3.8.1. Epidemiology............................................................................................................................................73
3.8.2. Risk factors.................................................................................................................................................74
3.8.3. Symptoms ..................................................................................................................................................74
3.8.4. Histopathological picture.......................................................................................................................74
3.8.5. Staging.......................................................................................................................................................75
3.8.6. Diagnostics and treatment ....................................................................................................................75
3.8.7. Prognosis ....................................................................................................................................................77
3.9. Gastrointestinal stromal tumor.............................................................................................................. 78
3.9.1. Epidemiology............................................................................................................................................78
3.9.2. Symptoms ..................................................................................................................................................79
3.9.3. Histopathological picture.......................................................................................................................79
3.9.4. Staging.......................................................................................................................................................79
3.9.5. Diagnostics and treatment ....................................................................................................................79
3.9.6. Prognosis ....................................................................................................................................................80
3.10. Colon cancer ................................................................................................................................. 81

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.10.1. Epidemiology................................................................................................................................81
3.10.2. Risk factors.....................................................................................................................................81
3.10.3. Symptoms ......................................................................................................................................82
3.10.4. Histopathological picture...........................................................................................................82
3.10.5. Staging...........................................................................................................................................82
3.10.6. Diagnostics and treatment........................................................................................................83
3.10.6.1 Screening examinations........................................................................................................................ 83
3.10.6.2 Physical examination............................................................................................................................. 83
3.10.6.3 Laboratory tests ...................................................................................................................................... 83
3.10.6.4 Endoscopy............................................................................................................................................... 83
3.10.6.5 Diagnostic imaging................................................................................................................................ 84
3.10.6.6 Surgery...................................................................................................................................................... 84
3.10.6.7 Supplementary treatment .................................................................................................................... 84
3.10.6.8 Treatment of disseminated disease.................................................................................................... 84
3.10.6.9 Evaluation of response to treatment .................................................................................................. 84
3.10.6.10 Follow-up.................................................................................................................................................. 84
3.10.7. Prognosis ........................................................................................................................................85
4. DESCRIPTION OF INTERVENTION........................................................................................... 86
4.1. Description of method ........................................................................................................................... 86
4.2. Examination protocol, absorbed dose................................................................................................ 87
4.3. Limitations of method ............................................................................................................................ 88
4.4. Uses of PET-CT ......................................................................................................................................... 89
4.4.1. Oncology...................................................................................................................................................89
4.4.2. Neurology..................................................................................................................................................90
4.4.3. Cardiology ................................................................................................................................................91
4.5. Results...................................................................................................................................................... 91
5. METHODOLOGY .................................................................................................................... 92
5.1. Purpose of study ..................................................................................................................................... 92
5.2. Method of clinical efficacy assessment.............................................................................................. 92
5.3. Search strategy for primary studies ..................................................................................................... 92
5.4. Medical database search .................................................................................................................... 93
5.5. Criteria for the inclusion of primary studies in the analysis ............................................................... 94
5.5.1. Population .................................................................................................................................................95
5.5.2. Intervention ...............................................................................................................................................95
5.5.3. Technologies compared (comparators) ............................................................................................95
5.5.4. End points ..................................................................................................................................................95
5.6. Trial quality assessment......................................................................................................................... 95
7

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
5.7. Statistical analysis .................................................................................................................................. 96
5.8. Conflict of interest .................................................................................................................................. 98
6. SEARCH RESULTS.................................................................................................................... 99
7. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS CT IN LUNG CANCER
STAGING.............................................................................................................................. 101
7.1. Results of trial search ........................................................................................................................... 101
7.2. Population characteristics .................................................................................................................. 101
7.3. Description of Intervention.................................................................................................................. 102
7.3.1. PET-CT imaging .......................................................................................................................................102
7.3.2. Diagnostic test compared ...................................................................................................................103
7.3.3. Reference test ........................................................................................................................................104
7.4. Findings ................................................................................................................................................. 106
7.4.1. T-staging...................................................................................................................................................106
7.4.2. Assessment of lymph node involvement (N feature)......................................................................109
7.4.3. Assessment of distant metastases (M feature).................................................................................114
7.4.4. TNM staging system ...............................................................................................................................115
7.4.5. Impact on therapy ................................................................................................................................120
7.4.6. Safety .......................................................................................................................................................120
7.5. Results.................................................................................................................................................... 120
8. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS CT IN LYMPHOMA
STAGING.............................................................................................................................. 122
8.1. Results of primary trial search............................................................................................................. 122
8.2. Population characteristics .................................................................................................................. 122
8.3. Description of intervention .................................................................................................................. 123
8.3.1. PET-CT imaging .......................................................................................................................................123
8.3.2. Diagnostic technology compared ....................................................................................................123
8.3.3. Reference test ........................................................................................................................................124
8.4. Findings ................................................................................................................................................. 124
8.4.1. Diagnosis efficacy in disease staging ................................................................................................124
8
8.4.1.1 In nodes.................................................................................................................................................. 124
8.4.1.2 Locations outside of nodes ................................................................................................................ 126
8.4.1.3 Total results............................................................................................................................................. 126
8.4.1.3.1 Sensitivity...................................................................................................................................... 127
8.4.1.3.2 Specificity .................................................................................................................................... 128
8.4.1.3.3 Positive likelihood ratio .............................................................................................................. 130
8.4.1.3.4 Negative likelihood ratio........................................................................................................... 132
8.4.1.3.5 Diagnostic odds ratio ................................................................................................................ 134
8.4.1.3.6 Diagnostic accuracy................................................................................................................. 136
8.4.1.3.7 Results........................................................................................................................................... 138

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
8.4.2. Accuracy of staging based on Ann Arbor staging system ...........................................................138
8.4.3. Safety .......................................................................................................................................................139
8.5. Results.................................................................................................................................................... 139
9. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS. CT IN ESOPHAGEAL CANCER
STAGING.............................................................................................................................. 141
9.1. Disease staging .................................................................................................................................... 141
9.1.1. Results of primary trial search ..............................................................................................................141
9.1.2. Population characteristics....................................................................................................................141
9.1.3. Description of intervention ...................................................................................................................142
9.1.3.1 PET-CT imaging ..................................................................................................................................... 142
9.1.3.2 Diagnostic technology compared ................................................................................................... 143
9.1.3.3 Reference test ...................................................................................................................................... 143
9.1.4. Findings ....................................................................................................................................................143
9.1.4.1 Diagnostic efficacy of test.................................................................................................................. 143
9.1.4.1.1 T-staging....................................................................................................................................... 143
9.1.4.1.2 N-staging...................................................................................................................................... 146
9.1.4.1.3 M-staging..................................................................................................................................... 147
9.1.4.1.4 CR – complete response........................................................................................................... 149
9.1.4.2 Safety...................................................................................................................................................... 150
9.1.5. Results.......................................................................................................................................................151
9.2. Diagnostics of primary esophageal cancer..................................................................................... 152
9.2.1. Primal tests search results .....................................................................................................................152
9.2.2. Population characteristics....................................................................................................................152
9.2.3. Description of intervention ...................................................................................................................153
9.2.3.1 PET-CT imaging ..................................................................................................................................... 153
9.2.3.2 Diagnostic technologies compared ................................................................................................ 153
9.2.3.3 Reference test ...................................................................................................................................... 154
9.2.4. Safety .......................................................................................................................................................154
9.2.5. Findings ....................................................................................................................................................154
9.2.6. Results.......................................................................................................................................................154
10. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS. CONVENTIONAL
IMAGING METHODS (CT, MRI, USG) IN CLINICAL STAGING, AND DETECTING
RECURRENCES OF, MALIGNANT FEMALE GENITAL TUMORS.............................................. 155
10.1. Results of primary study search.................................................................................................. 155
10.2. Population characteristics .......................................................................................................... 155
10.3. Description of intervention.......................................................................................................... 156
10.3.1. PET-CT imaging...........................................................................................................................156
10.3.2. Diagnostic technologies compared......................................................................................156
10.3.3. Reference test ............................................................................................................................156
10.4. Findings ......................................................................................................................................... 157
9

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
10.4.1. Disease staging ..........................................................................................................................157
10.4.2. Assessment of disease recurrence .........................................................................................159
10.4.3. Total assessment.........................................................................................................................160
10.5. Results............................................................................................................................................ 163
11. COMPARATIVE ANALYSIS OF PET-CT AND CT EFFICACY IN THE DIAGNOSTICS OF
OVARIAN CANCER ............................................................................................................. 164
11.1. Results of primary trial search .................................................................................................... 164
11.2. Population characteristics .......................................................................................................... 164
11.3. Description of intervention.......................................................................................................... 165
11.3.1. PET-CT imaging...........................................................................................................................165
11.3.2. Diagnostic technology compared ........................................................................................166
11.3.3. Reference test ............................................................................................................................166
11.4. Findings ......................................................................................................................................... 166
11.4.1. Diagnostic efficacy ...................................................................................................................166
11.4.2. Safety ...........................................................................................................................................170
11.5. Results............................................................................................................................................ 171
12. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS. TRADITIONAL IMAGING METHODS
IN THYROID CANCER DIAGNOSTICS .................................................................................. 172
12.1. Comparative analysis of the clinical efficacy of pet-ct vs. traditional imaging
methods (ct/mri and i131whole-body scintigraphy) in the diagnostics of thyroid cancer
recurrences........................................................................................................................................... 172
12.1.1. Results of primary trial search ..................................................................................................172
12.1.2. Population characteristics .......................................................................................................172
12.1.3. Description of intervention.......................................................................................................173
10
12.1.3.1 PET-CT imaging ..................................................................................................................................... 173
12.1.3.2 Diagnostic technologies compared ................................................................................................ 174
12.1.3.2.1 CT/MRI .......................................................................................................................................... 174
12.1.3.2.2 I131 whole-body scintigraphy (I131 WBS) .............................................................................. 174
12.1.3.3 Reference Test ...................................................................................................................................... 175
12.1.4. Findings ........................................................................................................................................175
12.1.4.1 Safety...................................................................................................................................................... 182
12.1.5. Impact on therapy ....................................................................................................................182
12.1.6. Results...........................................................................................................................................183
12.2. Comparative efficacy analysis of f pet-ct vs. traditional imaging methods (CT, I131
whole-body scintigraphy and USG) in the staging of differentiated thyroid cancer .................. 184
12.2.1. Results of primary trial search ..................................................................................................184
12.2.2. Population characteristics .......................................................................................................184
12.2.3. Description of intervention.......................................................................................................185
12.2.3.1 I 124 PET-CT imaging ............................................................................................................................... 185

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
12.2.3.2 Diagnostic technology compared ................................................................................................... 186
12.2.3.2.1 Computer tomography ............................................................................................................ 186
12.2.3.2.2 I131 whole-body scintigraphy.................................................................................................. 186
12.2.3.2.3 Ultrasound examination of the neck ...................................................................................... 186
12.2.3.3 Reference test ...................................................................................................................................... 186
12.2.4. Findings ........................................................................................................................................186
12.2.4.1 Safety...................................................................................................................................................... 188
12.2.5. Results...........................................................................................................................................188
13. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS. TRADITIONAL IMAGING METHODS
IN HEAD AND NECK CANCER DIAGNOSTICS .................................................................... 190
13.1. Diagnostics of malignant head and neck tumors (primary lesions, recurrence after
treatment, cervical lymph node metastasis from an unknown primary focus) ........................... 190
13.1.1. Results of primary trial search ..................................................................................................190
13.1.2. Population characteristics .......................................................................................................190
13.1.3. Description of intervention.......................................................................................................191
13.1.3.1 PET-CT imaging ..................................................................................................................................... 191
13.1.3.2 Diagnostic technology compared ................................................................................................... 191
13.1.3.3 Reference test ...................................................................................................................................... 191
13.1.4. Findings ........................................................................................................................................191
13.1.4.1 Diagnostic efficacy.............................................................................................................................. 191
13.1.4.2 Safety...................................................................................................................................................... 193
13.1.5. Results...........................................................................................................................................193
13.2. Detection of bone involvement by oral cancer ...................................................................... 194
13.2.1. Results of primary trial search ..................................................................................................194
13.2.2. Population characteristics .......................................................................................................194
13.2.3. Description of intervention.......................................................................................................194
13.2.3.1 PET-CT imaging ..................................................................................................................................... 194
13.2.3.2 Diagnostic test compared.................................................................................................................. 195
13.2.3.3 Reference test ...................................................................................................................................... 195
13.2.4. Findings ........................................................................................................................................195
13.2.4.1 Diagnostic efficacy.............................................................................................................................. 195
13.2.4.2 Safety...................................................................................................................................................... 197
13.2.5. Results...........................................................................................................................................197
13.3. Impact of PET-CT diagnostics on treatment revisions.............................................................. 198
13.3.1. Results of primary trial search ..................................................................................................198
13.3.2. Population characteristics .......................................................................................................198
13.3.3. Intervention description............................................................................................................199
13.3.3.1 PET-CT imaging ..................................................................................................................................... 199
13.3.3.2 Diagnostic technology compared ................................................................................................... 200
13.3.3.3 Reference test ...................................................................................................................................... 200
11

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
13.3.4. Results...........................................................................................................................................200
12
13.3.4.1 Impact on therapy............................................................................................................................... 200
13.3.4.2 Safety...................................................................................................................................................... 202
13.3.5. Results...........................................................................................................................................203
14. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS. CONVENTIONAL IMAGING
METHODS IN PANCREATIC CANCER DIAGNOSTICS.......................................................... 204
14.1. Results of primary trial search .................................................................................................... 204
14.2. Population characteristics .......................................................................................................... 204
14.3. Intervention description .............................................................................................................. 205
14.3.1. PET-CT imaging...........................................................................................................................205
14.3.2. Diagnostic technology compared ........................................................................................206
14.3.3. Reference test ............................................................................................................................206
14.4. Findings ......................................................................................................................................... 206
14.4.1. Tumor detection and analysis .................................................................................................206
14.4.2. Staging.........................................................................................................................................207
14.4.3. Revisions of oncological procedures.....................................................................................210
14.4.4. Safety ...........................................................................................................................................211
14.5. Results......................................................................................... Błąd! Nie zdefiniowano zakładki.
15. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS. CT IN THE STAGING AND
EVALUATING RESPONSE TO TREATMENT OF GASTROINTESTINAL STROMAL TUMOR......... 213
15.1. Results of primary trial search .................................................................................................... 213
15.2. Population characteristics .......................................................................................................... 213
15.3. Description of intervention.......................................................................................................... 213
15.3.1. PET-CT imaging...........................................................................................................................213
15.3.2. Diagnostic technology compared ........................................................................................214
15.3.3. Reference test ............................................................................................................................215
15.4. Findings ......................................................................................................................................... 215
15.4.1. Staging.........................................................................................................................................215
15.4.2. Response to treatment .............................................................................................................215
15.4.3. Safety ...........................................................................................................................................216
15.5. Results............................................................................................................................................ 216
16. COMPARATIVE EFFICACY ANALYSIS OF THE PET-CT AND CT IN ASSESSING RESIDUAL
LESIONS IN COLORECTAL LIVER METASTASIS ..................................................................... 218
16.1. Results of primary trial search .................................................................................................... 218
16.2. Population characteristics .......................................................................................................... 218
16.3. Description of intervention.......................................................................................................... 218

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
16.3.1. PET-CT imaging...........................................................................................................................218
16.3.2. Diagnostic technology compared ........................................................................................219
16.3.3. Reference test ............................................................................................................................220
16.4. Findings ......................................................................................................................................... 220
16.5. Results............................................................................................................................................ 221
17. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS OTHER IMAGING
TECHNIQUES (MRI OR CT) IN THE STAGING OF NEOPLASM IN VARIED LOCATIONS........ 222
17.1. Neoplasm in varied locations – disease staging (PET-CT vs. MRI) ......................................... 222
17.1.1. Results of trial search .................................................................................................................222
17.1.2. Population characteristics .......................................................................................................222
17.1.3. Description of intervention.......................................................................................................223
17.1.3.1 PET-CT ..................................................................................................................................................... 223
17.1.3.2 Compared diagnostic test ................................................................................................................. 224
17.1.3.3 Reference test ..................................................................................................................................... 225
17.1.4. Findings ........................................................................................................................................226
17.1.4.1 Diagnostic accuracy in detecting primary and recurring carcinomas..................................... 226
17.1.4.2 T-staging................................................................................................................................................. 227
17.1.4.3 N-staging................................................................................................................................................ 231
17.1.4.4 Assessment of distant metastases (M feature)................................................................................ 235
17.1.4.5 TNM staging system.............................................................................................................................. 240
17.1.4.6 Impact on therapy............................................................................................................................... 243
17.1.4.7 Safety...................................................................................................................................................... 244
17.1.5. Results...........................................................................................................................................244
17.2. Neoplasm in varied locations: disease staging(PET-CT versus CT)........................................ 246
17.2.1. Results of trial search .................................................................................................................246
17.2.2. Population characteristics .......................................................................................................246
17.2.3. Description of intervention.......................................................................................................247
17.2.3.1 PET-CT ..................................................................................................................................................... 247
17.2.3.2 Diagnostic trial compared.................................................................................................................. 248
17.2.3.3 Reference test ...................................................................................................................................... 248
17.2.4. Findings ........................................................................................................................................249
17.2.4.1 T-staging................................................................................................................................................. 249
17.2.4.2 N-staging................................................................................................................................................ 249
17.2.4.3 Assessment of distant metastasis....................................................................................................... 250
17.2.4.4 TNM staging system.............................................................................................................................. 252
17.2.4.5 Impact on therapy............................................................................................................................... 253
17.2.4.6 Safety...................................................................................................................................................... 254
17.2.5. Results...........................................................................................................................................254
17.3. Cancers of unknown primary origin: diagnostic efficacy ...................................................... 255
13

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
17.3.1. Results of trial search .................................................................................................................255
17.3.2. Population characteristics .......................................................................................................255
17.3.3. Description of intervention.......................................................................................................256
14
17.3.3.1 PET-CT ..................................................................................................................................................... 256
17.3.3.2 Diagnostic test compared.................................................................................................................. 257
17.3.3.3 Reference test ...................................................................................................................................... 258
17.3.4. Findings ........................................................................................................................................258
17.3.4.1 Diagnostic accuracy in detecting primary cancer of unknown origin...................................... 258
17.3.4.2 Safety...................................................................................................................................................... 262
17.3.5. Results...........................................................................................................................................262
18. APPENDICES ........................................................................................................................ 264
18.1. Tool for quality assessment of studies........................................................................................ 264
18.2. Detailed search results................................................................................................................ 290
19. LITERATURE USED IN THE ANALYSIS ..................................................................................... 296
19.1. Lung cancer ................................................................................................................................. 296
19.2. Neoplasm in varied locations .................................................................................................... 296
19.3. Lymphomas .................................................................................................................................. 296
19.4. Esophageal cancer ..................................................................................................................... 297
19.5. Cancer in the female genitals.................................................................................................... 297
19.6. Ovarian cancer............................................................................................................................ 297
19.7. Thyroid gland cancer .................................................................................................................. 297
19.8. Head and neck cancer .............................................................................................................. 297
19.9. Pancreatic cancer....................................................................................................................... 298
19.10. Sarcomas ...................................................................................................................................... 298
19.11. Colon cancer ............................................................................................................................... 298
20. TRIALS EXCLUDED FROM THE ANALYSIS ............................................................................. 300
21. TABLE OF ILLUSTRATIONS..................................................................................................... 321
22. TABLE OF GRAPHS ............................................................................................................... 326
23. TABLE OF FIGURES ............................................................................................................... 328

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
1. SUMMARY
AIM OF STUDY
The aim of this report is a comparative cost-effectiveness analysis of the PET-CT technology (positron emission
tomography - PET fused with computed tomography - CT) and the diagnostic technologies financed from public
sources in oncological diagnostics in Poland. This part of the report focuses on a clinical and epidemiological
analysis.
The study was prepared for the Agency for Health Technology Assessment in Poland.
METHODOLOGY
Clinical efficacy evaluation methods
The search strategy for primary studies, the evaluation of studies reliability, as well as data extraction,
statistical analysis and results interpretation methods were designed based on guidelines of the Medical Services
Advisory Committee [„Guidelines for the assessment of diagnostic technologies” August 2005, Australia].
Search strategy for primary studies
As the first step of searching for trials a general search strategy was adopted without further specifying the
target population, in order to locate a group of trials concerning the use of PET-CT in oncological diagnostics.
Additionally, for 12 indications individual searches were conducted with targeted population (breast cancer, lung
cancer, colorectal cancer, ovarian cancer, cervical cancer, endometrial cancer, lymphoma, gastric and
esophageal cancer, melanoma, glioma, sarcoma, head and neck cancer). In the process of searching for reports
on the technology under assessment, results of a high specificity strategy that identified only those publications
where the hybrid term “PET-CT” or its equivalents appeared (#8), were combined with results of a high sensitivity
strategy that identified all publications describing the diagnostic method under discussion (search for publications
with “PET” and “CT” titles, abstracts or keywords - #8).
ID search strategy
#1 „Positron-Emission Tomography” [MeSH] OR „Tomography, Emission-Computed” [MeSH]
#2 PET OR positron emission tomography
#3 #1 OR #2
#4 („Tomography, Spiral Computed” [MeSH] OR „Tomography, X-Ray Computed” [MeSH])
#5 CT OR computed tomography
#6 #4 OR #5
#7
dual OR integral OR integration OR combination OR combined OR fusion OR fused OR hybrid OR coincidental OR
combining OR coincidence OR coregistered
#8 #3 AND #6
#9 #3 AND #7
#10 #8 OR #9
15

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
#11 „Neoplasms” [MeSH]
#12 „Medical Oncology” [MeSH]
#13 #11 OR #12
#14 #10 AND #13
#15 #10 AND #13 Limits: English, Polish, Publication Date from 1998/01/01, Humans
Last search date: 20 Mar 2006
Search in medical databases
The above search strategy was applied to the following databases:
Medline via Pubmed,
Cochrane Library (The Cochrane Database of Systematic Reviews, The Cochrane Controlled Trials Register),
EmBase,
And medical web sites:
16
• NICE (National Institute for Clinical Excellence),
SBU (Statens beredning för medicinsk utvärdering),
NCCHTA (The National Coordinating Centre for Health Technology Assessment),
CADTH (The Canadian Agency for Drugs and Technologies in Health),
INAHTA (International Network of Agencies for Health Technology Assessment),
MSAC (Medical Services Advisory Committee).
Also, the bibliographies of the primary studies were searched. Secondary studies were reviewed (object articles,
systematic reviews, meta-analyses, agency reviews) for possible additional primary studies. Moreover, to make the list
of publications complete, manufacturers of diagnostic equipment were requested to provide all their studies,
especially those concerning the pre-marketing period, as well as marketing information on PET-CT scanners.
The search was conducted independently by two researchers. Trial reviews were also reviewed by two persons.
Criteria for the inclusion of primary studies in the analysis
Initially, titles and abstracts in the publications found were analyzed. If information on the use of PET (including PET-
CT) imaging or CT in a trial was found, it was qualified for further verification depending on how the full text was
evaluated.
As the second stage, full texts in an electronic version were analyzed with a special focus on trial methodology, in
order to identify information on the use of hybrid PET-CT scanners. Reports where the use of the technique under
discussion was confirmed were further verified. Based on the guidelines of the Medical Services Advisory Committee,
the verification process focused on the selection of trials, where two strategies were assessed at the same time: PET-
CT and another strategy financed in Poland. On this basis a decision was made whether to include or exclude a trial,
stating the reasons.
In case of primary studies, there were no restrictions on the period of follow-up or size of population. Trials done on
humans, for which full texts of reports are accessible in Polish libraries in English or Polish were included. Restrictions
were defined for the date of publication, which narrowed down the scope of search to studies published after 1 Jan
1998. This criterion was accommodated based on the results of database searches (publication of first reports on the

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
hybrid PET-CT scanner) and the date of launching the technology under assessment on the diagnostic procedures
market.
Population
The population were patients diagnosed for oncological indications.
Intervention
The analysis included primary prospective or retrospective clinical trials, where PET-CT results were assessed
(regardless of the type of radiopharmaceutical used). The essential criterion for the inclusion of a publication into the
analysis was whether the diagnostic techniques compared were verified using an independent reference test (gold
standard).
Technologies compared (comparators)
Diagnostic technologies financed in Poland from public sources and used in oncological diagnostics.
End points
• Diagnostic efficacy of testing methods in comparison to the respective reference method or clinical
observation;
• Change of therapeutic decision;
• Impact on clinical end points;
• Safety.
Trial quality assessment
The adopted scale of trial quality helps evaluate publications with regard to whether they are properly designed
and conducted, and ensures reliability of results.
In compliance with EBM requirements (Evidence Based Medicine), the process of trial quality assessment used the
QUADAS form, which consisted of 14 questions. The first four questions check whether the choice of population was
right; questions 5-9 assess whether the measurements and the reference test were executed correctly, the remaining
questions rated the interpretation and presentations of the results.
In order to standardize the assessment procedure, a single form was prepared to verify all the publications
included in the analysis.
Each study was rated independently by two analysts. In case of discrepancies, the final decision was made
through formal consensus.
Each question was evaluated “yes”, “no”, or “unclear”. Checklists of trial quality assessment for each study are given
in an appendix hereto.
Statistical analysis
Included in the analysis are trials that sought information on the results of the diagnostic methods under assessment
in comparison with a reference method. The results were grouped according to the parameters of a four-field table:
TP, TN, FP and FN.
17

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
18
Next, in order to assess the diagnostic efficacy, parameters such as sensitivity (Se), specificity (Sp), accuracy (Acc),
positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnostic odds ratio (DOR) were calculated with a
95% confidence interval. Whenever possible, a meta-analysis of results of studies was also conducted. To evaluate
differences in diagnostic efficacy of trials, McNemar’s test was done, provided data were available (test of
proportions with matched data array).
For a comparative rating of odds of accurate diagnosis (consistent with the reference standard) for the diagnostic
methods under assessment, the OR parameters statistical significance was rated based on EBM guidelines. For
statistically significant results, the NNT parameter was additionally calculated, specifying confidence intervals.
When no statistically significant discrepancies of study results were identified, a meta-analysis of the results was
conducted using the fixed effect model. For end points that were statistically significant in a heterogeneity test, the
random effect model was used. The statistical software MetaDiSc v.1.3 was used to calculate these parameters and
to carry out a meta-analyses of sensitivity and specificity. The meta-analysis of accuracy, OR and NNT, and graphs
representing this results were done in Stats Direct v. 2.5.2.
Conflict is interest
None of the authors of the study reported any conflict of interest.
Results
Lung cancer – T-staging (PET-CT vs. CT)
As a result of searching medical databases 4 primary prospective trials were identified (Antoch 2003, Lardinois
2003, Cerfolio 2005 and Shim 2005), where the PET-CT method was compared to CT in patients suffering from non-
small cell lung cancer (N=570). Both trials were verified histopathologically, however in case of metastasis clinical
follow-up, MRI as well as ultrasonography was used. Indications for scanning were based on results of T-staging.
In the assessment of T-status in all the trials under assessment, the proportion of correctly diagnosed patients is
higher when PET-CT is adopted in comparison to CT only. The diagnostic accuracy calculated by meta-analysis is
86% (95% CI: 81; 91) for PET-CT and 71% (95% CI: 55; 84) for CT.
Calculated by meta-analysis of three studies, the odds ratio of consistency between the reference test and T-
staging results for PET-CT vs. CT is 2.42 (95% CI: 1.36; 4.29). The value is statistically significant; NNT = 8 (95% CI: 5; 20).
Based on the analyses of all the diagnostic parameters established (sensitivity, specificity, accuracy), PET-CT is
more efficacious than CT in rating the involvement of lymph nodes (N-status). The diagnostic accuracy calculated
by meta-analysis is 85% (95% CI: 76; 93) for PET-CT and 61% (95% CI: 49; 72) for CT. Sensitivity is 85-89%, for PET-CT and
70% for CT, and specificity is 84-94% for PET-CT and 59-69% for CT.
The odds of N-staging results being consistent with the reference test is nearly 4 times higher for PET-CT versus CT
alone, and the value is statistically significant: OR=3.95 (95% CI: 1.65; 9.44); NNT = 4 (95% CI: 3; 10).
The accuracy of the TNM staging system evaluated by meta-analysis is 88% (95% CI: 83; 93) for PET-CT and 67%
(95% CI: 59; 74) for CT.
The odds of obtaining small cell lung cancer TNM staging results consistent with the reference test is higher for PET-
CT versus CT alone, and the differences observed are statistically significant; OR = 3.91 (95% CI: 2.04; 7.50); NNT = 5
(95% CI: 4; 9).
In summary, the PET-CT method has a higher diagnostic efficacy than CT in the staging of clinical non-small cell
lung cancer (NSCLC).

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Neoplasms in varied locations
1. Disease Staging (PET-CT vs. MRI)
Two primary clinical trials (Antoch 2003 and Schmidt 2005) were found, where the diagnostic efficacy of PET-CT in
the staging of neoplasms with varied locations was directly compared to magnetic resonance imaging – MRI
(N=136). Both trials were qualified based on a reference methods, which in this part of the study were
histopathological examination and/or clinical follow-up.
A single-trial-based rating of the efficacy of primary and secondary carcinoma detection showed that the
sensitivity of PET-CT is higher in comparison to magnetic resonance imaging: 100% (95% CI: 59; 100) vs. 86% (95% CI:
42; 100). The specificity of both methods was 100%. The differences between groups were not statistically significant.
For T-staging, the diagnostic accuracy established by meta-analysis of two trials was 89% (95% CI: 68; 100) for PET-
CT and 79% (95% CI: 26; 99) for MRI. Calculated by meta-analysis, the odds ratio for T-staging results being consistent
with the reference test using PET-CT versus MRI, is 3.29 (95% CI: 1.37; 7.90), and the value is statistically significant;
NNT=7 (95% CI: 4; 20).
Analysis showed that the PET-CT method was more accurate compared to MRI in the assessment of the
involvement of lymph nodes by cancer metastasis (N status). The accuracy established by meta-analysis is 94% (95%
CI: 89; 97) for PET-CT, as compared to 80% for MRI (95% CI: 73; 86). The odds of the staging results for the involvement
of lymph nodes by cancer metastasis being consistent with the reference test were four times higher for the PET-CT
method than for magnetic resonance. The result is statistically significant; OR = 4.00 (95% CI: 1.74; 9.19); NNT = 8 (95%
CI: 5; 17). The diagnostic sensitivity reported by the authors was 95% and 100% for PET-CT, and 79% for MRI, while
specificity is 92%-95% for PET-CT and 78%-95% for MRI.
Established by meta-analysis of two trials, the diagnostic accuracy of PET-CT vs. CT in distant metastasis staging (M
status) is 94% (95% CI: 90; 98) for PET-CT and 96% (95% CI: 86; 100) for magnetic resonance. The odds of obtaining
reference method-consistent staging results for distant metastasis using the PET-CT method are the same as the odds
for magnetic resonance: OR = 1.00 (95% CI: 0.34; 2.95). The result is statistically significant. Based on two trials included
in this analysis, sensitivity was 93% and 100% for PET-CT, and was 90% and 100% for MRI. Specificity was 95% and 98%
for PET-CT, and 95% and 100% for MRI.
A review of the diagnostic accuracy of the methods in total staging of cancer (TNM staging) was conducted by
meta-analysis of two trials, which showed that the accuracy is higher for PET-CT than for MRI. The values are 86%
(95% CI: 65; 98) and 75% (95% CI: 33; 99) respectively. The odds of obtaining results consistent with reference test are
2.61 times higher for PET-CT than for MRI. The result is statistically significant; OR = 2.61 (95% CI: 1.46; 4.67); NNT = 6 (95%
CI: 4; 15).
The use of PET-CT instead of MRI in the staging of cancer was conducive to changes in therapeutic
recommendations in 12% of patients suffering from cancer with varied locations, while the use of MRI instead of PET-
CT was conducive to changes in therapeutic recommendations in 2% of patients.
In summary, in patients with various cancer locations, the PET-CT method shows higher diagnostic efficacy in
comparison to MRI in detecting primary and recurring cancer, as well as in the staging of tumor (T-status), lymph
nodes involvement (N-status), and distant metastasis (M-status) and combined staging (TNM staging).
2. Cancer staging (PET-CT vs. CT)
One primary clinical trial (Antoch 2004) was identified, where the diagnostic efficacy of PET-CT in the staging of
neoplasm in varied locations was compared directly with CT (N=260). Both testing methods were verified against the
reference methods, i.e. histopathological tests and/or clinical follow-up.
The diagnostic accuracy of T-staging was 82% (95% CI: 71; 90) for PET-CT, and 66% (95% CI: 55; 77) for CT. The
differences between the groups under discussion are statistically significant (p = 0.0018). The odds of obtaining a T-
19

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
status consistent with the reference method is 2.29 times higher for PET-CT versus CT. The result is statistically
significant; OR = 2.29 (95% CI: 1.03; 5.25), NNT = 7 (95% CI: 4; 59).
20
Analysis showed that the PET-CT method is statistically significantly more accurate than CT in the staging of the
involvement of lymph nodes (N status). The diagnostic accuracy is 92% (95% CI: 88; 95) for PET-CT and 76% (95% CI:
70; 81) for CT. The odds of obtaining lymph nodes involvement staging results consistent with the reference test is
nearly four times higher for the PET-CT procedure versus CT. The result is statistically significant; OR = 3.84 (95% CI: 2.19;
6.93), NNT = 7 (95% CI: 5; 10).
The diagnostic accuracy of the methods compared in the staging of distant metastasis (M status) is 95% (95% CI:
92; 98) for PET-CT and 88% (95% CI: 84; 92) for CT, and the differences between the methods are statistically
significant (p=0.0001). The odds of M-staging results being consistent with the reference method is 2.7 times higher for
PET-CT versus CT. The result is statistically significant; OR = 2.70 (95% CI: 1.30; 5.92), NNT = 15 (95% CI: 7; 44).
Sensitivity, specificity and accuracy are higher for PET-CT compared to CT, including in staging metastasis to lungs,
liver and bones, as well as organs total.
Analysis showed that the diagnostic accuracy of the methods under assessment in cancer staging (TNM staging) is
higher when the PET-CT method is used compared to CT. The accuracy of PET-CT is 84% (95% CI: 79; 88), and for CT it
is 63% (95% CI: 57; 69). The odds of obtaining staging results consistent with the reference standard is more than three
times higher for PET-CT compared to CT. The result is statistically significant, OR = 3,09 (95% CI 2.00; 4.80), NNT = 5 (95%
CI: 4; 8).
Using PET-CT instead of CT in disease staging led to a different recommendation for further treatment in 15%
patients. Using CT instead of PET-CT caused therapeutic decisions to be changed for 0.8% patients.
3. Detecting primary origin of cancer in metastasis patients (PET-CT vs. CT)
Two primary clinical trials were found that compared directly the diagnostic efficacy of PET-CT with that of CT in
locating primary neoplasm in metastasis patients. Both testing methods were verified against a reference test
(histopathological examination and/or clinical observation).
Based on a meta-analysis, for patients with metastasis in the neck area the diagnostic sensitivity of PET-CT is higher
than the values established for CT: 47% (95% CI: 31; 64) vs. 26% (95% CI: 13; 44). Another meta-analysis showed that
the odds of determining the origin of primary neoplasm in a population of patients with metastasis in the neck area
using PET-CT was almost three times higher compared to CT, and the result was statistically significant; OR = 2.87 (95%
CI: 1.08; 7.63), NNT = 5 (95% CI: 3; 35).
A single-trial analysis of the diagnostic efficacy of the technologies compared in locating primary tumor in patients
with cancer metastasis outside the neck indicated no statistically significant differences between PET-CT and CT. The
diagnostic sensitivity of the PET-CT method was higher in versus CT, and stood at 36% (95% CI: 18; 57) vs. 15% (95% CI:
4; 35).
The results of a single trial also warranted the claim that the diagnostic sensitivity of PET-CT proved higher than the
sensitivity of CT in locating cancer focuses in the total population of patients with cancer metastasis both in and
outside the neck, and was 36% (95% CI: 22; 52) for PET-CT vs. 19% (95% CI: 9; 34) for CT.
Lymphoma staging and restaging (PET-CT vs. CT)
As a result of searching medical databases two primary studies were found: Freudenberg 2003 (N = 27) and
Schaefer 2004 (N = 60), which compared directly the diagnostic efficacy of PET-CT and CT in lymphoma staging and
restaging. The reference tests were histopathological tests, clinical follow-up and conventional staging of the disease
(clinical and laboratory tests, USG, MRI, scintigraphy).
A diagnostic efficacy review showed that PET-CT was diagnostically more efficacious than CT both for lymphatic
and extra-lymphatic locations individually, and for the total cohort.
In staging lesions in the lymphical area, the sensitivity and accuracy of both PET-CT and CT were 100% (95% CI: 82;
100).

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
In restaging, PET-CT sensitivity stood at 85% (95% CI: 55; 98) and specificity at 100% (95% CI: 88; 100); both were
higher than the respective parameters for CT. For CT the values were: 69% for sensitivity (95% CI: 39; 91) and 86% for
specificity (95% CI: 67; 96). The diagnostic accuracy of the methods discussed was 95% (95% CI: 83; 99) for PET-CT and
80% (95% CI: 65; 91) for CT.
PET-CT sensitivity and specificity in detecting pathological lesions located outside of lymph nodes stood at 75%
(95% CI: 19; 99) and 100% (95% CI: 78; 100), respectively. In restaging, both sensitivity and specificity were 100%. With
CT imaging, the values were: 25% for sensitivity (95% CI: 1; 81) and 100% for specificity (95% CI: 78; 100) for staging,
and 75% (95% CI: 19; 99) and 86% (95% CI: 71; 95) respectively for restaging. PET-CT scanning demonstrated higher
accuracy (95% for staging and 100% for restaging) compared to CT (84% and 85% respectively).
Meta-analysis of the tests included in this study showed that in disease staging in patients with lymphoma, PET-CT is
characterized by higher sensitivity and specificity compared to CT. The sensitivity of PET-CT is 93% (95% CI: 82; 98), vs.
80% for CT (95% CI: 66; 89). The specificity of the diagnostic methods discussed is 100% (95% CI: 96; 100) and 84% (95%
CI: 75; 91) respectively.
PET-CT is characterizes by a higher accuracy of 97% (95% CI: 93; 99) s. 78% for CT (95% CI: 57; 93).
Freudenberg 2003 analyses the consistency between the reference test and staging based on the Ann Arbor
system. Disease was staged correctly by PET-CT in 26 (96%) patients, and by CT in 13 (48%) patients. The difference
between PET-CT and CT was statistically significant (p=0.002). The odds of obtaining the correct staging were 28 times
for PET-CT than for CT: OR = 28 (95% CI: 3.35; 1227.94); NNT = 3 (95% CI: 2; 4).
PET-CT imaging is characterized by higher diagnostic efficacy than CT in the staging of lymphomas.
Esophageal cancer
1. Staging and response to treatment (PET-CT vs. CT, EUS
As a result of searching medical databases one primary study was found (Cerfolio 2005) that evaluated the
diagnostic efficacy of PET-CT versus CT and transesophageal endoscopic ultrasound-guided biopsy (EUS) in the
restaging of esophageal cancer and the assessment of response to treatment.
In the diagnostics of primary tumor (T status), the highest diagnostic accuracy was demonstrated by PET-CT: 83%
(95% CI: 68; 93) for stage T0, 80% (95% CI: 65; 91) for stages T1-T3, and 98% (95% CI: 87; 100) for stage T4. In the other
tests under assessment, the accuracy of CT was 61% (95% CI: 45; 76), 56% (95% CI: 40; 72) and 95% (95% CI: 83; 99)
respectively, and the accuracy of EUS was 66% (95% CI: 49; 80), 56% (95% CI: 40; 72) and 90% (95% CI: 77; 97).
PET-CT scanning allowed for correct (consistent with reference test) T-staging in 80% patients, while CT and EUS - in
56% each.
The odds of obtaining a correct T-status by using PET-CT is 3.23 times higher compared to CT alone, and to EUS;
OR = 3.23 (95% CI: 1.09; 10.00), both for the comparison PET-CT vs. EUS and for the comparison PET-CT vs. CT; NNT = 5
(95% CI: 3; 24).
In staging lymph nodes involvement (N status), the highest diagnostic accuracy was achieved for PET-CT: 93% (95%
CI: 80; 98), compared to 78% (95% CI: 62; 80) for CT and 78% (95% CI: 62; 80) for EUS. The difference in accuracy was
statistically significant (p=0.04).
The diagnostic efficacy of trials in M-staging was evaluated separately for stages M1a and M1b.
The highest accuracy in determining stage M1a metastasis was demonstrated by EUS – 92% (95% CI: 80; 98), while
the accuracy of PET-CT was 90% (95% CI: 77; 97), and the accuracy of CT was 88% (95% CI: 75; 95). The differences
between the groups were statistically insignificant. The sensitivity of PET-CT and EUS was 33% (95% CI: 4; 78), and the
sensitivity of CT imaging was 0% (95% CI: 0; 40). The specificity of PET-CT is 98% (95% CI: 87; 100), while that of CT
imaging and EUS is 100%.
In the diagnostics of stage M1b metastasis, the sensitivity of PET-CT was 67% (95% CI: 22; 96) and was higher than
the sensitivity of CT, which stood at 50% (95% CI: 12; 88).
21

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
22
In the assessment of complete response to treatment, PET-CT showed the highest sensitivity of 87% (95% CI: 60; 98).
The sensitivity of CT was 27% (95% CI: 8; 55), and the sensitivity of EUS was 20% (95% CI: 4; 48). The differences
between PET-CT and the methods compared are statistically significant. The specificity of PET-CT scanning stood at
88% (95% CI: 72; 97), of CT at 91% (95% CI: 76; 98), and of EUS-FNA at 94% (95% CI: 80; 99). The highest accuracy was
demonstrated by PET-CT, and stood at 88% % (95% CI: 75; 95) vs. 71% (95% CI: 56; 83) for CT and 71% (95% CI: 56; 83)
for EUS. The differences between PET-CT and the methods compared are statistically significant (p=0.045 for the
comparison with EUS-FNA, and p=0.05 for the comparison with CT).
In summary, in restaging esophageal cancer, and in determining complete response to treatment, PET-CT imaging
demonstrates higher diagnostic efficacy than CT or trans-esophageal ultrasound-guided biopsy.
2. The diagnostics of primary esophageal cancer (PET-CT vs. CT)
As a result of searching medical databases one primary trial was found (Kula 2005), which compared the
diagnostic efficacy of PET-CT with that of CT in the staging of esophageal cancer (N=12). The reference test was a
histopathological or cytological test.
Based on studies accessible, PET-CT is characterized by higher sensitivity (100%) in comparison to CT (92%) in
detecting esophageal cancer.
Cancer of the female genitals
1. Female genital cancer: staging and assessment of disease recurrence (PET-CT vs. CT, MRI,
ultrasonography)
As a result of searching medical databases one primary clinical trial was found (Grisaru 2004) that compared
directly the diagnostic efficacy of PET-CT vs. conventional imaging methods (CT, magnetic resonance and
ultrasonography) in the diagnostics of female genital cancer (N=53). Positive results of scanning were verified by
histopathological tests of material removed during a surgical procedure or obtained from guided biopsy. Negative
results were verified based on long-term clinical observation and repeated diagnostic imaging.
The assessment of the diagnostic efficacy of imaging methods discussed included both staging and detecting
recurrences of disease.
The sensitivity of PET-CT diagnostics in clinical staging is higher than the sensitivity of the conventional diagnostic
imaging and stands at 100% (95% CI: 66; 100) vs. 56% (95% CI: 21; 86). The difference is statistically insignificant
(p=0.13). The specificity of PET-CT is 100% (95% CI: 66; 100), and that of CT, MRI and ultrasound scanning is 78% (95%
CI: 40; 97). The difference is statistically insignificant (p=0.48). The diagnostic accuracy of PET-CT in the primary
staging of disease is 100% (95% CI: 81; 100) and is higher than the accuracy of the conventional imaging methods,
which is 67% (95% CI: 41; 87). The difference is statistically significant (p=0.04).
The sensitivity of PET-CT in detecting disease recurrence is 96% (95% CI: 80; 100) and is higher than the sensitivity of
the conventional imaging methods, which is 36% (95% CI: 18; 57). The difference is statistically significant, in favor of
PET-CT (p

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
As far as the diagnostic accuracy of the methods compared in the staging and detecting recurrences of
malignant female genital cancer, a statistically significant difference was observed in favor of PET-CT versus
conventional methods: 96% (95% CI: 87; 100) vs. 50% (95% CI: 36; 64); p < 0.01, respectively.
2. Ovarian cancer: detecting disease recurrences (PET-CT vs. CT)
As a result of searching medical databases two primary clinical trials were found (Hauth 2005 and Makhija 2001)
that compared directly the diagnostic efficacy of PET-CT with CT in the assessment of ovarian cancer recurrences
(N=27). The reference test was histopathological examination or, if histopathological examination was inaccessible,
clinical follow-up.
PET-CT is characterized by higher sensitivity than contrast CT. The sensitivity of PET-CT is 84% (95% CI: 60; 97) and
that of CT is 47% (95% CI: 24; 71).
The specificity of these methods, evaluated only in Hauth 2005, was 100% for both PET-CT and CT (95% CI: 63; 100).
That implies that a negative result was returned by the imaging methods under analysis for each patient with no
cancer recurrence.
The data provided testify to the superiority of PET-CT diagnostics over contrast CT imaging. The small size of
population in the primary studies limits the reliability of the analysis.
Thyroid cancer
1. Diagnostics of recurrence (PET-CT vs. CT/MRI; whole-body scintigraphy)
As a result of searching through medical databases two primary clinical studies were found (Zimmer 2003, Nahas
2005), in which PET-CT was compared to conventional diagnostics (CT/MRI and iodine 131 whole-body scintigraphy -
WBS) in detecting thyroid cancer (N = 41). The imaging methods compared were verified based on
histopathological tests, while for negative results verification was based on long-term clinical observation and a series
of diagnostic imaging.
In detecting recurrences of thyroid cancer, the sensitivity of PET-CT is 100% (95% CI: 40; 100), i.e. twice the sensitivity
of CT/MRI, 50% (95% CI: 7; 93). The difference is not statistically significant (p = 0.48). In detecting recurrences of
thyroid cancer, PET-CT is characterized by a higher specificity than CT and MRI. The calculated values were 100%
(95% CI: 29; 100) vs. 33% (95% CI: 1; 91) respectively. The difference is not statistically significant (p = 0.48). The
diagnostic accuracy of PET-CT is higher than that of CT/MRI, the values being 100% (95% CI: 59; 100) vs. 43% (95% CI:
10; 82) respectively. The difference is not statistically significant (p = 0.13).
Based on a comparison of PET-CT with iodine 131 whole body scintigraphy (I 131 WBS), the imaging sensitivity of PET-CT
is higher than that of scintigraphy. The established value is 87% (95% CI: 66; 97) for PET-CT, but for I 131 WBS it is 0-21%. In
detecting thyroid cancer recurrences, specificity is identical for PET-CT and whole-body scintigraphy and stands at
100%. Similarly, in detecting recurrences of thyroid cancer, the diagnostic accuracy of PET-CT is 89% (95% CI: 75; 97)
and is higher than that of I 131 WBS, which stands at 33% (95% CI: 18; 50).
In one of the studies included, the authors reported that PET-CT scanning supported early revisions of treatment
policies in 22 patients (67%). These patients were under observation following standard treatment of thyroid cancer.
Additionally, in some patients, the adopted treatment policy was confirmed by the data collected from PET-CT
scanning.
In summary, PET-CT is characterized by a higher diagnostic efficacy in detecting recurrences of thyroid cancer
than convectional imaging methods.
2. Staging (I124 – PET-CT vs. CT, I 131 WBS, USG)
23

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
24
As a result of searching through medical databases, one primary prospective trial was found (Freudenberg 2004)
that compared the diagnostic efficacy of I 124 PET-CT imaging with convectional diagnostic methods (CT, I 131 whole-
body scintigraphy and ultrasonography) in the staging of thyroid cancer (N = 12). All tests were verified based on
histopathological diagnostics and through formal consensus based on diagnostic imaging results.
In tumor staging (T-status), the sensitivity of I 124 PET-CT is 100% (95% CI: 80; 100), and is the same as the sensitivity of
I 131 whole-body scintigraphy (I 131 WBS), but higher than the sensitivity of CT and ultrasound scanning, for which the
values are 35% (95% CI: 14; 62) and 47% (95% CI: 23; 72) respectively.
In node involvement staging (N-status), I 124 PET-CT proved to be the most sensitive. The values are: 100% for PET-CT
(95% CI: 54; 100), 83% for I 131 WBS (95% CI: 36; 100), 50% for CT (95% CI: 12; 88) and 33% for ultrasonography (95% CI: 4;
78).
In distant metastasis staging (M-status), I 124 PET-CT is characterized by a higher sensitivity than I 131 WBS or
ultrasonography. The calculated values are 100% (95% CI: 92; 100), 76% (95% CI: 61; 87) and 65% (95% CI: 50; 79)
respectively.
The combined sensitivity of PET-CT imaging in clinical staging of thyroid cancer, irrespective of location, is 100%
(95% CI: 94; 100) and is higher than the sensitivity of I 131 WBS, CT or ultrasound scanning. The values established for
these methods are 83% (95% CI: 72; 91), 57% (95% CI: 44; 68) and 43% (95% CI: 23; 66) respectively. The differences
between PET-CT and each of the scanning method compared are statistically significant (p < 0.01).
In summary, I 124 PET-CT is characterized by a higher diagnostic efficacy than the conventional imaging methods in
primary diagnostics of clinical staging of thyroid cancer.
Head and neck cancer
1. Diagnostic of malignant head and neck tumors (PET-CT vs. CT)
As a result of searching through medical databases one primary study was found (Branstetter 2005) that
compared directly the diagnostic efficacy of PET-CT with CT in the diagnostics of malignant head and neck tumors
(primary lesions, recurrences following therapy, metastasis to cervical lymph nodes from an unknown primary focus;
N = 65). Biopsy of suspicious lesions, clinical observation, and additional diagnostic imaging were used as the
reference standard.
The sensitivity and specificity of PET-CT were 98% (95% CI: 88; 100) and 92% (95% CI: 84; 97) respectively, while for CT
scans the values were 74% (95% CI: 59; 86) and 75% (95% CI: 64; 84). The accuracy was rated 94% for PET-CT (95% CI:
89; 98) and 74% for CT (95% CI: 66; 82). The difference is statistically significant.
2. Detection of bone involvement by oral cavity cancer (PET-CT vs. SPECT/CT, CT)
As a result of searching through medical databases one primary trial was found (Goerres 2005) that compared
directly the diagnostic efficacy of PET-CT with SPECT/CT and CT in identifying bone involvement by oral cavity
cancer (N = 34). Histopathological examination following a surgical procedure was used as the reference standard.
The sensitivity of PET-CT was the highest and stood at 100% (95% CI: 74; 100), the sensitivity of SPECT/CT was 92%
(95% CI: 62; 100). The sensitivity of CT was 92% (95% CI: 62; 100). The specificity of PET-CT was 91% (95% CI: 71; 99),
compared to 86% for SPECT/CT (95% CI: 65; 97) and 100% for CT (95% CI: 85; 100).
The accuracy of PET-CT scanning was 94% (95% CI: 80; 99), compared to 88% for SPECT/CT (95% CI: 73; 97) and 97%
for CT (95% CI: 85; 100), which represents 94%, 88% and 97%, of properly diagnosed patients for PET-CT, SPECT/CT and

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
CT respectively. The differences in accuracy, sensitivity and specificity of PET-CT, CT and SPECT/CT tests in the
diagnostics of local involvement of bones by oral cavity cancer are not statistically significant.
3. The impact of PET-CT diagnostics on therapy (PET-CT vs. CT, MRI)
As a result of searching through medical databases two primary studies were found (Wild 2005, Koshy 2005) which
compared directly the impact of PET-CT scanning on therapeutic decisions with standard head and neck cancer
staging methods (CT, MRI, medical examination; N = 57).
Histopathological examination was used as the reference standard in Wild 2005, while in Koshy 2005, when distant
metastasis or synchronic tumors were suspected, histopathological tests or a combination of additional diagnostic
imaging and clinical observation were executed (no data are available on the reference standard in the remaining
patients).
In Wild 2005, PET-CT imaging results triggered revisions of treatment suggested based on conventional imaging in
43% patients, while in Koshy 2005 the value was 25%, which produced the total of 32% cases (95% CI: 21; 44).
Pancreatic cancer: diagnostics of primary focus and clinical staging system (PET-CT
vs CT, ERCP, MRI, EUS, laparoscopy)
As a result of searching through medical databases one primary clinical trial was found (Heinrich 2005) that
compared directly the diagnostic efficacy of PET-CT with conventional imaging methods (contrast CT, ERCP, MRI,
EUS, diagnostic laparoscopy) in diagnosing primary lesions and in staging pancreatic cancer (N = 59). The
comparison of imaging methods was verified by histopathological tests of material removed during a surgical
procedure or bioptates, or by long-term clinical observation.
The sensitivity of PET-CT scanning in detecting primary lesions of pancreatic cancer is 89% (95% CI: 76; 96), which is
lower than the sensitivity of contrast CT, which is 93%. PET-CT imaging has a higher sensitivity rating than contrast CT in
detecting pancreatic cancer, the estimated values being 69% (95% CI: 39; 91) vs. 21%, respectively. The accuracy of
PET-CT is 85% (95% CI: 73; 93). No statistically significant differences were observed between the groups for any of the
parameters of efficacy discussed.
In M-staging, PET-CT is characterized by a higher sensitivity than conventional imaging methods, the estimated
values being 81% (95% CI: 54; 96) vs. 56% (95% CI: 30; 80) respectively. The difference in favor of PET-CT is not
statistically significant (p = 0.22). Imaging specificity favors PET-CT, for which it stands at 100% (95% CI: 92; 100) vs. 95%
(95% CI: 84; 99) for the conventional methods compared. The accuracy of PET-CT in M-staging is 95% (95% CI: 86; 99)
and is higher than the accuracy of the conventional methods (CT, NMR and USG), 85% (95% CI: 73; 93). The
difference, although close to the threshold, did not reach statistical significance (p = 0.08).
A revision of oncological procedures as a result of PET-CT scanning was reported for 16% patients (95% CI: 6; 32)
with resectable pancreatic cancer. Procedure revision is more likely if PET-CT scanning is used in clinical staging than
if the conventional methods are used, the estimated values being 33% (95% CI: 20; 48) vs. 20% (9; 34) respectively.
The difference in favor of PET-CT is statistically significant (p = 0.03).
25

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Gastrointestinal stromal tumor: staging and evaluation of response to treatment (PET-
CT vs CT)
26
A single clinical trial was found (Antoch 2004) that compared the diagnostic efficacy of PET-CT with that of CT
imaging in GIST staging and in the evaluation of treatment response in patients with gastrointestinal stromal tumor
(N = 20). Long-term clinical observation was used as a reference standard.
In primary disease staging, PET-CT imaging is more effective as a diagnostics method than CT. The difference
between the diagnostic methods compared was statistically significant (p < 0.0001). In terms of response to
treatment, significant congruence of results between the method compared and the reference standard was
identified only for PET-CT. When PET-CT scanning was used, response to treatment was diagnosed correctly in 95%,
100% and 100% patients in 1, 3 and 6-month follow-up periods respectively. For CT, the respective values were 44%,
60% and 57%. The difference between particular diagnostic methods reached statistical significance in the 1 st month
(p = 0.001).
Colorectal liver metastasis: residual disease after ablation (PET-CT vs. CT)
As a result of searching through medical databases, a single primary prospective clinical trial was found (Veit 2006)
that compared directly the diagnostic efficacy of PET-CT and CT imaging in detecting residual lesions of colorectal
liver metastasis following a therapy that used high-current radio-frequency current ablation (N = 13).
The sensitivity of PET-CT in detecting residual disease is 65%, and is higher than that of CT, which stands at 44%. The
authors provide no data on the statistical significance of the results above.
The accuracy of PET-CT in detecting residual disease is 68%, and is higher than the accuracy of CT, which stands at
47%.
Analysis of imaging methods compared showed that in detecting residual lesions of colorectal liver metastasis
following high-current radio-frequency ablation, a higher efficacy is demonstrated by PET-CT diagnostics than by CT
imaging.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
2. INDEX OF ABBREVIATIONS
18 F-FDG [18F]-Fluoro-Deoxy-Glucose
3D 3 Dimensional Imaging
Acc Accuracy
AJCC American Joint Committee on Cancer
BAC Fine-needle aspiration biopsy
BD, bd No data available
CA 19-9 Carbohydrate antigen 19-9
CEA Carcinoembryonic antigen
CI Confidence Interval
CR Complete response
CT Computed Tomography
DOR Diagnostics Odds Ratio
EBM Evidence Based Medicine
ERCP Endoscopic retrograde cholangio- pancreatography
EUS-FNA Endoscopic ultrasound-guided fine-needle aspiration biopsy
FIGO International Federation of Gynecology and Obstetrics
FN False Negative
FP False Positive
GIST Gastrointestinal stromal tumor
I 124 Radioactive isotope of iodine-124
I 131 Radioactive isotope of iodine-131
IS Statistically significant
kg Kilogram
l Liter
LR- Negative likelihood ratio
LR+ Positive likelihood ratio
M Metastasis staging
M0 Absence of distant metastasis
M1 Presence of distant metastasis
MBq Becquerel, unit of radioactivity
MRI Magnetic resonance imaging
N Number of patients in group
n Number of patients with end point
N Llymph nodes involvement staging
N0 Absence of metastasis to lymph nodes
27

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
28
nd Not applicable
Ng Nanogram
NNT Number of patients needed to treat
NPV Negative predictive value
NS Not statistically significant
NSCLC Non-small cell lung cancer
NSE Neurospecific enolase
OR Odds ratio
pp. Percentage points
PET-CT, PET/CT Positron Emission Tomography and Computed Tomography
pg Pikogram
PPV Positive predictive value
RCT Randomized controlled trial
Re Reference method
rtg X-rays trial
SD Standard deviation
Se Sensitivity
Sp Specificity
T Identification of tumor size
Tis In situ tumor
TN True negative
TNM
Stage of disease: T – tumor size identification; N – assessment of lymph nodes involvement, M
– detecting metastasis
TP True positive
Tx Latent tumor
USG Ultrasonography
WBS Whole body scintigraphy
WMD Weighted mean difference

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3. DESCRIPTION OF HEALTH PROBLEM
3.1. Epidemiology of cancers
In 2002, 10.9 million of new cases of cancer, including 26 most common tumors and 6.7
million related deaths were reported in the world. The most common tumor is lung cancer,
with respect to both disease incidence (1.35 million) and mortality (1.18 million). This cancer
type is typified by poor prognosis, which is indicated by a high mortality to incidence ratio
(0.87). Breast cancer is the second leading malignant tumor in the world (1.15 million of new
cases), but is typified by more optimistic prognosis (mortality to incidence ration at 0.35).
Colorectal cancer was diagnosed in 1.02 million people, gastric cancer in 934,000, and liver
cancer in 626,000.
The most common malignant tumor among men is lung cancer, however in developed
countries it is second to prostate cancer. Cervical cancer is the second leading malignant
cancer among women in developing countries; in developed countries it ranks seventh.
Morbidity, i.e. the prevalence of cancer (number of patients) in a population in a specific
period of time, depends on the incidence of disease and its mortality. As regards morbidity,
the most common tumor types are breast cancer (17.9%), colorectal cancer (11.5%), and
prostate cancer (9.6%). The morbidity to disease incidence quotient is an index that
represents prognosis. For example, the world’s morbidity rate for breast cancer is the highest,
although it breast cancer has a lower incidence rate than lung cancer, which has a poor
prognosis.
Figure 1 shows disease incidence and death rates of the world’s most common tumors, in
developed and developing countries [1].
29

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Figure 1.
Global incidence and mortality rates for the most common tumors types in developing and developed countries [1]
30
After World War II in Europe, a rising trend in the incidence of malignant tumors was
observed, not only in women but also in men. Recently, in the countries of Western Europe,
the incidence of the prostate cancer in men has been going up in the first place, while the
incidence of lung cancer has been following a downward trend or staying flat. In these
countries, the incidence of gastric cancer has significantly dropped in men. The incidence
rates of breast cancer calculated for women in Western Europe keep rising, so does the

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
incidence of lung cancer, especially in young women. The incidence of cervical cancer and
gastric cancer is going significantly down in this group; however the incidence of cancer of
the large intestine and colon is increasing slightly regardless of gender. In Eastern Europe, the
rates of incidence of lung cancer in men and breast cancer in women keep growing. High
incidences of gastric cancer in both sexes and of cervical cancer in women are still
observed. The frequency of developing cancer is expected to grow gradually over the next
20 years, the reasons being, among other things, the ageing of the population and increased
exposure to risk factors [2]. In the member states of the European Union, a decrease in
cancer-related mortality has been observed, but in a number of countries of Eastern Europe,
including Poland, the trend continues along the rising path [2].
Based on data from the Central Statistical Office, in 2001 the incidence of malignant
cancer in Poland was 298 per 100,000 people annually. For a number of years this ratio has
been growing faster than the population. The disease is the cause of about 40% of deaths in
women and about 30% deaths in men aged 45–64 years [3].
Table 1 presents the morbidity and mortality rates for selected malignant cancer types in
men and women in Poland (2002) [4].
Table 1.
Morbidity and mortality rates for selected malignant cancer types in Poland in 2002 [4]
Type of
tumor
Incidence
of disease
Morbidity
(death
rate)*
Men Women
Number
of deaths
Mortality*
Incidence
of disease Morbidity*
Number
of deaths
Mortality
(death
rate)*
Oral cavity 1719 7.3 800 3.4 441 1.4 221 0.7
Nasal part
of the
pharynx
Other parts
of the
pharynx
141 0.6 81 0.3 63 0.2 37 0.1
1383 6.0 523 2.2 204 0.7 89 0.3
Esophagus 1408 6.0 1113 4.7 305 0.9 260 0.8
Stomach 4962 20.7 4017 16.6 2634 7.8 2188 6.2
Colorectum 7671 31.9 4432 18.2 7909 23.5 4082 11.4
Liver 851 3.6 1045 4.3 884 2.6 1141 3.2
Pancreas 2254 9.5 1914 8.0 2103 6.1 1849 5.3
Larynx 3062 13.2 1539 6.5 370 1.3 151 0.5
Lung 19478 82.0 16354 68.4 4534 14.6 3960 12.3
Skin
melanoma
881 3.8 463 2.0 1250 4.5 451 1.5
31

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
32
Prostate 6016 24.1 3114 12.4
Testicle 869 4.1 118 0.5
Breast 14358 50.3 4781 15.5
Uterine
cervix
Uterine
corpus
4901 18.4 2278 7.8
3824 13.0 963 2.8
Ovary 3570 12.5 2071 6.8
Kidney 3151 13.5 1477 6.2 1662 5.3 855 2.5
Gall
bladder
Central
nervous
system
Thyroid
gland
Non-
Hodgkin’s
lymphoma
Hodgkin's
disease
Multiple
myeloma
5215 21.8 2065 8.4 1181 3.6 498 1.4
1812 8.2 1291 5.8 1546 5.9 1148 4.1
422 1.8 82 0.3 1086 4.1 216 0.6
1574 7.0 781 3.4 1088 3.8 578 1.8
565 2.7 249 1.1 670 3.0 159 0.6
721 3.1 418 1.7 731 2.3 454 1.3
Leukaemias 1575 7.2 1252 5.4 1293 4.6 1050 3.3
Total 71349 301.8 48765 203.5 63220 210.3 36317 110.6
Prognosis varies depending on type of cancer as well as on expenditure on health care. In
1995, expenditure ranged from US$420 in Poland (parity of USD purchasing power per person
in population) to US$2555 (Switzerland) [5].
European 5-year mean survival rates range from 94% for lip cancer to < 4% for pancreatic
cancer. For 21 out of 42 cancer types in adults, the 5-year mean survival rate is ≥ 50%.
Generally, survival rates are high for lip, testicle and thyroid cancer, skin melanoma and
Hodgkin’s disease (the European 5-year mean survival rate is ≥ 80%). These high survival rates
are attributable to possibilities of efficacious treatment, as well as a good availability of tumor
location and early diagnosis opportunities. For a larger group of cancers, the 5-year mean
survival rate ranges from 60 to 79%, including breast cancer, prostate cancer, cancer of the
gall bladder, cervical cancer, uterine cancer and cancer of the larynx. This group represents
one-third of all tumors. Moderate prognosis (5-year survival rates of 40–59%) is common for
colorectal cancer, non-Hodgkin’s lymphomas, and renal cancer. Poor prognosis is associated
with about 10% of tumors (5-year survival rates of 20–39%), among them gastric cancer,
ovarian cancer, or multiple myeloma. The poorest prognosis (5-year survival rates < 20%) is
associated with tumors such as lung cancer, pancreatic cancer, esophageal cancer, brain
cancer, and liver cancer. Liver cancer represents one-fourth of all tumors. They are not as
easily accessible for diagnostic procedures and are usually diagnosed late.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Prognostic factors include the patient’s age. For example, the highest 5-year survival rate
in breast cancer in women is observed for ages 45-54, and for prostate cancer for ages 55-64.
Sex is another factor. A Higher 5-year survival rate has been observed in women compared
to men for four head and neck tumors: cancer of the salivary gland, oral cavity, tongue and
of oral part of pharynx (difference in 5-year survival rate ≥ 15%), for thyroid cancer (10%) and
for skin melanoma (10%). These differences probably stem from the fact that women and
tumors are diagnosed earlier on, hence their stage is lower.
5-year survivals differ between European countries. The lowest rate has been reported in
five countries of Eastern Europe (the Czech Republic, Estonia, Poland, Slovakia and Slovenia)
and in six countries of Western Europe (Germany, Great Britain, Wales, Scotland, Malta and
Portugal). Of all the countries of Eastern Europe, Poland has the lowest survival rates for
cancer [5].
Figure 2 shows the relative 5-year survival rates for selected cancer types in Europe [5] 1 .
1 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): pp 74–108.
2. Evidence-based Cancer Prevention: Strategies for NGOs – A UICC Handbook for Europe. http://www.uicc.org
3. Narodowy program zwalczania chorób nowotworowych. ZałoŜenia i cele operacyjne 2006–2015;
http://www.mz.gov.pl/wwwfiles/ma_struktura/docs/zalozenia_ustawy_o_npzchn.pdf
4. The Globocan 2002 database: http://www-dep.iarc.fr
5. Coleman MO et al. Eurocare-3 summary: cancer survival in Europe at the end of 20th century. Ann Oncol 2003; 1:
pp 128–149.
33

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Figure 2.
European average relative 5-year survival rates (%) for 42 selected tumor types; adults aged 15–99, diagnosed in
1990–1994, with the follow-up period till 1999 [5]
34
3.2. Lung cancer
3.2.1. Epidemiology
Malignant lung tumors are the most common tumor types in the world. In 2002, 1.35 million
persons had lung cancer and 1.18 million related deaths were reported globally. The high

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
morbidity to incidence ration (0.87) proves the disease has a poor prognosis. Currently, these
tumors represent 12.4% of all newly diagnosed malignant tumors [1. 14]. Since 1985, a 51%
growth in lung cancer incidence has been observed, the reasons seem to be the growing
and ageing population [1]. In Europe, growth in the incidence of lung cancer was observed
in the 1960’s and 1970’s; later, lung cancer began to fall (mostly in Great Britain) [2]. The
incidence of lung cancer varies significantly between men and women. It is estimated that
every 4th European men diagnosed with malignant tumor will develop lung cancer, while in
women this tumor type represents only 6% of all tumors diagnosed [14]. Unlike in men, for who
the growth of lung cancer incidence has been curbed, lung cancer incidence and mortality
rate in European women is increasing dramatically [2]. In Eastern Europe lung cancer is the
most frequent malignant tumor in men and the seventh leading cancer type in women [2].
Poland is among the countries with the highest incidence and mortality rate of lung
cancer. In 1999, the rates were: 83/100000 and 81.9/100000 in men, and 19.6/100000 and
18.4/100000 in women. Before 1995, an upsurge in the incidence and mortality caused by this
tumor had been observed. Since 1995, the growth pace has been slower [1, 2, 4, 14]. At the
same time, over the last 30 years, a significant increase of incidence and the mortality rate
has been reported in Poland for younger groups, both men and women [4]. 2002
epidemiological reports indicate that age-standardized lung cancer incidence and mortality
rates were 82 and 68.4 per 100,000 men, and 14.6 and 12.3 respectively per 100,000 women
[3].
Graph 1 illustrates mortality trends in 20 selected European countries.
35

ASRW (age-standardized incidece rate per world population) on 100000 persons
Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Chart 1.
Mortality trends associated with malignant lung cancer in 20 European countries (age-standardized rate); source:
WHO [2]
36
3.1.1. Risk factors
Source: WHO
The relation between smoking or exposure to carcinogenic substances contained in
cigarettes smoke and malignant lung tumor has been known for a long time. Addiction to
nicotine may be the cause of up to 90% of new cases. If a smoker quits smoking, cancer risk
decreases gradually. Also, second-hand smoking increases the risk of disease. Other
carcinogenic substances include industrial pollution, heavy metals, ionizing radiation, and
exposure to radon or asbestos, but their impact is not as high. Genetic predisposition to lung
tumors also exists [4, 6, 14].
3.1.2. Symptoms
Years: 1953–57 to 1993–97
Initially, lung cancer is asymptomatic; possible symptoms are associated in the main with
the location of the tumor. Squamous and small cell cancers are located centrally, while small
adenocarcinoma or giant cell cancer are more often situated peripherally in the lung.
Tumors located centrally block the bronchi, cause cough and haemoptysis. Peripheral tumors

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
cause pain, interstitial pneumonia or dyspnoea. The most common symptoms are cough
(>50% of patients), dyspnoea (30–40%), chest pain (25–35%), haemoptysis (15–30%), recurring
pneumonia (as the first symptom in 15–20% of patients) and atelectasis caused by poor
bronchial patency due to obstruction from tumor mass. Symptoms of local spread of the
tumor are: superior vena cava syndrome (compression of the superior vena cava), hoarse
throat (caused by paralysis of the recurrent laryngeal nerve), Horner’s syndrome. Pancoast’s
syndrome is associated with the presence of tumor in the apex of the lung, and is
accompanied by shoulder, arm and forearm pain. Other symptoms are disability of trachea
and loss of esophageal patency, which may lead to breathing disturbances or problems with
swallowing. Heart infiltration may lead to its functional disturbances, while carcinogenic
infiltration of the pleura may be conducive to accumulation of exudative fluid in the pleural
cavity, which additionally decreases the vital capacity of the lung and impedes ventilation.
Infiltration of the phrenic nerve leads to diaphragm paralysis, which additionally impedes lung
ventilation. Cancer invasion in the thoracic wall causes strong pain. A number of ailments
beside those listed above are related to metastasis, the most frequent being osseal pains
(bone metastasis), headaches and neurological symptoms (brain metastasis), pain in
hypergastrium, nausea, loss of body weight, jaundice (liver metastasis) [4, 6, 8].
Paraneoplastic syndromes can be observed in the course of lung tumors, mostly as
hormonal or neurological disorders. Endocrinological disorders occur mainly in small cell
cancer. The most common endocrinological paraneoplastic syndrome is the syndrome of
inappropriate antidiuretic hormone secretion (ADH). Secretion of atrial natriuretic peptide
manifests itself by a low content of sodium in urine and low blood pressure. Increased
concentration of corticotrophin may cause Cushing’s syndrome. In patients suffering from
non-small cell lung cancer, hypocalcaemia is observed. Neurological paraneoplastic
syndromes include Lambert and Eaton syndrome (i.e. weakness of the extremities, which
manifests itself during exercise), polymiositis and dermatomyositis. The disease may also be
accompanied by cerebritis and inflammation of the spinal cord, cerebellum degeneration,
sensory neuropathy, or blunt vision. It is believed that all the neurological syndromes
mentioned are of autoimmune origin [9, 10].
At the advanced stages of the disease, syndromes are associated mainly with distant
metastasis. Cancer spreads most of all to the liver, bones, brain, skin, suprarenal glands, and
small cell lung cancer can also invade bone marrow [4, 6 and 8]. At initial diagnosis, small cell
cancer of lung is usually diffused; only in 1/3 of patient the tumor is low stage cancer [10].
General cancer symptoms include weakness, cachexia, loss of body weight and fever.
37

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
38
3.1.3. Histopathological picture
The classification of primary lung tumors is based on the morphologic picture, biological
features, clinical course and treatment procedures. Of all the numerous existing histological
classifications of lung cancer, the most widespread is the classification accepted by WHO
in 1999 [4]. Diagram 1 presents the classification of lung tumors based on WHO
recommendations.
Diagram 1.
WHO classification of lung tumors, 1999
1. Squmous cell carconoma
a. Papillary
b. Clear cell
c. Small cell
d. Basaloid
2. Small cell cancer
a. Combined small cell carcinoma
3. Adenocarcinoma
a. Acinar
b. Papillary
c. Bronchoalveolar carcinoma
I. Nonmucinous
II. Mucinous
III. Mixed mucinous and nonmucinous or indeterminate cell type
d. Solid adenocarcinoma with mucin formation
e. Adenocarcinoma with mixed subtypes and variants (mucinous cystadenocarcinoma, signet ring
adenocarcinoma, clear cell adenocarcinoma)
4. Large cell carcinoma
a. Large-cell neuroendocrine carcinoma
I. Combined large cell neuroendocrine carcinoma
b. Basaloid carcinoma
c. Lymphoepithelioma-like carcinoma
d. Clear cell carcinoma
e. Large cell carcinoma with rhabdoid phenotype
5. Adenosquamous carcinoma
6. Carcinomas with pleomorphic, sarcomatoid or sarcomatous elements
a. Carcinomas with spindle and/or giant cells
I. Pleomorphic carcinoma
II. Spindle cell carcinoma
III. Giant cell carcinoma
b. Carcinosarcoma
c. Pulmonary blastoma
d. Others
7. Carcinoid tumors
a. Typical carcinoid

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
b. Atypical carcinoid
8. Carcinomas of salivary gland type
a. Mucoepidermoid carcinoma
b. Adenoid cystic carcinoma
c. Others
9. Unclassified carcinoma
Considering different clinical courses, prognosis and treatment, lung cancers are, in most
cases, divided into non-small cell cancers, which represent 80% of all lung tumors (including
squamous cell cancer, adenocarcinoma and giant cell carcinoma), and small cell cancers
(20% of all).
Non-small cell cancers are tumors of small chemosensivity. The first-choice therapy is
surgical excision of the tumor. Small cell cancer is characteristic for its fast growth, tendency
to rapid metastasis formation and high vulnerability to chemotherapy.
Squamous cell carcinoma (carcinoma planoepitheliale) represents about 40% of all
primary lung tumors. Most commonly it is located in the large bronchi, and associated above
all with cigarettes smoking. It develops from metaplasia of respiratory track epithelium, and is
slow-growing. Symptoms of bronchus narrowing, such as atelectasis, or pneumonia are
common in the course of the disease.
Adenocarcinoma represents about 30% of primary lung tumors. Most often it is located in
the small bronchi and is not as strongly associated with smoking. Atypical alveolar
hyperplasia is considered to precede the development of adenocarcinoma. A special type
of this tumor is bronchoalveolar cancer (carcinoma bronchoalveolare). This cancer can
occur multifocally.
Giant cell cancer (carcinoma macrocellulare) is the most rare (10%) of all cancer types. Its
localization is the large bronchi. The clinical course is similar to adenocarcinoma.
Small cell cancer (carcinoma microcellulare) is distinguishable for the highest cellular
proliferation index. At diagnosis, haematogenous metastases are usually formed. This cancer
type is particularly strongly associated with cigarettes smoking. As a rule, it is located close to
pulmonary hiluses. Metastasis occurs mainly in the liver, bones, bone marrow, central nervous
system, skin and soft tissues. Symptoms of endocrinological or neurological nature are often
present [4, 6, 7].
A histopathological picture helps determine the histological malignancy grade (G trait).
Table 2 presents the classification.
39

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Table 2.
histological malignancy grades of lung cancer
Gx Grade of differentiation cannot be assessed
G1 Highly differentiated
G2 Moderate degree of differentiation
G3 Low degree of differentiation
G4 Undifferentiated
40
3.1.4. Staging
Table 3 presents the commonly used TNM system for the staging of lung cancers [15].
Table 3.
TNM staging system of the clinical advancement of the lung cancer
Primary tumor
Tx Primary tumor cannot be evaluated
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1
T2
T3
T4
Regional lymph nodes
Tumor 3 centimeters (< 3 cm) or less in greatest dimension, surrounded by
lung or pleura
Tumor more than 3 centimeters (> 3 cm) in greatest dimension, or tumor
invading the visceral pleura, atelectasis or lung infection
Tumor that invades the chest wall, diaphragm, pleura, or pericardium, or the
main stem bronchus less than 2 centimeters (< 2 cm) from the carina but
without involvement of the carina
Invasion of mediastinum, heart, great vessels, trachea, carina, esophagus,
vertebral body, tumor with a malignant pleural effusion
N0 No regional lymph node metastasis
N1 Metastasis to same-side peribronchial and/or hilar lymph nodes tumor
N2 Metastasis to same-side mediastinal and/or subcarinal lymph nodes
N3
Distant metastasis
M0 No distant metastasis
M1 Distant metastasis present
Staging
Latent cancer Tx N0 M0
Stage 0 Tis
Stage I
Stage II
Stage IIIA
Stage IIIB
Metastasis to opposite-side mediastinal or hilar nodes or to same- or oppositeside
supracalvicular lymph nodes.
T1 N0 M0
T2 N0 M0
T1 N1 M0
T2 N1 M0
T3 N0 M0
T3 N1 M0
T1-3 N2 M0
Every T N3 M0
T4, N (any), M0
Stage IV T (any), N (any), M1

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
It should be noted that the classification above particularly important for non-small cell
lung cancers, because small cell cancers are usually diagnosed in a diffused form. For small
cell cancers, a two-stage classification of tumor is used:
1. Limited stage – tumor is confined to one side of the chest, also with same-side
carcinogenic exudation; involvement of same-side hilar region, and the involvement
of mediastinal and supraclavicular, lymph nodes on both sides are possible,
2. Extensive stage – tumor outside the limited disease area.
3.1.4.1. Non-small cell cancer staging
In patients for whom surgical excision of tumor is considered, it is particularly important to
determine the local and regional cancer stage. For this purpose, CT with contrast is
indispensable. The study covers the upper part of the chest to examine the liver, suprarenal
glands, lymph nodes (frequent metastatic location). Other imagining studies are performed if
clinical symptoms occur suggesting involvement of these organs.
3.1.4.2. Small cell cancer staging
As small cell cancer diffuses early, it is particularly important to identify cancer foci outside
the chest. If at least one focus of distant metastasis is present general disease is diagnosed
positively. Therefore further screening for distant metastasis is pointless as is has no effect on
the procedure with the patient. It is necessary to perform CT of the abdominal cavity, and CT
or magnetic resonance imagining of the brain because asymptomatic brain metastasis is
frequent. As a result of frequent bone marrow metastasis, scintigraphic study of the skeletal
system is recommended. Trepanobiopsy of bone marrow is performed in patients with
positive results of scintigraphy, with high lactic dehydrogenase level in plasma or with
thrombocytopenia.
3.1.5. Diagnostics and treatment
3.1.5.1. Case history
Identifies the disorders described above.
3.1.5.2. Physical examination
Symptoms depend mainly on the disease stage, location of primary tumor, as well as
metastatic location. Examination may help detect auscultatory changes over lung fields,
which correspond to pneumonia, atelectasis, fluids in pleura or infiltration by tumor. In
advanced cases, enlarged cervical, supraclavicular, and axillary lymph nodes are
detectable. Liver metastasis produces liver enlargement, tenderness under the right costal
arch or jaundice. Brain metastasis leads to neurological disorders such as focal symptoms or
41

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
sensory disorders. Strong bone pains and tenderness may be caused by metastasis. Quite
common symptoms are clubbed fingers [4, 6, 8].
42
3.1.5.3. Diagnostic imaging
Apart from case history and physical study, the basic method of lung diagnostics is chest X-
ray in the anterolateral position, with additional lateral projections. It helps detect lesions that
often do not produce clinical symptoms typical of cancer yet. Diagnostic imaging is not
recommended as lung cancer screening examinations in asymptomatic patients or patients
without tumor in history. In a routine chest radiogram, small, 1cm-big tumors can be seen [9,
12]. Apart from tumor-like lesions, a chest radiogram may reveal other lesions that are
manifestations of cancer: inflammatory interstitial densities, atelectatic symptoms, exudation
to the pleural cavity. If tumor-like changes are present in a chest radiogram, the radiogram
needs to be compared with previous imaging studies of the chest. If the picture of the lesion
remains stable within a period ≥ 2 years, or if changes typical of benign tumors, such as
calcifications within tumor limits are visible, further diagnostics is not recommended [9].
Contrast CT is more accurate and it reveals a few millimeter large tumor-like changes, or
carcinogenic changes that are invisible in X-ray pictures, where they are overshadowed by
mediastinum or interstitial densities. CT helps identify not only primary tumors, but also lymph
node metastasis. However, tomography scanning has minor importance in tumor staging in
atelectatic areas (tumor is hard to separate from the atelectatic focus), or in the staging of
small infiltrations by cancer of the mediastinum (which is essential for diagnostics and
therapy). The value of CT is also limited in the evaluation metastasis to mediastinal lymph
nodes because morphologic criteria (enlargement of lymph node > 1cm as a criterion of
metastatic diagnosis) are characterized by low sensitivity. Magnetic resonance is not
commonly used in the diagnostics of lung changes. Recently, PET has been used more and
more often for N-staging. PET helps to find small metastasis to mediastinal lymph nodes, and
to determine the extension of the tumor in atelectatic lung areas with more precision than
CT. Whole-body PET helps detect metastatic foci outside of the chest. As the availability of
PET is still low in Poland, N-staging of mediastinal lymph nodes is done using invasive methods,
such as mediastinoscopy [6, 9].
3.1.5.4. Microscopic diagnosis
Microscopic diagnosis can be assessed on the basis of cytological or histopathological
examinations. In 50–70% of cases, cytological evaluation of sputum is sufficient, in 80–90% of
cases microscopic diagnosis can be made by bronchofiberoscopy. Bronchoscopy permits
macroscopic evaluation of the bronchi and sampling for histopathological tests. What’s
more, in this procedure bronchial stem washings are collected, which, when assessed
cytologically, may help diagnose changes invisible to imaging studies or bronchoscopy.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Image-guided (CT or ultrasound-guided) biopsy of peripheral lesions through the chest wall is
recommended. When fluid is detected in the pleural cavity, it can be sampled using
transthoracal biopsy to be examined cytologically. If the studies above are insufficient for
diagnosis, supplemental mediastinoscopy, thoracoscopy or thoracotomy should be carried
out. If lymph nodes are enlarged, biopsy or surgical excision may be recommendable [4, 6, 8,
9].
3.1.5.5. Other tests
Biochemical tests identify anemia, or high concentration of alkaline phosphatase (for
bone metastasis) or high levels of liver enzymes in blood (for liver metastasis), as well as
improper sodium concentration or low serum calcium concentration. For small cell cancer,
bone marrow trepanobiopsy to evaluate bone marrow infiltration is indicated. Also,
increased concentration level of cancer markers, such as carcinoembryonic antigen (CEA),
CK 19 section of cytokeratin (CYFRA 21.1), or neuron-specific enolase (NSE) can be found In
cancer patients [6].
3.1.5.6. General principles in small cell lung cancer diagnosis
The diagnostic procedure depends on the disease stage, clinical condition, and outcome
of additional studies. If based on the clinical picture, small cell lung cancer is suspected,
diagnosis should be obtained using the least invasive method possible. In patients with
suspected non-carcinogenic exudation in pleura, fluid should be taken for cytological
examination using biopsy through the chest wall, and if infiltration of the chest wall and
parietal pleura is suspected, pleura can be sampled by blind biopsy through the chest wall
with the use of a special needle. When histopathological tests do not confirm suspicions in
patients with fluid in the pleural cavity, thoracoscopy should be done for sampling as the next
step. In patients with suspected lung cancer and single out-of-lung, presumably metastatic,
lesions, diagnosis should be done by large-needle biopsy, or a specimen of the lesion should
be taken. In patients with extensive infiltration of the mediastinum, diagnosis should be
established by examining tissue specimens taken from the mediastinum using the most
efficacious method possible (bronchoscopy with peribronchial biopsy, biopsy through the
chest wall or mediastinoscopy). Patients diagnosed with a single peripheral tumor-like,
presumably carcinogenic, lesion, in whom the disease seems to be at an early stage, are
qualified to surgery and intraoperational tumor evaluation [6, 8, 9].
3.1.5.7. General principles of treatment
Primary prevention of lung cancer by promoting non-smoking attitudes is of paramount
importance. Smokers should be identified, because quitting smoking curbs the risk of lung
cancer and as such it should be recommended. Smokers should have access to
psychosocial and behavioral therapies whenever recommended [4, 6, 8, 9, 11].
43

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
44
3.1.5.8. Non-small cell cancer
The choice of treatment method depends mainly on the tumor stage. Surgery is the basic
type of treatment. For stages I and II, complete tumor resection with lobotomy or
pulmectomy is performed. Stage IIIA tumors have border-line operability. Stage IIIB tumors are
no longer operable. The extent of resection is determined by the R-trait: R0 are macro- and
microscopic resections; R1 is macroscopic-only resection; and R2 is incomplete resection in
macroscopic evaluation. Not all patients can qualify for operation. The necessary
requirements include: the simple exercise tests such as walking up and down the stairs, the 6-
minute walk test or, finally, spirometric examination (mainly the expiratory volume in the first
second and vital capacity). Postoperative complications include respiratory and
cardiovascular insufficiency. Operation can be supplemented with other therapeutic
procedures such as neoadjuvant radiotherapy, postoperational radiotherapy,
postoperational radiotherapy coupled with chemotherapy, or chemotherapy. The routine
procedure in inoperable patients is radiotherapy. Radical radiotherapy is an option for
patients with limited-mass tumor, without exudation in the pleural cavity and with an efficient
respiratory track. Doses >65 Gy and fraction doses 1.8–2.5 Gy are administered. Because the
radiated tumor is located in the chest in the environment of radiosensitive structures of critical
importance for life, such as the heart and the great vessels, so-called three-dimensional
conformal radiation therapy id used (3D-CRT). With this technology, the radiation area can
be adjusted to the tumor shape with great precision, ensuring maximum preservation of the
surrounding structures. In some cases integrated treatment is used (chemotherapy with
radiotherapy). However, this policy increases the early toxicity of therapy. With locally
advanced lung tumors, palliative radiotherapy is used to help shrink the tumor, alleviate pain,
and reduce the symptom of tumor pressure on the adjacent structures. Radiation doses are
reduced (20–30 Gy in a few fractions or a single higher dose, e.g. 10 Gy). Chemotherapy uses
platinum derivatives (cisplatin, carboplatinum), ifosphamide, mitomycine, or alcaloids
(vinblastin). New drugs include taxoids (paclitaxel, docetaxel), gemcitabine, vinorelbin. Two-
drug combinations comprising platinum-based agents are currently the preferred standard
regimens. Drugs that act on epithelial cell growth factor receptor tyrosine kinase inhibitors,
such as gefitinib or erlotinib, arouse great expectations. Other additional treatment methods
that may be applied to specific clinical conditions are brachytherapy, electrocoagulation,
phototherapy, cryotherapy, or laser therapy. They affect cancer tissues locally. In the case of
atelectasis caused by tumor growing into and narrowing the bronchial lumen, bronchial
patency should be improved and a stent placed in the narrowing. In patients with bone
metastasis, radiotherapy may significantly decrease pain. Symptomatic brain metastasis is an
indication for radiation or excision. For patients in good general condition, diagnosed with
disease dissemination, chemotherapy should be considered [4, 6, 8, 9, 11].

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.1.5.9. Small cell carcinoma
Small cell carcinoma is the most aggressive type of cancer. Chemotherapy is the
fundamental treatment. More active drugs against this cancer type include cisplatin,
etoposide, cyclophosfamide, doxorubicin, vincristin. The most often applied is a combination
of cisplatin with etoposide; or, less frequently, vincristin with doxorubicin and
cyclophosphamide. Chemotherapy leads to total remission in about 80–90% of patients. The
therapy is supplemented by radiotherapy of the primary cancer focus. The recommended
doses are 55–60 Gy. A combination of chemotherapy and radiotherapy helps attain a higher
rate of long-term survivals. In patients with total remission of cancer in the chest, additional
brain radiation is used. The recommended doses are 25–30 Gy. This procedure reduces the
number of distant metastasis.
The efficacy of surgical treatment is low with small cell cancer, and is always combined
with chemotherapy. For recurrent limited-stage cancer, chemotherapy can be repeated.
The regimen is repeated not earlier than 3 months after therapy is completed; in other cases
different drug combinations are administered [4, 6, 8, 9, 10, 11].
3.1.6. Prognosis
Lung cancer has a poor prognosis. Epidemiologic studies indicate that the 5-year survival
rate in Poland for malignant lung cancer patients is 6.1% in men and 6.8% in women, and is
lower than in the European population [5.13]. Mortality as a cause of malignant lung tumors is
still growing in Poland. However, this factor is expected to stabilize in the nearest years [5].
The survival period in non-small lung cancer depends on the disease stage at diagnosis.
The only efficacious therapeutic method is surgical treatment. 5-year survivals after complete
resection of stage I, II and IIIA tumors are 50–70%, 30–50% and 10–30% respectively. Patients
with disseminated non-small lung cancer do not survive a year. In the majority of patients
diagnosed with non-small lung cancer, disseminated disease is found at the first diagnosis.
The median period of survival without treatment is 6–8 weeks, only a few percent of patients
survive 5 years [6] 2 .
2 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): pp 74–108.
2. Evidence-based Cancer Prevention: Strategies for NGOs – A UICC Handbook for Europe. http://www.uicc.org
3. The Globocan 2002 database: http://www-dep.iarc.fr
4. Roszkowski-ŚliŜ K. Cancer płuca – aspekty epidemiologiczne i diagnostyczne. Pneumonologia 2005;
http://www.terapia.com.pl/archiwum
5. Narodowy program zwalczania chorób nowotworowych. ZałoŜenia i cele operacyjne 2006–2015;
http://www.mz.gov.pl/wwwfiles/ma_struktura/docs/zalozenia_ustawy_o_npzchn.pdf
6. Szczeklik A. i wsp. Choroby wewnętrzne. Kraków, Medycyna Praktyczna, 2005.
7. Coran R, Kumar V, Ramzi T. Robbins pathologic basis of disease. Elsevier/Saunders, 1999, wydanie 6.
8. Pawlicki M i wsp. Leczenie nowotworów. Bielsko Biała, Alfa Medica Press, 1996.
9. Diagnosis and management of lung cancer: ACCP evidence-based guidelines. American College of Chest
Physicians. Chest 2003; 123 (1): pp 1S–337S.
10. Adjei AA, Marks RS, Bonner JA. Current guidelines for the management of small cell lung cancer. Mayo Clin
Proc 1999; 74: pp 809–881.
45

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
46
3.3. Lymphomas
3.3.1. Epidemiology
3.3.1.1 Non-Hodgkin’s lymphomas
In 2002, 301,000 new cases of non-Hodgkin’s lymphomas were reported in the world. They
represents 2.8% of all tumors and occur most often in developed societies (50.5% of all cases
in the world), with the highest incidence rates reported in Australia and North America,
average-level incidence in Europe (excluding Eastern Europe) and on Pacific Islands, and
relatively low incidence in Asia and Eastern Europe [1]. Men are affected 1.5 times more ften
than women [2]. In Poland, 7 out of 100,000 men and 4 out of 100,000 women get non-
Hodgkin’s lymphomas every year [3]. Mortality in men is 3.4, in women it is and 1.8 per
100,000. AIDS Patients suffer from non-Hodgkin’s lymphomas 1000 times more frequently [2].
3.3.1.2 Hodgkin’s disease
Hodgkin’s disease represents 1% of all the tumors diagnosed, and 10% of haematopoietic
tumors. The disease is more frequent with young people aged 20-30 [4]; men are diagnosed
1.6 times more frequently [1]. In developing countries, the disease affects mainly children and
adults, and the histopathological texture is dominated by the mixed cell type. In developed
countries, mainly young adults suffer from Hodgkin’s disease; in the histopathological picture,
nodular sclerosis Hodgkin’s disease prevails.
The highest incidence was reported in developed countries (North America, Europe), the
lowest in Asian populations [1]. 2002 data indicate that annually, 2.7 out of 100,000 men and
3 out of 100,000 women develop Hodgkin’s disease in Poland. At the same time, the mortality
in Poland amounts 1.1 in men and 0.6 among women [3].
3.3.2. Risk factors
The etiopathogenesis of non-Hodgkin’s lymphomas is unclear. Clinical data suggest a
relationship with viral infections. For example, non-Hodgkin’s lymphoma develops in 10% of
AIDS patients. Other risk factors are immunological disturbances, such as organ transplants,
immunosuppressive therapy, autoimmune diseases, or congenital immunodeficiency
11. Clinical Guideline 24. Lung cancer: the diagnosis and treatment of lung cancer. National Institute for Clinical
Excellence 2005; http://www.nice.org.uk
12. Rojek M i wsp. Biopsja aspiracyjna cienkoigłowa w diagnostyce nowotworów płuc. Medycyna Rodzinna 2002;
19; http://www.borgis.pl/czytenia
13. Coleman MO et al. Eurocare-3 summary: cancer survival in Europe at the end of 20th century. Ann Oncol 2003;
1: pp 128–149.
14. Tyczyński JE, Bray F, Parkin DM. Lung cancer In Europe. European Network of Cancer Registries, International
Agency for Research on Cancer, ENCR Cancer Fact Sheets 2002; 1; http://www.encr.com.fr/lung-factsheets.pdf
15. AJCC cancer staging manual, sixth edition. http://www.cancerstaging.org/education/tnmschema/lung.ppt

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
syndromes. The hypothesis whereby ultraviolet radiation increased the risk of non-Hodgkin’s
lymphomas is reliable but requires epidemiological confirmation.
Hodgkin’s disease is associated with genetic predisposition; however, environmental
factors seem to have influence on it as well. In Europe and North America, epidemiological
studies point to a relationship between the incidence of Hodgkin’s disease and low socio-
economic status. A significant role in the disease is attributed to Epstein-Barr virus, as well as
HIV. Occupational hazards may stimulate the disease (woodcutter) [1, 5].
3.3.3. Symptoms
In most cases patients seek initial medical help due to asymmetrical enlargement of lymph
nodes, usually cervical or supraclavicular. Raised temperature or recurrent fever, weakness,
drenching night sweats, and severe itching of the skin may appear. The disease causes body
weight losses. Physical examination reveals lymph node enlargement, also liver or spleen
enlargement may occur. If the central nervous system is involved, dysaesthesia, palsies and
pains are observed [4, 5].
3.3.4. Histopathological picture
A generally acceptable and commonly used division distinguishes between two types of
lymphomas: Hodgkin’s disease and all other non-Hodgkin’s lymphomas.
Hodgkin’s disease is a lymphoma that is histologically unique for the presence of Reed-
Sternberg cells, which arise probably from the monoclonal line, most frequently from B
lymphocytes. Non-Hodgkin’s lymphomas are the other neoplastic proliferations from B or T-
lymphocytes.
3.3.4.1 Hodgkin’s disease
Typical histopathological symptoms include giant Reed-Sternberg cells arising from single
nuclear Hodgkin cells, and cellular polymorphism, i.e. an accumulation of varied cells of the
lymphatic system. Four histological types of Hodgkin lymphoma are distinguished (Rye’s
classification) [4, 5, 6]:
1. nodular sclerosis type (82%): the most frequent type, with best prognosis,
characterized by the presence of nodes built of pathologic cells;
2. mixed cellularity type (14%): varied cells in various proportions present in infiltrations,
accompanied by slight sclerosis;
3. lymphocyte-rich classical (3%): the lymph nodes tissue is composed largely of
lymphocytes, rarely other cells;
47

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
48
4. lymphocyte depleted type (1%) – the lymph nodes are characterized by a small
number of lymphocytes and distinct sclerosis.
3.3.4.2 Non-Hodgkin’s lymphomas
Non-Hodgkin’s lymphomas are divided in the Killonian classification based on their
morphological and immunohistochemic features. Table 4 presents the classification [4].
Table 4.
Killonian classification of non-Hodgkin’s lymphomas
Low grade lymphomas
B- cell T - cell
Lymphocyte lymphomas Lymphocyte lymphomas
Chronic lymphatic leukaemia and prolymphocytic
leukaemia
Chronic lymphatic leukaemia and prolymphocytic
leukaemia
Hairy cell leukaemia Mycosis fungoides
Lymphoplasmacytic lymphoma (immunocytoma) Sezary’s syndrome
Plasmacytic lymphomas Angioimmunoblastic lymphoma
Centroblastic-centrocytic lymphomas T-zone lymphoma
Nodular diffused or non-diffused lymphomas Small cell pleomorphic lymphoma
Inter mediate grade lymphomas
Some types of lymphoplasmacytoidal lymphomas
Pleomorphic lymphomas
Centroblastic-centrocytic centroblast-rich lymphomas
High grade lymphomas
Centroblastic lymphomas Pleomorphic transitional and large cell lymphomas
Immunoblastic lymphomas Immunoblastic lymphomas
Anaplastic large cell lymphomas (Ki-1+) Anaplastic large cell lymphomas (Ki-1+)
Burkitt’s lymphoma
Lymphoblastic lymphoma Lymphoblastic lymphoma
3.3.5. Staging
Table 5 presents the Ann Arbor system of Hodgkin’s disease and non-Hodgkin’s
lymphomas. This classification is commonly used for disease staging.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Table 5.
Hodgkin’s disease and non-Hodgkin’s lymphomas staging according to Ann Arbor staging system
Disease stage Characteristics
I
II
III
IV
A
B
Involvement of a single lymph node group and/or a single organ or site other than the lymph
node (IE)
Involvement of two or more lymph node groups on the same side of the diaphragm (II) or
limited involvement of one extranodal organ or site with the involvement of one or more
group of lymph nodes on the same side of the diaphragm (IIE)
Involvement of lymph nodes on both sides of the diaphragm (III), may be accompanied by
limited involvement of an estranodal organ or site (IIIE), or involvement of spleen (IIIS) or both
(IIIES)
Diffused or disseminated involvement of one or more extranodal organs or tissues with or
without the involvement of lymph nodes
No general symptoms
With general symptoms: weight loss of 10% or more within the last 6 months and/or fever
above 38 C and/or drenching night sweats
The International Lymphoma Study Group (ILSG) has proposed another classification of
lymphomas based on the American and European (Killonian) classification, called the
Revised European-American Classification of Lymphoid Neoplasms (REAL). A combination of
morphological, immunophenotypical, genetic and clinical features was used in the
classification [4].
Table 6.
REAL classification of lymphoid tumors
B-cell tumors T and NK-cell tumors
Benign and chronic (survival without treatment calculated in years)
B-cell chronic lymphocytic leukaemia (CLL), small
lymphocytic lymphoma (SLL), prolymphocytic leukaemia
(PLL)
Lymphoplasmacytic lymphoma
Hairy cell leuekmia
Multiple myeloma
Splenic marginal zone lymphoma (splenic lymphoma
with villous lymphocytes – SLVL)
Extranodal marginal zone lymphoma
Mucosa associated lymphatic tissue lymphoma – MALT
lymphoma
Nodal marginal zone lymphoma
Follicular lymphoma-FH, follicle centre lymphoma – FCL
Mantle-cell lymphoma – MCL
Benign and diffused lymphomas and leukaemias
Benign non-nodular lymphomas
Benign nodular lymphomas
T-cell CLL, PLL
large granular lymphocyte leukaemia – LGL
Mycosis fungoides
Malignant lymphomas (survival without treatment counted in months)
Diffused large B-cell lymphoma – DLCL
Anaplastic large-cell lymphoma – ALCL
Peripheral T-cell lymphomas (many types)
Aggressive lymphomas (survival without treatment counted in weeks)
49

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Lymphoblastic leukaemias and lymphomas \ from pre-B
cells
50
Burkitt’s lymphoma
lymphocyte predominance
Hodgkin’s disease
3.3.6. Diagnostics and treatment
3.3.6.1 Additional tests
Pre-T Lymphoblastic leukaemias and lymphomas
Adult T-cell leukaemia and lymphoma (HTLV1)
Hodgkin-like ALCL
Classical Hodgkin's disease
nodular sclerosis – NS
mixed cellularity – MC
lymphocyte depletion – LD
lymphocyte-rich – LR
As regards biochemical diagnostics, note needs to be taken of a high erythrocyte
sedimentation rate (ESR, Biernacki’s test) where results have two- or three-digit values. The
increased concentration of lactic dehydrogenase (LDH) is observed. As regards
morphological blood examinations, a low number of lymphocytes and a high proportion of
eosynophils or monocytes are observed. At advanced stages, anemia and other
disturbances in hematopoiesis may occur as a result of bone marrow involvement.
3.3.6.2 Diagnostic imaging
A chest radiogram may reveal involvement of mediastinal lymph nodes, apparent from a
widening of the central shade. In such situations, CT of the chest is required to make diagnosis
complete. In bones roentgenograms presence, osteolysis foci can be detected and
ultrasound scanning of the abdomen may reveal enlarged lymph nodes [4].
3.3.6.3 Cytological and histopathological study
Material collected by bone marrow biopsy from a Hodgkin’s disease patient usually does
not show any deviation from standard; in 10% of patients, involvement of bone marrow with
Reed-Sternberg and Hodgkin cells present in it is visible. With non-Hodgkin’s lymphomas,
apart from examination of histological bioptates of bone marrow, it is diagnostically critical to
do cytochemical tests, which are aimed at identifying nuclear or cytoplasmic enzymes
typical of specific cells types and stages of their development. A specimen of tumor tissue
(e.g. from lymph nodes) need to be taken for a histopathological study to confirm the
diagnosis of lymphoma.
3.3.6.4 Molecular tests
The method of immunophenotyping bone marrow cells in a flow cytometer to assess
superficial antigens is helpful in lymphomas differentiation [4]. Superficial antigens
examinations is also done using the immunohistochemical method. At present, the most
important techniques in the diagnostics of lymphomas are genetic methods, such as

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
polymerase chain reaction or fluorescence in situ hybridization. They are helpful in detecting
features such as monoclonality, chromosomal aberrations and genetic mutations [7].
3.3.6.5 Treatment of Hodgkin’s disease
Treatment depends on the disease stage. For stages I and II, radiotherapy with isotope
60Co or megavolt X-ray therapy are used. It achieves total remission in 80–90% of patients. For
stage IIB, radiotherapy and chemotherapy bring better effects (in keeping with the MOPP
protocol: mechloretamine, vincristine, procarbasine, prednisone). For stage III A, radiation or
radiation with chemotherapy are used. For stages IIIB and IV, chemotherapy based on the
protocol above or a combination of doxorubicin, bleomycin, vinblastin, dacarbasine (ABVD)
are administered. Another protocol is BEACOPP chemotherapy.
If disease recurs after chemotherapy, other drug regimens such as DHAP and EPOCH are
implemented.
For some patients, bone marrow auto transplant can be considered. Bone marrow cells
are first taken and frozen, next high-dose chemotherapy and radiotherapy are implemented,
and subsequently the bone marrow is cleaned and transplanted.
Treatment is not neutral for the patient and has a number of serious side effects, mainly
complications resulting from direct action of cytostatic drugs and radiotherapy, such as
secondary infections, local radiation-induced changes. Distant consequences of the therapy
include secondary tumors (leukemia, lymphomas, cancers), cardiovascular complications
(pericarditis, cardiosclerosis), pulmonary complications (radiation-induced pneumonia,
pulmonary fibrosis), radiation-induced disorders of the thyroid gland, reproductive
disturbances (risk of infertility increases) [4].
When therapy is completed, patients should be examined for complete/incomplete
remission. The necessary measures include repeated physical examination, monitoring of
general blood count with smear, and diagnostic re-imaging if abnormalities were detected
before. In case of partial radiological response, it is advisable to evaluate disease activity by
histopathological assessment of lesion biopsy, or, as minimum, repeated radiological studies.
Whenever possible, a PET study should be done for patients with partial response to identify
those with high risk.
After treatment, follow-up check-ups and examination are recommended every 3 months
in the first year, every 6 months in the following 3 years, and then once a year. Laboratory
tests and chest radiogram are done after 6, 12 and 24 months after therapy is finished. CT
and other radiological studies are recommended to confirm remission, but further
observation is not recommended, with the exception of assessment of residual disease.
Follow-up examination of the thyrotropine hormone is recommended one, two and five years
after neck irradiated. In the case of chest radiation, women at premenopausal age should
51

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
be especially observed for secondary breast tumors. mammography is indicated for women
aged 40–50 [8].
52
3.3.6.6 Treatment of non-Hodgkin’s lymphomas
Therapy is complex and depends, among others, the on grade of lymphoma malignancy,
intensity of clinical symptoms, and location of changes. For giant cell lymphoma, which
represent 30–50% of all non-Hodgkin’s lymphomas, the CHOP protocol in combination with
rituximab is standard treatment. Stem cells transplantation is still an experimental method. If
treatment fails for patients in good general condition, conventional treatment followed by
high-dose therapy and stem cells administration is recommended. Other chemotherapy
regimens used are DHAP, ESHAP, or EPOCH. Treatment can be supplemented with
radiotherapy. If patients cannot take high-dose treatment, it is recommended that
conventional doses of drugs and radiotherapy are implemented. Also, palliative methods are
used, depending on recommendations. Follicular lymphoma is the second leading non-
Hodgkin’s lymphoma. In a small proportion of patients with stage I disease, the first-choice
therapy is radiotherapy. Systemic therapy is acceptable in patients with large tumors, as for
higher disease stages. In the majority of patients with grade III and IV disease, fully effective
treatment is not possible. Since spontaneous remission occurs in 15–20% of patients,
chemotherapy is launched if B-symptoms, disturbed hematopoiesis or disease progression are
observed. When long-term remission is obtained, administration of rituximab with other
regimens such as COP, CHOP should be considered. An alternative therapy is fludarabin or
chlorambucil. When contraindications to chemotherapy exist, monoclonal antibodies are an
option. Research suggests that beta-interferon as supportive therapy can produce good
effects. Bone marrow auto transplant is still an experimental method for this tumor type.
The disease should be monitored after treatment every 3 months in the first 2 years, every 6
months in the next 3-year period, and then once a year. Peripheral blood tests are done 3, 6,
12 and 24 months after therapy, and whenever alarming symptoms are observed. Thyroid
gland functions are assessed after neck radiation and should be performed after 1, 2 and 5
years. Diagnostic imaging is repeated 3, 6, 12 and 24 months after treatment is completed.
Patients who had their chest irradiated, especially people under 25 or before the
postmenopausal age, should be under observation and take screening examinations for
secondary breast cancer are necessary [9, 10, 11].
3.3.7. Prognosis
Prognosis in Hodgkin’s disease is relatively good: about 80% of patients survive more than 5
years and 60% more than 10 years. Negative prognostic factors include massive nodular
changes, progression of the disease during therapy or within a year after chemotherapy,

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
advanced disease (stage IV), general symptoms, histopathological LD type of Hodgkin’s
disease, age over 40 years, male sex.
Prognosis for non-Hodgkin’s lymphomas depends on their grade of malignancy. High-
grade lymphomas represent more than 70% of all lymphomas. Centrocytic lymphoma and T-
cell proliferations have a poor prognosis. Prognosis is adversely affected by general
symptoms such as fever, sweats, or loss of body weight. Five-year survivals for non-Hodgkin’s
lymphomas generally represent about 40–59%. [4, 12] 3 .
3.4. Esophageal cancer
3.4.1. Epidemiology
It is estimated, that esophageal cancer is the eighth leading tumor in the world: in 2002,
462,000 new cases (4.2%) were reported. At the same time it is the sixth leading cause of
death (5.7%, 386,000 deaths in 2002). Men suffer more often, almost exclusively older than 40.
In 2002, the incidence in men was estimated at 315,000 globally, and in women – 146,000
globally [1]. However, in Asian and African countries, the incidence in men and women is the
same [1]. In Poland, about 1300 cases of esophageal cancer are diagnosed every year [2].
The incidence and mortality rates for the Polish female and male populations are: 0.9 and 0.8
per 100,000, and 6.0 and 4.7 per 100,000 respectively [3].
Considerable geographical differentiation of incidence rates is observed. The highest
incidence is reported in China, the lowest in western Africa. Other regions with relatively high
rates in southern and eastern Africa, south-eastern Asia and Japan [1]. The geographical
differentiation in esophageal cancer incidence proves that environmental factors are
instrumental [1].
3 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): pp 74–108.
2. Herold G at all. Medycyna wewnętrzna. PZWL 2001.
3. The Globocan 2002 database: http://www-dep.iarc.fr
4. Skotnicki AB, Nowak WS. Podstawy hematologii. Kraków, Medycyna Praktyczna 1998.
5. The Merck manual of diagnosis and therapy. http://www.merck.com
6. Coran R, Kumar V, Ramzi T. Robbins pathologic basis of disease. Elsevier/Saunders, 1999, 6th edition.
7. B7CSH guidelines on nodal non-Hodgkin’s lymphoma – draft 2, August 2002.
8. ESMO minimum clinical recommendations for diagnosis, treatment and follow-up of Hodgkin disease. Ann Oncol
2005; 16: pp 54–55.
9. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of newly diagnosed large cell
on-Hodgkin’s lymphoma. Ann Oncol 2005; 16: pp 58–59.
10. ESMO Minimum Clinical Recommendations for diagnosis,treatment and follow-up of relapsed large cell non-
Hodgkin’s ’s lymphoma. Ann Oncol 2005; 16: pp 60–61.
11. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of newly diagnosed follicular
lymphoma. Annals of Oncology 2005; 16: pp 56–57.
12. Coleman MP I at all. EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Annals of
Oncology 2003; 14: pp 128–149.
53

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
54
The incidence of squamous carcinoma, which is a major type of this tumor, has been
stable recently. However, the increasing incidence of esophageal adenocarcinoma is
observed [1, 4]. The most probable explanation of this phenomenon is the increasing
occurrence of Barrett’s esophagus, or gastroesophageal reflux-based precancerous
conditions, which is very likely to be associated with the increasing obesity in societies.
3.4.2. Risk factors
Special note is taken of environmental factors in the development of squamous cell
carcinomas. It is believed that poor diet may predispose to this tumor type. What is more,
vitamin deficit in diet (vitamins A, C, riboflavin, thiamine, pyridoxine), trace elements, food
contamination with mould or high content of nitrates are also pointed up. Other risk factors
include alcohol abuse and cigarettes smoking. Chronic diseases of esophagus, such as
esophagitis, achalasi or chronic celiac disease, as well as genetic factors may predispose to
the disease. It is also a well known fact that black people get the disease more frequently [1,
4].
Esophageal sdenocarcinoma often develops from a change in the esophageal lining
(mucosa) called Barrett’s esophagus. Typically, Barrett’s esophagus occurs when normal
squamous lining cells of the esophagus are replaced by columnar cells in response to long-
term exposure to damage from chronic gastroesophageal reflux [4]. Research on
carcinogenic transformation confirms that one of the essential staged that directly precede
invasive esophageal cancer is high-grade dysplasia [5].
3.4.3. Symptoms
Initially, the disease is asymptomatic. Ailments caused by the esophagus blocked by tumor
mass occurs later on. Problems with swallowing (74%) are the key symptom: first the
swallowing solid food is impaired, then liquid food become hard to swallow as well. Other
symptoms include loss of body weight (57%) and painful swallowing (17%). Less frequent
ailments are dyspnoea, cough, hoarse throat and chest pain [2].
3.4.4. Histopathological picture
The most frequently diagnosed are squamous cell cancers. Cancers of this type usually are
well or moderately differentiated. Regardless of the degree of differentiation, when
symptoms occur the disease is advanced and prognosis is poor. Adenocarcinomas, the
incidence of which is growing, are usually located in lower esophagus and may infiltrate
stomach. The majority of tumors of this type produce mucus and are histologicaly similar to
gastric cancer. Sometimes, the visible texture resembles small intestine cells [4]. Also,

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
gastrointestinal stromal sarcomas are located in the esophagus, where they transform into
benign growths [6].
3.4.5. Staging
Table 7 presents the TNM staging system for esophageal cancer, as well as tumor stages
according to the American Joint Committee on Cancer (AJCC) [7].
Table 7.
TNM and AJCC staging system of esophageal cancer
Primary tumor
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor invades lamina propria or submucosa
T2 Tumor invades muscular membrane
T3 Tumor invades adventitia
T4 Tumor invades adjacent structures
Regional lymph nodes
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant metastasis
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
Tumors of the lower thoracic esophagus
M1a Metastasis in celiac lymph nodes
M1b Other distant metastasis
Tumors of the midthoracic esophagus
M1a Not applicable
M1b Nonregional lymph nodes and/or other distant metastasis
Tumors of the upper thoracic esophagus
M1a Metastasis in cervical nodes
M1b Other distant metastasis
AJCC stage groupings
Grade 0 Tis N0 M0
Grade I T1 N0 M0
Grade IIA T2 N0 M0
T3 N0 M0
Grade IIB T1 N1 M0
T2 N1 M0
Grade III T3 N1 M0
T4 any N M0
Grade IV Any T any N M1
Grade IVA Any T any N M1a
Grade IVB Any T any N M1b
55

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
56
3.4.6. Diagnostics and treatment
3.4.6.1 Physical examination
On physical examination, enlargement of lymph nodes (e.g. cervical) or liver can be
found.
3.4.6.2 Diagnostic imaging
A contrast radiological study of esophagus is done as the first diagnostic step. It helps
detects tumor in the lumen of the esophagus, which obstructs the flow of a contrast medium
through the esophagus to the stomach.
Precise imaging studies can be done by CT. It seems that PET diagnostics is more accurate
than CT in disease staging. A fusion of these two methods, PET and CT, is a promising tool that
may significantly improve the accuracy of pre-surgery diagnostics [8].
3.4.6.3 Endoscopy
It is the first-choice examination in esophageal tumor diagnostics. It detects lesions in the
mucous membrane of the esophagus that are invisible in other diagnostic methods. It also
helps to sample tissues from suspected areas to confirm cancer histopathologically.
Endoscopically, esophageal cancer may have polypoid (60%), ulcerative (25%) or flat,
intraparietally spreading form (15%) [4]. The newest diagnostic method is endosonography,
which not only helps assess the mucous membrane, like conventional endoscopy, but also,
through the use of ultrasound, allows a non-invasive evaluation of the depth of carcinogenic
infiltration and size of regional lymph nodes [2].
3.4.6.4 Cancer markers
Identification of cancer markers is characterized by low sensitivity and specificity.
Carcinoembryonic antigen (CEA) or other cancer antigens (CA 19-9, CA 125) tests can be
helpful in monitoring disease recurrences.
3.4.6.5 Histopathological study
Histopathological examinations are indispensable for final diagnosis of esophageal tumor.
3.4.6.6 Radical treatment
Qualified to radical treatment are patients with no metastasis found. Operational excision
of carcinogenic infiltration is used, ranging from mucous membrane ablation to esophagus
resection. Another standard policy is pre-surgery chemoradiotherapy or radiochemotherapy
if the patient is inoperable. The choice of method depends on the disease stage. 5-
fluorouracyl and cisplatin are used in the main. For stage I, initial surgery or

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
radiochemotherapy is implemented. For grade T4 N1 M0, chemoradiotherapy is used, but for
grade T2/3 N0/1 M0/1a, surgical treatment with support therapy, or chemoradiotherapy plus
another surgery, or sole chemoradiotherapy be considered [2, 9].
3.4.6.7 Palliative treatment
The aim of palliative treatment is to reduce pain, and to improve nutrition and quality of
life. Various methods are used to reduce disorder of esophageal passage or to support
esophageal patency. This function is performed by radiochemotherapy in some patients, in
other endoscopic procedures or esophageal stenting is used. If total occlusion of the
esophagus occurs, gastrostomy may be required to feed the patient.
3.4.7. Prognosis
Esophageal cancer has a very poor prognosis (5-year survivals < 20%). Estimated 5-years
survivals in the Polish population are 5.6% in men and 4.1% in women [10, 11] 4 .
3.5. Cancer of the female genitals
3.5.1. Endometrial cancer
3.5.1.1 Epidemiology
The geographical distribution of uterine corpus cancer resembles the distribution of
ovarian cancer. However, prognosis for cervical tumor is definitely more optimistic than for
ovarian cancer. In 2002, 199,000 cases of uterine cancer were reported, which represents
3.9% of all tumors in women. The incidence of uterine cancer in the world is 6.5 for per 100,000
[1]. Also that year, 50,000 deaths caused by this disease were reported, which represents 1.7%
of all cancer-related deaths in women. The annual death toll of uterine cancer is 1.6 per
100,000 women. This tumor is the most commonly diagnosed in women in their
4 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): pp 74–108.
2. Szczeklik A. i wsp. Choroby wewnętrzne. Kraków, Medycyna Praktyczna 2005.
3. The Globocan 2002 database: http://www-dep.iarc.fr
4. Coran R, Kumar V, Ramzi T. Robbins pathologic basis of disease. Elsevier/Saunders, 1999, 6th edition.
5. Postępy w chirurgii przełyku w 2005 roku. Medycyna Praktyczna 2006; 01: pp 9–14.
6. National Cancer Institute. Esophageal cancer. http://cancerweb.ncl.ac.uk/cancernet/100089.html
7. AJCC cancer staging manual, sixth edition;
http://www.cancerstaging.org/education/tnmschema/esophagus.ppt
8. Kato H, Miyazaki T, Nakajima M, et al. The incremental effect of positron emission tomography on diagnostic
accuracy in the initial staging of esophageal carcinoma. Cancer 2005; 103: pp 148–156.
9. ESMO Minimal Clinical Recommendations for diagnosis, treatment and follow-up of esophageal cancer. Ann
Oncol 2005; 16: pp 26–27.
10. Narodowy program zwalczania chorób nowotworowych. ZałoŜenia i cele operacyjne 2006–2015.
http://www.mz.gov.pl/wwwfiles/ma_struktura/docs/zalozenia_ustawy_o_npzchn.pdf
11. Coleman MO et al. Eurocare-3 summary: cancer survival in Europe at the end of 20th century. Annals of
Oncology 2003; 1: pp 128–149.
57

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
postmenopausal years. Globally, 91% of new cases are diagnosed in women aged 50 or
older [1]. The highest incidence is observed in Europe (11.8 to 12.5 per 100,000) and in North
America (22 per 100,000). The lowest incidence is reported in southern and eastern Asia
(including Japan) and in Africa (incidence below 3.5 per 100,000) [1]. Based on 2002
epidemiological data, the annual incidence of uterine cancer in Poland is 13 per 100,000
women. It is also the cause of death of 2.8 per 100,000 women (age-standardized values) [2].
58
3.5.1.2 Risk factors
Endometrial cancer is more frequent in developed countries, where the consumption of
dietary fat is higher. The most important risk factor is obesity, which increases the risk 3–10
times. Endometrial cancer occurs in case of imbalance between progesterone and
estrogen, with estrogen dominance (hormone replacement therapy, obesity, polycystic
ovarian syndrome, nulliparity, late menopause, estrogen-secreting tumors, and lack of or rare
ovulations. Irradiation of the pelvis, breast or ovarian cancers in the family increase the risk of
endometrial cancer.
Endometrial hyperplasia usually precedes endometrial cancer.
3.5.1.3 Symptoms
In over 90% of patients pathological bleedings from the genitals (postmenopausal
bleedings, irregular intermenstrual bleedings) are observed. It is estimated, that about 30% of
women with abnormal postmenopausal bleedings have endometrial cancer.
3.5.1.4 Histopathological picture
In over 80% of cases, histopathological texture corresponds to adenocarcinoma; 60% of
these are well differentiated, and 20% are non-differentiated. Infiltration of deeper layers of
the wall, as well as the risk of distant metastasis depend on the stage of the tumor. Sarcomas
represent 5% of all tumors of the uterine corpus, including leyomiosarcomas, mixed
mesodermal tumors, and endometrial stromal sarcomas. Sarcomas have a poorer prognosis
[3,4].
3.5.1.5 Staging
The tumor staging system takes into account the grade of histological differentiation (G
grades), as well as features of clinical advancement as established during operation, among
them depth of infiltration, involvement of the cervix, lymph node or peritoneal cavity
metastasis [3,4].
Table 8 presents the 1988 generally approved staging system of the International
Federation of Gynecology and Obstetrics (FIGO).

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Table 8.
FIGO staging for endometrial cancer
Grade Description
Stage 0 In situ cancer
Stage I IA – tumor confined to the corpus uteri, length of the uterine cavity does not exceed 8 cm
IB – tumor confined to the corpus uteri , length of the uterine cavity exceeds 8 cm
Stage II Cancer involves the corpus and the cervix
Stage III Cancer extends outside the uterus, but is confined to the true pelvis
Stage IV Cancer extends outside the true pelvis or infiltrates bladder mucosa or rectum (confirmed by
histological study of samples)
IVA – invasion of adjacent organs
IVB – metastasis to distant organs
3.5.1.6 Diagnostics and treatment
In some patients, diagnosis is done based on anomalies revealed in a cytological smear. A
microscopic study of cervical canal and uterine cavity scrapings obtained by fractionated
microabrasia is necessary for diagnosis. Also, gynecological per-vaginam and per-rectum
examination of true pelvis, and a chest radiogram are necessary [3, 4].
Prophylaxis of uterine cancer involves observation and proper treatment of women in the
high risk group. Abnormal bleedings are indications for curettage of the uterine cavity. In
young patients, anovulation cycles should receive treatment. When adenomatous
hyperplasia of the endometrium is identified, hormonal therapy or simple uterine
hysterectomy can be attempted. The basic procedure for uterine cancer is surgery,
recommended for all patients with stage I–III disease and no contraindications to surgery.
During the procedure, it is necessary to sample material from the peritoneal cavity for
cytological examination, and to revise the peritoneal cavity carefully, taking specimens of
the suspected places. In high risk patients, pelvic and periaortic lymph nodes should be
sampled for histopathological examination or excised completely whenever metastasis is
suspected. Supplementary treatment involves 40–50 Gy radiation and is applied to patients
with lymph node or adnexa metastasis, deep infiltration of the muscular layer, or surgical
margin involvement. Local radiation through brachytherapy may be considered.
Radiotherapy is the only procedure for non-operational stages III and IV. Hormonal therapy is
the first-choice systemic treatment; its efficacy is 75% if hormonal receptor is detected.
Usually, progestogens are used. The hormonal therapy is the first-choice therapy in advanced
stages; however whether it should be part of supplementary treatment is open to discussion.
Moreover, the administration of progestogens should be considered in patients with
hypertension, obesity and diabetes, because the therapy may increase these disorders [3, 4].
59

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
60
3.5.1.7 Prognosis
Uterine cancer has a high survival rate: 86% in the United States and 78% in Europe, which
is higher than the survival expected for breast cancer, especially in developing countries.
Therapeutic effects depend on the tumor stage: for stage grade I, the 5-year survival is 80–
90%; for stage II: 30–70%; for stage III: 15–40%; and for stage IV: 0–3% [1, 5] 5 .
3.5.2. Cervical cancer
3.5.2.1 Epidemiology
Cervical cancer is one of the most frequent malignant tumors in women, and the seventh
leading malignant tumor in the world, but second leading in women. In 2002, 493,000 new
cases of cervical cancer and 274,000 deaths were reported. Cervical cancer is more
frequent in developing countries (83% of all cases), where it represents 15% of all tumors in
women. In developed countries, this tumor represents only 3.8% of new cases. The highest
incidence rate is reported in regions such as Africa, Latin America, southern Asia, the
Caribbean Islands. In developed countries, the incidence of cervical cancer is 14.5 per
100,000 (age-standardized values). However, the incidence in regions such as Europe and
North America has changed remarkably after screening programs were implemented. A very
low incidence is observed in China (6.8 per 100,000), Western Asia (5.8 per 100,000). Mortality
is clearly lower compared to incidence. The mortality to incidence ratio is 55% globally [1].
The screening examinations implemented in the past few years pushed down the incidence
and mortality rates significantly in well-developed countries. In some developing countries
these rates are going down too (e.g. China) [1]. In Poland, the 2002 incidence of cervical
cancer was 18.4 per 100,000 women, and morbidity stood at 7.8 per 100,000 (age-
standardized values) [2].
3.5.2.2 Risk factors
One of the main etiological factors is infection with the human papilloma virus (HPV).
Other infections that increase the risk of cervical cancer include HIV and Chlamydia [3].
Recent epidemiological studies carried out with the use of high-sensitivity HPV detection
methods have showed a correlation between the incidence of virus detection and the
incidence of cervical cancer. Other risk factors include multiparity, smoking and oral
contraceptives [1]. Women who do not eat enough fruit and vegetables, or are overweight,
5 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin 2005; 55; pp 74–108.
2. Globocan 2002 database. http://www-dep.iarc.fr/
3. The Merck manual of diagnosis and therapy. www.merck.com
4. Pawlicki M I wsp. Leczenie nowotworów. Bielsko-Biała, Alfa Medica Press, 1996.
5. Coleman MP, Gatta G, Verdecchia A, Estève J, Sant M, Storm H, Allemani C, Ciccolallo L, Santaquilani M, Berrino
F and the EUROCARE Working Group. EUROCARE-3 summary: cancer survival in Europe at the end of the 20th
century. Ann Oncol 2003; 14: pp 128–149.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
are at greater risk. Low socioeconomic status predisposes to cervical cancer. Family
predisposition to cervical cancer is observed in some patients [3].
3.5.2.3 Symptoms
The earliest and often the first symptom is abnormal bleeding from the genitals. it is often
ignored by doctors and patients as incidental. Other symptoms include pain in the lumbar-
sacral region, irregular menstruations. In 5–10% of cases no suspicious symptoms are found.
Late symptoms are the reason why diagnoses of cervical cancer are late. The advanced
stages may be dominated by dysuria, urgency, symptoms of renal insufficiency caused by
pressure on the uterus from cancerous infiltration, or enlarged lymph nodes of the true pelvis
[4].
3.5.2.4 Histopathological picture
Microscopic examination usually detects squamous cell carcinoma, which represents 95%
of all malignant tumors of the cervix. Adenocarcinoma is less frequent (4–5%), and including
varieties such as endometrioidal, mesonefroidal and adenosquamous cancer. Non-
differentiated cancer, cylindroma, sarcoma, melanoma and lymphoma are very rare [4].
3.5.2.5 Staging
The system introduced by the International Federation of Gynecology and Obstetrics
(FIGO) is generally used in staging. Table 9 presents the classification.
61

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Table 9.
FIGO staging for cervical cancer
Stage Description
Stage 0
Stage I
Stage II
Stage III
Stage IV
62
Carcinoma in situ
Cervical carcinoma confined to uterus (extension to corpus should be disregarded)
IA – invasive cancer, preclinical, diagnosed only by microscopy
IA1 – minimal microscopical infiltration of the lining
IA2 – invasion into lining less than 5 mm in depth, measured from the basement membrane, less
than 7 mm in horizontal spread
IB – invasion of cancer is greater (microscopically) than IA2, usually visible infiltration confined to
the cervix only
Cervical carcinoma invades beyond the uterus but not to the pelvic wall or to the lower third of
the vagina
IIA – cancer invades vaginal fornix and its walls, but the lower third of the vagina
IIB – cancer invades parametrium, but does not spread to the pelvic walls
Carcinoma extends to the pelvic wall and/or involves the lower third of the vagina (in per rectum
examination free space between cervical tumor and pelvis wall is not found). All cases of
hydronephrosis or nonfunctioning kidneys should be included.
IIIA –cancer involves the lower third 3 of the vagina, without infiltrating parametrium to the bone
IIIB – cancer invades parametrium to the bone or causes hydronephrosis or dysfunction of the
kidney
Cancer extends beyond the true pelvis or invades bladder mucosa and/or rectum bullous edema
is not sufficient not classify a tumor as stage IV by cytoloscopy; only specimens from bladder or
rectum tested by microscopy may qualify a tumor as stage IV (or a cytological study of urine)
IVA – cancer invades bladder or rectal mucosa and/or extends beyond the true pelvis
IVB – distant metastasis
3.5.2.6 Diagnostics and treatment
The key diagnostic phase is gynecological examination. Cytology is of paramount
importance in early detection of cervical cancer in situ. The Papanicolau classification has
been the most widely accepted in gynecological cytology, and is still in use in Poland. Grade
I corresponds to normal picture, grade III requires more extensive diagnostics and treatment
(features of strong inflammatory state and cellular dysplasia), group IV corresponds to
squamous cell carcinoma in situ, and grade V is invasive cancer. Colposcopy helps locate
abnormal lesions. Ultimate diagnosis can be made by histopathological examination of
material from cervix obtained by curettage of the cervical canal and uterine corpus.
A number of other diagnostic studies are performed but unnecessary for diagnosis.
Diagnostics is supplemented by imaging studies, predominantly CT of the pelvis or magnetic
resonance imaging. PET diagnostics is used if cancerous dissemination is suspected. Venal
urography helps expose urine flow disorders, which can be caused by tumor mass pressure
[3].
Basic treatment policies for invasive cervical cancer are surgery and radiotherapy. The
choice of method depends on the tumor stage. Radiotherapy is a radical therapy method
for all stages; however, surgical treatment is used with patients with stage I and, to some
extent, stage IIA disease. The extent of surgery depends on the tumor stage. In non-invasive

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
states cryotherapy and laser therapy are used. Cone biopsy (excision of a wedge of the
cervix uteri that includes the tumor zone through the vagina), is hardly ever the only
treatment. The extent of surgery ranges from simple hysterectomy to surgical excision of all
organs and tissues of the true pelvis. Outcomes of surgery and radiation are similar. Other
approach is to combine radiotherapy and chemotherapy. At present multi-drug regimens
are used that are based on cisplatin and contain combinations of many other cytostatic
drugs. They attain about 50% response to treatments, but total regressions are rare and short-
lived. Cisplatin, paclitaxel, topotecan, ifosphamide or fluorouracil are most frequently used [3,
4].
3.5.2.7 Prognosis
Recently, the survival rate has improved for cervical cancer. However, that is not true for
countries in Eastern Europe. It is estimated that the average 5-year survival in Europe is about
60%, and differences between particular territories in Europe are relatively small. A survival
rate higher than in other European countries is observed in the Czech Republic.
Epidemiological data point to the crucial role of screening programs in improving survival
rates in Western Europe. Screening programs comprise cytological examination of cervical
smears [5] 6 .
3.5.3. Ovarian cancer
3.5.3.1 Epidemiology
Ovarian cancer is the sixth leading tumor diagnosed in women and the seventh leading
cause of death caused by malignant tumors in women. In 2002, 204,000 new cases of ovarian
cancer and 125,000 deaths were reported globally. Incidence is higher in developed
countries, where it is reaches 9 per 100,000, with the exception of Japan, where incidence is
the lowest (6.4 per 100,000) [5]. The highest incidence rates are observed in the United States,
Europe and Israel, while the lowest in Japan [3]. The incidence of ovarian cancer in Europe is
18 per 100,000 people, and mortality is 12 per 100,000 people yearly [2]. In Eastern Europe,
ovarian cancer is the sixth leading malignant tumor, but in Western Europe it is the third [1].
The median age of women diagnosed with ovarian cancer 63. Morbidity increases with age,
and peaks in the eighth decade of life [2]. In 2002 in Poland, the incidence of ovarian cancer
in women was 12.5 per 100,000 and morbidity was 6.8 per 100,000.
6 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): pp 74–108.
2. The Globocan 2002 database: http://www-dep.iarc.fr
3. American Cancer Society. Detailed guide: cervical cancer. http://www.cancer.org/
4. Pawlicki M i wsp. Leczenie nowotworów. Bielsko Biała, Alfa Medica Press, 1996.
5. Coleman MO et al. Eurocare-3 summary: cancer survival in Europe at the end of 20th century. Ann Oncol 2003; 1:
pp 128–149.
63

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
64
Figure 3 presents the incidence and mortality rates for ovarian cancer in selected regions
of the world.
Figure 3.
Incidence and mortality rates for ovarian cancer in selected geographic regions [7]
3.5.3.2 Risk factors
The disease occurs at any age, more frequently in patients above age 40. Also familiar
incidence of disease is rare. The disease is more frequent in highly industrialized countries.
3.5.3.3 Symptoms
Ovarian cancer develops asymptomatically for a long time, and symptoms are
uncharacteristic. As a result, the disease is usually diagnosed at advanced stages (FIGO
stages III or IV) [4]. The most common symptoms are: pressure symptoms in the abdomen,
gain of body weight, a feeling of fullness, bloating, belching. Bleeding from vagina and pain
on one side of the hypogastrium may be present [4]. Acute symptoms are occasional and
involve torsion of the ovarian peduncle and hemorrhage.
3.5.3.4 Histopathological picture
Histological classification is done based on the WHO division. Three types of ovarian tumors
are distinguished: epithelial ovarian tumors, primary germ cell tumors and ovarian stromal

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
tumors. Occasionally, sarcomas or metastatic tumors (breast cancers, gastrointestinal
cancers, cancers of other genital organs and lymphomas) can be found in this location. The
most frequent are epithelial ovarian tumors. It is estimated that they represent over 85% of all
ovarian tumors.
3.5.3.5 Staging
When no distant metastasis is found, staging requires laparotomy. If the disease seems
limited, it is essential to proceed with laparotomy and assessment of diaphragm, intestines,
peritoneum, regional lymph nodes, omentum or to sample washings of the peritoneal cavity
for a histopathological study [4, 5].
The International Federation of Gynecology and Obstetrics (FIGO) and the American Joint
Committee on Cancer (AJCC) have proposed a staging system that is presented in Table 10.
Table 10.
AJCC and FIGO staging for ovarian cancer
Stage Characteristics
I
II
III
IV
Stage I: Growth limited to the ovaries.
IA: Growth limited to one ovary; no ascites. No tumor on the external surface; capsule intact.
IB: Growth limited to both ovaries: no ascites. No tumor on the external surfaces; capsules intact.
IC: Tumor either stage Ia or Ib but with tumor on surface of one or both ovaries, or with capsule
ruptured; or with ascites present containing malignant cells or with positive peritoneal washings.
Stage II: Growth involving one or both ovaries with pelvic extension.
IIa Extension and/or metastases to the uterus and/or fallopian tubes.
IIb Extension to other pelvic tissues.
IIc Tumor either stage IIa or IIb. but with tumor on surface of one or both ovaries: or with capsule(s)
ruptured; or with ascites present containing malignant cells or with positive peritoneal washings
Differences in inclusion criteria for stages IC or IIC have impact on diagnosis. It is critical to assess
whether damage to capsule is a result of tumor invasion or surgical intervention, or whether cancer
cells are present in peritoneal fluid, or in peritoneal washings.
Stage III: Tumor involving one or both ovaries with positive peritoneal implants outside the pelvis
and/or positive retroperitoneal or inguinale nodes. Superficial liver metastasis equals stage III. Tumor
is limited to the true pelvis but with histologically proven malignant extension to small bowel or
omentum.
IIIa Tumor grossly limited to true pelvis with negative nodes but with histologically confirmed
microscopic seeding of abdominal peritoneal surfaces.
IIIb Tumor of one or both ovaries with histologically confirmed implants of abdominal peritoneal
surfaces none exceeding 2 cm in diameter. Nodes are negative.
IIIc Abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or inguinale
nodes.
Stage IV: Growth involving one or both ovaries, with distant metastases. If pleural effusion is present,
there must be positive cytology. Parenchymal liver metastases equal stage IV
65

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
66
3.5.3.6 Diagnostics and treatment
If growth is advanced, the abdomen perimeter increases, fluid is present in the abdomen,
sometimes tumor is palpable on physical examination [4]. On gynecological examination,
enlarged adnexa are palpable; sometimes tumor is palpable in the true pelvis. Enlargement
of the ovaries, tumor-like or cysts-like lesions within adnexa or fluid in the abdominal cavity
can be detected by ultrasonography of the abdominal cavity, or by transvaginal ultrasound.
Ultrasound scanning is only tentative, and CT of the abdominal cavity is recommended.
Rectoscopy and cystoscopy are done before surgery for initial staging and to plan
therapeutic procedures.
Ca-125 cancer marker is relatively specific and sensitive. However, its usefulness in initial
diagnostics is limited, but is used to monitor the course of the disease [4]. High concentration
of Ca-125 is associated with high odds of positive ovarian cancer diagnosis, but negative
tests do not exclude the disease. Definite diagnosis of the ovarian cancer is based on a
histopathological study of samples taken at surgery, often as part of laparotomy.
Basic treatment is surgery, which can be sufficient only for stage IA. Other patients require
systemic therapy, which is supplementary for stages I and II, and basic for stages III and IV
following a cytoreduction procedure or exploratory laparotomy. Chemotherapy is
implemented 4 weeks after surgery, with the regimen based on platinum derivatives
(cisplatin, carboplatinum). Radiotherapy is not the first-choice therapy in ovarian cancer,
however radiation is used in many centers as alternative supplementary treatment [7].
3.5.3.7 Prognosis
The 5-year survival rate in Europe is estimated at 37%, but remarkable differences between
countries are observed [8]. The mortality rate for this tumor type has remained unchanged
over the past few years [1]. The 10-year survival rate for stage IA disease may reach up to 86–
92% 7 .
7 1. Evidence-based cancer prevention: strategies for NGOs- a UICC handbook for Europe. http://www.uicc.org
2. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of epithelial ovarian
carcinoma. Ann Oncol 2005; 16: pp 13–15.
3. Coleman MP, Esteve J, Damiecki P, Arslan A, Renard H. Trends in cancer incidence and mortality. IARC Sci Publ.
1993; 121: pp 1–806.
4. Senn HJ I wsp. Kompendium onkologii. PZWL 1995.
5. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin 2005; 55: pp 74–108.
6. Globocan 2002 database. http://www-dep.iarc.fr/
7. Pawlicki M i at all. Leczenie nowotworów. Bielsko Biała, Alfa Medica Press, 1996.
8. Sant M, Aareleid T, Berrino F, Bielska Lasota M, Carlin P. M, Faivre J, Grosclaude P, Hédelin G, Matsuda T, Møller H,
Möller T, Verdecchia A, Capocaccia R, Gatta G, Micheli A, Santaquilani M, Roazzi P, Lisi D and the EUROCARE
Working Group. EUROCARE-3: survival of cancer patients diagnosed 1990–94 – results and commentary.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.6. Thyroid gland cancer
3.6.1. Epidemiology
In 2002, 141,000 cases of thyroid gland cancer were reported globally. It is one of the few
tumor type that is more frequent in women than in men. The global incidence rate of thyroid
cancer is 1.3 for men and 3.3 for women. This tumor represents 2.1% of all tumors in women [1,
2]. Diagnostic practice seems to have impact on the frequency of positive thyroid cancer
diagnosis (e.g. histological post-mortem assessment of goiter may have significant impact on
the frequency of positive diagnosis). This may be the reason for the high incidence rate
observed in the United States (incidence rates for women and men: 8.1 and 3.9) [1, 2]. The
rates are also high in Australia/New Zealand, Japan and Central America [1]. In Poland. the
incidence of thyroid cancer is 1.4 per 100,000 in men, and 4.1 per 100,000 in women. Disease-
related mortality is 0.3 per 100,000 in men and 0.6 per 100,000 in women.
3.6.2. Risk factors
To estimate prognosis, four factors should be considered: age, sex, histological
differentiation grade and tumor stage. Also, prognosis depends on whether or not treatment
has been implemented. The age of the patient at initial positive diagnosis is important
especially in the case of papillary and follicular thyroid gland cancers. The risk of death
increases in patients over 40 years of age and is higher in children. It has been pointed out
that male sex may affect prognosis negatively. Prognosis for papillary cancer is better than
for follicular cancer; however, with regard to parameters such as sex and extension of
primary tumor, survival in both cases is similar. Poorly differentiated follicular cancers, as well
as Hürtle cell cancer have a bad prognosis. The size of the tumor at the outset of treatment is
a basic prognostic factor. Invasion of adjacent tissues, lymph node metastasis and distant
metastasis significantly influence prognosis [4].
3.6.3. Symptoms
The disease is often asymptomatic. Symptoms can be divided into local, systemic and
paraneoplastic. The most frequent symptom is a tumor in the neck. Also, enlarged cervical
lymph nodes, swallowing problems, hoarseness or dyspnoea may appear. The presence of
generalized symptoms may be indicative of a higher stage or aggressiveness of thyroid
cancer. Systemic symptoms include loss of body weight, and for medullary thyroid cancer -
washy diarrheas. Paraneoplastic syndromes are grossly typical of medullary thyroid cancer,
and are associated with imbalance of the adrenocorticotropic hormone and calcitonine [3,
4].
67

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
68
3.6.4. Histopathological picture
Five histopathological types of thyroid cancer are distinguished: papillary, follicular, Hürtle
cell, medullary and anaplastic. Papillary (60–70%) and follicular cancer (10–15%) are the most
common types. The other types represent 20% of cancer cases total [3].
3.6.5. Staging
Table 11, presents the TNM staging system designed by the American Joint Committee on
Cancer (AJCC) [5].
Table 11.
TNM staging system by AJCC
Primary tumor
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor is ≤2 cm in greatest dimension , limited to thyroid gland
T2 Tumor is >2 cm in greatest dimension, but ≤ 4 cm, limited to thyroid gland
T3 Tumor is >4 cm in greatest dimension and tumor limited to thyroid gland or any tumor
with minimal extrathyroid extension (extension to sternothyroid muscle soft or
perithyroid tissues)
T4 T4a – tumor of any size extending beyond the thyroid capsule to invade subcutaneous
soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve
T4b – tumor invades paravertebral fascia or carotid artery, or mediastinal vessels
Or anaplastic thyroid carcinomas are considered T4:
T4a – intrathyroid anaplastic carcinoma, surgically resectable
T4b – extrathyroid anaplastic carcinoma, surgically unresectable
Regional lymph nodes (regional lymph nodes are cervical and upper mediastinal nodes)
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph nodes metastasis
N1a – metastasis to pretracheal, paratracheal, and prelaryngeal lymph nodes
N1b – metastasis to cervical (unilateral, bilateral or superior mediastinal) lymph nodes
Distant metastasis
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
AJCC stage groupings for thyroid cancer
Younger than 45
Stage I Any T, any N, M0
Stage II Any T, any N, M1
Age 45 and over
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
Follicular or papillary carcinoma

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
T1–T3 N1a M0
Stage IV A T4a N0–N1a M0
T1–T4a N1b M0
Stage IV B T4b any N M0
Stage IV C Any T, any N M1
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
T1–T3 N1a M0
Stage IVA T4a N0–N1a M0
T1–T4a N1b M0
Stage IVB T4b any N M0
Stage IVC Any T, any N M1
Medullary carcinoma
Anaplastic carcinoma All anaplastic carcinomas are only stage IV
IVA T4a any N M0
IVB T4b any N M0
IVC Any T, any N M1
3.6.6. Diagnostics and treatment
Physical examination detects nodules and enlargement of the thyroid gland. Precise
assessment of regional cervical, supraclavicular lymph nodes is necessary. Before a patient is
qualified to surgery, the vocal cords should be examined.
When differentiating nodular lesions in the thyroid gland, the level of thyroid hormones
should be measured. If no hormonal disturbances are found, this may be indicative of thyroid
cancer. Patients with hypothyroidisms or hyperthyroidisms should be referred to an
endocrinologist. Other recommended tests are tests of antibodies directed against thyroid
antigens. Ultrasound-guided or unguided fine-needle biopsy of the lesion is necessary. No
other studies are required for routine procedure. Ultrasound scanning of the thyroid gland is
particularly helpful if same-time fine-needle aspiration biopsy is planned, or if enlarged lymph
nodes or other additional nodules are palpable in physical examination. CT or MRI of the
thyroid gland is helpful when other techniques are insufficient to determine the boundaries of
cancer infiltration, or when haemoptysis occurs. Measurements of calcitonine level in blood
serum are recommended in medullary thyroid cancer. A chest radiogram and spirometry
help evaluate the patient’s general condition and other accompanying diseases. Isotopic
studies are diagnostically irrelevant in thyroid cancer, however they may have impact on
preoperative and postoperative staging, just as ultrasonography or CT of the abdominal
cavity have. With differentiated cancers, open biopsy of the thyroid gland is not used usually.
However, it is sometimes necessary in the diagnostics of lymphomas [3, 4].
The only radical treatment method for thyroid cancer is surgery. The extent of surgery
depends on the stage and histological features of the tumor. The most often used
supplementary treatment of highly differentiated tumors is iodine 131 radiotherapy, which is
69

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
helpful in procedures against not only primary tumor but also distant metastasis. Sometimes
external radiation of 5 000 Gy in fractions is used. Chemotherapy is not a routine procedure
for thyroid cancer, but is used with recurrent disease, after partial tumor resection or lack of
response to the therapeutic methods described above. Doxorubicin or cisplatin are used, but
partial responses do not exceed 20% for papillary cancer. Chemotherapy should be
administered only in symptomatic patients with disease progression.
70
When response to treatment is positive, the average survival period may be expected to
grow from 3–5 to 15–20 months [3, 4].
3.6.7. Prognosis
Prognosis in thyroid cancer is usually good, which is proved by a low ratio of the mortality
to incidence rate (0.25), one of the reasons being good access of tumor location procedures
[6]. Thyroid cancer is responsible for a small proportion of deaths compared to other tumors
(0.5% of all tumor-related deaths) [1]. Based on 1985–1991 data, the 5-year relative survivals
for papillary cancer range from 100% for stage I to 45.3% for stage IV. For follicular cancer,
survivals are similar, and ranged depending on the stage from 100% to 47.1%. The value for
medullary cancer is 100%–24.3%; and for anaplastic cancer it is only 9.1% [5] 8 .
3.7. Head and neck cancer
3.7.1. Classification
Classifications used in oncology include the following under head and neck cancer: lip
cancer, oral cavity cancer, pharyngeal cancer, laryngeal cancer, paranasal sinuses cancer
and salivary glands cancer. The most frequently diagnosed cancer in this location is
squamous cell laryngeal cancer, less frequently squamous cell tonsil and pharynx cancer.
3.7.2. Epidemiology
Every year, 500,000 people develop head and neck cancer [1]. The incidence of head
and neck cancer is significantly higher in men than in women, with relatively small regional
differences in incidence and survival [2, 3]. Based on 2002 data, the incidence of oral cavity
8 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): pp 74–108.
2. The Globocan 2002 database: http://www-dep.iarc.fr
3. Pawlicki M et all. Leczenie nowotworów. Bielsko Biała, Alfa Medica Press, 1996.
4. British Thyroid Association. Royal College of Physicians. Guidelines for the management of thyroid cancer in
adults. http://www.rcplondon.ac.uk/pubs/books/thyroidcancer/thyroid_guidelines.pdf
5. AJCC cancer staging manual, 6th edition. http://www.cancerstaging.org/education/tnmschema/thyroid.ppt
6. Coleman MO et al. Eurocare-3 summary: cancer survival in Europe at the end of 20th century. Ann Oncol 2003;
1: pp 128–149.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
cancers in Poland in men and women is 7.3 and 1.4 per 100,000 respectively; the incidence
of nasopharyngeal cancer is 0.6 and 0.2 per 100,000 respectively; and the incidence of other
pharyngeal cancers is 6 and 0.7 per 100,000 respectively [4].
3.7.3. Risk factors
Risk factors of laryngeal cancer are similar to those of lung cancer. In 85% of patients,
smoking and alcohol abuse are identified as part of case history [3, 5]. Oral cavity cancer
may be caused by poor oral hygiene, ill-fitting dentures or tobacco and betel chewing [5].
Infection with the Epstein-Barr virus also have a role in developing head and neck cancers.
Patients with a history of low-dose radiation have a predisposition to thyroid cancer and
salivary gland cancer [5].
3.7.4. Symptoms
Precise clinical evaluation is a precondition for early diagnosis. Hard-healing wounds and
ulcerations, dyskeratosis, leucoplakias (white stains on mucous membranes), and papillary or
inflammatory changes should be monitored. These can be the first symptoms of tumor. Other
symptoms include obstruction of the nasal ducts, pains of sinuses, hoarseness [1].
3.7.5. Histopathological picture
Squamous cell carcinomas represent the majority of tumors in this location. The small
proportion of other types include lymphoepithelioma, which arises from lymphatic epithelium,
and transitional cell carcinoma, which arises from transitional cells [1].
3.7.6. Staging
For many years, head and neck tumors are confined to head and neck. Local extensions
to tissues lead to the involvement of regional lymph nodes. Metastasis via lymphatic vessels
occur late, and dissemination via the circulatory system occurs mainly with big tumors or in
immunocompromised patients [5]. A broadly used classification is the TNM staging system of
the American Joint Committee on Cancer. Stage T (T1–T4) is related to the location and size
of a primary tumor; stage N (N0–N1) reflects the number and size of cervical lymph nodes
involved, and stage M (M0–M1) is determined by distant metastasis. The TNM staging system is
diversified and its criterion is tumor location [5, 6]. Stage I corresponds to a primary tumor
below 2 cm in diameter, confined to one anatomical zone, with no metastasis to lymph
nodes and no distant metastasis (T1 N0 M0). Stage II covers tumors below 4 cm in diameter or
in two locations in one anatomical region (for example larynx) without regional or distant
metastasis (T2 N0 M0). Stage III covers tumors over 4 cm in diameter or involving three
71

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
adjacent areas in the head and neck and/or isolated regional metastasis below 3 cm in
diameter (T3 N0 M0 or T1–T3 N1 M0). Stage IV is a massive tumor that invades bones,
cartilages and/or spreads from the primary location to other region (for example from the
oral cavity to the pharynx); metastasis to cervical lymph nodes greater than 3 cm, with
numerous same-side, both-sides or opposite-side lymph nodes. Distant metastasis (T1–4 N1–3
M0–1) is found. Clinical staging is supplemented with diagnostic imaging [5].
72
3.7.7. Diagnostics and treatment
Enlarged cervical lymph nodes or neck tumor can be detected by physical examination.
A lesions is definitely confirmed by a histopathological study of samples taken from it.
Multifocal growth of a tumor, which is frequently observed, and superficial sampling may
hinder histopathological verification. In about 10% of patients, initial diagnosis is based on a
histopathological test of specimens from enlarged lymph nodes. Treatment of head and
neck tumors requires a multidisciplinary approach and full cooperation between a
laryngologist, surgeon, radiotherapist and chemotherapist. Response to treatment,
chemosensitivity and radiosensitivity vary in this group [1]. The choice of treatment depends
on the stage, location and microscopic texture of a primary tumor. Surgical excision is the
first-choice therapy for lesions located in the lip or oral cavity, or metastasis to cervical lymph
nodes. However, radiation is the basic procedure for pharyngeal and laryngeal tumors [1]. In
many stage I tumors, response to surgical treatment and radiotherapy is similar regardless of
location. Radiation of primary tumor and cervical lymph nodes is used. Tumors > 2 cm in
diameter and with extensions to regional lymph nodes require surgery. If metastasis to
regional lymph nodes is detected, the region is radiated postoperatively. Another surgery is
possible with recurrent tumors. With advanced tumors (most of stage II tumors and all stage III
and IV tumor), combined therapy is implemented (surgery and radiotherapy). Surgery is more
effective in monitoring large primary head and neck tumors that radiotherapy or
chemotherapy, but radiotherapy is a better way to monitor peripheral tumors
and micrometastasis inaccessible by palpation. Radiotherapy can be used before and after
surgery but the latter method is preferred. It is not clear whether adjuvant chemotherapy (in
combination with surgery or radiotherapy) increases the number of recoveries but it may
prolong the period of no symptoms of disease. Drugs used for this purpose include cisplatin,
bleomycin, fluorouracil, metotrexat are used [5].
Whether tumor resection and response to treatment are complete is assessed by
diagnostic imaging (PET, CT or MRI of the neck) [5].

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.7.8. Prognosis
Unfortunately, despite a relatively good accessibility and self-assessment opportunities, the
majority of patients consult a doctor as late as stage III or IV, and roughly 50% receive
improper therapy for many months before they are diagnosed correctly [1].
The survival rate for head and neck tumors is largely contingent on their location. Lip
cancer has the best prognosis (94% of 5-year survivals) [6]. Depending on tumor location, 5-
year survivals for head and neck tumors in Europe range from 62% for laryngeal cancer, to
61% for salivary glands cancer, 43% for nasopharyngeal cancer, 45% for oral cavity cancer,
40–50% for nasal cavity cancer, nearly 39% for tongue cancer, 32% for oropharyngeal
cancer, 25% for laryngopharyngeal cancer, to only 10% for esophageal cancer [2, 7]. The
survival rate is higher in women than in men, especially for oral cavity and pharyngeal cancer
[2, 8].
If tumor is managed properly, the 5-year survival rate for stage I disease is 90%. For more
advanced stages, the expected 5-year survival rate is 75% for stage II; 45–75% for stage III;
and < 35% for stage IV. The 5-year survival rate calculated for stage II and III total is 65%.
When metastasis to lymph nodes is found, prognosis is much poorer: 5-year survival does not
exceed 30%. Older patients survive longer and have longer asymptomatic periods after
treatment than younger patients [5] 9 .
3.8. Pancreatic cancer
3.8.1. Epidemiology
Every year, 227,000 people die of pancreatic cancer. This is the eighth leading cause of
death of all the tumors, and the thirteen with respect to incidence. Its high mortality relative
to incidence proves its poor prognosis: the mortality to incidence ratio is 98%. The frequency
9 1. Pawlicki M. Leczenie nowotworów. Bielsko-Biała, Alfa Medica Press, 1996.
2. Sant M, Aareleid T, Berrino F, Bielska Lasota M, Carli PM, Faivre J, Grosclaude JP, Hédelin G, Matsuda T, Møller H,
Möller T, Verdecchia A, Capocaccia R, Gatta G, Micheli A, Santaquilani M, Roazzi P, Lisi D and the EUROCARE
Working Group. EUROCARE-3: survival of cancer patients diagnosed 1990–94 – results and commentary. Ann Oncol
2003; 14: pp 61–118.
3. Evidence-based Cancer Prevention: Strategies for NGOs - A UICC Handbook for Europe Evidence-based
Cancer Prevention: Strategies for NGOs – A UICC Handbook for Europe. http://www.uicc.org
4. Globocan 2002 database; http://www-dep.iarc.fr/
5. The Merck manual of diagnosis and therapy. Merck and Co. 17 th edition; www.merck.com
6. Snehal G, Patel and Jatin P. Shah. TNM Staging of Cancers of the Head and Neck: Striving for Uniformity Among
Diversity. CA Cancer J Clin 2005; 55: pp 242–258.
7. Coleman MP, Gatta G, Verdecchia A, Estève J, Sant M, Storm H, Allemani C, Ciccolallo L, Santaquilani M,
Berrino F and the EUROCARE Working Group. EUROCARE-3 summary: cancer survival in Europe at the end of the
20th century. Ann Oncol 2003; 14: pp 128–149.
8. Berrino F, Gatta G. Variation in survival of patients with head and neck cancer in Europe by the site of origin of
the tumors. The EUROCARE Working Group. Eur J Cancer 1998; 34: pp 2154–2161.
73

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
of pancreatic cancer in women and men is similar. Most cases are reported in developed
countries (61%), where incidence and mortality in men are 7 and 9 per 100,000 of the
population, in women – 4.5 and 6 per 100,000. It seems that lower incidence in developing
countries is attributable to poorer diagnostic efficacy rather than to real differences. The
highest incidence rates in developing countries is observed in Central and South America [1].
In Poland, in 2002, the incidence of pancreatic cancer in men was 9.5 per 100,000, and
morbidity was 8 per 100,000 (age-standardized values). In women, the rates were 6.1 per
100,000 and 5.3 per 100,000 respectively [2].
74
3.8.2. Risk factors
The etiology of the disease is unknown. Risk factors include age (the highest risk of
morbidity is in the 6th and 7th decades of life), sex (slightly more frequent in men), race
(Polynesians, Hawaiians, Jews, American Indians), tobacco smoking (twice as frequent in
people smoking at least 2 packs daily), diet (none of the factors analyzed was definitely
identified as a risk factor: alcohol, coffee, diet rich in fats), prior pancreas diseases, low
socioeconomic status, occupational exposure (chemical, coke, metal, gas industry),
participation of genetic factors were not found [3].
3.8.3. Symptoms
Early symptoms are occasional and uncharacteristic, which prevents early diagnosis. Pain
in the mesogastrium may occur. Late symptoms include jaundice caused by tumor pressure
on biliary ducts; or enlarged gall bladder detectable in physical examination (Courvoisier’s
symptom), loss of body weight, or pain in the lumbar region. A frequent manifestation of the
tumor is recurrent athero-thrombotic disease [4].
3.8.4. Histopathological picture
Histopathological diagnosis should be made in compliance with WHO criteria based on
an examination of material from biopsy or fine-needle aspiration [5]. The most common type
of tumors of the exocrine part of pancreas is ductal carcinoma (90%), which arises from the
epithelium of the pancreatic ducts. Much less frequent is adenoid cystic cancer
(cystadenocarcinoma) and acinar cell carcinoma. Relatively rare are oncocytic cancer,
clear cell cancer, signet ring cell cancer, mucosal and squamous cell carcinoma. Extremely
rare in the pancreas are tumors of other histopathological textures such as sarcomas,
lymphomas or pancreatoblastoma, which is most frequent in children. About 5% of all
cancerous hyperplasia of pancreas arises from cells of the exocrine system: they are so-
called insulomas, benign or malignant, which overproduce pancreatic enzymes [6].

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
[7].
3.8.5. Staging
Table 12 presents the classification and stages of pancreatic cancer according to AJCC
Table 12.
AJCC staging system for exocrine pancreatic cancer
Primary tumor
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor limited to the pancreas, ≤2 cm in greatest dimension
T2 Tumor limited to the pancreas, >2 cm in greatest dimension
T3 Tumor invades the duodenum, common biliary duct, peripancreatic tissues
T4 Tumor invades the stomach, spleen, large intestine, adjacent vessels
Regional lymph nodes
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N2 Regional lymph node metastasis
Distant metastasis
Mx Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
Stage 0 Tis N0 M0
Stage I T1–T2 N0 M0
Stage II T3 N0 M0
Stage III T1–T3 N1 M0
Stage IVA T4, any N, M0
Stage IVB Any T, any N, M1
Stage groupings for pancreatic cancer
3.8.6. Diagnostics and treatment
Before a decision on therapy is made, apart from a precise case history and physical
examination, peripheral blood morphology, liver enzyme levels and the level of glycaemia in
blood serum should be tested. Other a radiogram of the chest, and abdomen imaging by
ultrasonography and CT or magnetic resonance are required. Other diagnostic methods
include endoscopic retrograde cholangiopancreatography (ERCP), endoscopic
ultrasonography (EUS), laparoscopy with biopsy and laparoscopic ultrasonography [6].
75

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
76
Surgical treatment of pancreatic cancer is the only effective procedure. However, the 5-
year survival rate after surgery is 10–20%, Pancreas surgery is done by:
• radical resection (R0 – complete resection of tumor, no micro- or macroscopic
involvement),
• palliative resection (R1 – resection of tumor with residual microscopic involvement, R2 –
resection of tumor with residual macroscopic involvement),
• palliative procedures (bypass) [6].
Pre- and postoperative chemotherapy, with or without radiotherapy, remain
controversial.
For disease with distant metastasis, treatment focuses in the main on symptoms. In some
patients, radiotherapy may help to relieve pain. Patients may require the stenting of the
biliary ducts due to jaundice that arises from tumor’s pressure on the biliary ducts; or it is
necessary to unblock the ducts [4, 5]. An initial evaluation of response to therapy may be
carried out by follow-up imaging. However, imaging is not required in properly managed
patients. Response to treatment should be evaluated mostly based on clinical symptoms [5].
Figure 4 presents an algorithm of a therapeutic procedure for pancreatic cancer [6].

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Figure 4.
Algorithm of therapeutic procedure for pancreatic cancer; source: The Polish Oncology Union, Zalecenia
postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych u dorosłych, edited by M. Krzakowski [6]
3.8.7. Prognosis
Pancreatic cancer is among the tumors with the poorest prognosis. The average European
5-year survival rate for pancreatic cancer is below 4% [8]. Prognosis depends on disease
77

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
stage, but as epidemiological studies show, the patient’s age is a stronger factor [5]. Table 13
presents the proportion of patients with 5 years’ survival by disease stage [5] 10 .
Table 13.
5-year survivals in pancreatic cancer by disease stage
78
Stage 0 -
Stage I 5–35%
Stage II 2–15%
Stage III 2–15%
Grade IVA 1–5%
Grade IVB < 1%
3.9. Gastrointestinal stromal tumor
3.9.1. Epidemiology
Sarcomas of soft tissues are a group of heterogeneous tumors of mesenchymal origin. In
Poland, a few hundred cases of sarcomas are diagnosed annually, most frequently in
patients aged 60 plus [1]. One type is gastrointestinal stromal tumor (GIST). It is believed that
GISTs represent about 0.1 to 0.3% of all tumors of the stomach and intestines [5].
Epidemiological data on gastrointestinal stromal sarcomas published to date are not fully
reliable [2]. The exact proportion of benign and malignant GIST types (sarcomas generating a
potential risk of recurrence and/or inoperable dissemination) is not known either.
Retrospective studies carried out in Sweden show that the mortality rate for GIST (benign and
malignant) is 16 cases per year per million. For Poland, the incidence of about 600 new cases
yearly is suggested. In the United States, the number of metastatic or inoperable GISTs is
estimated at over 1000 new cases annually, which gives 3–4 cases per 1 million inhabitants.
Other estimates imply that in Poland about 120–195 new cases can be expected every year.
It seems that the incidence of this tumor type is similar in men and women [2].
10 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: pp 74–108.
2. Globocan 2002 database. http://www-dep.iarc.fr/
3. Pawlicki M et all, Leczenie nowotworów. Bielsko-Biała, Alfa Medica Press, 1996.
4. Strum A, Largiader F, Wicki O. Kompendium onkologii. Warszawa, PZWL, 1995.
5. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of pancreatic cancer. Annals
of Oncology 2005; 16: pp 124–125.
6. Krzakowski M. et all, Zalecenia postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych u
dorosłych. http://www.puo.pl/ksiazka.php
7. AJCC cancer staging manual, sixth edition.
http://www.cancerstaging.org/education/tnmschema/exocrinepancreas.ppt
8. Coleman MO et al. Eurocare-3 summary: cancer survival in Europe at the end of 20th century. Annals of
Oncology 2003; 1: pp 128–149.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.9.2. Symptoms
Complaints are usually non-characteristic and may include abdominal pains, symptoms
resembling occlusion of, or chronic bleeding from, the gastrointestinal tract; tumor palpable
in the abdomen; or occasional acute abdomen symptoms. Small lesions may be long
asymptomatic. The results we obtained as well as data from other authors suggest that the
asymptomatic period preceding dissemination may be long, with the median exceeding 2
years [2].
3.9.3. Histopathological picture
GIST-type sarcomas have been diagnosed more commonly for the past 4–5 years. Until
recently, these tumors had been known and diagnosed under various names. Now the term
“benign” is avoided with reference to GIST, and replaced with the descriptor “low-
aggressiveness” because in some cases, generalization disease traits were found over longer
periods of observation. GISTs derive most probably from precursors of pace-making
neurological interstitial cells of Cajal. The most important prognostic factors are the size of
primary cancer focus, and the number of mitoses observed in 50 fields of vision in large
magnification [2].
3.9.4. Staging
At present there is no widely acceptable staging system. A suggested classification takes
into account aspects such as growth size, involvement of regional lymph nodes, distant
metastasis and histopathological picture [5].
3.9.5. Diagnostics and treatment
Because GIST is a disease recently isolated based on its molecular and histological
features, no standard diagnostic or therapeutic procedure exist.
The most efficacious method in GIST treatment is radical surgery. The majority of patients
(92%) are first operated without prior histopathological diagnosis of GIST (only in 8% have
histological suspicions of GIST).
In nearly 74% of patients, the first therapeutic surgery is possible by resecting stomach,
small intestine or large intestine, or by excising a intraperitoneal/retroperitoneal tumor with
macroscopic margin. Surgical treatment is highly efficacious mainly for low and intermediate
degrees of aggressiveness. With stomach GIST, local excision of the tumor along with a
section of the stomach wall is most frequent. Complete or incomplete resection is rarely
performed. It seems, that the extent of stomach resection is neutral for recurrence.
79

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Subsequent operations of recurrent tumors do not lead to recovery. In other locations,
segmental resection of the small bowel or hemicolectomy are used.
80
Current scientific knowledge does not support the use of supplementary treatment of GIST.
Inoperable or disseminated GIST is resistant to conventional chemotherapy and
radiotherapy. Clinical researches focuses on treatment based on imatinib, a tyrosine kinase
inhibitor.
Recurrences after treatment are most frequently found in the abdominal cavity. Usually
liver metastasis (54%), isolated metastasis (22%), or metastasis accompanied by
intraperitoneal dissemination (32%) occur. Intraperitoneal dissemination without liver
metastasis is observed in about 31% of patients. In a proportion of patients (15%), inoperable
local recurrence is observed, which is a good proof of the surgical potential of locally radical
excision of the tumor [2, 3, 4].
3.9.6. Prognosis
Prognostic factors include the size of primary focus of the tumor and the number of
mitoses observed in 50 fields of vision under high magnification. About 20–30% of GIST tumors
are malignant. Gastric cancer up to 5 cm in tumor size, and small bowel tumors up to 2 cm in
size are benign as a rule. Following radical excision of the tumor, 35–65% 5-year survival is
observed. Prognosis for patients with inoperable lesions or with metastasis is poor (median
survival under 12 months or 8% 5-year survivals). The worst results are reported for patients with
intraperitoneal dissemination caused by gastrointestinal tract obstruction [2, 4, 5] 11 .
11 1. Pawlicki M et all, Leczenie nowotworów. Bielsko Biała, Alfa Medica Press, 1996.
2. Ruka W, Rutkowski P, Nowecki Z, Nasierowska-Guttmejer A, Grzesiakowska U. Mięsaki podścieliskowe przewodu
pokarmowego (GIST) – zalecenia postępowania diagnostyczno-terapeutycznego.
http://www.coi.waw.pl/miesaki/index.htm
3. Blay J-Y, Bonvalot S, Casali P, Choi H, Debiec-Richter M, Dei Tos AP, Emile J-F, Gronchi A, Hogendoorn PCW,
Joensuu H, Le Cesne A, Mac Clure J, Maurel J , Nupponen N, Ray-Coquard I, Reichardt P, Sciot R, Stroobants S,
van Glabbeke M, van Oosterom A, Demetri GD. Consensus meeting for the management of gastrointestinal
stromal tumors. Report of the GIST Consensus Conference of 20–21 March 2004, under the auspices of ESMO. Ann
Oncol 2005; 16: pp 566–578.
4. DeMatteo RP, Lewis JJ, Leung D et all, Two hundred gastrointestinal stromal tumors. Recurrence patterns and
prognostic factors for survival. Ann Surg 2000; 231: pp 51–58.
5. Crosby JA, Catton CN, Davis A, Couture J, O’Sullivan B, Kandel R, Swallow CJ. Malignant Gastrointestinal Stromal
Tumors of the Small Intestine: A Review of 50 Cases From a Prospective Database. Ann Surg Oncol 2001; 8 (1): pp
50–59.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.10. Colon cancer
3.10.1. Epidemiology
In 2002, about million new cases of colon cancer were reported globally (9.4% of all
tumors). No significant differences in incidence between men and woman are found for this
cancer type. As regards incidence, it is the fourth leading tumor in men and the third leading
tumor in women globally [4]. In 2002 in Poland, the standardized incidence rates for
colorectal cancer were 31.9 per 100,000 men and 23.5 per 100,000 women. Mortality was
18.2 per 100,000 and in women it was 11.4 per 100,000 [2]. The incidence of this tumor type is
still growing [3], but mortality in Europe has decreased over the last decade [5].
Approximately 25-time differences in the incidence of this tumor are observed in the world.
The highest incidence rates are reported in North America, Australia, New Zealand, and
Western Europe, and the lowest in Africa, Asia, South America. These differences may be
attributable to different exposure to environmental impacts.
In fast developing countries, the incidence of colorectal cancer is growing but in highly
developed countries these rates tend to stabilize or even fall (North America) [4].
Colorectal tumors are rare for people younger than 40. Above this age, risk increases [3].
3.10.2. Risk factors
It is believed, that genetic and environmental factors play an important role in developing
colon cancer.
Precancerous conditions that predispose to cancer include benign adenomas of the
large intestine, polipomatosis syndromes and inflammatory bowel diseases. The majority of
occasional cancers arise from acquired mutations of suppressor genes such as p53, APC [3].
It is believed that the risk factors of colon cancer may include improper diet (high intake of
meat, meals rich in animal fats). Epidemiological studies showed that no physical exercise,
obesity, and central distribution of the fatty tissue are risk factors of colorectal cancer too [4].
It seems that diet rich in fats and animal meat but calcium and selenium-deficient may
adversely affect bacterial flora, trigger the synthesis of carcinogenic compounds, and
increase the time of exposition of the bowel mucosa to these substances by slowing down
their passage through the large intestine [3].
A major portion of colon cancers arise from adenomas.
81

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
82
3.10.3. Symptoms
The disease may be asymptomatic, or may cause symptoms initially ignored by the
patient. The most frequent are latent bleeding and abdominal pain. Alterations of the normal
defecation rhythm, diarrheas or constipations may occur. Hemorrhage, bowel ruptures or
ileus are rare [3].
3.10.4. Histopathological picture
Almost all colorectal cancers arise from adenomatous polyps. In about 10% of cases,
cancer cells are of endocrine type [11]. The most frequent type is adenocarcinoma, which
represents 85% of all colon cancers. Mucous cancer represents about 10%. Other types are
mucocellular carcinoma, squamous cell carcinoma, mixed and non-differentiated
carcinomas [12].
3.10.5. Staging
Table 14 presents the TNM staging system for colorectal cancer [7].
Table 14.
TNM staging system and tumor classification for colon cancer
Primary tumor
Tx Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Cancer in situ
T1 Tumor invades submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into the subserosa
T4 Tumor invades through the visceral peritoneum or invades adjacent structures
Regional lymph nodes
Nx Regional nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in 1–3 lymph nodes
N2 Metastasis in 4 or more lymph nodes
N3 Metastasis in mesenteric lymph nodes
Distant metastasis
M0 No distant metastasis
M1 Distant metastasis
TNM stage groupings
Stage 0 Tis N0 M0
Stage I T1 N0 M0
T2 N0 M0
Grade II T3 N0 M0

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
T4 N0 M0
Stage III Any T N1 M0
Any T N2, N3 M0
Stage IV Any T any N M1
There is a range of clinical pathological classifications of colon cancer. One of them a
classification of colorectal cancers proposed by Astler-Coller [7]. This classification is
presented in Table 15.
Table 15.
Astler-Coller classification of colorectal cancers
Stage Histological features of tumor
A Tumor limited to mucosa
B1 Growth invades through muscularis propria, lymph nodes not involved
B2 Tumor grows beyond muscularis propria, lymph nodes not involved
C1 Growth invades through muscularis propria, lymph nodes not involved
C2 Growth invades through muscularis propria, lymph nodes involved
D Distant metastasis
3.10.6. Diagnostics and treatment
3.10.6.1 Screening examinations
The key aim of screening examinations is to reduce the mortality rate of colon cancer. For
this purpose fecal occult blood tests, sigmoidoscopy or full colonoscopy are performed [3].
3.10.6.2 Physical examination
Per rectum examination is essential. In some cases, a tumor is palpable during finger
examination of the final section of the rectum.
3.10.6.3 Laboratory tests
Laboratory tests can detect iron deficiency anemia. Cancer diagnosis may be suggested
by a high level of carcinoembryonic antigen (CEA) in blood serum. Fecal occult blood tests
are positive.
3.10.6.4 Endoscopy
Colonoscopy is the most important diagnostic study. It helps evaluate the mucous
membrane of the large intestine microscopically, and to sample lesions for histopathological
examination. Recently, endosonography (fused ultrasonography and colonoscopy), has
been used. It helps to estimate the depth of carcinogenic infiltration into the bronchial wall
and to assess local lymph nodes and node metastasis in a non-invasive way.
83

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
84
3.10.6.5 Diagnostic imaging
Ultrasound scanning, or the more precise CT, of the abdominal cavity provides grounds to
suspect distant metastasis, for example to the liver.
PET is used to evaluate disease recurrence when the patient has completed therapy.
However, it is believed to be of little value for T-staging [3].
3.10.6.6 Surgery
Surgery is the basic therapy for colorectal cancer. The aim of the surgery is total resection
of the tumor with regional lymph nodes. A traditional method is laparotomy; lately
laparoscopic methods are used with similar distant results.
3.10.6.7 Supplementary treatment
Systemic chemotherapy with 5-fluorouracyl and levamisole, administered for one year
following a surgery of stage C1, C2 cancer reduces the risk of local recurrences by 41% and
of deaths by 33% compared to surgery-only therapy. A combination of 5-fluorouracyl
with foline acid is also used for stage B2 [3]. Monoclonal antibodies against receptors for
epithelial growth factor or endothelial growth factor are new drugs that can be used in
combination with other chemotherapeutics. Second-line chemotherapy can be considered
in patients with good general condition [6].
3.10.6.8 Treatment of disseminated disease
Inoperable tumors are treated with combined chemotherapy (5-fluorocytosine in
combination with foline acid). Capecitabin or irinotecan with oxaliplatin are an alternative
therapy. If intestinal passage is impaired due to tumor mass, its patency can be restored by
surgery or using laser rays. Liver metastasis can be treated with transcutaneus alcohol
injection or injection of cytostatic drugs to the hepatic artery [3]. Surgical excision of a single
liver or lung metastasis should be considered [6].
3.10.6.9 Evaluation of response to treatment
Recommended are physical examination, measurement of CEA level, ultrasound
scanning of the liver, and/or tomography of primary involvements 2–3 months after palliative
therapy is completed.
3.10.6.10 Follow-up
There is no proof that regular monitoring of the disease improves the efficacy of colon
cancer management. Follow-up consultations in case of disease symptoms are
recommended. Laboratory tests and imaging diagnostics should be used in patients with
suspected disease progression if future palliative treatment is planned [6].

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
3.10.7. Prognosis
Five-year survival rates vary depending on geographical location. In North America, the
survivals are 65%, in Western Europe - 54%, but in Eastern Europe only 34%. A relatively good
prognosis for this tumor means that the mortality rate is half the incidence rate [4].
The findings of Eurocare-3 indicate that in the early 1990s, the 5-year survival rate for colon
cancer patients in Poland was 26.3% in men and 28.7% in women. The five-year survival rate
for colon cancer patients is about 50% lower in Poland compared to the survival rate for the
whole Europe [9, 10].
Prognosis in colon cancer depends on the tumor stage. The odds of 5-year survival for
patients with stage A disease according to the Astler-Coller classification are 100%, for
patients with stage B1 disease: 67%; for patients with stage B2 disease: 54%; for patients with
stage C1 disease: 43%; and for patients with stage C2 disease: only 23% [11] 12 .
12 1. Europe 1995, Estmates of cancer incidence and mortality in Europe in 1995.
http://www.encr.com.fr/europe95.htm
2. Globocan 2002: http://www-dep.iarc.fr/
3. Szczeklik A et all, Choroby wewnętrzne. Kraków, Medycyna Praktyczna, 2005.
4. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): pp 74–108.
5. Europe’s cancer burden http://www.uicc.org/fileadmin/manual/5burden.pdf
6. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of advanced colorectal
cancer. Ann Oncol 2005; 16: pp 18–19.
7. Astler VB, Coller FA. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann
Surg 1954; 139: p 846.
8. AJCC cancer staging manual, sixth edition.
http://www.cancerstaging.org/education/stagingmomentscolon06.ppt.
9. Narodowy program zwalczania chorób nowotworowych. ZałoŜenia i cele operacyjne 2006–2015.
http://www.mz.gov.pl/wwwfiles/ma_struktura/docs/zalozenia_ustawy_o_npzchn.pdf
10. Coleman MO et al. Eurocare-3 summary: cancer survival in Europe at the end of 20th century. Ann Oncol 2003;
1: pp 128–149.
11. Coran R, Kumar V, Ramzi T. Robbins pathologic basis of disease. Elsevier/Saunders, 1999, wydanie 6.
12. Pawlicki M et all, Leczenie nowotworów. Bielsko Biała, Alfa Medica Press, 1996.
85

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
4. DESCRIPTION OF INTERVENTION
86
4.1. Description of method
PET is a diagnostic method that produces images of metabolic processes at the molecular
level. The PET technology has been developing since the early 1970s [1].
CT is an accepted tool used in imaging diagnostics. Currently, multi-detector-row spiral
tomography scanners prevail on the market.
The first PET/CT fused scanning system was marketed in 2001 [1, 2]. PET/CT scanners are
now manufactured by 4 companies: CPS Innovations, GE Medical Solutions, Philips Medical
Systems and Siemens Medical Solutions [12]. In 2003, PET/CT systems represented 79% of total
PET scanner sales. In 2004, the figure grew to 91% [13]. The first PET/CT unit in Poland was
installed in Bydgoszcz in 2002.
PET tomography uses the fact that metabolic processes have different dynamics in
pathologically changed cells. These can be located using radionuclide-traced molecules,
which are incorporated into metabolic cycles without no impact on physiological processes.
Scintigraphic tracers are highly specific and a small amount of radionuclide is enough to
produce diagnostic images.
Intracellular processes can be examined by PET indirectly by locating positron-emitting
tracers. A positron is a particle of the same mass as an electron but of the opposite charge.
After leaving the where the deposited radionuclide disintegrates, it travels the distance of
about 4–5 mm, gradually loosing its kinetic energy in the surrounding tissue and then, when it
collides with the nearest electron, annihilation occurs, resulting in the production of two
gamma ray photons, each with the energy of 511 keV. The photons move in opposite
directions and are registered by a system of detectors located in the ring [9] (Figure 5).
Information on the number of gamma ray photons captured by the detectors is transmitted
to the computer, which reconstructs, three-dimensionally, the distribution of radioactivity in
the patient’s body.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Figure 5.
Annihilation and detection of gamma rays
The most frequently used in PET is radioisotope-traced glucose ( 18 F fluorodeoxyglucose, 18 F-
FDG). The physical half-life of 18 F-FDG is 110 min. Other tracers are carbon 11 C (half-life of 20
min), nitrogen 13 N (half-life of 10 min), oxygen 15 O (half-life of 122 s), rubidium 82 Rb (half-life of
75 s).
4.2. Examination protocol, absorbed dose
Before the examination, the patient should not eat for minimum 4 hours. After the
radiopharmaceutical is given intravenously, the patient needs to lie down for an hour and
drink a liter of water. Then CT and PET scanning is performed. Depending on indications,
whole-body or selected region are scanned. After the image is reconstructed and processed
the findings help not only determine the type of lesion, but also its exact localization [3]
(Figure 6).
87

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Figure 6.
Dissemination of tumor: metastatic lymph nodes in the left groin
a) CT mage; b) PET/CT image; c) PET image
88
For standard whole-body scanning with 18 F-FDG, the activity administered is about 370
MBq (10 mCi), but the effective dose absorbed by the patient is about 10mSv [10], and only
about 3 times higher than natural background radiation [2]. Obviously, this dose is received in
a single test, while radiation from natural sources is taken in gradually over the whole year.
Radiation effects are known to depend not only on the dose, but also on distribution in time.
What is more, the dose absorbed in PET should be added to the dose absorbed from CT
scanning, which is about 5–10mSv, depending on the test protocol.
4.3. Limitations of method
The resolution of a PET scanner is currently 3–5 mm [1, 10], and is limited by the total
distance traveled by the positron after annihilation, as well as by the fact, that the angular
distribution is not exactly 180° (the acceptable difference is ±0.5°) [9, 10]. The efficiency and
resolution of the method are also contingent on the distance between detectors and their
sizes: the smaller the detectors and closer to each other and to the source of radiation, the
higher resolution can be achieved. On the other hand, the smaller the scanner’s ring in
diameter, the higher the probability of dispersion and coincidences [9]. Currently, scintillator
detectors with Bi4Ge3O12 (BGO) crystals are the most frequently used. Contemporary PET
scanners are used for 3D visualization [10].
Due to low spatial resolution multi-modal examination is used: a PET image is superimposed
by rotation, shift and calibration on a high-resolution anatomical picture from CT or MRI [10].
A CT scanner fused with a PET scanner should have at least 4 rows of detectors [13].

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Another problem is short half-life of the tracer, therefore miniature cyclotrons need to be
installed close to the PET/CT scanner. The synthesis of the radiopharmaceutical must occur
within a short time between manufacture and administration [9].
4.4. Uses of PET-CT
PET/CT is particularly useful in oncology, neurology and cardiology.
4.4.1. Oncology
In cancer diagnostics, 18 F-FDG is used in the first place. Oncological indications for PET
scanning include:
1. Assessment of nodular lesions in pulmonary parenchyma.
For malignant lesions, PET sensitivity is 97% and PET specificity is 78%, but for benign lesions,
the values are 89% (sensitivity) and 100% (specificity) [4, 5]. The standardized uptake value
(SUV) is used to assess the type of lesion. The SUV tells us how intense the uptake of 18 F-FDG is
[1, 6]. A nodule with the SUV below 1.5 has low odds of malignancy [1].
2. Staging
Currently, PET has an important role in the diagnostics of non-small cell lung cancer, colon
and esophageal cancer, thyroid cancer, breast cancer, melanoma, lymphomas and
malignant head and neck tumors [1, 2]. PET helps to determine boundaries of carcinogenic
lesions in a primary growth, and to distinguish it from an oedema zone, atelectasis or
inflammatory changes. In the case of lung tumors, PET helps to recognize the character of
the fluid in the pleura: it distinguishes benign exudations from fluid containing cancer cells
with 92% precision [7]. Also, PET helps assess lymph nodes, especially those below 1 cm: for
mediastinal lymph nodes its sensitivity is 80–90%, and specificity is 85–100% [8]. Note that the
inflammatory condition of lymph nodes reduces PET sensitivity by giving false positive results
[1, 6]. PET is also helpful in assessing distant metastasis. Often, these lesions are not revealed
by any other imaging technologies. Detecting metastatic foci in brain causes difficulties,
because the cortex has the highest physiological level of FDG accumulation in the human
body [1].
3. Follow-up examination to determine the risk of recurrence after therapy is completed.
PET is more sensitive to recurrent carcinogenic processes, i.e. in esophageal cancer the
sensitivity to local recurrences is 100%, but specificity is 57% due to false positive results
produced by inflammatory changes [1]. Also, PET helps tell postoperative or post-
radiotherapy cicatrix from recurrent tumor [2].
4. Radiotherapy planning
89

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
90
PET helps detect additional disease foci that are not apparent in CT, which results in
greater radiation areas. PET detects the most metabolically active regions within a tumor,
based on which doses can be adjusted [1].
4.4.2. Neurology
In imaging of neurological diseases with PET, the radiotracers used include 18 F-FDG, 18 F-
fluorodopa, 11 C- methionine, 11 C-flumazenil, 15 O-water. Neurological indications for PET
scanning include [11]:
1. Brain tumor staging (neurooncology).
PET is a non-invasive, preoperational method to stage tumors, especially gliomas, based
on the activity of glucose uptake in white matter. Highly malignant gliomas display a higher
use of glucose than low-grade tumors. Post-surgery PET helps detect residual tumor mass and
to recurrence from radionecrosis.
2. Detecting and assessing epileptic foci.
PET is helpful especially in evaluating temporal epilepsy. During epileptic seizures, the
glucose intake level of the epileptic focus grows, but drops between seizures. PET is also useful
in evaluating drug-resistant childhood epilepsy.
3. Evaluation of dementia-type disorders
In Alzheimer’s disease patients, low glucose metabolism, and low regional brain blood flow
and regional oxygen consumption are observed in frontal, parietal and temporal lobes. In
multi-infarct dementia, the disorders above are anatomically associated with the regions of
pathological changes of arterial vascularization.
4. Motoric dysfunction
In Parkinson’s disease patients, low uptake of 18 F-fluorodopa in the putamen is apparent. In
Huntington’s disease, decrease in glucose metabolism is evident in the striatum, at later
stages also in the frontal lobes. Other motoric dysfunction syndromes assessable by PET
include multisystemic atrophy, corticobasal degeneration, progressive supranuclear palsy,
and Wilson’s disease.
5. Assessment of brain tissue ischemia.
PET is helpful in assessing cortical strokes, where it is used to measure changes in regional
brain blood flow before and after therapeutic intervention. It also allows for an early
identification of low regional brain blood flow in patients with subarachnoidal hemorrhage
symptoms.
6. Neuroactivation.
15 O-water PET is used to evaluate neuronal activity for the purposes of locating specific
brain functions such as motoric behaviors or cognitive functions.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
4.4.3. Cardiology
PET scanning of the heart uses 82 Rb-chloride, 13 N-ammoniac, 18 F-FDG and 11 C- palmitic
acid. Cardiologic indications for PET studies include [14]:
1. Diagnostics of coronary disease.
PET is used to determine the extent and intensiveness of heart muscle damage arising from
ischemic disease, by indicating loss of perfusion in the heart muscle.
2. Assessment heart muscle vitality
18 F-FDG examination is essential before the revascularisation procedure as it differentiates
regions of “frozen” myocardium from postinfarct scars.
4.5. Results
PET/CT fusion in diagnostic imaging allows more precise classification of lesions visible in
PET studies as it narrows down their anatomical location. These days, PET/CT is replacing PET
and is the fastest developing imaging method. Modern PET scanners and multi-detector-row
CT scanners reduce the testing time remarkably, and faster scanning makes the use of
radiopharmaceuticsals more efficient 13 .
13 1. Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004; 231: pp 305–
332.
2. Pruszyński B. Osiągnięcia diagnostyki obrazowej na przełomie roku 2003/2004. www.schering.pl
3. Hany TF, Steinert HC, Goerres GW et al. PET diagnostic accuracy: improvement with in-line PET-CT system; initial
results. Radiology 2002; 225: pp 575–581.
4. Gould MK, Maclean CC, Kuscher WG et al. Accuracy of positron emission tomography for diagnosis of
pulmonary nodules and mass lesions; a meta analysis. JAMA 2001; 285: pp 914–924.
5. Patz EF, Lowe VJ, Hoffman JM et al. Focal pulmonary abnormalities: evaluation with F-18 fluorodeoxyglucose PET
scanning. Radiology 1993; 188: pp 487–490.
6. Shim SS, Lee KS, Kim BT et al. Focal parenchymal lung lesions showing a potential of false positive and falsenegative
interpretations on integrated PET/CT. AJR 2006; 186: pp 639–648.
7. Erasmus JJ, McAdams HP, Rossi SE et al. FDG PET of pleural effusions in patients with non- small lung cancer. AJR
2000; 175: pp 245–249.
8. Patz EF, Lowe VJ, Goodman PC et al. Thoracic nodal staging with PET imaging with 18-FDG in patients with
bronchogenic carcinoma. Chest 1995; 108: pp 1617–1621.
9. Jednoróg S, Mazur G, Janiak KM et all, KrótkoŜyciowe izotopy pierwiastków lekkich jako znaczniki tomografii
pozytronowej (PET). Problemy Medycyny Nuklearnej 1998; 12 (24): pp 191–200.
10. Kochanowicz E, Kulka J. Detekcja i rekonstrukcja obrazu w PET. Problemy Medycyny Nuklearnej 2002; 16 (31):
pp 123-132.
11. Chmielowski K. Emisyjna tomografia pozytronowa (PET) w neurologii. Problemy Medycyny Nuklearnej 2002; 16
(31): pp 143–150.
12. PET-CT Consensus Conference: SNMTS; American Society of Radiologic Technologist (ASRT). Fusion imaging:
a new type of technologist for a new type of technology. J Nucl Med Technol 2002; 30: pp 201–204.
13. Brink JA. PET/CT unplugged: the merging technologies of PET and CT imaging. AJR 2005; 184: pp S135–S137.
14. Thrall JH, Ziessman HA. Nuclear Medicine. Mosby 2001 St. Louis.
91

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
5. METHODOLOGY
92
5.1. Purpose of study
The purpose of this report is a comparative cost effectiveness analysis of PET-CT with
diagnostic technologies financed in Poland from public sources in oncological
diagnostics. This part of the report provides a clinical and epidemiological analysis.
The study was ordered by the Agency for Health Technology Assessment in Poland.
5.2. Method of clinical efficacy assessment
Clinical questions were prepared consistent with the subject of the analysis;
A search strategy for scientific studies was designed;
The world’s key medical databases and clinical studies registers were searched for
primary studies;
Primary studies were selected based on pre-defined inclusion criteria;
Trial results and their statistical and clinical significance were reviewed;
A meta-analysis of the results of the trials included was executed;
The comparative analysis results were interpreted and conclusions formulated.
The search strategy for primary studies, the assessment of studies reliability, as well as data
extraction, statistical analysis and results interpretation methods were designed based on
guidelines of the Medical Services Advisory Committee [„Guidelines for the assessment of
diagnostic technologies” August 2005, Australia].
5.3. Search strategy for primary studies
As the first step of searching for trials a general search strategy was adopted without
further specifying the target population, in order to locate a group of trials concerning the
use of PET-CT in oncological diagnostics. Additionally, for 12 indications individual searches
were conducted with targeted population (breast cancer, lung cancer, colorectal
cancer, ovarian cancer, cervical cancer, endometrial cancer, lymphoma, gastric and
esophageal cancer, melanoma, glioma, sarcoma, head and neck cancer). In the process
of searching for reports on the technology under assessment, results of a high specificity

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
strategy that identified only those publications where the hybrid term “PET-CT” or its
equivalents appeared (#9) – on the basis of search strategy presented in „Revision
Sistematica Sobre la Efectividad E Indicationes del Sistema Hibrido PET-TAC.” Unidad de
Evaluacion de Tecnologias Sanitarias 2006. Agencia Lain Entralgo, were combined with
results of a high sensitivity strategy that identified all publications describing the diagnostic
method under discussion (search for publications with “PET” and “CT” titles, abstracts or
keywords - #8).
Table 16.
Search strategy
ID
Search strategy
#1 „Positron-Emission Tomography” [MeSH] OR „Tomography, Emission-Computed” [MeSH]
#2 PET OR positron emission tomography
#3 #1 OR #2
#4 („Tomography, Spiral Computed” [MeSH] OR „Tomography, X-Ray Computed” [MeSH])
#5 CT OR computed tomography
#6 #4 OR #5
#7
dual OR integral OR integration OR combination OR combined OR fusion OR fused OR hybrid OR
coincidental OR combining OR coincidence OR coregistered
#8 #3 AND #6
#9 #3 AND #7
#10 #8 OR #9
#11 „Neoplasms” [MeSH]
#12 „Medical Oncology” [MeSH]
#13 #11 OR #12
#14 #10 AND #13
#15 #10 AND #13 Limits: English, Polish, Publication Date from 1998/01/01, Humans
Last search date: 20-03-2006.
To design the search strategy, a database of medical terms was used (Medical Subject
Headings – MeSH). The database includes thematic entries with synonyms and terms
close in meaning assigned to them. Linking the database search with the broad terms of
the MeSH database allows to avoid ignoring publications with non-standard terminology.
Detailed search results including described search strategies are presented in appendix.
Reviews and metaanalysis were searched on the grounds of search strategy given in table
16 with replacement RCT filter with “review” or “metaanalysis” limitations.
5.4. Medical database search
The above search strategy was applied to the following databases:
Medline by Pubmed,
93

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
94
Cochrane Library (The Cochrane Database of Systematic Reviews, The Cochrane
Con- trolled Trials Register),
EmBase,
and medical web sites:
NICE (National Institute for Clinical Excellence),
SBU (Statens beredning för medicinsk utvärdering),
NCCHTA (The National Coordinating Centre for Health Technology Assessment),
CADTH (The Canadian Agency for Drugs and Technologies in Health),
INAHTA (International Network of Agencies for Health Technology Assessment),
MSAC (Medical Services Advisory Committee),
CRD (Centre for Reviews and Dissemination):
DARE (Database of Abstracts of Reviews of Effects),
NHS EED (NHS Economic Evaluation Database),
Health Technology Assessment Database,
Ongoing Reviews Database
Also, the bibliographies of the primary studies were searched. Secondary studies were
reviewed (object articles, systematic reviews, meta-analyses, agency reviews) for possible
additional primary studies. Moreover, to make the list of publications complete,
manufacturers of diagnostic equipment were requested to provide all their studies,
especially those concerning the pre-marketing period, as well as marketing information
on PET-CT scanners.
The search was conducted independently by two researchers. Next, trial abstracts were
reviewed for inclusion into the analysis, also by two independent researchers.
5.5. Criteria for the inclusion of primary studies in the analysis
Initially, titles and abstracts in the publications found were analyzed. If information on the
use of PET (including PET-CT) imaging or CT in a trial was found, it was qualified for further
verification depending on how the full text was evaluated.
As the second stage, full texts in an electronic version were analyzed with a special focus
on trial methodology, in order to identify information on the use of hybrid PET-CT scanners.
Reports where the use of the technique under discussion was confirmed were further verified.
Based on the guidelines of the Medical Services Advisory Committee, the verification process
focused on the selection of trials, where two strategies were assessed at the same time: PET-
CT and another strategy financed in Poland. On this basis a decision was made whether to
include or exclude a trial, stating the reasons.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
In case of primary studies, there were no restrictions on the period of follow-up or size of
population. Trials done on humans, for which full texts of reports are accessible in Polish
libraries in English or Polish were included. Restrictions were defined for the date of
publication, which narrowed down the scope of search to studies published after 1 Jan 1998.
This criterion was accommodated based on the results of database searches (publication of
first reports on the hybrid PET-CT scanner) and the date of launching the technology under
assessment on the diagnostic procedures market.
5.5.1. Population
The population were patients diagnosed for oncological indications.
5.5.2. Intervention
The analysis included primary prospective or retrospective clinical trials, where PET-CT results
were assessed (regardless of the type of radiopharmaceutical used). The essential criterion
for the inclusion of a publication into the analysis was whether the diagnostic techniques
compared were verified through an independent reference test (gold standard).
5.5.3. Technologies compared (comparators)
Diagnostic technologies financed in Poland from public sources and used in oncological
diagnostics: computed tomography, magnetic resonance image, endoscopic ultrasoundith
fine needle aspiration, scintigraphy I131, and the others.
5.5.4. End points
• Diagnostic efficacy of testing methods in comparison to the respective reference
method or clinical observation;
• Change of therapeutic decision;
• Impact on clinical end points;
• Safety.
5.6. Trial quality assessment
The adopted scale of trial quality helps evaluate publications with regard to whether they
are properly designed and conducted, and ensures reliability of results.
95

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
96
In compliance with EBM requirements (Evidence Based Medicine), the process of trial
quality assessment used the QUADAS 14 form, which consisted of 14 questions. The first four
questions check whether the choice of population was right; questions 5-9 assess whether the
measurements and the reference test were executed correctly, the remaining questions
rated the interpretation and presentations of the results. Questions 3-7 were acknowledged
as critical, becouse answer “yes” was a requirement for study inclusion into analysis. Residual
questions provided additional study quality assessment.
In order to standardize the assessment procedure, a single form was prepared to verify all
the publications included in the analysis.
Each study was rated independently by two analysts. In case of discrepancies, the final
decision was made through formal consensus.
Each question was evaluated “yes”, “no”, or “unclear”. Checklists of trial quality assessment
for each study are given in an appendix hereto.
5.7. Statistical analysis
The calculation of the basic parameters of the diagnostic efficacy of a screening
method is based on the data scheme in table 17, which indicate the number of patients
testing positive (T+) and negative (T-) in experimental tests administered to patients with
(D+) or without (D-) a disease as established based on reference (index) test (also called
the gold standard).
Table 17.
Measurement results of assessing diagnostic tests
Reference test
Test under assessment
Positive result of test under assessment (T+)
Negative result of test under assessment
(T-)
Disease (D+)
No disease (D+)
a (TP) b (FP)
c (FN) d (TN)
a - number of patients testing positive (i.e. number of true positives - TP)
B - number of patients without disease but testing positive (i.e. number of false
positives - FP)
c - number of patients testing negative (i.e. number of false negatives - FN)
14 Whiting P, Rutjes AWS, Reitsma JB, Bossuyt PMM, Kleijen J. The development of QUADAS: a tool for the quality
assessment of studiem of diagnostic accuracy included in systematic reviews. BMC Medical Research Methodology
2003; 3 (25).

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
d - number of patients without disease but testing negative (i.e. number of true
negatives - TN)
Table 18 gives the definitions of the basic parameters of diagnostic efficacy applied in
the report.
Table 18.
Characteristics of parameters of diagnostic efficacy
Parameter
of diagnostic efficacy
Sensitivity
Specificity
Accuracy
Positive likelihood ratio
Negative likelihood ratio
Diagnostic odds ratio
Positive predictive value
Negative predictive value
Interpretation
Mathematical formula
Se =
Proportion of patients testing positive;
reflect the test’s ability to detect disease a + c
Proportion of patients testing negative;
describes the test’s ability to confirm
absence of disease
Proportion of patients correctly
diagnosed by the test
Likelihood quotient for positive test results
in patients with disease and for the same
result in patients not diagnosed with
disease
Likelihood quotient for negative test results
in patients with disease and for the same
result in patients not diagnosed with
disease
Odds ratio of testing positive by patients
with disease and the odds of obtaining
the same test result for patients without
disease; alternative interpretation: the
odds of disease developing in patients
testing positive and of disease
developing in patients testing negative
The likelihood of the disease tested
actually developing in patients testing
positive
a
d
Sp =
b + d
a + d
Acc =
a + b + c + d
a / a + c Se
LR+
= =
b / b + d 1−
Sp
c / a + c 1−
Se
LR−
= =
d / b + d Sp
a / c
DOR =
b / d
=
a
PPV =
a + b
NPV
The likelihood of absence of the disease
tested in patients testing negative c + d
d
LR +
LR −
Included in the analysis are trials that sought information on the results of the diagnostic
methods under assessment in comparison with a reference method. The results were grouped
according to the parameters of a four-field table: TP, TN, FP and FN.
Next, in order to assess the diagnostic efficacy, parameters such as sensitivity (Se),
specificity (Sp), accuracy (Acc), positive likelihood ratio (LR+), negative likelihood ratio (LR-)
and diagnostic odds ratio (DOR) were calculated with a 95% confidence interval. Whenever
=
97

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
possible, a meta-analysis of results of studies was also conducted. To evaluate differences in
diagnostic efficacy of trials, McNemar’s test was done, provided data were available (test of
proportions with matched data array).
98
For a comparative rating of odds of accurate diagnosis (consistent with the reference
standard) for the diagnostic methods under assessment, the OR parameters statistical
significance was rated based on EBM guidelines. For statistically significant results, the NNT
parameter was additionally calculated, specifying confidence intervals.
When no statistically significant discrepancies of study results were identified, a meta-
analysis of the results was conducted using the fixed effect model. For end points that were
statistically significant in a heterogeneity test, the random effect model was used. The
statistical software MetaDiSc v.1.3 was used to calculate these parameters and to carry out a
meta-analyses of sensitivity and specificity. The meta-analysis of accuracy, OR and NNT, and
graphs representing this results were done in Stats Direct v. 2.5.2.
5.8. Conflict of interest
None of the authors of the study reported any conflict of interest.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
6. SEARCH RESULTS
Based on the results of a search for publications that describe the diagnostic efficacy
of the hybrid PET-CT scanner, which was executed in keeping with the search strategy
presented above, a list of trials that tentatively met the inclusion criteria was compiled.
Next, the full texts of these trials were reviewed, and consequently a final list of trials
included was established. The results of this review are given in Table 19.
Table 19.
List of the results of a search targeted at selected patient populations.
Name of cancer
Number of abstracts read
Number of full texts
received from libraries
Number of trials included
in analysis
1. Lung cancer 1520 250 4
2. Ovarian cancer 138 96 2
3. Cervical cancer 248 86 0
4. Sarcoma 210 111 1
5. Glioma 269 192 0
6. Lymphoma 641 72 2
7. Head and neck cancer 932 331 4
8. Esophageal and gastric
cancer
393 117 2
9. Colorectal cancer 422 190 1
10. Breast cancer 545 86 0
11. Melanoma 213 113 0
12. Endometrial cancer 32 24 0
Total 5563 1754 16
5563 publications describing clinical trials in form of abstracts were found as a result of
searching databases according to the established strategy extended with population
selection. Those abstracts were initially reviewed with respect to the diagnostic
technology applied. The full texts of the items selected (1754) were next reviewed taking
into account all inclusion criteria. Finally, 16 trials, that met the inclusion criteria were
selected and reviewed in detail for the results reported. Detailed general search results
without aiming at patient population are given in section “18 Appendix”. As a result of
that search strategy 10 clinical trials were included additionally: 3 trials for thyroid cancer,
1 for gynecological malignancies, 1 for pancreatic cancer and 5 for various oncological
diseases. Finally, 26 clinical trials were incuded into analysis.
Three HTA reports concerning PET-CT were found:
99

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
100
• „CT-PET scanners - systematic review, expert panel”. Paris: Comite d'Evaluation et
de Diffusion des Innovations Technologiques (CEDIT), 2002 – only abstract in english;
• „Revision Sistematica Sobre la Efectividad E Indicationes del Sistema Hibrido PET-
TAC.” Unidad de Evaluacion de Tecnologias Sanitarias 2006. Agencia Lain
Entralgo. – available in spanish only;
• „Combined positron emission tomography (PET-CT)”. Cigna Healthcare Coverage
Position 2005 – available only with high fee.

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
7. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS
CT IN LUNG CANCER STAGING
7.1. Results of trial search
As a result of searching medical databases 4 primary prospective trials were identified:
Antoch 2003 (tab. 135, app. 18.1), Lardinois 2003 (tab. 136, app. 18.1), Cerfolio 2005 (tab.
137, app. 18.1) and Shim 2005 (tab. 138, app. 18.81), where PET-CT was used in lung
cancer staging.
In each of the trials, a hybrid PET-CT scanner was compared with CT. Both methods
were verified based on a histopathological index test.
7.2. Population characteristics
In all the four studies, patients with non-small cell lung cancer (NSCLC) took part.
Pre-surgery staging was executed in three of the trials (Lardinois 2003, Cerfolio 2005, Shim
2005). In Antoch 2003, staging was executed for 19 out of 27 patients (70%), and restaging
following neoadjuvant chemotherapy was executed for 8 out of 27 patients (30%).
Cerfolio 2005 and Shim 2005 excluded patients receiving pre-surgery chemotherapy or
radiotherapy. Cerfolio 2005 additionally excluded patients with type I diabetes. The authors
of the report in Shim 2005 reported that 33% patients had had tuberculosis confirmed
clinically or by imaging.
Table 20 lists the initial characteristics of patients for each of the trials.
Table 20.
Initial characteristics of patients by trial
Parameter
Size of population
Age [years]
Male proportion
Histology
adenocarcinoma
squamous cell
carcinoma
(proportion of
patients)
large cell carcinoma
bronchoalveolar
carcinoma
Antoch
2003
27
mean: 56
85%
no data
no data
no data
no data
Lardinois
2003
50
mean: 62
57%
57%
27%
16%
0%
Cerfolio
2005
383
mean: 68
59%
38%
44%
0%
3%
Shim 2005 Total
110
mean: 56
74%
51%
41%
4%
3%
570
mean: 58*
63%
42%
42%
2%
3%
101

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
102
neuroendocrinal
carcinoma
carcinoid
pleomorphic cancer
no data
no data
no data
other NSCLC types,
mixed types or no data 0%
unidentified type
*average weighted by the number of patient participating in the three trials
In Antoch 2003, 27 patients diagnosed with NSCLC were included. In Lardinois 2003, 50
patients with documented or suspected NSCLC were included, but ultimately 49
participated (one patient was diagnosed with lymphoma). In Cerfolio 2005, patients with
confirmed non-small cell lung cancer or a lung nodule were been included. Ultimately 383
patients were included.
110 patients with documented NSCLC were included in Shim 2005; surgeries and
histopathological tests were done for 106 patients and the results were reviewed.
The total of 570 patients aged 56-68 on the average, with the male population
representing 57–85% took part in the study. The proportion of patients with
adenocarcinoma identified histologically ranged from 38% to 57%,, and the proportion of
patients with squamous cell carcinoma ranged from 27% to 44%. Other histological
cancer types represented a small proportion.
7.3. Description of Intervention
7.3.1. PET-CT imaging
In three trials included in the study (Lardinois 2003, Cerfolio 2005 and Shim 2005)
the Discovery LS system manufactured by General Electric Medical Systems (Milwaukee,
USA) was used for staging, and in Antoch 2003 the system was Biograph by Siemens
Medical Solutions (Hoffman Estates, USA). The authors of Lardinois 2003 and Shim 2005
noted that the PET-CT system consisted of a PET scanner (Advance NXi, GE Medical
Systems) and a CT scanner (LightSpeed Plus, GE Medical Systems).
In all the trials included, FDG (fluoro-deoxy-glucose) was used as radiopharmaceutical, its
activity ranging from 350 MBq in Antoch 2003, to 350 - 400 MBq in Lardinois 2003, 370 MBq in
Shim 2005, and 555 MBq in Cerfolio 2005. The radiopharmaceutical was administered 50
and 60 minutes before a PET-CT scan was taken in Lardinois 2003 and Antoch 2003,
respectively. The authors of the other two trials give no information on FDG.
Table 21 contains a detailed description of PET-CT scanning
0%
0%
0%
2%
3%
0%
11%
0%
0%
2%
0%
1%
2%
0,4%
8%

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Table 21.
Description of intervention
Trial
Antoch 2003
Lardinois
2003
Cerfolio
2005
Shim
2005
PET-CT
scanner
type
Biograph
Discovery
LS
Discovery
LS
Discovery
LS
PET-CT scanner
manufacturer
Siemens Medical
Solutions
(Hoffman Estates, Ill)
GE Medical Systems
(Milwaukee, WI)
GE Medical Systems
(Milwaukee, WI)
GE Medical Systems
(Milwaukee, WI)
Radiopharmace
utical type and
administration
method
FDG intravenous
FDG intravenous
FDG intravenous
FDG intravenous
Trial range
whole body
whole body
whole body
whole body
Radiomarker
activity
[MBq]
350
350–400
In Cerfolio 2005 and Shim 2005, patients had not eaten 4 and 6 hours prior to the test
respectively. This information is unavailable for the other studies.
In Antoch 2003, the image obtained from PET-CT scanning was evaluated by a team
made up of a radiologist and nuclear medicine expert, each with 1.5 years’ experience
with PET-CT. They had had access to the patient’s case history (so did the CT team).
For Lardinois 2003, two medical boards were created, each composed of a nuclear
radiology expert and thoracic surgeon. One of the boards first evaluated the result of PET
scanning and next of PET-CT scanning. The board knew no clinical data or other diagnostic
imaging results. In Cerfolio 2005, a PET-CT image was analyzed by a nuclear medicine
consultant. In Shim 2005, the assessment was done by one of two nuclear medicine
consultants.
7.3.2. Diagnostic test compared
In all the trials included in this analysis, PET-CT tests were compared with CT.
In Antoch 2003, CT was executed using the Somaton Emotion spiral technique
(Siemens Medical Solutions, Erlangen, Germany); in Lardinois 2003, the Light Speed Plus
scanner was used; in Shim 2005, the HighLight or Light Speed Ultra 16 spiral technique
(GE Medical Systems) was used; in Cerfolio 2005, the authors give no information on the
CT scanner used.
Whole-body scans were taken in Antoch 2003, while in Lardinois 2003 the CT image
covered the thorax and pelvis. In Shim 2005, the area scanned extended from the
supraclavicular area halfway through the kidneys, while for Cerfolio 2005 this information
is unavailable.
Intravenous and oral contrast medium was used in Antoch 2003; intravenous contrast
555
370
103

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
104
medium was used in Shim 2005 and Lardinois 2003; the authors of Cerfolio 2005 provide
no information on the contrast medium use.
Table 22 provides detailed descriptions of CT for each of the trials.
Table 22.
Description of diagnostic tests compared
Trial
Antoch 2003
Lardinois 2003
Cerfolio 2005
Shim 2005
CT scanner type
Somaton Emotion
Light Speed Plus
no data
HighLight or Light
Speed Ultra 16
CT scanner producer
Siemens Medical
Solutions
GE Medical Systems
no data
GE Medical Systems
Contrast medium
type and method
intravenous and oral
contrast medium
intravenous contrast
medium
no data
intravenous contrast
medium
Study range
whole body
from head to
pelvis
no data
from supraclavicular to
half the height of
kidneys
In Antoch 2003, diagnostic images were evaluated by two radiologists with 8 and 11
years’ experience. In Lardinois 2003, the other board analyzed CT scans, followed by PET
scans, and next compared the images. In Cerfolio 2005 and Shim 2005, the results were
interpreted by an experienced thoracic radiologist, who in Shim 2005 was not familiar
with the results of PET-CT scanning, pathological tests, or the clinical condition, save for
the information on the presence of lung cancer.
7.3.3. Reference test
Histopathological examination was a reference test for all the trials included in this
analysis. In two clinical trials metastases were confirmed also by clinical follow-up
(Lardinois 2003) or MRI (Cerfolio 2005), morover in the second trial ultrasonography was
used in nodal staging.
In Antoch 2003, mediastinal endoscopy and resection of lymph nodes were executed
by an experienced thoracic surgeon. Mediastinal endoscopy was recognized sufficient
as long as it helped remove, and complete Histopathological examination of
paratracheal, tracheobronchial and subcranial lymph nodes. A precise dissection of
lymph nodes was executed as part of thoracotomy, but supraclavicular lymph nodes
were spared in both mediastinal endoscopy and thoracotomy. Tumor and lymph nodes
were removed in a surgical procedure in 16 patients, and only for this group was T-staging
possible. Mediastinoscopy was done for 11 patients. No other treatment was applied in

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
between the imaging and surgery.
In Lardinois 2003, histopathological tests were done following lung resection with
dissection of mediastinal lymph nodes. 82% of patients were given a surgery: 71% had
mediastinal lymph nodes removed, 6% underwent exploratory thoracotomy, and 4%
underwent sphenoid resection. Surgery was not possible in 9 patients due to metastases
outside thorax (8 patients) and the presence of carcinomous cells in the pleural fluid (1
patient). A limitation of lung functions was observed during a sphenoid resection in 2
patients, which prevented lobectomy. Lymph nodes were not removed in these patients
either as the size of mediastinal lymph nodes was less than 5 mm. Out of the three patients
who had an exploratory thoracotomy, one was diagnosed with dissemination of
carcinoma within lungs, and one with aorta infiltration. Therefore full staging was possible
with 35 patients only. Lesions outside the chest were graded on clinical observation and
biopsy.
In Lardinois 2003, the disease was staged with respect to lymph nodes metastasis by
averaging the score ranging from 0 to 3, where 0 meant incorrect staging, 1 – ambiguous
but incorrect staging, 2 – correct but ambiguous staging, and 3 - correct staging. Scores
of 0 and 1 were considered jointly in the results analyses as both implied incorrect staging.
In Cerfolio 2005, histopathological examination of cancer was executed following the
resection and biopsy of all spots suspected of metastases (N2, N3, M1). Mediastinal
endoscopy was done in order to perform a biopsy of paratracheal areas, while
transesophageal endoscopic ultrasonography was used to perform biopsy of the nodes in
the back of the aorto-pulmonary window, subcranial nodes, peri-esophageal nodes and
lung ligament nodes suspected of metastasis. The nodes were initially scanned using
ultrasound, and the examiner was blinded to the results of other diagnostic imaging. For
M-staging of liver, adrenal glands or the opposite lung, biopsy was performed, and lesions in
bones and brain were scanned using MRI. Next, the lesions were removed along with lymph
nodes in N2 negative patients.
In Shim 2005, tumor resection of mediastinal lymph nodes dissection were performed by
one of a pair of experienced thoracic surgeons, who had reviewed the imaging tests results.
All palpable lymph nodes were removed. Pneumonectomy, including lobectomy and
removal of part of a lung with mediastinal lymph node was performed in 106 patients. In 83%,
lobectomy only was possible because the primary tumor was limited to the lobe only; in 8.5%
only bilobectomy was performed because the tumor had disseminated onto another lobe or
bronchi, and in 8.5% part of a lung was removed. In this trial, the tumor (histopathological
grade, size, involvement of adjacent organs, necrosis, distance to the edge of resection)
and the lymph nodes were described by a pathologist with 10 years' experience. Lymph
105

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
nodes were numbered according to the map proposed by Mountain and Dresler.
Ultimately, 393 groups of lymph nodes in 106 patients were staged. It is worth mentioning
that in Shim 2005 node lesions instead of patients number were used as the basis of N-
staging.
106
7.4. Findings
7.4.1. T-staging
T-staging was performed in three of the trials included in this part of the analysis (Antoch
2003, Lardinois 2003 and Shim 2005).
In each of the trials the T-staging was based on the TNM system created by the AJCC
(American Joint Committee on Cancer) 15 . The results of PET-CT and CT scanning were
verified histopathologically.
Table 23 presents the consistency between the reference test and the results of T-
staging done using of the methods compared, as quoted by the authors of each trial.
Table 23.
Consistency between T-staging and reference test, by PET-CT vs. CT trial.
trial
Antoch
2003
Lardinois
2003
N*
16
40
Shim 2005 106
Correct staging
(accuracy)
n (%)
15 (94%)
35 (88%)
91 (86%)
PET-CT
Ambiguous
staging
n (%)
0**
4 (10%)
0**
Incorrect staging
n (%)
Overstag
ed
1 (6%)
4 (4%)
*Number of patients verified using reference test
**Ambiguous results were not taken into account in the trial
1 (2%)
Understag
ed
0 (0%)
11
(10%)
Correct
staging
(accuracy)
n (%)
12 (75%)
23 (58%)
84 (79%)
CT
Ambiguous
staging
n (%) Overstag
ed
0**
8 (20%)
0**
Incorrect staging
n (%)
Understag
ed
3 (19%) 1 (6%)
13
(12%)
9 (22%)
The data presented above show that in all these trials, the proportion of correctly
classified patients was higher for PET-CT than for CT. The accuracy of PET-CT is 86 and 94%,
and the accuracy of CT is 58 and 79%. The percentage of overstaged and understaged
cases is 4 and 6% and 0 and 10% respectively for PET-CT and 12 and 19% and 6 and 8.5%
for CT respectively.
In Antoch 2003, the authors described PET-CT as more accurate than CT alone. The
15 AJCC cancer staging manual. 6th ed. New York, NY: Springer, 2002: 165-177
9
(8,5%)

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
difference between the groups is not statistically significant. In Lardinois 2003, the
difference between the diagnostic efficacy of PET-CT and CT was statistically significant
(p = 0,001, a paired sign test) in favor of PET-CT. In Shim 2005, the authors did not report
statistically significant differences between tests in this respect (p=0.25).
The results of meta-analysis of diagnostic accuracy of PET-CT in T-staging are presented in
graph 1.
107

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Graph 1.
Meta-analysis of the diagnostic accuracy of PET-CT in T-staging
The diagnostic accuracy of PET-CT in T-staging as calculated by meta-analysis of three trials is
86% (95% CI: 81; 91).
108
Antoch 2003 0,94 (0,70, 1,00)
Lardinois 2003 0,88 (0,73, 0,96)
Shim 2005 0,86 (0,78, 0,92)
Result of metaanalysis 0,86 (0,81, 0,91)
0,6 0,7 0,8 0,9 1,0
Meta-analysis of the diagnostic accuracy of CT in T-staging is presented in graph 2. As
there was significant heterogeneity between trials (p = 0.0372) meta-analysis was
performed using the random effects method.
Graph 2.
Meta-analysis of the diagnostic accuracy of CT results in T-staging
Antoch 2003 0,75 (0,48, 0,93)
Lardinois 2003 0,58 (0,41, 0,73)
Shim 2005 0,79 (0,70, 0,87)
Meta-analysis result 0,71 (0,55, 0,84)
Diagnostic accuracy (95% confidence interval)
0,4 0,6 0,8 1,0 1,2
Diagnostic accuracy (95% confidence interval)

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
The diagnostic accuracy of CT as calculated by meta-analysis of three trials is 71% (95%
CI: 55; 84).
Meta-analysis of the proportion of patients for whom T-staging with the use of PET-CT or
CT was consistent with histopathological examination results is presented in graph 3.
Graph 3.
Odds ratio for the consistency between the reference test and T-staging results, PET-CT vs. CT.
.
Antoch 2003 5,00 (0,40, 262,30)
Lardinois 2003 5,17 (1,52, 20,08)
Shim 2005 1,59 (0,73, 3,52)
Meta-analysis result [fixed] 2,42 (1,36, 4,29)
0,2 0,5 1 2 5 10 100 1000
Odds ratio (95% confidence
interval)
Calculated by meta-analysis, the odds ratio is 2.42 (95% CI: 1.36; 4.29). It means that the
odds ratio of T-staging consistent with the reference test is 2.42 times higher for PET-CT than
for CT. The result is statistically significant.
In order to obtain one additional case of correct T-staging, PET-CT instead of CT scanning
needs to be done with 8 patients with non-small cell lung carcinoma; NNT = 8 (95% CI: 5;
20).
7.4.2. Assessment of lymph node involvement (N feature)
In three of the trials, the disease was assessed with respect to the presence of metastases
to lymph nodes.
In two studies (Antoch 2003 and Lardinois 2003), the disease was staged based on the
TNM lung cancer classification system designed by the AJCC (American Joint Committee
on Cancer). In Shim 2005, metastasis to lymph nodes was assessed and located in 10
groups, according to the definition of lymph nodes map for lung cancer staging proposed
109

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
by Mountain and Dresler.
110
The N-status was verified by in the course of tumor resection coupled with mediastinal
lymph nodes dissection (Antoch 2003, Lardinois 2003, Shim 2005) or mediastinal endoscopy
(Antoch 2003).
The number true positives (TP), false positives (FP), false negatives (FN) and true
negatives (TN) for PET-CT and CT scanning is presented in table 24.
Table 24.
Number of TP, FP, FN and TN patients in N-staging using PET-CT and CT.
Study
Antoch 2003
Shim 2005**
TP
8*
28
FP
1*
58
PET-CT
*Calculated based on data available
**The values reflect the number of lymph nodes, not the number of patients as for the other trials.
FN
1*
5
In Antoch 2003, the difference between the diagnostic accuracy of PET-CT and CT in
N-staging is statistically significance in favor of PET-CT (p = 0.004). Lardinois 2003 provides
no information on the statistical significance of the differences between the two
diagnostic methods. In Shim 2005, the difference between PET-CT and CT in detecting
malignant tumors in lymph node groups were not statistically significant (p = 0.249).
PET-CT helped diagnose 23 out of 33 lymph node groups with malignant tumor (85%),
and for CT the value was 70%. At the same time, the differences in specificity and
accuracy between the two methods were statistically significant (p < 0.001).
Table 25 presents the following diagnostic parameters: sensitivity (Se), specificity (Sp),
accuracy (Acc), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and
diagnostic odds ratio (DOR) calculated for the methods under discussion (PET-CT and CT).
No meta-analysis of the diagnostic efficacy could be performed as the data presented
by the authors were not sufficient and the results presented differed.
TN
17*
302
TP
7*
23
FP
7*
112
CT
FN
3*
10
TN
10*
248

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Table 25.
Evaluation of the diagnostic accuracy of PET-CT and CT in N-staging.
Shim 2005
Lardinois 2003
Antoch 2003
Parameter
Statistical
significance
(PET-CT vs CT)
CT
PET-CT
Statistical
significance
(PET-CT vs CT)
CT
PET-CT
Statistical
significance
(PET-CT vs CT)
CT
PET-CT
no data
70%
(51; 84)*
85%
(68; 95)*
no data
no data
no data
no data
70%
(35; 93)*
89%
(52; 100)*
Se
(95% CI)
p < 0,001
69%
(64; 74)*
84%
(80; 88)*
no data
no data
no data
no data
59%
(33; 82)*
94%
(73; 100)*
Sp
(95% CI)
no data
2,24
(1,71; 2,94)*
5,27
(4,00; 6,94)*
no data
no data
no data
no data
1,70
(0,85; 3,42)*
16,00
(2,35; 108,99)*
LR+
(95% CI)
no data
0,44
(0,26; 0,74)*
0,18
(0,08; 0,41)*
no data
no data
no data
no data
0,51
(0,18; 1,42)*
0,12
(0,02; 0,75)*
LR-
(95% CI)
p < 0,001
69%
(64; 74)*
271/393**
84%
(80; 87)*
330/393**
p = 0,12
59%
(42; 75)*
22/37
81%
(65; 92)*
30/37
p = 0,004
63%
(34; 86)*
17/27
93%
(66; 100)*
25/27
Acc
(95% CI)
n/N
no data
5,09
(2,35; 11,06)*
29,16
(10,81; 78,64)*
no data
no data
no data
no data
3,33
(0,63; 17,57)*
136,00
(7,51; 2462,80)*
DOR
(95% CI)
*Calculated based on data available
**The values reflect the number of lymph nodes, not the number of patients, as in the other studies.
111

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
112
Based on the data above PET-CT sensitivity is 0.85 and 0.89, and CT sensitivity is 0.70, which
means that the probability of patients with metastasis to lymph nodes testing positive is 85–
89% for PET-CT and 70% for CT.
The specificity of PET-CT is within the range 0.84-0.94, so the probability of negative results
in patients without metastasis to lymph nodes is 84-94%. The specificity of CT is 0.59 and 0.69,
which means that the probability of negative result is 59-69% for patients who tested
negative for metastasis to lymph nodes in the reference test.
The positive likelihood ratio for PET-CT is 5.27–16.00, therefore the probability of positive
results in patients with metastasis to lymph nodes is 5.27-16 times higher than for patients
without metastasis. The positive result likelihood ratio for CT is 1.70-2.24. Therefore the
probability of positive results in patients with metastasis to lymph nodes is 1.70-2.24 of that
for patients diagnosed negatively for metastasis in histopathological tests.
The negative likelihood ratio for PET-CT study, is 0.12-0.18, so the probability of negative
results in patients with metastasis to lymph nodes is 0.12-0.18 of that for patients without
metastasis. The negative likelihood ratio for CT is 0.44-0.51. Therefore the probability of
negative results in patients with metastasis to lymph nodes is 0.44-0.51 of that for patients
without metastasis.
Graph 4 illustrates the diagnostic accuracy of PET-CT in N-staging as calculated by meta-
analysis of two trials.
Graph 4.
Meta-analysis of PET-CT diagnostic accuracy in N-staging
Antoch 2003 0,93 (0,76, 0,99)
Lardinois 2003 0,81 (0,65, 0,92)
Meta-analysis result 0,85 (0,76, 0,93)
0,6 0,7 0,8 0,9 1,0
Diagnostic accuracy (95% confidence interval)

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
The diagnostic accuracy of PET-CT established by meta-analysis is 85% (95% CI: 76; 93).
Graph 5 illustrates a meta-analysis of the diagnostic accuracy of CT for patients with
non-small cellular lung carcinoma.
Graph 5.
Meta-analysis of the diagnostic accuracy of CT in N-staging
Antoch 2003 0,63 (0,42, 0,81)
Lardinois 2003 0,59 (0,42, 0,75)
Meta-analysis result 0,61 (0,49, 0,72)
0,4 0,6 0,8 1,0
Diagnostic accuracy (95% confidence interval)
The diagnostic accuracy of CT as calculated by meta-analysis of two trials is 61% (95%
CI: 49; 72).
The diagnostic odds ratio calculated for PET-CT is 29.16 and 136.00. The probability of
positive results is 29-136 times higher for patients with metastasis to lymph nodes than for
patients with no metastasis detected by the reference test. The diagnostic odds ratio for CT is
3.33–5.09, so the probability of positive results in patients with metastasis detected by the
reference test is 3.33–5.09 of the probability for patients without metastasis to lymph nodes.
Graph 6 presents the odds ratio for N-staging consistent with the reference test as
calculated by meta-analysis of two trials. Shim 2005 was not taken into account in the
meta-analysis since its authors provided the number of correctly staged lymph nodes, not
the number of correctly diagnosed patients, as in the other trials.
113

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Graph 6.
Odds ratio for the consistency of N-staging with the reference test, PET-CT vs. CT.
114
Antoch 2003 7,35 (1,28, 74,58)
Lardinois 2003 2,92 (0,92, 9,86)
Meta-analysis result [fixed] 3,95 (1,65, 9,44)
0,5 1 2 5 10 100
Odds ratio (95% confidence
interval)
The odds ratio is 3,95 (95% CI: 1,65; 9,44) so the probability of proper assessment of
lymph node involvement is almost four times higher for PET-CT than for CT. The result is
statistically significant.
In order to have one additional case of correct N-staging in patients with non-small cell
lung carcinoma it is necessary to use PET-CT instead of CT with 4 patients, NNT = 4 (95% CI: 3;
10).
7.4.3. Assessment of distant metastases (M feature)
Cancer staging based on the TNM system with a special attention to the presence of
distant metastases was executed for two trials included in the analysis: Antoch 2003 and
Lardinois 2003.
In Antoch 2003, the presence of distant metastases was verified based on clinical follow-
up for two patients, and on biopsy for another two. In Lardinois 2003, the authors verified the
presence of extrathoracic metastasis based on biopsy or other imaging techniques.
In Antoch 2003, 17 distant metastases were detected with 4 patients using PET-CT, while
when CT scanning was used only 14 metastases were detected with 4 patients. For both
methods compared, no false positive results were detected. In 1 patient metastasis was
detected 8 months later (false negative result).

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Lardinois 2003 reported only that metastasis to pelvis was identified in 2 patients.
7.4.4. TNM staging system
In all the trials included in this analysis (Antoch 2003, Lardinois 2003, Cerfolio 2005, Shim
2005), disease staging was done based on the TNM lung cancer classification system
designed by the AJCC (American Joint Committee on Carcinoma).
Detailed results provided by the authors of each study are given in table 26.
115

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
Table 26.
Lung cancer staging results for PET-CT and CT by trial
Shim 2005
Cerfolio 2005
Antoch 2003
Statistical
significance
PET-CT vs CT
Disease
stage
Parameter
CT
n/N (%)
PET-CT
n/N (%)
Statistical
significance
PET-CT vs CT
CT
n/N (%)
PET-CT
n/N (%)
PET-CT
n/N (%)
no data no data no data no data
Statistical
CT
significance
n/N (%) PET-CT vs CT
no data no data
49%
44%
no data
I
no data no data no data no data
no data no data
46%
34%
no data
II
no data no data no data no data
no data no data
60%
66%
no data
III
Se
no data no data no data no data
no data no data
67%
83%
no data
IV
no data no data no data no data no data no data no data no data
no data
total
no data no data no data no data
no data no data
79%
76%
no data
I
no data no data no data no data
no data no data
93%
92%
no data
II
no data no data no data no data
no data no data
75%
79%
no data
III
Sp
no data no data no data no data
no data no data
92%
93%
no data
IV
no data no data no data no data no data no data no data no data
no data
total
no data
no data
no data no data
47/71 (66%)
63/71 (89%)
66%
68%
no data
I
no data
no data
no data no data
14/ 18 (78%)
17/18 (94%)
82%
84%
no data
II
no data
no data
no data no data
9/17 (53%)
12/17 (71%)
69%
74%
no data no
data
III
Acc
no data no data no data no data
no data no data
92%
93%
no data
IV
p = 0,001
no data no data no data
70/106 (66%)
92/106 (87%)
p = 0,008
19/27 (70%*)
26/27 (96%*)
total
116

Cost-effectiveness analysis of PET-CT positron emission tomography In oncological diagnostics
*Value calculated based on data availabl
117

Antoch 2003 notes that the difference in accuracy of cancer staging is statistically significant in
favor of PET-CT scanning (p = 0.008). Lardinois 2003 reports that in the staging of the disease,
PET-CT testing proved more accurate compared with CT alone.
118
In Shim 2005, PET-CT was statistically more accurate in disease staging compared to CT (p
= 0,001). Cerfolio 2005 provided no additional data.
Graph 7 shows the diagnostic accuracy of PET /CT in cancer staging as established by
meta-analysis of two trials.
Graph 7.
Diagnostic accuracy of PET-CT in cancer staging (TNM)
Antoch 2003 0,96 (0,81, 1,00)
Shim 2005 0,87 (0,79, 0,93)
Results of meta-analysis 0,88 (0,83, 0,93)
0,700 0,775 0,850 0,925 1,000
The diagnostic accuracy of PET-CT tests in the staging of non-small cellular lung cancer is
88% (95% CI: 83; 93).
Graph 8 illustrates the meta-analysis of two trials that evaluated the diagnostic accuracy
of CT in cancer staging.
Diagnostic Accuracy (95% confidence interval)

Graph 8.
Meta-analysis of the diagnostic accuracy of CT in cancer staging (TNM)
Antoch 2003 0,70 (0,50, 0,86)
Shim 2005 0,66 (0,56, 0,75)
Results of meta-analysis 0,67 (0,59, 0,74)
The diagnostic accuracy of CT as calculated by meta-analysis is
67% (95% CI: 59; 74).
0,4 0,6 0,8 1,0
Diagnostic accuracy (95% confidence interval)
Graph 9 shows the results of meta-analysis for the proportion of patients in whom the
disease was staged correctly using PET-CT as compared to CT alone.
Graph 9.
Odds ratio for the consistency between the reference test and total cancer staging results, PET-CT vs. CT
Antoch 2003 10,95 (1,24, 503,96)
Shim 2005 3,38 (1,62, 7,29)
Meta-analysis result [fixed] 3,91 (2,04, 7,50)
1 2 5 10 100 1000
Odds ratio (95% confidence
The odds ratio is 3.91 (95% CI: 2,04; 7,50), so the probability of correct cancer staging for
119

patients with non-small cell lung carcinoma is 3.91 times higher for PET-CT scanning than for
CT. The difference is statistically significant.
120
In order to obtain one additional case of correct staging PET-CT scanning needs to be
performed instead of CT for 5 patients with non-small cell lung cancer NNT = 5 (95% CI: 4;
9).
7.4.5. Impact on therapy
Information on the impact of the use of PET-CT instead of standard imaging methods (CT)
on the therapeutic procedure is given only in one of the trials analyzed (Antoch 2003).
Staging with the use of PET-CT allowed for correct tumor classification to a higher stage
in 1 out of 27 patients (4%), and to a lower stage in 7 patients (26%), which led to new
recommendations for further treatment in case of 5 patients (18.5%). For 1 out of the 5
patients plans of surgery, which had been made based on CT scanning, were
abandoned, while 4 patients were scheduled for surgeries.
7.4.6. Safety
None of the trials reported on the safety of the diagnostic procedures used.
7.5. Results
As a result of searching medical databases 4 primary prospective trials were identified
(Antoch 2003, Lardinois 2003, Cerfolio 2005 and Shim 2005), where the PET-CT method was
compared to CT in patients suffering from non-small cell lung cancer (N=570). All the trials
were verified histopathologically. Indications for scanning were based on results of T-
staging.
In the assessment of T-status in all the trials under assessment, the proportion of correctly
diagnosed patients is higher when PET-CT is adopted in comparison to CT only. The diagnostic
accuracy calculated by meta-analysis is 86% (95% CI: 81; 91) for PET-CT and 71% (95% CI: 55;
84) for CT.
Calculated by meta-analysis of three studies, the odds ratio of consistency between the
reference test and T-staging results for PET-CT vs. CT is 2.42 (95% CI: 1.36; 4.29). The value is
statistically significant; NNT = 8 (95% CI: 5; 20).
Based on the analyses of all the diagnostic parameters established (sensitivity,
specificity, accuracy), PET-CT is more efficacious than CT in rating the involvement of lymph
nodes (N-status). The diagnostic accuracy calculated by meta-analysis is 85% (95% CI: 76;

93) for PET-CT and 61% (95% CI: 49; 72) for CT. Sensitivity is 85-89%, for PET-CT and 70% for CT,
and specificity is 84-94% for PET-CT and 59-69% for CT.
The odds of N-staging results being consistent with the reference test is nearly 4 times
higher for PET-CT versus CT alone, and the value is statistically significant: OR=3.95 (95% CI:
1.65; 9.44); NNT = 4 (95% CI: 3; 10).
The accuracy of the TNM staging system evaluated by meta-analysis is 88% (95% CI: 83; 93)
for PET-CT and 67% (95% CI: 59; 74) for CT.
The odds of obtaining small cell lung cancer TNM staging results consistent with the
reference test is higher for PET-CT versus CT alone, and the differences observed are
statistically significant; OR = 3.91 (95% CI: 2.04; 7.50); NNT = 5 (95% CI: 4; 9).
In summary, the PET-CT method has a higher diagnostic efficacy than CT in the staging of
clinical non-small cell lung cancer (NSCLC).
121

8. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS
CT IN LYMPHOMA STAGING
122
8.1. Results of primary trial search
As a result of searching medical databases, two primary studies were found
(Freudenberg 2003; tab. 144, app. 18.1 and Schaefer 2004; tab. 145, app. 18.1) that
met the inclusion criteria for this analysis, and compared directly PET-CT and CT
diagnostic efficacy in lymphoma staging.
8.2. Population characteristics
The target population were patients with lymphoma confirmed histologically or
cytologically. Both studies were retrospective.
Freudenberg 2003 included patients who had taken lymphoma therapy for the
purposes of restaging.
In Schaefer 2004, the key objective was to evaluate diagnostic efficacy in staging and
restaging. The inclusion criterion in this study was PET-CT and contrast CT scanning of
patients, assuming time intervals of up to 24 days between tests, and assuming no other
treatment was implemented in the meantime.
Table 27 contains the initial characteristics of the patients.
Table 27.
Initial characteristics of lymphoma patients
Hodgkin
disease
Parameter Freudenberg 2003 Schaefer 2004
Number of patients included in study 27 60
Number of patients (men/women) 18
Disease stage according to Ann Arbor classification no data
Number of patients (men/women) 9
Non-
Hodgkin
lymphoma Initial disease stage according to Ann Arbor classification no data
42
(15/27)
I – 9
II – 24
III – 7
IV – 2
18
(8/10)
I – 8
II – 5
III – 0
IV – 5
Women 11 23
Men 16 37
Age (years)
median age:
46 (17–70)
median age:
39,6±17,1

8.3. Description of intervention
8.3.1. PET-CT imaging
In both studies, imaging diagnostics was executed using a PET-CT scanner with a hybrid
head. Also for both studies, the radiopharmaceutical used for PET images was 18-FDG (18-
fluoro-deoxy-glucose).
In Freudenberg 2003, Biograph scanning system manufactured by Siemens Medical was
used. PET scans were done approx. 1 hour after 360 ± 20 MBq 18-FDG was administered. The
tests were interpreted as follows: PET-CT by two nuclear medicine consultants independently,
and CT by two experienced radiologists. The teams were mutually blinded to the results of
scans they interpreted. Next, combined FDG-PET and CT images were assessed by one
doctor.
In Schaefer 2004, Discovery LS manufactured by GE Medical Systems (Wukesha, Wis.)
was used. 370 MBq of fluoro-deoxy-glucose was administered. The authors provide no
information on the way PET-CT scans were interpreted.
Table 28 provides a detailed description of the PET-CT tests.
Table 28.
Description of PET-CT imaging for both studies
Study
PET-CT
Scanner
type
Freudenberg 2003 Biograph
Schaefer 2004
Discovery
LS
PET-CT
scanner
manufacturer
Siemens
Medical
Solutions
(Hoffman
Estates, III)
Ge Medical
Systems
(Milwaukee)
Radiomarker
type
FDG-PET
intravenously
FDG-PET
intravenously
8.3.2. Diagnostic technology compared
Scanning
scope
Radiomarker
activity
(MBq)
Whole body 360± 20
intravenously 370
In both studies included, PET-CT was compared with CT with contrast medium.
Spiral CT was performed in several hospitals for Schaefer 2004. Contrast medium was
administered intravenously in all tests (approx. 120 to 220 ml contrast medium). The test was
done within 24 days following PET-CT scanning (9.1±7.0 days on average).
In Freudenberg 2003, a standard protocol was used. Oral or intravenous contrast
medium was used for scanning.
123

124
8.3.3. Reference test
Biopsy of lymph node with suspected cancer was the reference (index) test or gold
standard confirming the disease for lymphoma; for cancers located outside nodes the
reference test was biopsy of the organ with suspected lesions.
Not all patients were tested with the reference test in both studies. In addition to
biopsy and clinical observation, the authors mention the following as reference tests:
• conventional disease staging by clinical examination, laboratory diagnostic
tests, USG, MRI, scintigraphy,
• clinical observation.
A list of reference methods used is given in table 29.
Table 29.
List of diagnosis reference tests
Study
Reference test
8.4. Findings
Freudenberg 2003
1. Biopsy: in 7 patients
2. Other imaging studies: 8/27
patients
3. Clinical observation
4. USG: 23/27
5. PET
8.4.1. Diagnosis efficacy in disease staging
Schaefer 2004
1. Biopsy; no data on patients with biopsy
performed
2. Clinical observation
3. Other diagnosis methods, such as MRI,
scintigraphy, laboratory tests
Disease staging based on the Ann Arbor classification was done for all tests included
in this analysis.
In Schaefer 2004, the efficacy in detecting lymphomas in and outside of lymph nodes
was evaluated.
8.4.1.1 In nodes
Study results concerning the diagnostic efficacy in detecting cancer in node locations
is given in table 30.

Table 30.
Test diagnostic efficacy in detecting cancer in node locations
Results /
parameters
TP true positive
dodatni
PET-CT CT
Staging Restaging Staging Restaging
19 11 19 9
FP false positive 0 0 0 4
TN true negative 0 28 0 24
FN false negative 0 2 0 4
SE sensitivity
100%
(82; 100)
SP specificity -
LR+ -
LR- -
ACC
100%
(82; 100)
DOR -
85%
(55; 98)
100%
(88; 100)
47,64
(3,02; 751,73)
0,18
(0,06; 0,56)
95%
(83; 99)
262,20
(11,66; 5 894,2)
100%
(82; 100)
-
-
-
100%
(82; 100)
In case of staging, both sensitivity and accuracy of PET-CT and CT were 100%.
-
69%
(39; 91)
86%
(67; 96)
4,85
(1,82; 12,87)
0,36
(0,16; 0,82)
80%
(65; 91)
13,50
(2,77; 65,78)
In restaging, PET-CT sensitivity was 85% (95% CI: 55; 98), representing 11 out of 13
patients; PET-CT specificity was 100% (95% CI: 88; 100) representing 28 out of 28 patients.
Both these parameters had higher values than with CT, where sensitivity was 69% (95% CI:
39; 91), and specificity was 86% (95% CI: 67; 96).
In restaging, test accuracy was 95% (95% CI: 83; 99) for PET-CT, and 80% (95% CI: 65; 91)
for CT.
125

126
8.4.1.2 Locations outside of nodes
Table 31.
Test diagnostic efficacy in detecting cancer locations outside of nodes
Results /
parameters
TP true
positive
FP false
negative
TN true
negative
FN false
negative
SE sensitivity
SP specificity
LR+
LR-
ACC
DOR
PET-CT CT
Staging Restaging Staging Restaging
3 4 1 3
0 0 0 5
15 37 15 32
1 0 3 1
75%
(19; 99)
100%
(78; 100)
22,40
(95% CI: 1,38;
363,91)
0,31
(95% CI: 0,08;
1,19)
95%
(95% CI: 74; 100)
72,33
(95% CI: 2,40;
2176,8)
100%
(40; 100)
100%
(91; 100)
68,40
(95% CI: 4,29; 1090,5)
0,10
(95% CI: 0,01; 1,41)
100%
(95% CI: 90; 100)
675,0
(95% CI: 11,88;
38359,8)
25%
(1; 81)
100%
(78; 100)
9,60
(95% CI: 0,46; 200,49)
0,72
(95% CI: 0,40; 1,29)
84%
(95% CI: 60; 97)
13,29
(95% CI: 0,44; 399,82)
75%
(19; 99)
86%
(71; 95)
5,55
(95% CI: 2,06; 14,97)
0,29
(95% CI: 0,05; 1,59)
85%
(95% CI: 71; 94)
19,20
(95% CI: 1,65; 222,85)
PET-CT sensitivity and specificity of lesion detection in location outside of nodes 75% (3
out of 4 patients) and 100% (15 out of 15 patients) respectively for staging, and 100% (4 out
of 4 patients) and 100% (37 out of 37 patients) for restaging. For CT the results were: 25%
sensitivity (1 out of 4 patients) and 100% specificity (15 out of 15 patients) for staging, and
75% sensitivity (3 out of 4 patients) and 86% specificity (32 out of 37 patients) for restaging.
For both staging and restaging, PET-CT demonstrated higher accuracy (95% for staging
and 100% for restaging). The accuracy of CT was 84% for staging and 85% for restaging.
McNemar’s test executed for staging and restaging showed statistically significant
difference in specificity, in favor of PET-CT (p = 0.004), and no significant differences were
found for sensitivity (p = 0.11).
8.4.1.3 Total results
Total results for the staging and restaging of disease in lymphatic and extra-lymphatic,
locations in Schaefer 2004 and Freudenberg 2003, are given in table 32.

Table 32.
Diagnostic efficacy in lymphomas detection in locations in and outside of nodes.
Study
Schaefer 2004
Freudenberg
2003
TP
37
13
8.4.1.3.1 Sensitivity
FP
0
0
PET-CT
Graph 10 illustrates PET-CT sensitivity calculated by meta-analysis.
Graph 10.
PET-CT sensitivity
Schaeffer 2004
Meta-analysis results
TN
80
13
PET-CT scanning sensitivity was 93% (95% CI: 80; 98) in Schaefer 2004, and 93% (95% CI:
66; 100) in Freudenberg 2003. Total sensitivity for PET-CT as calculated by meta-analysis was
93% (95% CI: 82; 98).
0,5 1
FN
Sensitivity (95% confidence interval)
CT imaging sensitivity as calculated by meta-analysis is presented in graph 11.
3
1
TP
32
11
FP
9
6
CT
TN
71
7
0,93 (0,80, 0,98)
Freudenberg 2003 0,93 (0,66, 1,00)
0,93 (0,82, 0,98)
FN
8
3
127

Graph 11.
CT sensitivity
128
Schaeffer 2004
Freudenberg 2003 0,79 (0,49, 0,95)
Meta-analysis results 0,80 (0,66, 0,89)
0,2 0,5 1
CT imaging sensitivity was 80% (95% CI: 64; 91) in Schaefer 2004, and 79% (95% CI: 49; 95)
in Freudenberg 2003. Total sensitivity for CT as calculated by meta-analysis was 80% (95%
CI: 66; 89). Heterogeneity was not affirmed.
8.4.1.3.2 Specificity
Sensitivity (95% confidence
interval)
PET-CT specificity as calculated by meta-analysis is presented in graph 12.
0,80 (0,64, 0,91)

Graph 12.
PET-CT specificity
Schaeffer 2004 1,00 (0,95, 1,00)
Freudenberg 2003
Meta-analysis result 1,00 (0,96, 1,00)
0,5 1
Specificity (95% confidence interval)
PET-CT specificity was 100% (95% CI: 95; 100) in Schaefer 2004, and 100% (95% CI: 75; 100)
in Freudenberg 2003. PET-CT specificity as calculated by meta-analysis was 100% (95% CI: 96;
100). No heterogeneity was found in the meta-analysis.
CT sensitivity as calculated by meta-analysis is presented in graph 13.
1,00 (0,75, 1,00)
129

Graph 13.
CT specificity
130
Schaeffer 2004 0,89 (0,80, 0,95)
Freudenberg 2003
Meta-analysis result
0,0 0,2 0,4 0,6 1,0
CT specificity was 89% (95% CI: 80; 95) in Schaefer 2004, and 54% (95% CI: 25; 81) in
Freudenberg 2003. Total CT specificity as calculated by meta-analysis was 84% (95% CI: 75;
91). Significant heterogeneity of the results was observed (p = 0,0048).
8.4.1.3.3 Positive likelihood ratio
Specificity (95% confidence interval)
The positive likelihood ratio for PET-CT scanning is presented in graph 14.
0,54 (0,25, 0,81)
0,84 (0,75, 0,91)

Graph 14.
Positive likelihood ratio for PET-CT scanning
Schaeffer 2004 148,17 (9,33, 2352,41)
Freudenberg 2003 25,20 (1,65, 385,27)
Result of meta-analysis 60,37 (8,66, 420,73)
The positive likelihood ratio (LR+) as calculated by meta-analysis was 60.37 (95% CI:
8.66; 420.73), which means that the probability of positive results with PET-CT scanning is
almost 60 times higher for patients with lesions in and outside of lymph nodes than for
patients without such lesions.
1 2 5 10 100 1000 1,00E+05
Positive likelihood ratio (95%
confidence interval)
The positive likelihood ratio for CT study is presented in graph 15.
131

Graph 15.
Positive likelihood ratio for CT study.
132
Schaefer 2004 7,11 (3,77, 13,41)
Freudenberg 2003 1,70 (0,89, 3,25)
Meta-analysis result 3,48 (0,81, 15,01)
The positive likelihood ratio (LR+) as calculated by meta-analysis was 3,48 (95% CI:
0,81; 15,01), which means that the probability of positive results with CT scanning of patients
with lesions in and outside of lymph nodes was 348% of the probability for patients without
such lesions.
0,5 1 2 5 10 100
8.4.1.3.4 Negative likelihood ratio
Positive result likelihood ratio (95% confidence)
Graph 16 illustrates the negative likelihood ratio for PET-CT.

Graph 16.
Negative likelihood ratio for PET-CT study
Schaefer 2004
Freudenberg 2003
Meta-analysis result 0,09 (0,04, 0,21)
The negative likelihood ratio (LR-) as calculated by meta-analysis was 0,09 (95% CI:
0,04; 0,21), which means that the probability of negative results with PET-CT scanning of
patients with lesions in and outside of lymph nodes was 9% of the probability for patients
without such lesions.
0,01 0,1 0,2 0,5
Negative likelihood ratio (95% confidence
Graph 17 illustrates the negative likelihood ratio for CT.
0,09 (0,03, 0,23)
0,10 (0,02, 0,47)
133

Graph 17.
Negative likelihood ratio for CT study
134
Schaefer 2004
Freudenberg 2003
Meta-analysis result
The negative likelihood ratio (LR-) as calculated by meta-analysis is 0.26 (95% CI: 0,15;
0,44), which means that the probability of negative results with CT scanning for patients with
lesions in and outside of lymph nodes is 26% of the probability for patients without such
lesions.
0,1 0,2 0,5 1 2
8.4.1.3.5 Diagnostic odds ratio
Negative likelihood ratio (95% confidence
Graph 18 illustrates the diagnostic odds ratio for PET-CT.
0,23 (0,12, 0,42)
0,40 (0,13, 1,22)
0,26 (0,15, 0,44)

Graph 18.
Diagnostic odds ratio for PET-CT
Schaefer 2004 1725,00 (86,88, 34248,86)
Freudenberg 2003 234,00 (9,07, 6511,88)
Meta-analysis result 710,84 (77,86, 6490,00)
5 10 100 1000 1,00E+05
Diagnostic odds ratio (95% confidence interval)
The odds ratio as calculated by meta-analysis is 710.84 (95% CI: 77,86; 6490,00), which
means that the probability of positive results with CT scanning of patients with lesions in or
outside of lymph nodes is approx. 710 times higher than for patients without such lesions.
Graph 19 illustrates the diagnostic odds ratio for CT.
135

Graph 19.
Diagnostic odds ratio for CT
136
Schaefer 2004 31,56 (11,16, 89,26)
Freudenberg 2003 4,28 (0,80, 22,93)
Meta+analzsis result 13,01 (1,85, 91,34)
0,5 1 2 5 10 100
The odds ratio as calculated by meta-analysis is 13.01 (95% CI: 1,85; 91,34), which
means that the probability of positive results with CT scanning of patients with lesions in and
outside of lymph nodes is more than 13 times higher than for patients without such lesions.
8.4.1.3.6 Diagnostic accuracy
Diagnostic odds ratio (95% confidence interval)
Graph 20 illustrates the diagnostic accuracy of PET-CT scanning.

Graph 20.
PET-CT accuracy
Schaefer 2004
Freudenberg 2003
Meta-analysis result
PET-CT accuracy as calculated by meta-analysis is 97% (95% CI: 93; 99).
Graph 21 illustrates the diagnostic accuracy of CT scanning.
Graph 21.
CT accuracy
Schaefer 2004
Meta-analysis result
0,5 1
Meta-analysis of accuracy (95% confidence interval
0,2 0,5 1
Accuracy meta-analysis (95% confidence interval)
CT accuracy as calculated by meta-analysis is 78% (95% CI: 57; 93).
0,98 (0,93, 0,99)
0,96 (0,81, 1,00)
0,97 (0,93, 0,99)
0,86 (0,78, 0,92)
Freudenberg 2003 0,67 (0,46, 0,83)
0,78 (0,57, 0,93)
137

138
8.4.1.3.7 Results
Table 33.
Diagnostic accuracy in detecting lymphomas
Se[%]
Sp[%]
LR-
LR+
DOR
Acc
PET-CT
93%
(95% CI: 80; 98)
100%
(95% CI: 95;
100)
0,09
(95% CI: 0,03;
0,23)
148,17
(95% CI: 9,33;
2352,41)
1725,00
(95% CI: 86,88;
34248,86)
98%
(95% CI: 93; 99)
Schaefer 2004
CT
80%
(95% CI: 64; 91)
89%
(95% CI: 80; 95)
0,23
(95% CI: 0,12;
0,42)
7,11
(95% CI: 3,77;
13,41)
31,56
(95% CI: 11,16;
89,26)
86%
(95% CI: 78; 92)
Freudenberg 2003
PET-CT
93%
(95% CI: 66;
100)
100%
(95% CI: 75;
100)
0,10
(95% CI: 0,02;
0,47)
25,20
(95% CI: 1,65;
385,27)
234,00
(95% CI: 9,07;
6511,88)
96%
(95% CI: 81;
100)
CT
79%
(95% CI: 49; 95)
54%
(95% CI: 25; 81)
0,40
(95% CI: 0,13;
1,22)
1,70
(95% CI: 0,89;
3,25)
4,28
(95% CI: 0,80;
22,93)
67%
(95% CI: 46; 83)
PET-CT
Total result
93%
(95% CI: 82; 98)
100%
(95% CI: 96;
100)
0,09
(95% CI: 0,04;
0,21)
60,37
(95% CI: 8,66;
420,73)
710,84
(95% CI: 77,86;
6490,0)
97%
(95% CI: 93; 99)
8.4.2. Accuracy of staging based on Ann Arbor staging system
Freudenberg 2003 compared the usefulness of diagnostic tests in disease staging
according to the Ann Arbor staging system.
CT
80%
(95% CI: 66; 89)
84%
(95% CI: 75; 91)
0,26
(95% CI: 0,15;
0,44)
3,48
(95% CI: 0,81;
15,01)
13.01
(95% CI: 1,85;
91,34)
78%
(95% CI: 57; 93)
In Freudenberg 2003, staging based on CT scans was correct for 13 patients (48%), and
staging based on PET-CTscans was correct for 26 patients (96%). The difference between
PET-CT and CT is statistically significant (p = 0.002).
PET-CT scanning allowed to classify correctly disease at a higher stage than identified by
CT in 6 patients (26%), and to classify correctly disease at a lower stage in 7 patients (26%).
Table 34 provides results of lymphoma staging using PET-CT as compared to CT in
Freudenberg 2003.
Table 34.
Results of lymphoma staging by PET-CT as compared to CT.
Freudenberg 2003
Correct staging by PET-CT Correct staging by CT
96%
(95% CI: 81; 100)
48%
(95% CI: 29; 68)
Statistical
significance
The odds ratio for correct staging of lymphomas based on the Ann Arbor system for PET-
CT vs. CT.
0,002

Table 35.
Odds ratio for correct lymphoma staging: PET-CT vs. CT
PET-CT vs CT
OR NNT
28,00
(95% CI: 3,35; 1227,94)
3
(95% CI: 2; 4)
The odds ratio was calculated at 28.00 (95% CI: 3.35; 1227.94), which means that the
probability of correct lymphoma staging according to the Ann Arbor system is 28 times
higher for PET-CT than for CT imaging. The difference is statistically significant.
In order to obtain one additional case of correct lymphoma staging it is necessary to
use PET-CT instead of CT with 3 patients with esophageal cancer, NNT = 3 (95% CI: 2; 4).
8.4.3. Safety
The authors identified no undesirable effects of the use of the diagnostic methods
described.
8.5. Results
As a result of searching medical databases two primary studies were found: Freudenberg 2003
(N = 27) and Schaefer 2004 (N = 60), which compared directly the diagnostic efficacy of PET-CT
and CT in lymphoma staging and restaging. The reference tests were histopathological tests,
clinical follow-up and conventional staging of the disease (clinical and laboratory tests, USG, MRI,
scintigraphy).
A diagnostic efficacy review showed that PET-CT was diagnostically more efficacious than CT
both for lymphical and extralymphical locations individually, and for the total cohort.
In staging lesions in the lymphical area, the sensitivity and accuracy of both PET-CT and CT were
100% (95% CI: 82; 100).
In restaging, PET-CT sensitivity stood at 85% (95% CI: 55; 98) and specificity at 100% (95% CI: 88;
100); both were higher than the respective parameters for CT. For CT the values were: 69% for
sensitivity (95% CI: 39; 91) and 86% for specificity (95% CI: 67; 96). The diagnostic accuracy of the
methods discussed was 95% (95% CI: 83; 99) for PET-CT and 80% (95% CI: 65; 91) for CT.
PET-CT sensitivity and specificity in detecting pathological lesions located outside of lymph
nodes stood at 75% (95% CI: 19; 99) and 100% (95% CI: 78; 100), respectively. In restaging, both
sensitivity and specificity were 100%. With CT imaging, the values were: 25% for sensitivity (95% CI: 1;
81) and 100% for specificity (95% CI: 78; 100) for staging, and 75% (95% CI: 19; 99) and 86% (95% CI:
71; 95) respectively for restaging. PET-CT scanning demonstrated higher accuracy (95% for staging
and 100% for restaging) compared to CT (84% and 85% respectively).
Meta-analysis of the tests included in this study showed that in disease staging in patients with
139

lymphoma, PET-CT is characterized by higher sensitivity and specificity compared to CT. The
sensitivity of PET-CT is 93% (95% CI: 82; 98), vs. 80% for CT (95% CI: 66; 89). The specificity of the
diagnostic methods discussed is 100% (95% CI: 96; 100) and 84% (95% CI: 75; 91) respectively.
140
PET-CT is characterizes by a higher accuracy of 97% (95% CI: 93; 99) s. 78% for CT (95% CI: 57; 93).
Freudenberg 2003 analyses the consistency between the reference test and staging based on
the Ann Arbor system. Disease was staged correctly by PET-CT in 26 (96%) patients, and by CT in 13
(48%) patients. The difference between PET-CT and CT was statistically significant (p=0.002). The
odds of obtaining the correct staging were 28 times for PET-CT than for CT: OR = 28 (95% CI: 3.35;
1227.94); NNT = 3 (95% CI: 2; 4).
PET-CT imaging is characterized by higher diagnostic efficacy than CT in the staging of
lymphomas.

9. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS. CT IN
ESOPHAGEAL CANCER STAGING
9.1. Disease staging
9.1.1. Results of primary trial search
As a result of searching through medical databases, one primary study was found
(Cerfolio 2005; tab. 146, app. 18.1), that met the inclusion criteria and compared
directly the diagnostic efficacy of PET-CT with that of other technologies used in
cancer restaging.
9.1.2. Population characteristics
The aim of Cerfolio 2005 was a prospective assessment of the accuracy of three
testing technologies in the restaging of esophageal cancer following neoadjuvant
therapy. The studies evaluated were: PET-CT, transesophageal endoscopic
ultrasound-guided biopsy (EUS) and CT.
Only patients for whom scans had been done using all the three technologies
mentioned above prior to surgery were included in the study. Following preliminary
staging, all the patients took neoadjuvant chemotherapy with concomitant
radiotherapy. After the treatment, total restaging was done for these patients (TNM).
The results were entered into a database by a blinded researcher.
Initially, 67 patients were included in the study. Four out of that group refused to
take part in the trial. Following neoadjuvant therapy, disease progression occurred
but still they refused to take biopsy. Another 2 patients could take PET-CT tests
(authors did not provide reasons). The serious health condition of another four
patients prevented the procedure or they refused to take the procedure. Ultimately,
48 patients were included in the study. 41 had undergone Ivor Lewis
esophagogastrectomy (resection of stomach and esophagus) with
lymphadenectomy.
The characteristics of the patients included is presented in table 36.
141

Table 36.
Patient characteristics in Cerfolio 2005
142
Parameter Cerfolio 2005
Number of patients included in study 48
Disease staging based on
TNM system
Before therapy After therappy
0 - 15 (31%)
I 0 5 (10%)
IIa 22 (46%) 10 (22%)
IIb 5 (10%) 4 (8%)
III 15 (33%) 2 (4%)
T4 2 (4%) 1 (2%)
IV (M1a) 3 (6%) 5 (10%)
IV (M1b) 1 (2%) 6 (13%)
Women 7 (15%)
Men 41 (85%)
Median age [years] 68 (48-76)
Histopathological examination results
9.1.3. Description of intervention
9.1.3.1 PET-CT imaging
Adenocarcinoma: 43 patients
(85%)
Squamous cell carcinoma: 5 patients
(15%)
In the study, imaging diagnostics was executed using a PET-CT scanner with a hybrid
head. The radiopharmaceutical used for PET was FFDG (F-18 fluoro-deoxy-glucose)
administered intravenously in 555 MBq doses. PET-CT image was obtained using a GE
Discovery LS PET-CT Scanner (GE, Milwaukee, Wis). The researcher interpreting the test had
access to CT images but did not know EUS-FNA results.
Table 37.
PET-CT imaging Cerfolio 2005
Study
PET-CT scanner
type
Cerfolio 2005 Ge Discovery LS
PET-CT scanner
manufacturer
Ge Medical
Systems
(Milwaukee)
Radiomarker
type
FDG
intravenously
Radiomarker
activity
(MBq)
555
Test
coverage
Thorax,
abdomen,
pelvis

9.1.3.2 Diagnostic technology compared
1. The diagnostic efficacy of PET-CT was compared with CT and transesophageal
endoscopic ultrasound-guided biopsy.
2. Transesophageal endoscopic ultrasound-guided biopsy was done under anesthetic
and assessed by an experienced ultrasonography specialist, who knew no CT or PET-CT
results. The scanning involved the visualization of internal organs of the abdominal cavity with
the aim of identifying the tumor location and the involvement of adjacent lymph nodes. The
test was initially done using a GF-UM130 unit, and when lesions were located, an Olympus
UC-30P or VTC 140 endoscope was used for fine-needle biopsy. If lymph nodes were
involved, no biopsy was done for fear of aspiration of tumor material. Where sampling of
regional lymph nodes was impossible, an experienced ultrasonography specialist assessed
lymph nodes involvement as positive or negative.
CT had to be done with the use of a third generation unit as minimum requirement.
Imaging covered the thorax, abdominal cavity and pelvis. Images were assessed by one of
four radiologists experienced in assessing thorax organs.
9.1.3.3 Reference test
Histopathological examination was used to confirm the presence of esophageal cancer.
41 patients in Cerfolio 2005 underwent stomach and esophagus resection using the Ivor
Lewis method (esophagogastrectomy) with lymphadenectomy, followed by
histopathological examination.
9.1.4. Findings
9.1.4.1 Diagnostic efficacy of test
Cerfolio 2005 evaluated the diagnostic efficacy of tests based on pre-defined end points.
Test efficacy in:
Disease staging:
o T feature (tumor size),
o N feature (involvement of lymph nodes),
o M feature (presence of distant metastases),
Assessing total response to therapy.
9.1.4.1.1 T-staging
The accuracy of each diagnostic test was assessed based on its ability to differentiate
between stages T1-T3, and T0 and T4 (PET-CT does not differentiate between stages T1, T2
143

144
and T3).
Table 38 presents staging results for the diagnostic technologies as compared to the
reference method.
Table 38.
T-staging results for each of the diagnostic methods as compared to the reference test (Cerfolio 2005)
T0
T1–T3
T4
TP FP FN TN
PET-CT 13 4 3 21
EUS 3 1 13 24
CT 4 4 12 21
PET-CT 18 4 4 15
EUS 20 16 2 3
CT 18 14 4 5
PET-CT 2 0 1 38
EUS 0 1 3 37
CT 1 0 2 38
Table 39 presents the diagnostic efficacy parameters by disease stage.
Table 39.
PET-CT, EUS-FNA and CT diagnostic efficacy in tumor restaging
Se
(95% CI)
Sp
(95% CI)
Acc
(95% CI)
LR+
(95% CI)
PET-CT
EUS
CT
PET-CT
EUS
CT
PET-CT
EUS
CT
PET-CT
T0 T1–T3 T4
81%
(54; 96)
19%
(4; 46)
25%
(7; 52)
84%
(64; 96)
96%
(80; 100)
84%
(64; 96)
83%
(68; 93)
66%
(49; 80)
61%
(45; 76)
5,08
(2,01; 12,85)
EUS 4,69
(0,53; 41,24)
CT
1,56
(0,45; 5,38)
82%
(60; 95)
91%
(71; 99)
82%
(60; 95)
79%
(54; 94)
16%
(3; 40)
26%
(9; 51)
80%
(65; 91)
56%
(40; 72)
56%
(40; 72)
3,89
(1,59; 9,49)
1,08
(0,85; 1,37)
1,11
(0,80; 1,55)
67%
(9; 99)
0%
(0; 71)
33%
(1; 91)
100%
(91; 100)
97%
(86; 100)
100%
(91; 100)
98%
(87; 100)
90%
(77; 97)
95%
(83; 99)
48,75
(2,80; 848,44)
3,25
(0,16; 67,31)
29,25
(1,41; 605,81)

LR-
(95% CI)
DOR
(95% CI)
PET-CT
EUS
CT
PET-CT
EUS
CT
0,22
(0,08; 0,63)
0,85
(0,66; 1,09)
0,89
(0,64; 1,24)
22,75
(4,37; 118,34)
5,54
(0,52; 58,76)
1,75
(0,37; 8,30)
0,23
(0,09; 0,58)
0,58
(0,11; 3,09)
0,69
(0,22; 2,21)
16,88
(3,60; 79,19)
1,88
(0,28; 12,61)
1,61
(0,36; 7,12)
0,38
(0,11; 13)
0,91
(0,63; 1,33)
0,63
(0,30; 1,35)
128,33
(4,09; 4029,60)
3,57
(0,12; 105,20)
46,20
(1,47; 1450,60)
With respect to test efficacy in correct identification of stage T0, PET-CT accuracy was
83% (95% CI: 68; 93), CT accuracy was 61% (95% CI: 45; 76) and EUS accuracy was 66% (95%
CI: 49; 80).
For stages T1–T3, accuracy was 80% (95% CI: 65; 91) for PET-CT, 56% (95% CI: 40; 72) for CT
and 56% (95% CI: 40; 72) for EUS.
For stage T4, the accuracy of PET-CT was the highest and stood at 98% (95% CI: 87; 100),
while for the other analyzed tests, the accuracy was 90% (95% CI: 77; 97) for EUS, and 95%
(95% CI: 83; 99) for CT.
In each case, the diagnostic accuracy of PET-CT was higher than that of the other
technologies.
Table 40 lists the proportions of patients with the T-feature staged correctly, understaged
and overestaged for the methods compared: PET-CT, EUS and CT.
Table 40.
Proportion of cases correctly staged, understaged and overstaged by the diagnostic methods analysed.
PET-CT EUS CT
Staged correctly 0,80 0,56 0,56
Understaged 0,12 0,10 0,15
Overstaged 0,07 0,34 0,29
PET-CT correctly identified the T-status in 80% patients (95% CI: 65; 91), as compared to
56% patients for CT and EUS (95% CI: 40; 72).
The odds ratio for correct T-staging and NNT were also calculated for the diagnostic
methods. Table 41 provides the results obtained.
145

Table 41.
Odds ratio for correct T-staging NNT for diagnostic methods analyzed: PET-CT vs. EUS and PET-CT vs. CT
146
PET-CT vs. EUS
PET-CT vs. CT
OR NNT
3,23
(1,09; 10,00)
3,23
(1,09; 10,00)
5
(3; 24)
5
(3; 24)
The odds ratio calculated for PET-CT vs., EUS and for PET-CT vs., CT is 3.23 (95% CI:
1.09;10.00). It means that the probability of correct T-staging with the use of PET-CT is 3.23
times higher compared to CT and EUS.
In order to obtain one additional case of correct T-staging it is necessary to use PET-CT
instead of CT or EUS with 5 esophageal cancer patients, NNT = 5 (95% CI: 3; 24).
9.1.4.1.2 N-staging
The diagnostic methods compared were used to assess the lymph node involvement.
This feature was not assessed for 7 patients for want of full histopathological results.
Table 42.
Diagnostic efficacy of PET-CT, EUS-FNA and CT in assessing lymph node involvement
Parameter PET-CT CT EUS-FNA Statistical significance*
TP 5 1 1 -
FP 0 2 2 -
TN 33 31 31 -
FN 3 7 7 -
SE
SP
LR+
LR-
ACC
63%
(24; 91)
100%
(89; 100)
41,55
(2,53; 683,56)
0,39
(0,17; 0,90)
93%
(80; 98)
13%
(0,3; 53)
94%
(80; 99)
2,06
(0,39; 176,84)
0,63
(0,71; 1,23)
78%
(62; 80)
* Statistical significance for the comparison of PET-CT vs. EUS-FNA
13%
(0,3; 53)
94%
(80; 99)
2,06
(0,39; 176,84)
0,63
(0,71; 1,23)
78%
(62; 80)
p = 0,12
p = 0,98
-
-
p = 0,04
Based on the data above, PET-CT sensitivity is 63% (95% CI: 24; 91), and CT and EUS
sensitivity is 13% (95% CI: 0.3; 53), which means that the probability of positive results in patients
diagnosed with metastasis to lymph nodes is higher for PET-CT than for CT and EUS.

PET-CT specificity is 100% (95% CI: 89; 100), while CT and EUS specificity is 94% (95% CI: 80;
99), which means that the probability of negative results in patients with no metastasis to
lymph nodes identified by the reference test is 100%, 94% and 94% respectively.
The positive likelihood ratio for PET-CT is 41.55, so the probability of positive results in patients
diagnosed with metastasis to lymph nodes is 41.55 times higher than the probability of positive
results in patients without metastasis. The positive likelihood ratio for CT is 2.06 (95% CI: 0.39;
176.84), which means that the probability of positive results in patients diagnosed with
metastasis to lymph nodes is 2.06 of the probability of positive results in patients with no
metastases diagnosed histopathologically. The positive likelihood ratio for EUS-FNA is 2.06 (95%
CI: 0.39; 176.84), which means that the probability of positive results in patients diagnosed with
metastasis to lymph nodes is 2.06 of the probability of positive results in patients with no
metastasis diagnosed histopathologically.
The negative likelihood ratio for PET-CT is 0.39 (95% CI: 0.17; 0.90), which means that the
probability of negative results in patients diagnosed with metastasis to lymph nodes is 0.39
of the probability of negative results in patients with no metastasis detected. The negative
likelihood ratio calculated for CT is 0.63 (0.71; 1.23) so the probability of negative results in
patients diagnosed with metastasis to lymph nodes is 0.63 of the probability of negative
results in patients with no metastasis detected. The negative likelihood ratio calculated for
EUS-FNA is 0.63 (0.71; 1.23) so the probability of negative results in patients diagnosed with
metastasis to lymph nodes is 0.63 of the probability of negative results in patients with no
metastasis detected.
Diagnostic accuracy in N-staging is 93% (95% CI: 80; 98) for PET-CT, and 78% (95% CI: 62;
80) for both CT and EUS-FNA. The differences between PET-CT and EUS-FNA and CT
reached statistical significance (p=0.04, test for proportions).
PET-CT demonstrated the highest sensitivity, specificity, as well as negative and positive
likelihood ratio in N-staging.
9.1.4.1.3 M-staging
The authors of Cerfolio 2005 evaluated the diagnostic accuracy of PET-CT vs. CT vs. EUS
in assessing distant metastasis at stages M1a and M1b.
The efficacy of each of the technologies in diagnosing metastasis is presented in tables
43 and 44.
147

Table 43.
Diagnostic efficacy of PET-CT, EUS-FNA and CT in M-staging: stage M1a
148
PET-CT CT EUS
Statistical
significance*
TP 2 0 2 -
FP 1 0 0 -
TN 41 42 42 -
FN 4 6 4 -
Se
(95% CI)
Sp
(95% CI)
LR+
(95% CI)
LR-
(95% CI)
DOR
(95% CI)
Acc
(95% CI)
33%
(4; 78)
98%
(87; 100)
0%
(0; 46)
100%
(92; 100)
- -
- -
- -
90%
(77; 97)
* Statistical significance for PET-CT vs. EUS-FNA comparison
88%
(75; 95)
33%
(4; 78)
100%
(92; 100)
0,56
(0,03; 10,02)
1,05
(0,78; 1,42)
0,53
(0,02; 12,83)
92%
(80; 98)
p = 1,00
p = 1,00
-
-
-
p = 0,76
The highest accuracy in assessing the metastatic stage M1a is demonstrated by EUS: 92%
(95% CI: 80; 98); PET-CT accuracy is 90% (95% CI: 77; 97), and CT accuracy is 88% (95% CI: 75;
95). The differences between groups are not statistically significant. The sensitivity of PET-CT
and EUS is 33% (95% CI: 4; 78), and for CT imaging, sensitivity is 0%, as no true positive results
were reported.
PET-CT specificity is 98% (95% CI: 87; 100) while for CT and EUS imaging, specificity is 100%.
The metastatic stage M1b was assessed by two diagnostic technologies: PET-CT and CT.
Table 44.
Diagnostic efficacy of PET-CT and CT in M-staging: stage M1b
PET-CT
TP 4 3
FP 4 3
TN - -
FN 2 3
Se
(95% CI)
67%
(22; 96)
CT
50%
(12; 88)
PET-CT sensitivity is higher compared to CT, stands at 67% (95% CI: 22; 96); for CT
imaging, sensitivity is 50% (95% CI: 12; 88). The difference is statistically significant.

9.1.4.1.4 CR – complete response
Complete response occurred in 15 (31%) patients. Table 45 presents efficacy values for
detecting complete response using the diagnostic methods compared.
149

Table 45.
Diagnostic efficacy of PET-CT, EUS-FNA and CT in assessing complete response
150
Parameter PET-CT CT EUS-FNA
Statistical
significance *
TP 13 4 3 -
FP 4 3 2 -
TN 29 30 31 -
FN 2 11 12 -
SE
SP
LR+
LR-
ACC
87%
(60; 98)
88%
(72; 97)
7,15
(2,79; 18,30)
0,15
(0,04; 0,56)
88%
(95% CI: 75; 95)
27%
(8; 55)
91%
(76; 98)
2,93
(0,75; 11,51)
0,80
(0,58; 1,12)
71%
(95% CI: 56; 83)
20%
(4; 48)
94%
(80; 99)
3,30
(0,61; 17,74)
0,85
(0,65; 1,11)
71%
(95% CI: 56; 83)
p = 0,01
p = 0,60
p = 0,045
*Statistical significance of the difference in diagnostic efficacy between PET-CT and EUS in assessing complete
response.
In the assessment of complete response to treatment, PET-CT demonstrated the highest
sensitivity: 87% (95% CI: 60; 98), compared to 27% (95% CI: 8; 55) for CT, and 20% (95% CI: 4;
48) for EUS. The differences between PET-CT and the reference (index) tests are statistically
significant (p = 0,01 for the comparison with EUS-FNA; test for proportions).
PET-CT specificity is 88% (95% CI: 72; 97), CT specificity is 91% (95% CI: 76; 98), and EUS-FNA
specificity is 94% (95% CI: 80; 99). The differences are not statistically significant.
The highest accuracy was demonstrated by PET-CT: 88% (95% CI: 75; 95), as compared
with 71% (95% CI: 56; 83) for CT and 71% (95% CI: 56; 83) for EUS-FNA. The differences
between PET-CT and reference tests are statistically significant (p = 0,045 for the comparison
with EUS-FNA, and p = 0.05 for the comparison with CT, test for proportions).
9.1.4.2 Safety
The authors identified no undesirable effects of the use of the diagnostic technologies
compared.

9.1.5. Results
As a result of searching medical databases one primary study was found (Cerfolio 2005)
that evaluated the diagnostic efficacy of PET-CT versus CT and transesophageal endoscopic
ultrasound-guided biopsy (EUS) in the restaging of esophageal cancer and the assessment of
response to treatment.
In the diagnostics of primary tumor (T status), the highest diagnostic accuracy was
demonstrated by PET-CT: 83% (95% CI: 68; 93) for stage T0, 80% (95% CI: 65; 91) for stages T1-
T3, and 98% (95% CI: 87; 100) for stage T4. In the other tests under assessment, the accuracy of
CT was 61% (95% CI: 45; 76), 56% (95% CI: 40; 72) and 95% (95% CI: 83; 99) respectively, and
the accuracy of EUS was 66% (95% CI: 49; 80), 56% (95% CI: 40; 72) and 90% (95% CI: 77; 97).
PET-CT scanning allowed for correct (consistent with reference test) T-staging in 80%
patients, while CT and EUS - in 56% each.
The odds of obtaining a correct T-status by using PET-CT is 3.23 times higher compared to CT
alone, and to EUS; OR = 3.23 (95% CI: 1.09; 10.00), both for the comparison PET-CT vs. EUS and
for the comparison PET-CT vs. CT; NNT = 5 (95% CI: 3; 24).
In staging lymph nodes involvement (N status), the highest diagnostic accuracy was
achieved for PET-CT: 93% (95% CI: 80; 98), compared to 78% (95% CI: 62; 80) for CT and 78%
(95% CI: 62; 80) for EUS. The difference in accuracy was statistically significant (p=0.04).
The diagnostic efficacy of trials in M-staging was evaluated separately for stages M1a and
M1b.
The highest accuracy in determining stage M1a metastasis was demonstrated by EUS – 92%
(95% CI: 80; 98), while the accuracy of PET-CT was 90% (95% CI: 77; 97), and the accuracy of
CT was 88% (95% CI: 75; 95). The differences between the groups were statistically
insignificant. The sensitivity of PET-CT and EUS was 33% (95% CI: 4; 78), and the sensitivity of CT
imaging was 0% (95% CI: 0; 40). The specificity of PET-CT is 98% (95% CI: 87; 100), while that of
CT imaging and EUS is 100%.
In the diagnostics of stage M1b metastasis, the sensitivity of PET-CT was 67% (95% CI: 22; 96)
and was higher than the sensitivity of CT, which stood at 50% (95% CI: 12; 88).
In the assessment of complete response to treatment, PET-CT showed the highest sensitivity
of 87% (95% CI: 60; 98). The sensitivity of CT was 27% (95% CI: 8; 55), and the sensitivity of EUS
was 20% (95% CI: 4; 48). The differences between PET-CT and the methods compared are
statistically significant. The specificity of PET-CT scanning stood at 88% (95% CI: 72; 97), of CT at
91% (95% CI: 76; 98), and of EUS-FNA at 94% (95% CI: 80; 99). The highest accuracy was
demonstrated by PET-CT, and stood at 88% % (95% CI: 75; 95) vs. 71% (95% CI: 56; 83) for CT
and 71% (95% CI: 56; 83) for EUS. The differences between PET-CT and the methods
compared are statistically significant (p=0.045 for the comparison with EUS-FNA, and p=0.05
for the comparison with CT).
151

In summary, in restaging esophageal cancer, and in determining complete response to
treatment, PET-CT imaging demonstrates higher diagnostic efficacy than CT or trans-
esophageal ultrasound-guided biopsy.
152
9.2. Diagnostics of primary esophageal cancer
9.2.1. Primal tests search results
As a result of searching medical databases, one primary trial was found (Kula 2005; tab.
147, app. 18.1) that met the inclusion criteria and compared directly the diagnostic
efficacy of PET-CT with other methods in esophageal cancer diagnostics.
9.2.2. Population characteristics
The target population were patients with esophageal cancer confirmed histologically or
cytologically, and patients with suspected recurrence of esophageal cancer.
The purpose of the study was to evaluate the usefulness of PET-CT in staging esophageal
cancer. The trial covered 12 men aged from 36 to 78 (59 on average) who had taken
therapy.
The inclusion requirement was esophageal cancer diagnosed previously based on
endoscopic and histopathological tests of tumor samples, as well as disease staging
using CT of the thorax with the use of a contrast medium.
The initial patient characteristics is presented in table 46.
Table 46.
Initial patient characteristics in Kula 2005
Staging based on the TNM system
Parameter Kula 2005
Number of patients included 12
I 1
IIa 1
IIb 0
III 2
T4 2

IV(M1a) 3
IV(M1b) 3
Prior therapy: chemotherapy 1
Prior therapy:
chemo-radiotherapy
Resection, chemotherapy 2
Surgery 3
Radiotherapy 2
No therapy: exploratory surgery 2
Women 0
Men 12
Age (years)
9.2.3. Description of intervention
9.2.3.1 PET-CT imaging
2
36–78
(average 59.1)
Diagnostic imaging was performed using a PET-CT scanner with a hybrid head. PET-CT
scanning was done approx. 60-90 minutes after 370-480 MBq of FDG was administered.
The radiopharmaceutical could not be given unless the glucose level in blood was
below 8.4 mmol/l.
Table 47.
PET-CT test characteristics
Study
PET-CT
scanner
type
Kula 2005 Biograph
PET-CT
scanner
manufacturer
Siemens
Medical
Solutions
(Hoffman
Estates, III)
Type of
radiomarker
FDG-PET
intravenously
9.2.3.2 Diagnostic technologies compared
PET-CT was compared with CT.
Radiomarker
activity
(MBq)
370–480
Test coverage
From orbital
cavities level to
below natis
No data on the type of CT units used is given in Kula 2005. No detailed description of
outcome evaluation is given either.
153

154
9.2.3.3 Reference test
In Kula 2005, esophageal cancer had been determined histopathologically or
cytologically for all the patients.
9.2.4. Safety
The authors found no undesirable effects of the use of the diagnostic methods assessed.
9.2.5. Findings
Primary esophageal cancer was detected in all the 12 patients based on PET-CT
images. No false positive results were identified in the PET-CT tests. CT detected primary
esophageal cancer in 11 primary esophageal cancer patients only. In one case, PET-CT
identified a metastasis to lungs, which could not be imaged by CT scanning.
Thus, PET-CT sensitivity can be described as 100% (95% CI: 74; 100), and CT sensitivity as
92% (95% CI: 62; 100).
The remaining data could not be analyzed for want of a clear description of results or
data for the method compared (CT).
9.2.6. Results
As a result of searching medical databases one primary trial was found (Kula 2005), which
compared the diagnostic efficacy of PET-CT with that of CT in the staging of esophageal
cancer (N=12). The reference test was a histopathological or cytological test.
Based on studies accessible, PET-CT is characterized by higher sensitivity (100%) in
comparison to CT (92%) in detecting esophageal cancer.

10. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS.
CONVENTIONAL IMAGING METHODS (CT, MRI, USG) IN
CLINICAL STAGING, AND DETECTING RECURRENCES OF,
MALIGNANT FEMALE GENITAL TUMORS
10.1. Results of primary study search
As a result of searching medical databases, a single prospective clinical trial was
found (Grisaru 2004, tab. 148, zał. 18.1) that compared the diagnostic efficacy of
PET coupled with x-ray CT with conventional imaging methods (computed x-ray
tomography, magnetic resonance imaging and ultrasonography) in staging, and
detecting recurrences of, malignant tumors of the female genitals.
10.2. Population characteristics
The population in the trial comprised 53 patients diagnosed with malignant
tumors of the female genitals (cervical cancer, endometrial cancer, ovarian
cancer, vulvar cancer, vaginal cancer, uterine tube cancer, trophoblast malignant
disease). Indications for PET-CT diagnostics were based on clinical staging in 18
patients, and suspected recurrence after previous treatment in 35 patients.
Table 48 presents the initial characteristics of the population diagnosed.
Table 48.
Characteristics of patients diagnosed with malignant female genital tumor in Grisaru 2004.
PARAMETER
Number of patients
Median age (SD)
POPULATION
53
56 (15)
The median age of subjects was 56 (SD = 15). 21 were diagnosed with cervical cancer
(40%), 8 were diagnosed with endometrial cancer (15%), 19 were diagnosed with
ovarian cancer (36%), while miscellaneous female genital tumors were detected in the
others.
PET-CT scanning was planned to stage the disease in 34% of patients; the other 66% of
patients underwent the test to determine possible recurrences of the disease.
155

156
10.3. Description of intervention
10.3.1. PET-CT imaging
PET-CT scans were done using the Discovery LS PET-CT system (GE Medical Systems,
Milwaukee, WI, USA). Fluorine-18 deoxy-glucose was used as a marker. Patients were not
allowed to eat for 4 hours before the test. Also, they were advised to hold their breath
during CT scan acquisition. PET was performed directly following CT, with no change to
the patient's body position. Scans covering the area from cranium to mid thigh were
recorded in 5 to 8 bed positions; the acquisition time of a single scan was 5 minutes.
Table 49.
Information on PET-CT scanner type and scanning method
PET-CT scanner
type
PET-CT Scanner
Discovery LS
Radiomarker type
F18-deoxyglucose
Radiomarker
activity
[MBq]
370–666
Contrast medium
type CT
not used
Coverage
whole body
The scans were interpreted by an experienced physician blinded to the results of other
tests.
10.3.2. Diagnostic technologies compared
Before included in the trial, each patient had had her genitals scanned using standard
diagnostic methods (CT, MRI and ultrasonography). The authors provide no information on
the time intervals between conventional scanning and PET-CT scanning.
10.3.3. Reference test
In order to verify the results of diagnostic imaging, samples taken during surgeries or
obtained from guided biopsy were tested histopathologically. All negative results of
histopathological tests were confirmed by further clinical observation and radiological
tests. The authors provide no information on the follow-up period for the population
screened.

10.4. Findings
10.4.1. Disease staging
The EBM parameters of diagnostic efficacy (sensitivity, specificity, accuracy, positive
likelihood ratio, negative likelihood ratio and diagnostic odds ratio) were calculated for
two groups separately: patients diagnosed for the purposes of disease staging, and
patients with suspected disease recurrence. In both cases, the statistical significance of
sensitivity and specificity of the methods compared were evaluated.
Table 50 presents the number of patients with true positive, false positive, false
negative and true negative results of PET-CT and conventional imaging tests for the
subjects diagnosed for the purposes of disease staging. For two patients, conventional
imaging results qualified as indecisive (+/-) in the publication were classified as true
positive.
Table 50.
Number of patients with TP, FP, FN and TN results in the group with the disease staged: PET-CT vs. conventional
methods (CT, MRI and USG)
Study
Grisaru 2004
TP
9
FP
0
PET-CT
FN
0
TN
TP
Conventional method
(CT, MRI and USG)
Table 51 presents the parameters of the diagnostic efficacy of PET-CT and the
conventional imaging methods (CT, MRI and USG) for the patient group diagnosed for the
purposes of disease staging.
Table 51.
EBM parameters of the diagnostic efficacy in disease staging: PET-CT vs. conventional methods (CT, MRI and USG)
Parameter
Se
(95% CI)
Sp
(95% CI)
Acc
(95% CI)
LR+
(95% CI)
Diagnostic method
Conventional
PET-CT
imaging
(CT, MRI and USG)
100%
(66; 100)
100%
(66; 100)
100%
(81; 100)
19,0
(1,3; 284,2)
9
5
56%
(21; 86)
78%
(40; 97)
67%
(41; 87)
2,5
(0,6; 9,7)
FP
2
FN
4
TN
7
Statistical significance
of differences
between groups
compared *
p = 0,48
p = 0,04
-
p = 0,13
157

158
LR-
(95% CI)
DOR
(95% CI)
0,05
(0,004; 0,8)
361,0
(6,5; 20143,8)
* p-value for chi-square test (McNemar’s test) Yates corrected
0,6
(0,2; 1,3)
4,4
(0,6; 33,9)
PET-CT sensitivity in malignant tumor staging is 100% (95% CI: 66; 100), and is higher
than the sensitivity of the conventional imaging methods (CT, MRI and USG), which is 56%
(95% CI: 21; 86). That means that the probability of positive results in patients with
malignant genital tumor metastasis is 100% for PET-CT, and 56% for the conventional
imaging methods. The result is not statistically significant (p = 0.13).
PET-CT specificity in disease staging for the group with miscellaneous cancers of the
female genitals is 100% (95% CI: 66; 100), and is higher compared to the specificity of the
conventional imaging methods, which is 78% (95% CI: 40; 97). That means that for patients
with no metastasis, the probability of correct clinical staging is 100% for PET-CT, and is higher
than for the conventional imaging methods (78%). The difference is not statistically
significant (p = 0.48).
PET-CT accuracy is 100% (95% CI: 81; 100), and is higher compared with the accuracy
of the conventional imaging methods, which is 67% (95% CI: 41; 87). That means that the
probability of correct clinical staging is 100% for PET-CT, and is higher compared with the
conventional imaging methods (67%). The difference is statistically significant (p = 0.04).
The positive likelihood ratio for PET-CT is 19.0 (95% CI: 1.3; 284.2), and is higher compared
with the ratio for the conventional imaging methods, which is 2.5% (95% CI: 0.6; 9.7). For PET-
CT, the probability of positive results is 19 times higher for patients with malignant genital
tumor metastasis than for patients without such metastasis.
For the conventional methods, the probability of positive results is 2.5 times higher for
patients with malignant genital tumor metastasis than for patients without such metastasis.
The negative likelihood ratio for PET-CT is 0.05 (95% CI: 0.004; 0.8), and is higher than the
ratio for the conventional imaging methods, which is 0.6% (95% CI: 0,2; 1,3). For PET-CT, the
probability of negative results in patients with malignant genital tumor metastasis represents
5% of the probability of negative results in patients without such metastasis.
For the conventional methods, the probability of negative results in patients with
malignant genital tumor metastasis represented 60% of the probability of negative results
in patient with no such metastasis.
The diagnostic odds ratio for PET-CT in the staging of disease in patients with
miscellaneous cancers of the female genitals is 361.0 (95% CI: 6.5; 20143.8), and is higher
than the diagnostic odds ratio for the conventional imaging methods, which is 4.4 (95% CI:
0,4; 33,9).
-
-

10.4.2. Assessment of disease recurrence
Table 52 provides the count of patients with true positive, false positive, false negative or
true negative results of PET-CT tests and conventional imaging for the group diagnosed for
the purposes of disease recurrence assessment. The outcome of a conventional imaging
test for one patient was not taken into account due to an anaphylactic reaction to the
contrast medium given intravenously; a PET-CT scan for this patient gave a positive result,
and the reference test confirmed disease recurrence. For two patients, the results of
conventional tests qualified as indecisive (+/-) for the publication are considered true
positive.
Table 52.
Patients with TP, FP, FN and TN results in the group with disease recurrence assessed, PET-CT vs. conventional methods
(CT, MRI and USG)
Study
Grisaru 2004
TP
25
FP
1
PET-CT
FN
1
TN
8
TP
9
Conventional method
(CT, MRI and USG)
Table 53 presents EBM parameters of the diagnostic methods compared for the group
of patients with suspected disease recurrence.
Table 53.
EBM parameters of the diagnostic efficacy in assessing disease recurrence: PET-CT vs. conventional methods (CT, MRI
and USG)
Parameter
(95% CI)
Se
(95% CI)
Sp
(95% CI)
Acc
(95% CI)
LR+
(95% CI)
LR-
(95% CI)
Diagnostic method
Conventional imaging
PET-CT
(CT, MRI, USG)
96%
(80; 100)
89%
(52; 100)
94%
(81; 99)
8,7
(1,4; 55,0)
0,04
(0,006; 0,3)
DOR
200,0
(95% CI)
(11,2; 3576,7)
* p-value for chi-square test (McNemar’s test) Yates corrected
36%
(18; 57)
56%
(21; 86)
41%
(25; 59)
0,8
(0,3; 2,0)
1,2
(0,6; 2,2)
0,7
(0,1; 3,3)
FP
4
FN
16
TN
Statistical significance
of difference between
groups compared *
p < 0,01
p = 0,37
p < 0,01
PET-CT sensitivity in detecting disease recurrence is 96% (95% CI: 80; 100), and is higher
than the sensitivity of the conventional imaging methods (CT, MRI and USG), which is 36%
(95% CI: 18; 57). For PET-CT, the probability of positive results in patients diagnosed with
-
-
-
5
159

160
disease recurrence is 60 p.p. higher than for the conventional methods. The difference is
statistically significant in favor of PET-CT (p < 0,01).
A difference in favor of PET-CT was also observed in test specificity. PET-CT specificity is
89% (95% CI: 52; 100) and is higher than the specificity of the conventional imaging
methods, which is 56% (95% CI: 21; 86), which means that the probability of negative
results of PET-CT scanning is 89% in patients with no disease recurrence detected, which is
33 p.p. higher than for the conventional methods. The difference is not statistically
significant (p = 0.37).
PET-CT accuracy in detecting disease recurrence is 94% (95% CI: 81; 99), and is higher than
the accuracy of the conventional imaging methods (CT, MRI and USG), which is 41% (95%
CI: 25; 59). The difference is statistically significant in favor of PET-CT study (p < 0,01).
The positive likelihood ratio for PET-CT is 8.7 (95% CI: 1.4; 55.0), and is higher than the
same ratio for the conventional imaging methods, which stands at 0.8 (95% CI: 0.3; 2.0). For
PET-CT scanning, the probability of positive results in patients diagnosed with disease
recurrence is almost 9 times higher than the probability of positive results in patients with no
disease recurrence detected.
For the conventional methods, the probability of positive results in patients diagnosed
with disease recurrence represents 80% of the probability of positive results in patients with
no disease recurrence detected.
The negative likelihood ratio for PET-CT is 0.04 (95% CI: 0.006; 0.3) and is lower compared to
the ration for the conventional imaging methods, which is 1.2% (95% CI: 0,6; 2,2). For PET-CT,
the probability of negative results in patients diagnosed with disease recurrence is 4% of the
probability of negative results in patients with no disease recurrence detected.
For the conventional methods, the probability of negative results in patients diagnosed
with disease recurrence is 110% of such probability in patients with no recurrence detected.
The diagnostic odds ratio for detecting disease recurrence in the group with various
female genital cancer types is 200.0 (95% CI: 11.2; 3576.7) for PET-CT, and is higher than the
diagnostic odds ratio for the conventional imaging methods, which is 0.7 (95% CI: 0,1; 3,3).
10.4.3. Total assessment
Grisaru 2004 presented the sensitivity, specificity, and the negative and positive
likelihood ratios for PET-CT study and conventional methods (CT, MRI and USG) for both
groups of patients.
Table 54 provides patient counts for the results determining the diagnostic efficacy of
tests in the total population of patients for who T-status and disease recurrence were
assessed. One patient who had had an anaphylactic reaction to the CT contrast medium
given intravenously is left out from the results for the conventional methods; that patient

tested positive in PET-CT scanning, and the reference test confirmed disease recurrence.
Table 54.
Number of patients with TP, FP, FN and TN results, PET-CT vs. conventional methods (CT, MRI and USG)
Study
Grisaru 2004
TP
34
FP
1
PET-CT
FN
1
TN
17
TP
14
Conventional method
(CT, MRI and USG)
Table 55 presents sensitivity and specificity values as quoted by the authors of the
study, as well as some additional EBM parameters calculated for the imaging methods
compared.
Table 55.
EBM parameters of diagnostic efficacy in disease staging and disease recurrence assessment; PET-CT vs.
conventional methods (CT, MRI and USG)
Parameter
(95% CI)
Se
(95% CI)
Sp
(95% CI)
Acc
(95% CI)
LR+
(95% CI)
LR-
(95% CI)
Diagnostic method
Conventional imaging
PET-CT
(CT, MRI, USG)
97%
(85; 100)
94%
(73; 100)
96%
(87; 100)
17,5
(2,6; 117,6)
0,03
(0,004; 0,2)
DOR
578,0
(95% CI)
(34,0; 9817,0)
* p-value for chi-square test (McNemar’s test) Yates corrected
41%
(25; 59)
67%
(41; 87)
50%
(36; 64)
1,2
(0,6; 2,7)
0,9
(0,6; 1,4)
1,4
(0,4; 4,6)
FP
6
FN
20
TN
12
Statistical significance
of difference between
groups*
p < 0,01
p = 0,13
p < 0,01
PET-CT is characterized by higher sensitivity and specificity compared to the
conventional imaging methods (CT, MRI and USG) in the staging and recurrence
assessment of malignant female genital tumors.
PET-CT sensitivity is 97% (95% CI: 85; 100), and is higher compared with the sensitivity of
the conventional imaging methods (CT, MRI and USG), which is 41% (95% CI: 25; 59). That
means that the probability of positive results in patients diagnosed with malignant tumor
metastasis to genitals or patients with disease recurrence detected is 97% for PET-CT and
41% for the conventional imaging methods. The difference is statistically significant and is
56 p.p. (p < 0.01).
PET-CT specificity in disease staging and recurrence detection is 94% (95% CI: 73; 100),
-
-
-
161

and is higher compared with the specificity of the conventional imaging methods, which
stands at 67% (95% CI: 41; 87). The probability of negative results in patients with no
metastasis of malignant female genital tumors or with no disease recurrence detected is
94% for PET-CT, which is 27 p.p. higher than for the conventional imaging methods (67%).
The difference is not statistically significant (p = 0.13).
162
PET-CT accuracy is 96% (95% CI: 87; 100), and is higher compared with the accuracy of
the conventional imaging methods (CT, MRI and USG), which is 50% (95% CI: 36; 64). The
probability of correct assessment is 96% for PET-CT, which is 46 p.p. higher than for the
conventional imaging methods. The difference between the groups is not statistically
significant (p < 0.01).
Based on the data available in the study, additional parameters of diagnostic efficacy
were calculated: negative likelihood ratio, positive likelihood ratio and diagnostic odds
ratio.
The positive likelihood ratio for PET-CT is 17.5 (95% CI: 2.6; 117.6), and is higher than the ratio
for the conventional imaging methods, which is 1.2% (95% CI: 0.6; 2.7). For PET-CT, the
probability of positive results in patients diagnosed with metastasis of malignant genital
tumors or patients with disease recurrence detected is almost 17 times higher compared to
the probability of positive results in patients with no metastasis of malignant genital tumors or
disease recurrence.
For the conventional methods, the probability of positive results in patients diagnosed
with metastasis of malignant genital tumors or with disease recurrence detected is 120% of
the probability of positive results in patients with no metastasis of malignant genital tumor or
disease recurrence.
The negative likelihood ratio for PET-CT is 0.03 (95% CI: 0.004; 0.2), and is lower than the ratio
for the conventional imaging methods, which is 0.9 (95% CI: 0.6; 1.4).
For PET-CT, the probability of negative results in patients diagnosed with metastasis of
malignant genital tumors or with disease recurrence detected represented 3% of the
probability of negative results in patients with no metastasis of malignant genital tumor or
disease recurrence.
For the conventional methods, the probability of negative results in patients diagnosed
with metastasis of malignant genital tumors or with disease recurrence detected is 90% of
the probability of negative results in patients without metastasis of malignant genital tumors
or disease recurrence.
For PET-CT, the diagnostic odds ratio for clinical disease staging and recurrence
detection in the group with miscellaneous genital cancers is 578.0 (95% CI: 34.0; 9817.0),
and is higher compared with the diagnostic odds ratio for the conventional imaging
methods, which stands at 1.4 (95% CI: 0,4; 4,6).

10.5. Results
As a result of searching medical databases one primary clinical trial was found (Grisaru
2004) that compared directly the diagnostic efficacy of PET-CT vs. conventional imaging
methods (CT, MRI and ultrasonography) in the diagnostics of female genital cancer (N=53).
Positive results of scanning were verified by histopathological tests of material removed
during a surgical procedure or obtained from guided biopsy. Negative results were verified
based on long-term clinical observation and repeated diagnostic imaging.
The assessment of the diagnostic efficacy of imaging methods discussed included both
staging and detecting recurrences of disease.
The sensitivity of PET-CT diagnostics in clinical staging is higher than the sensitivity of the
conventional diagnostic imaging and stands at 100% (95% CI: 66; 100) vs. 56% (95% CI: 21; 86).
The difference is statistically insignificant (p=0.13). The specificity of PET-CT is 100% (95% CI: 66;
100), and that of CT, MRI and ultrasound scanning is 78% (95% CI: 40; 97). The difference is
statistically insignificant (p=0.48). The diagnostic accuracy of PET-CT in the primary staging of
disease is 100% (95% CI: 81; 100) and is higher than the accuracy of the conventional imaging
methods, which is 67% (95% CI: 41; 87). The difference is statistically significant (p=0.04).
The sensitivity of PET-CT in detecting disease recurrence is 96% (95% CI: 80; 100) and is higher
than the sensitivity of the conventional imaging methods, which is 36% (95% CI: 18; 57). The
difference is statistically significant, in favor of PET-CT (p

11. COMPARATIVE ANALYSIS OF PET-CT AND CT EFFICACY IN
THE DIAGNOSTICS OF OVARIAN CANCER
164
11.1. Results of primary trial search
As a result of searching through medical databases, two primary studies were found
(Hauth 2005; tab. 149, app. 18.1 and Makhija 2001; tab. 150, app. 18.1), that satisfied the
inclusion criteria and compared directly the diagnostic efficacy of PET with CT in the
assessment of ovarian cancer recurrences.
11.2. Population characteristics
Hauth 2005 is a prospective clinical trial that included 19 patients. They had taken surgeries
to have ovarian cancer with suspected recurrence removed. The median of time from
diagnosis to PET-CT scanning was one year (range: 0.5–4 years).
Makhija 2001 is a retrospective trial. The population comprised patients with ovarian or
fallopian tube adenocarcinoma recurrence confirmed in histopathological tests taken
following a surgery. Six patients had ovarian cancer, and two had fallopian tube cancer.
The initial characteristics of the subject populations is given in table 56.

Table 56.
Characteristics of population included in the analysis of PET-CT efficacy in the assessment of ovarian cancer
recurrences
* average weighted according to the size of population
11.3. Description of intervention
11.3.1. PET-CT imaging
Hauth 2005
PET-CT scanning was carried out using a Biograph TM unit (Siemens Medical Solutions). Scans
were taken 60 minutes after 350 MBq of FDG was administered. Attenuation was revised by
CT. The imaging covered whole body. PET scans were taken in 6 table positions, for 4 minutes
each. PET images were interpreted by two nuclear medicine specialists, and CT images by
tworadiologists. PET-CT images were interpreted by consensus by all the specialists
mentioned.
Makhija 2001
Parameter Hauth 2005 Makhija 2001 Total
Size of population 19 8 27
Average age (range) [years] 67 (49–80) 55 (50–73) 63,5*
Primary FIGO stage
[persons]
I IA - 1 1
II
III
IIA 1
IIC
PET-CT scanning was carried out using a prototype hybrid scanner consisting of a ECAT
ART PET unit (System CTI PET ) and a Somatom AR.SP CT unit (Siemens Medical Systems). Scans
of pelvis and abdomen were taken one hour after 6 to 8 mCi of FDG was administered
intravenously. Oral contrast was used in two patients, and dynamic intravenous injections of
contrast were given to four. Attenuation was revised by the CT component. A group of
radiologists and nuclear medicine specialists interpreted the PET-CT scans. Lesions of SUV
3
IIIA 1
IIIC
13
IV IVB 3 1 4
1
3
5
17
165

equal or higher than 2.5 were regarded malignant. The researchers interpreting PET-CT
images had access to clinical data.
166
11.3.2. Diagnostic technology compared
Hauth 2005
CT scanning was carried out using a Somatom Emotion unit (Siemens Medical Solutions).
Patients were contrasted both intravenously and orally. The image was interpreted by two
radiologists. There is no information on blinding the researchers.
Makhija 2001
CT scanning. There are no data on the way the trial was carried out, the equipment used
or the way results were evaluated.
11.3.3. Reference test
In Hauth 2005, post-operational histopathological examinations were done as reference
test in five out of eleven patients with disease recurrence. The other patients underwent 6-
months’ observation that covered all clinical data available (general examination, set of
laboratory tests including CA125 antigen, as well as PET-CT and CT scanning).
The reference test in Makhija 2001 was post-operational histopathological examination.
11.4. Findings
11.4.1. Diagnostic efficacy
The results of whole-body contrast scanning using the PET-CT technology in Hauth 2005
were as follows:
• PET-CT returned positive results in all the confirmed cases of cancer: eleven patients;
for all negative PET-CT results the reference test showed no recurrence;
• Contrast CT detected cancer in eight out of eleven positive patients; negative results
of CT were true for eight and false for three patients.
Table 57.
Number of patients with TP, FP, FN and TN results in Hauth 2005
Study
PET-CT CT
TP FP FN TN TP FP FN TN
Hauth 2005 11 0 0 8 8 0 3 8

Table 58 presents diagnostic efficacy parameters as calculated for PET-CT and CT in
detecting recurrences of ovarian cancer.
Table 58.
PET-CT and CT diagnostic efficacy in assessing ovarian cancer recurrences.
Results /
parameters
PET-CT CT
Statistical significance of
difference between groups
*
Se (95% CI) 100% (72; 100) 73% (39; 94) p = 0.25
Sp (95% CI) 100% (63; 100) 100.0% (63; 100) NS
Acc (95% CI) 100% (82; 100) 84% (60; 97) p = 0.25
LR+ (95% CI) 1725 (1.16; 255.73) 12,75 (0.84; 193.18) -
LR- (95% CI) 0.04 (0.003; 0.67) 0.31 (0.13; 0.76) -
DOR (95% CI)
391.00 (7.03;
21756.1)
41.29 (1.84; 927.50) -
* p-value for chi-square test(McNemar’s test) Yates corrected
PET-CT Sensitivity was 100% (95% CI: 72; 100), and CT sensitivity was 73% (95% CI: 39; 94).
That means that PET-CT detected correctly cancer recurrence in all cases, whereas CT
detected changes in only 73% of patients with recurrence.
The specificity of PET-CT and CT was 100% (95% CI: 63; 100), which means that for all the
patients with no cancer recurrence the result was negative.
PET-CT accuracy was 100% (95% CI: 82; 100), which means that all the patients were
diagnosed correctly. The accuracy of CT was 84% (95% CI: 60; 97), which means that
diagnosis was correct for 84% patients.
Group differences for the above-mentioned parameters had no statistical significance.
The positive likelihood ratio was calculated for PET-CT at 17.25 (95% CI: 1,16; 255,73), so the
probability of positive results in patients with recurrence is 17.25 times higher than for patients
with no recurrence. The positive likelihood ratio was calculated for CT at 12.75 (95% CI: 0.84;
193.18), which means that the probability of positive results in patients with recurrence is 12.75
times higher than the likelihood for patients with no recurrence.
The negative likelihood ratio was 0.04 for PET-CT (95% CI: 0.003; 0.67), which means that the
probability of negative results in patients with ovarian cancer recurrence represents 0.04 of
the likelihood for patients with no recurrence. The negative likelihood ratio was 0.31 for CT
(95% CI: 0.13; 0.76), so the probability of positive results in patients with cancer recurrence
represents 0.31 of the likelihood for patients with no recurrence.
167

168
The diagnostic odds ratio as calculated for PET-CT is 391.00 (95% CI: 7,03; 21756,1). That
means that the probability of positive results is 391 times higher in patients with cancer
recurrence than the probability in the patient group with no recurrence detected using the
reference test. The diagnostic odds ratio for CT is 41.29 (95% CI: 1.84; 927.50), which means
that the probability of positive results in patients diagnosed with cancer recurrence by the
reference test is 41.29 times higher than the probability in patients with no recurrence.
CT scanning detected ovarian cancer in 12 locations, whereas PET-CT in 18. In 4 out of 6
cases of local recurrence or involvement of lymph nodes in the pelvis detected by PET-CT, CT
returned negative results. Moreover, CT failed to detect metastasis located in the thoracic
wall or diaphragm, which were detected by PET-CT.
Table 59.
Location of lesions detected by PET-CT and CT scanning, Hauth 2005
Location of tumor PET-CT CT
Local recurrence 3 1
Metastasis to pelvic lymph
nodes
Metastasis to periaortic,
mediastinal and neck
lymph nodes
3 1
6 6
Remote metastasis 4 2
Infiltration of the peritoneum 2 2
Total 18 12
In Makhija 2001, PET-CT detected cancer in five patients, while CT detected ovarian
cancer in one patient and in another it accidentally detected a liver cyst, unrelated to
cancer.
The reference test found carcinoma recurrences in all the patients examined. PET-CT failed
to detect three out of eight cases of cancer, while CT failed to detect seven out of eight
recurrences.
Table 60.
Number of patients with TP, FP, FN and TN results in Makhija 2001
Study
PET-CT CT
TP FP FN TN TP FP FN TN

Makhija 2001 5 0 3 0 1 0 7 0
The sensitivity of the diagnostic tests was calculated on the basis of the number of
correctly and incorrectly diagnosed patients.
Table 61.
Sensitivity of PET-CT and CT in Makhija 2001
Parameter PET-CT CT
Statistical significance of
difference between
groups *
Se (95% CI) 63% (24; 91) 13% (0; 53) p = 0,22
* p-value for chi-square test (McNemar’s test) Yates corrected
PET-CT sensitivity was 63% (95% CI: 24; 91), and CT sensitivity was 13% (95% CI: 0; 53), which
means that PET-CT identified 63% of the patients with carcinoma, and CT merely 13%.
According to McNemar’s test, the difference in sensitivity between PET-CT and CT, was not
statistically significant (p = 0,22) due to the small number size of subject population.
Graph 22 presents the results of sensitivity meta-analysis (the only meta-analyzable
parameter in view of the data deficiency of Makhija 2001).
Graph 22.
Meta-analysis of PET-CT sensitivity in detecting ovarian cancer recurrence.
Hauth 2005
Makhija 2001 0.63 (0.24, 0.91)
Result of meta-nalysis 0.84 (0.60, 0.97)
0.0 0.2 0.4 0.6 0.8 1.0
Sensitivity (95% range of confidence)
The result of PET-CT sensitivity meta-analysis was 84% (95% CI: 60; 97), which means that
84% of patients with cancer recurrence were diagnosed correctly using PET-CT.
1.00 (0.72, 1.00)
169

Graph 23.
Meta-analysis of CT sensitivity in detecting ovarian cancer recurrence
170
Hauth 2005 0.73 (0.39, 0.94)
Makhija 2001 0.13 (0.00, 0.53)
Result of metanalysis
The result of CT sensitivity meta-analysis was 47% (95% CI: 24; 71), which means that 47% of
patients with cancer recurrence were diagnosed correctly using CT.
Table 62 lists meta-analysis results for PET-CT and CT sensitivity.
Table 62.
Meta-analysis of PET-CT and CT sensitivity in detecting ovarian cancer recurrence
Results/ parameters PET-CT CT
Se (95% CI) 84% (60; 97) 47% (24; 71)
The sensitivity of PET-CT in the diagnostics of ovarian cancer recurrences is 84% (95% CI: 60;
97), and the sensitivity of CT is 47% (95% CI: 24; 71).
Clearly, the sensitivity of PET-CT in diagnosing ovarian cancer recurrence is significantly
higher than the sensitivity of CT. However, the high heterogeneity of test results and the small
size of subject populations make the final results less reliable.
11.4.2. Safety
None of the trials included in this study provides information on the safety of the diagnostic
procedures used.
0.0 0.2 0.4 0.6 0.8 1.0
Sensitivity (95% range of confidence)
0.47 (0.24, 0.71)

11.5. Results
As a result of searching medical databases two primary clinical trials were found (Hauth
2005 and Makhija 2001) that compared directly the diagnostic efficacy of PET-CT with CT in
the assessment of ovarian cancer recurrences (N=27). The reference test was
histopathological examination or, if histopathological examination was inaccessible, clinical
follow-up.
PET-CT is characterized by higher sensitivity than contrast CT. The sensitivity of PET-CT is 84%
(95% CI: 60; 97) and that of CT is 47% (95% CI: 24; 71).
The specificity of these methods, evaluated only in Hauth 2005, was 100% for both PET-CT
and CT (95% CI: 63; 100). That implies that a negative result was returned by the imaging
methods under analysis for each patient with no cancer recurrence.
The data provided testify to the superiority of PET-CT diagnostics over contrast CT imaging.
The small size of population in the primary studies limits the reliability of the analysis.
171

12. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS.
TRADITIONAL IMAGING METHODS IN THYROID CANCER
DIAGNOSTICS
172
12.1. Comparative analysis of the clinical efficacy of pet-ct vs.
traditional imaging methods (ct/mri and i131whole-body
scintigraphy) in the diagnostics of thyroid cancer
recurrences
12.1.1. Results of primary trial search
As a result of searching medical databases, two original trials (Zimmer 2003; tab. 153, app.
18.1, Nahas 2005; tab. 151, zał. 18.1) were found that compare the diagnostic efficacy of PET-
CT with that of other imaging methods (CT/MRI and whole-body scintigraphy using I 131) in the
diagnostics of thyroid cancer recurrence. Zimmer 2003 was a prospective trial, whereas
Nahas 2005 involved a retrospective analysis of the impact of additional PET-CT findings on
how earlier treatment plans were revised for patients under observation for thyroid cancer
recurrence.
12.1.2. Population characteristics
The subjects of both studies were adult patients with thyroid cancer confirmed
histopathologically. All patients were under observation following prior standard treatment
(thyreoidectomy and ablation of thyroid gland using iodine 131). The majority of patients
(88%) in both Zimmer 2003 and Nahas 2005 had been diagnosed with papillary carcinoma; in
Zimmer 2003, additionally patients with follicular and medullary thyroid cancer took part.
Cancer recurrence was suspected in all the participants of Zimmer 2003 based on the above-
limit level of thyroglobulin or activity of calcitonin in blood, in spite of negative results of
whole-body I 131 scintigraphy. The top limit was: for thyroglobulin in blood - 1.0 ng/mL in
patients treated with suppressive doses of thyroid gland hormone; or 10 ng/mL when no
suppressive doses of thyroid gland hormone were applied, and for calcitonin activity in
plasma – more than 4 pg/ml.
In Nahas 2005,the authors give no limit values for recurrence markers. The suspicion of
recurrence was determined based on overall clinical picture and extra tests.
Table 63 shows the initial characteristics of the subjects of each trial.

Table 63.
Initial characteristics of subjects of each study
Parameters Zimmer 2003 Nahas 2005
Size of population 8 33
Median age (range)
53.6
(SD 20,7)
43.8
(12–72)
Male proportion 12.5% 39.4%
Patients treated by surgery due
to thyroid cancer recurrence
Average number of operations
per patient before PET-CT
examination
Patients testing negative in
thyroid scintigraphy
Patients treated with suppressive
doses of thyroid gland hormones
Average concentration of
thyroglobulin in plasma, ng/ml
(from-to)
no data 66.7%
no data 1.5
no data 75.7%
no data 67%
95.2*
(2.5–747)
70.0**
(1.2–629)
* value calculated for 7 patients with various thyroid gland cancer types; a single patient with medullary thyroid
cancer was excluded
** value calculated for 26 patients; in 5 patients thyroglobulin was not markable, in 2 thyroglobulin antibodies were
present
The size of population in Zimmer 2003 was 8, and in Nahas 2005 – 33. The median age in
Zimmer 2003 was slightly higher than in Nahas 2005: 53.6 (SD 20.7) vs. 43.8 (between 12 and
72). The male proportion in Zimmer 2003 was 12.5%, and in Nahas 2005 it was 39.4%. In Nahas
2005, 67 % of patients were receiving suppressive doses of thyroid hormone when they took
PET-CT tests, whereas Zimmer 2003 informs that all the patients examined had attained
euthyreosis.
12.1.3. Description of intervention
12.1.3.1 PET-CT imaging
In Zimmer 2003, PET-CT imaging was done with a prototype PET-CT scanner consisting of an
AR.SP spiral CT scanner (Siemens Medical Systems, Erlanger, Germany) and an ECAT ART PET
scanner (CTI, Knoxville, TN). A Discovery LS unit made by the General Electric Company was
used in Nahas 2005.
In both studies, deoxy-glucose marked with radioactive F18 fluorine was used as a marker.
In Zimmer 2003, the activity of the radiomarker was 260 MBq, and the examination covered
173

the neck and the chest. No data on the activity of the marker or the scope of the tests are
provided in Nahas 2005.
174
Tests were carried out one hour after FDG was given orally. No iodized contrast medium
was administered intravenously in either of the trials. CT scanning was followed by PET. Two-
dimensional (2D) visualization was used in PET examinations.
Table 64 provides detailed information on the type of scanner and method used.
Table 64.
Description of scanner and method used for PET-CT examination.
Study
Zimmer 2003
Type of PET-CT
scanner
Prototype
scanner
Nahas 2005 Discovery LS
Manufactrer of
PET-CT scanner
-
General
Electric
Type of
radiomarker
FDG
intravenously
FDG
intravenously
Coverage
Neck and
chest
Activity of
radiomarker
[MBq]
260
No data No data
In both cases PET-CT tests were evaluated by specialists blinded to the patients' clinical
condition and other test results. A team consisting of nuclear medicine and radiology
specialists determined the results by consensus. The marker uptake by thyroid gland
parenchyma was assessed visually and quantitatively.
In Zimmer 2003, the patients who tested negative in PET-CT examination were under
observation for disease recurrence; serial follow-up PET-CT scans and who-body scintigraphy
were done.
The authors of the studies do not report on the duration of observation.
12.1.3.2 Diagnostic technologies compared
12.1.3.2.1 CT/MRI
Zimmer 2003 provides no data on the procedures of computer tomography (CT) or
magnetic resonance imaging (MRI), or on the type of scanner used or time interval to the
PET-CT study.
12.1.3.2.2 I131 whole-body scintigraphy (I131 WBS)
Neither of the studies provides details of the method of I 131 whole-body scintigraphy (I 131
WBS) or the time interval between this tests and PET-CT.

12.1.3.3 Reference Test
In both trials, positive results of PET-CT studies were verified based on histopathological tests
of material from surgeries. 3 patients (37.5%) in Zimmer 2003, and 20 (61%) patients in Nahas
2005 had had a surgery.
The remaining patients were under long-term clinical observation to confirm negative
results of PET-CT; they had I 131 whole-body scintigraphy and PET-CT examinations. Neither of
the trials gives details of the duration of observation for the cohort examined.
12.1.4. Findings
In Zimmer 2003, the authors evaluated the diagnostic efficacy of PET-CT in detecting
disease recurrences in a group of eight patients with thyroid cancer confirmed
histopathologically. For four patients, PET-CT examinations were preceded by CT imaging that
revealed a soft tissues asymmetry, which suggested disease recurrence.
In three patients with papillary thyroid cancer and one patient with medullary thyroid
cancer, PET-CT detected eleven focuses of heightened marker uptake. Seven focuses of
heightened marker uptake were identified in three patients, for whom postoperative material
was verified histopathologically. One patient had not been operated on but qualified for
chemotherapy based on PET-CT scanning.
Features indicative of cancer recurrence were found in the postoperative material of six
out of eight lesions. The authors give no data on the presence or absence of recurrence in
the remaining two lesions.
No pathological lesions were found by PET-CT in four other patients. The results were
confirmed through long-term clinical observation.
Table 65 specifies the number of patients with true positive, false positive, false negative
and true negative results of PET-CT and CT/MRI in a group of patients with suspected thyroid
cancer recurrence in Zimmer 2003. The table leaves out one patient who could not be
CT/MRI-scanned.
Table 65.
Number of patients with TP, FP, FN and TN results in Zimmer 2003, PET-CT vs. CT/MRI
Study
PET-CT CT/MRI
TP FP FN TN TP FP FN TN
Zimmer 2003 4 0 0 3 2 2 2 1
175

176
The EBM parameters that characterize the diagnostic efficacy in detecting thyroid cancer
recurrence are presented in Table 66.
Table 66.
EBM parameters of diagnostic efficacy in detecting thyroid cancer recurrence, PET-CT vs. CT/MRI
Parameter
Se
(95% CI)
Sp
(95% CI)
LR+
(95% CI)
LR-
(95% CI)
Acc
(95% CI)
DOR
(95% CI)
Diagnostic method
PET-CT CT/MRI
100%
(40; 100)
100%
(29; 100)
7,2
(0,5; 97,8)
0,1
(0,008; 1,6)
100%
(59; 100)
63,0
(1,0; 4042,1)
* p-value for chi-square test (McNemar’s test) Yates corrected
50%
(7; 93)
33%
(1; 91)
0,7
(0,2; 2,7)
1,5
(0,2; 9,8)
43%
(10; 82)
0,5
(0,02; 11,1)
Statistical
significance of
difference between
groups compared *
p = 0,48
p = 0,48
-
-
p = 0,13
PET-CT sensitivity in detecting the thyroid cancer recurrence is 100% (95% CI: 40; 100) and is
higher than CT/MRI sensitivity, which is 50% (95% CI: 7; 93). That means that the probability of
positive results for patients with thyroid cancer recurrence is twice as high for PET-CT than for
CT/MRI, and stands at 100%. The difference is not statistically significant (p = 0.48).
PET-CT specificity in detecting thyroid cancer recurrence is 100% (95% CI: 29; 100) and is
higher than the specificity of whole-body scintigraphy, which is 33% (95% CI: 1; 91). That
means that the probability of negative results for patients without thyroid cancer recurrence
is 100% for PET-CT, and is three times higher than the probability of negative results for CT/MRI.
The difference is not statistically significant (p = 0.48).
The positive likelihood ratio of PET-CT is 7.2 (95% CI: 0.5; 97.8) and is higher than that of
CT/MRI- 0.7 (95% CI: 0.2; 2.7). The probability of positive results of PET-CT for patients with
thyroid cancer recurrence is more than 7 times higher than the probability of positive results
for patient with no recurrence. In the case of CT/MRI, the likelihood of positive results of PET-CT
for patients with thyroid cancer recurrence represents 70% of the likelihood for patients with
no thyroid cancer recurrence.
The negative likelihood ratio of PET-CT is 0.1 (95% CI: 0.008; 1.6) and is lower than that of
CT/MRI, which is 1.5 (95% CI: 0.2; 9.8). In the case of PET-CT, the likelihood of negative result for
patients with thyroid cancer recurrence represents 10% of the likelihood of negative results for
-

patients with no recurrence. In the case of CT/MRI, the likelihood of negative results for
patients with thyroid cancer recurrence is 150% of the likelihood for patients with no cancer
recurrence.
The accuracy of PET-CT in detecting thyroid cancer recurrence is 100% (95% CI: 59; 100)
and is higher than CT/MRI accuracy, which is 43% (95% CI: 10; 82). The proportion of people
(both with and without the disease) diagnosed correctly by PET-CT is 100% and more than
twice as high as for CT/MRI; however, the difference observed as evaluated using
McNemar’s test is not statistically significant (p = 0.13).
The diagnostic odds ratio for PET-CT is 63.0 (95% CI: 1.0; 4042.1), and is higher than the odds
ratio for CT/MRI, which is 0.5 (95% CI: 0.02; 11.1). That means that the probability of thyroid
cancer for patients with positive PET-CT results is 63 times higher than the probability for
patients with negative results. However, the probability of positive CT/MRI results represents
50% of the probability for patients with negative result of CT/MRI imaging.
PET-CT efficacy in detecting thyroid cancer recurrence was compared to iodine 131
whole-body scintigraphy in Zimmer 2003 and Nahas 2005. Zimmer 2003 included patients with
negative results of I 131 whole-body scintigraphy and raised concentration level of cancer
markers (thyroglobulin, calcitonin) in blood serum. In Nahas 2005, serial imaging and
biochemical test were done for all the patients at the follow-up stage of standard cancer
treatment. 20 subjects (61%) of that trial were classified based on the overall clinical picture
and additional examinations. Postoperative material was verified by an experienced
histopathologist. 36 anatomical locations were identified and assessed by standard
histopathological tests. They were located mainly in the thyroid bed and lateral neck
neighborhood. The authors provide results of histopathological verification of each lesion for
PET-CT only, without specifying their scintigraphic characteristics, therefore, for the purposes
of this analysis, true positive, false positive, false negative and true negative results are
presented for each patient.
The number of patients assigned to each group in both studies included is presented in the
Table 67.
Table 67.
Number of patients with TP, FP, FN and TN results in both studies, PET-CT vs. I 131 whole-body scintigraphy
Study
PET-CT I 131 whole-body scintigraphy
TP FP FN TN TP FP FN TN
Zimmer 2003 4 0 0 4 0 0 4 4
177

178
Nahas 2005 16 0 3 1 4 0 15 1
Table 68 presents sensitivity values calculated for each study (PET-CT and I 131 whole-body
scintigraphy).
Table 68.
Sensitivity calculated for each study, PET-CT vs I 131 whole-body scintigraphy
Study
Se
(95% CI)
PET-CT I 131 whole-body scintigraphy
Zimmer 2003 100% 0%
Nahas 2005
84%
(60; 97)
21%
(6; 46)
The sensitivity of PET-CT in detecting thyroid cancer recurrence is bigger than the sensitivity
of the whole-body scintigraphy in both studies. In view of the type of data available, the
confidence interval for scintigraphy findings in Zimmer 2003 cannot be calculated.
Graph 24 illustrates a meta-analysis of PET-CT sensitivity in detecting thyroid cancer
recurrence in both studies included.
Graph 24.
Meta-analysis of PET-CT sensitivity in detecting thyroid cancer recurrence
Nahas 2005 0.84 (0.60; 0.97)
Zimmer 2003 1.00 (0.60, 1.00)
Result of meta-analysis [fixed] 0.87 (0.66; 0.97)
0,0 0,2 0,4 0,6 0,8 1,0
Sensitivity (95% confidence interval)

The sensitivity of PET-CT is calculated at 87% (95% CI: 66; 97). The probability of positive
results of PET-CT is 87% for patients with recurrence.
Table 69 presents the data accumulated with respect to the sensitivity of the methods
compared in recurrence evaluation.
Table 69.
Comparison of sensitivity in evaluating recurrence, PET-CT vs I 131 whole-body scintigraphy
Study
Se
(95% CI)
Diagnostic method
PET-CT I 131 whole-body scintigraphy
87%
(66; 97)
0–21%
The sensitivity of PET-CT is 87% (95% CI: 66; 97). The probability of positive results with PET-CT
scanning is 87% for patients with disease recurrence. Calculated for each of the studies
included separately, the sensitivity of I 131 whole-body scintigraphy ranges from 0 to 20%.
Table 70 presents specificity values for the methods compared (PET-CT vs. I 131 whole-body
scintigraphy), as calculated separately for both studies included.
Table 70.
Comparison of specificity, PET-CT vs. I 131 whole-body scintigraphy
study
Zimmer 2003
Nahas 2005
Sp
(95% CI)
PET-CT I 131 whole-body scintigraphy
100%
(40; 100)
100%
(3; 100)
100%
(40; 100)
100%
(3; 100)
The specificity of PET-CT in detecting thyroid cancer recurrence is in both studies
comparable with the specificity of whole-body scintigraphy.
For both imaging technologies, the probability of negative results for patients with no
thyroid cancer recurrence is 100%.
Table 71 presents diagnostic accuracy values for the methods compared (PET-CT vs. I 131
whole-body scintigraphy), as calculated separately for both studies included.
179

Table 71.
comparison of diagnostic accuracy, PET-CT vs. I 131 whole-body scintigraphy
180
Study
Zimmer 2003
Nahas 2005
Acc
(95% CI)
PET-CT I 131 whole-body scintigraphy
100%
(63; 100)
85%
(62; 97)
50%
(16; 84)
25%
(9; 49)
The diagnostic accuracy of PET-CT is in both cases higher than the diagnostic accuracy of
whole-body scintigraphy.
The diagnostic accuracy of PET-CT in evaluating cancer recurrence as calculated by
meta-analysis of two trials is presented in graph 25.
Graph 25.
Meta-analysis of diagnostic accuracy of PET-CT
Zimmer 2003 1.00 (0.63, 1.00)
Nahas 2005 0.85 (0.62, 0.97)
Meta-analysis result [mixed]
0,5 0,6 0,7 0,8 0,9 1,0
Diagnostic accuracy (95% confidence range)
Graph 26 illustrates a meta-analysis of the diagnostic accuracy of I 131 whole-body
scintigraphy in detecting thyroid cancer recurrence.
0.89 (0.75, 0.97)

Graph 26.
Meta-analysis of diagnostic accuracy of I 131 whole-body scintigraphy
Zimmer 2003 0.50 (0.16; 0.84)
Nahas 2005 0.25 (0.09; 0.49)
Meta-analysis result
[fixed]
0,0 0,3 0,6 0,9
Table 72 presents the diagnostic accuracy of the methods compared (PET-CT vs. I 131
whole-body scintigraphy) calculated by meta-analysis of data provided in both trials.
Table 72.
Diagnostic accuracy in evaluating disease recurrence, PET-CT vs. I 131 whole-body scintigraphy
Test
Acc
(95% CI)
Diagnostic result (95% confidence interval)
Diagnostic method
PET-CT I 131 whole-body scintigraphy
89%
(75; 97)
33%
(18; 50)
The meta-analyzed diagnostic accuracy of PET-CT in detecting thyroid cancer recurrence
is 89% (95% CI: 75; 97) and is higher than the accuracy of scintigraphy, which is 33% (95% CI:
18; 50). The proportion of people (both of sick and healthy) diagnosed correctly is approx. 56
pp. higher for PET-CT than for I 131 whole-body scintigraphy.
Table 73 presents other EBM parameters that characterize the diagnostic efficacy of the
imaging methods compared (PET-CT vs. I 131 whole-body scintigraphy), as calculated by
meta-analysis of data from both trials.
0.33 (0.18\; 0.50)
181

Table 73.
EBM parameters of diagnostic efficacy of imaging methods compared, PET-CT vs I 131 whole-body scintigraphy
182
Parameters
LR+
(95% CI)
LR-
(95% CI)
DOR
(95% CI)
Diagnostic method
PET-CT I 131 whole-body scintigraphy
5.2
(0.9; 30.9)
0.2
(0.1; 0.6)
28.6
(2.1; 395.7)
1.4
(0.2; 95)
0.9
(0.6; 1.4)
1.6
(0.14; 17.7)
The positive likelihood ratio for PET-CT is 5.2 (95% CI: 0.9; 30.9), and is higher than the ratio
for I 131 whole-body scintigraphy, which is 1.4 (95% CI: 0.2; 9.5). The probability of positive PET-
CT test results for a patient with thyroid cancer recurrence is 5 times higher than the likelihood
of positive results for a patient with no such recurrence. For scintigraphy, the likelihood of
positive results is almost 1.5 times higher for patients with thyroid cancer recurrence than for
patients without cancer recurrence.
The negative likelihood ratio calculated for PET-CT is 0.2 (95% CI: 0.1; 0.6), and is lower than
the ratio for whole-body scintigraphy, which is 0.9 (95% CI: 0.6; 1.4). With PET-CT, the
probability of negative results for patients diagnosed with thyroid cancer recurrence
represents 20% of the probability for patients without cancer. With scintigraphy, the
probability of negative results for patients diagnosed with thyroid cancer represents 90% of
the probability for patients without thyroid cancer.
The diagnostic odds ratio for PET-CT is 28.6 (95% CI: 2.1; 395.7), and is higher than the ratio
for whole-body scintigraphy, which is 1.6 (95% CI: 0.14; 17.7). That means that the probability
of cancer in patients testing positive with PET-CT is more than 28 times higher than the
probability for patients testing negative. The probability of thyroid cancer in patients testing
positive with PET-CT is more than 1.5 times higher than the probability for patients testing
negative in I 131 whole-body scintigraphy tests.
12.1.4.1 Safety
The authors of the studies included do not provide data on undesirable effects of the use
of PET-CT imaging in the trial population.
12.1.5. Impact on therapy
The authors of Nahas 2005 analyzed the impact of PET-CT findings on the previous
therapeutic policy for 33 patients who were under observation following standard treatment

of papillary thyroid cancer. Physical examination of the head and neck was done
repeatedly, with special emphasis on palpation, examination of vocal cords flexibility and
examination of cranial nerves in order to detect possible recurrences.
PET-CT tests caused previous treatment plans to be revised for 13 patients, and confirmed
the adopted treatment plans for 9 patients. In total, for 22 patients (67%) PET-CT yielded
additional information that influenced their therapy. The authors do not specify what revisions
in treatment resulted from PET-CT findings.
12.1.6. Results
As a result of searching through medical databases two primary clinical studies were found
(Zimmer 2003, Nahas 2005), in which PET-CT was compared to conventional diagnostics
(CT/MRI and iodine 131 whole-body scintigraphy - WBS) in detecting thyroid cancer (N = 41).
The imaging methods compared were verified based on histopathological tests, while for
negative results verification was based on long-term clinical observation and a series of
diagnostic imaging.
In detecting recurrences of thyroid cancer, the sensitivity of PET-CT is 100% (95% CI: 40; 100),
i.e. twice the sensitivity of CT/MRI, 50% (95% CI: 7; 93). The difference is not statistically
significant (p = 0.48). In detecting recurrences of thyroid cancer, PET-CT is characterized by a
higher specificity than CT and MRI. The calculated values were 100% (95% CI: 29; 100) vs. 33%
(95% CI: 1; 91) respectively. The difference is not statistically significant (p = 0.48). The
diagnostic accuracy of PET-CT is higher than that of CT/MRI, the values being 100% (95% CI:
59; 100) vs. 43% (95% CI: 10; 82) respectively. The difference is not statistically significant (p =
0.13).
Based on a comparison of PET-CT with iodine 131 whole body scintigraphy (I 131 WBS), the
imaging sensitivity of PET-CT is higher than that of scintigraphy. The established value is 87%
(95% CI: 66; 97) for PET-CT, but for I 131 WBS it is 0 and 21%. In detecting thyroid cancer
recurrences, specificity is identical for PET-CT and whole-body scintigraphy and stands at
100%. Similarly, in detecting recurrences of thyroid cancer, the diagnostic accuracy of PET-CT
is 89% (95% CI: 75; 97) and is higher than that of I 131 WBS, which stands at 33% (95% CI: 18; 50).
In one of the studies included, the authors reported that PET-CT scanning supported early
revisions of treatment policies in 22 patients (67%). These patients were under observation
following standard treatment of thyroid cancer. Additionally, in some patients, the adopted
treatment policy was confirmed by the data collected from PET-CT scanning.
In summary, PET-CT is characterized by a higher diagnostic efficacy in detecting
recurrences of thyroid cancer than convectional imaging methods.
183

184
12.2. Comparative efficacy analysis of f pet-ct vs. traditional
imaging methods (CT, I131 whole-body scintigraphy and
USG) in the staging of differentiated thyroid cancer
12.2.1. Results of primary trial search
As a result of searching medical databases, one primary prospective clinical study was
found (Freudenberg 2004; tab. 152, app. 18.1), which compared the diagnostic efficacy of
PET-CT with other imaging methods such as X-ray CT, I 131 whole-body scintigraphy and
ultrasound examination) in the primary staging of differentiated thyroid cancer.
12.2.2. Population characteristics
The subjects in Freudenberg 2004 were twelve patients with differentiated thyroid cancer,
who had been qualified for ablation of thyroid gland with iodine 131 . The mean age of the
patients was 59 (ranging from 31 to 76); men represented 58.3% of the population. Three of
them had been diagnosed histopathologically with follicular thyroid cancer, nine with
papillary thyroid cancer. Eleven patients were examined at the postoperative stage following
thyroidectomy under maximum TSH stimulation (the average activity of hormone in blood
was 52 mU/l, SD 21). One patient, in whom lung metastasis had been detected, was
examined after exogenous stimulation with human TSH. The level of urinary secretion of iodine
was found to be within the physiological limits in all the patients (128 µg/l, SD 50). In six
patients, thyroglobulin concentration in blood was high; none of them was diagnosed with a
high concentration level of thyroid antibodies.
Table 74 shows the initial characteristics of the subjects.
Table 74.
Initial characteristics of patients examined
Parameter Freudenberg 2004
Size of population 12
Median age (from - to)
59
(31–76)
Male proportion 58.3%
Patients after thyroidectomy 100%
Patients with high concentration level of
thyroglobulin
50%

Concentration of thyroglobulin in blood serum,
ng/ml (fro - to)
Patients diagnosed under maximum TSH
stimulation
Patients with pT1 / pT2 / pT3 / pT4** features
according to the AJCC classification
279*
(0.4–122)
91.6%
0/33%/17%/50%
* Value calculated for 11 patients
** pT1 – tumor

5 times or more was deemed to indicate a tumor or persistent thyroid tissue. This criterion was
confirmed histopathologically in 6 cases (for 69 lesions).
186
12.2.3.2 Diagnostic technology compared
The authors report that all the diagnostic imaging to stage the disease was executed
within a two-week period. Two experienced radiologists interpreted the findings and set the
results via consensus.
12.2.3.2.1 Computer tomography
Computer tomography scans were executed in a standard way; no iodized contrast
medium was administered intravenously. The authors provide no details of the type of
scanner.
12.2.3.2.2 I131 whole-body scintigraphy
High-dose I 131 whole-body scintigraphy (I131 WBS) was done using a two-head gamma
camera. A Bodyscan unit manufactured by Siemens (Erlangen, Germany) was used in the
tests. Examination was carried out within 5–8 days after iodine 131 was administered;
radiomarker activity was 3000 MBq.
12.2.3.2.3 Ultrasound examination of the neck
Ultrasound Sonoline Elegra scanner (Siemens, Erlangen, Germany) was used for ultrasound
examinations. The Görgesa criteria, which cover the Solbiati-Index (relation of the biggest to
the smallest node size) were applied to stage node involvement, to determine the internal
structure of the node and vascularization.
12.2.3.3 Reference test
Histopathological test was used to validate the results for six lesions (8.6%). Wherever such
data were not available, a team of specialists (two of each: radiologists and nuclear
medicine doctors) worked out a consensus based on all the clinical data available as well as
results of diagnostic imaging (including results of I 131 WBS and USG), for each patient
separately, with respect to the presence or absence of disease, as well as the number and
location of changes.
12.2.4. Findings
Freudenberg 2004 presents efficacy details of the imaging methods compared, with
respect to disease staging. The number of lesions was determined in each location, and the
diagnostic efficacy was evaluated versus the reference method.
Table 76 gives the number of lesions detected with the use of each imaging method,
along with the results of test diagnostic efficiency evaluation.

Table 76.
Number of lesions detected with the imaging methods compared vs. the reference test for each feature of the TNM
staging system.
Parameter
Primary
tumor (T)
Metastasis to
lymph nodes
(N)
Distant
metastasis
(M)
I 124 PET-CT I 131 WBS CT USG
TP FP FN TN TP FP FN TN TP FP FN TN TP FP FN TN
17 0 0 - 17 0 0 - 6 1 11 - 8 0 9 - 17
6 0 0 - 5 0 1 - 3 1 3 - 2 0 4 - 6
46 1 0 - 35 2 11 - 30 2 16 - - - - - 46
Total 69 1 0 - 57 2 12 - 39 4 30 - - - - - 69
* Re – reference method
Based on data available, the sensitivity of each imaging method in lesion staging was
calculated for individual features and for features total. The data are compiled in Table 77.
Table 77
Diagnostic sensitivity in lesion staging for each feature of the TNM system: I 124 PET-CT vs. traditional methods (CT, I 131
WBS, USG)
Imaging
method
I 124 PET-CT
I 131 WBS
CT
USG
Diagnostic sensitivity in lesions staging in individual
locations (95% CI)
T N M
100%
(80; 100)
100%
(80; 100)
35%
(14; 62)
47%
(23; 72)
100%
(54; 100)
83%
(36; 100)
50%
(12; 88)
33%
(4; 78)
* p-value for the chi-square (McNemar’s) test Yates corrected
100%
(92; 100)
76%
(61; 87)
65%
(50; 79)
-
Diagnostic
sensitivity in
lesion staging
irrespective of
location
100%
(94; 100)
83%
(72; 91)
57%
(44; 68)
43%
(23; 66)
Re
*
Statistic
significance of
difference:
PET-CT vs.
method
compared *
(lesion staging
irrespective of
location)
-
p < 0,01
p < 0,01
p < 0,01
The sensitivity of I 124 PET-CT in T-staging is 100% (95% CI: 80; 100), and is the same for I 131 WBS.
The probability of detecting a primary tumor is 100% for I 124 PET-CT, and is higher than that for
CT and USG; the sensitivity of these imaging methods is 35% (95% CI: 14; 62) and 47% (95% CI:
23; 72) respectively.
The sensitivity of I 124 PET-CT in N-staging is 100% (95% CI: 54; 100), and is higher than the
sensitivity of traditional methods; the sensitivity of I 131 WBS, CT and USG is 83%(95% CI: 36; 100),
50% (95% CI: 12; 88) and 33% (95% CI: 4; 78) respectively. That means that the likelihood of in
187

detecting lesions in this location is 100% with I 124 PET-CT, while for I 131 WBS, CT and USG the
values are 83%, 50% and 33% respectively.
188
I 124 PET-CT is characterized by higher sensitivity in detecting distant metastasis than I 131 WBS
or USG; the likelihood of detecting distant metastasis using I 124 PET-CT is 100% (95% CI: 92; 100),
whereas for I 131 WBS and CT, sensitivity is 76% (95% CI: 61; 87) and 65% (95% CI: 50; 79)
respectively.
Another finding was that the combined sensitivity of I 124 PET-CT was higher in comparison to
the traditional methods (I 131 WBS, CT and USG) in thyroid cancer staging. The likelihood of
detecting a reference test-validated lesion, irrespective of location, is 100%(95% CI: 94; 100)
with I 124 PET-CT, and is higher than with I 131 WBS, CT and USG; the sensitivity values calculated
for these methods are: 83% (95% CI: 72; 91), 57% (95% CI: 44; 68) and 43% (95% CI: 23; 66)
respectively. The differences between PET-CT and each of the methods compared are
statistically significant (p < 0.01; McNemar's test).
12.2.4.1 Safety
The study provides no information on any undesirable effects of PET-CT imaging in the cohort.
12.2.5. Results
As a result of searching through medical databases, one primary prospective trial was
found (Freudenberg 2004) that compared the diagnostic efficacy of I 124 PET-CT imaging with
convectional diagnostic methods (CT, I 131 whole-body scintiscanning and ultrasound
scanning) in the staging of thyroid cancer (N = 12). All tests were verified based on
histopathological diagnostics and through formal consensus based on diagnostic imaging
results.
In tumor staging (T-status), the sensitivity of I 124 PET-CT is 100% (95% CI: 80; 100), and is the
same as the sensitivity of I 131 whole-body scintigraphy (I 131 WBS), but higher than the sensitivity
of CT and ultrasound scanning, for which the values are 35% (95% CI: 14; 62) and 47% (95% CI:
23; 72) respectively.
In node involvement staging (N-status), I 124 PET-CT proved to be the most sensitive. The
values are: 100% for PET-CT (95% CI: 54; 100), 83% for I 131 WBS (95% CI: 36; 100), 50% for CT (95%
CI: 12; 88) and 33% for ultrasonography (95% CI: 4; 78).
In distant metastasis staging (M-status), I 124 PET-CT is characterized by a higher sensitivity
than I 131 WBS or ultrasonography. The calculated values are 100% (95% CI: 92; 100), 76% (95%
CI: 61; 87) and 65% (95% CI: 50; 79) respectively.
The combined sensitivity of PET-CT imaging in clinical staging of thyroid cancer, irrespective
of location, is 100% (95% CI: 94; 100) and is higher than the sensitivity of I 131 WBS, CT or

ultrasound scanning. The values established for these methods are 83% (95% CI: 72; 91), 57%
(95% CI: 44; 68) and 43% (95% CI: 23; 66) respectively. The differences between PET-CT and
each of the scanning method compared are statistically significant (p < 0.01).
In summary, I 124 PET-CT is characterized by a higher diagnostic efficacy than the
conventional imaging methods in T-staging of differentiated thyroid cancer.
189

13. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS.
TRADITIONAL IMAGING METHODS IN HEAD AND NECK
CANCER DIAGNOSTICS
190
13.1. Diagnostics of malignant head and neck tumors (primary
lesions, recurrence after treatment, cervical lymph node
metastasis from an unknown primary focus)
13.1.1. Results of primary trial search
As a result of searching medical databases a single primary trial was found (Branstetter
2005; tab. 155, app. 18.1) that compared directly the diagnostic efficacy of PET-CT and of CT
in the diagnostics of malignant head and neck tumors (primary lesions, recurrences after
treatment, cervical lymph node metastasis from an unknown primary focus).
13.1.2. Population characteristics
Branstetter 2005 is a prospective clinical study on a sample of 65 patients: their neck and
head tumors were scanned using the PET-CT technology. The patients were referred to
examination:
a. for cancer staging (11 patients),
b. for detecting recurrences during treatment (46 patients),
c. for locating unknown primary foci in patients with lymph node involvement (8 patients).
Table 78 presents the characteristics of the subject population.
Table 78.
Characteristics of subject population in Branstetter 2005
Female
Male
Purpose [people]
Parameter Branstetter 2005
Size of population 65
Median age (from – to) [years] 63 (43–83)
Number [persons] 23
Median age (from – to) [years] 61 (43–83)
Number [persons] 42
Median age (from – to) [years] 64 (46–82)
Staging 11
Detection of recurrence 46
Detection of primary focus 8

13.1.3. Description of intervention
13.1.3.1 PET-CT imaging
PET-CT scanning was done using two combined scanners: EXACT HR+ (CPS Innovations)
and Somatom Emotion (Siemens Medical Solutions); Reveal (CTI Medical Systems). PET-CT
scanning from the cranial base to hypogastrium was done 1 hour following intravenous
administration of 8-15 mCi (296–555 MBq) of FDG. An intravenous contrast medium was used
in the CT component of the examination for all the patients without contraindications.
Attenuation was corrected using the CT component.
PET and CT scans were interpreted by groups of radiologists and nuclear medicine
specialists working separately, who were blinded to the findings of the other imaging test. The
researchers interpreting combined PET-CT images had access to complete data.
The localization was found radiologically incorrect if tumor was suspected or could not be
rationally excluded.
13.1.3.2 Diagnostic technology compared
CT image from PET-CT examination carried out using two combined scanners: EXACT HR+
(CPS Innovations) and Somatom Emotion (Siemens Medical Solutions); Reveal (CTI Medical
Systems). An intravenous contrast medium was used in the CT component of the examination
for all the patients without contraindications.
13.1.3.3 Reference test
The reference test included:
• biopsy,
• imaging examinations (CT, PET-CT),
• clinical observation for at least 6 months; the average period of observation was 8.9
months (from 6 to 12 months).
For all the patients with tumor, diagnosis was confirmed with histopathological
examination.
Observation was possible in 64 patients. One was eliminated from the study because the
period of observation was too short.
13.1.4. Findings
13.1.4.1 Diagnostic efficacy
In Branstetter 2005, 125 lesions were identified in 58 patients (91%). Out of these 125 lesions,
20 were confirmed by biopsy, 15 by additional imaging and 90 were confirmed clinically. No
191

additional lesions were detected through observation except those revealed by PET-CT
imaging. Statistically, both in terms of accuracy in lesion diagnostic and with respect to the
patients, PET-CT turned out considerably more efficacious than CT (p < 0.5); results on the
basis of comparison of fields under ROC curves.
Table 79.
Test results for each of the of methods compared vs. reference test: Branstetter 2005; per number of lesions
192
Study
PET-CT CT
TP FP FN TN TP FP FN TN
Branstetter 2005 45 6 1 73 34 20 12 59
Table 80 presents the efficacy of the testing technologies compared in detecting lesions
(per number of lesions, n = 125).
Table 80.
Diagnostic efficacy parameters of the methods compared in Branstetter 2005 per number of lesions
Parameter
Se
(95% CI)
Sp
(95% CI)
LR+
(95% CI)
LR-
(95% CI)
Acc
(95% CI)
DOR
(95% CI)
Branstetter 2005
PET-CT CT
98%
(88; 100)
92%
(84; 97)
12,88
(5,96; 27,83)
0,02
(0,003; 0,16)
94%
(89; 98)
547,50
(63,82; 4697,20)
74%
(59; 86)
75%
(64; 84)
2,92
(1,93; 4,43)
0,35
(0,21; 0,58)
74%
(66; 82)
8,36
(3,64; 19,18)
The sensitivity of PET-CT was 98% (95% CI: 88; 100) and the sensitivity of CT was 74% (95% CI:
59; 86). That means that PET-CT detected lesions correctly in 98% cases, whereas CT detected
only 74% of all the cancer lesions.
The specificity of PET-CT was 92% (95% CI: 84; 97), and the specificity of CT was 75% (95%
CI: 64; 84). That means that PET-CT test results were negative in 92% of patients without
cancer tumor. CT test results were negative only in 75% of patients without cancer.

PET-CT accuracy was 94% (95% CI: 89; 98), which means that 94% of lesions were correctly
diagnosed. The accuracy of CT was 74% (95% CI: 66; 82), which means that diagnosis was
accurate for 74% of lesions. The difference is significant statistically (p < 0.05; McNemar's test).
The positive likelihood ratio as calculated for PET-CT is 12.88 (95% CI: 5.96; 27.83), so the
probability of a positive results is 12.88 times higher for a tumor focus than the probability of
positive results for no lesion. The positive likelihood ratio as calculated for CT is 2.92 (95% CI:
1.93; 4.43), which means that the probability of positive results is 2.92 times higher for tumor
focus than the probability that exists for no lesion.
The negative Likelihood ratio as calculated for PET-CT is 0.02 (95% CI: 0.003; 0.16), which
means that the probability of negative results for tumor lesions represents 0.02 of the
probability that exists for no tumor focus. The negative likelihood ratio as calculated for CT is
0.35 (95% CI: 0.21; 0.58), so the probability of negative results for tumor lesions represents 0.35
of the probability for no lesions.
The diagnostic odds ratio as calculated for PET-CT was 547.5 (95% CI: 63.82; 4697.20), which
means that the probability of positive results is 547.5 times higher for tumor lesions than the
probability existing for the group of patients in ho no lesions were detected using the
reference test. The diagnostic odds ratio is 8.36 (95% CI: 3.64; 19.18) for CT, which means that
the probability of positive results in situations when lesions were detected by the reference
test is 8.36 times higher than the probability for patients with no disease focus.
The study provides no results per patient.
13.1.4.2 Safety
No information on the safety of the diagnostic procedures was found in the study.
13.1.5. Results
As a result of searching through medical databases one primary study was found
(Branstetter 2005) that compared directly the diagnostic efficacy of PET-CT with CT in the
diagnostics of malignant head and neck tumors (primary lesions, recurrences following
therapy, cervical lymph node metastasis from an unknown primary focus; N = 65). Biopsy of
suspicious lesions, clinical observation, and additional diagnostic imaging were used as the
reference standard.
The sensitivity and specificity of PET-CT were 98% (95% CI: 88; 100) and 92% (95% CI: 84; 97)
respectively, while for CT scans the values were 74% (95% CI: 59; 86) and 75% (95% CI: 64; 84).
The accuracy was rated 94% for PET-CT (95% CI: 89; 98) and 74% for CT (95% CI: 66; 82). The
difference is statistically significant.
193

194
13.2. Detection of bone involvement by oral cancer
13.2.1. Results of primary trial search
As a result of searching through medical databases one primary study was found (Goerres
2005; tab. 156, app. 18.1) that compared the diagnostic efficacy of PET-CT with that of CT
and SPECT/CT in detecting bone infiltration by oral cancer.
13.2.2. Population characteristics
Goerres 2005 is a retrospective trial on a population of 34 more patients with oral cancer in
who involvement of lower and upper jaw was suspected based on the clinical picture.
All the patients took surgical treatment, contrast CT and SPECT/CT scanning of the head
and neck, bone scintigraphy, and PET-CT scanning was acquired from head to pelvic fundus
or covering lower limbs.
The time interval between the PET-CT and SPECT/CT tests was 0-10 days (2.7 day average;
SD 2.4 day; 2 days median). The time difference was 0-24 days (5 days average; SD 5.2 day; 4
days median).
Table 81 presents the characteristics of the population.
Table 81.
Population characteristics in Goerres 2005
Location of primary focus [persons]
Parameter Goerres 2005
Size of population 34
Median age (from - to) [years] 64,2 (46,0–84,6)
Female [persons] 17
13.2.3. Description of intervention
13.2.3.1 PET-CT imaging
Male [persons] 17
Lower alveolar process 28
Upper alveolar process 4
Upper gum in the
retromolar area
The PET-CT scanning was executed using a Discovery LS (GE Medical Systems) unit. After
four hours’ starving, the patients were given 370 MBq FDG intravenously. Imaging was done 1
2

hour after FDG had been given. Moreover, a contrast medium was administered orally.
Corrections of attenuation were done based on CT images. The interpretation of images was
done by experienced radiology and nuclear medicine specialists.
13.2.3.2 Diagnostic test compared
CT imaging was done using a Somatom VolumeZoom (Siemens) unit. Scans were taken
from cervical base to collarbone with the patient in the supine position. Contrast was given
intravenously before the examination.
Scintigraphy was taken using the SPECT/CT technology, with the following contrast media
and equipment:
• 3 hours before the examination a patient was given, intravenously, the contrast medium
Teceos (Schering), which contained 99m technetium of the activity of 650 MBq;
• preliminary whole-body study was done with a Bodyscan set (Siemens);
• final SPECT/CT study was done with the use of a Hawkeye Millennium VG8 instrument (GE
Medical Systems).
CT image was used to correct attenuation.
13.2.3.3 Reference test
All the patients in Goerres 2005 had their tumors resected surgically and examined
histopathologically. Bone surgeries were performed only if one of the imaging methods
suggested bone involvement or if such suspicion appeared during resection.
13.2.4. Findings
13.2.4.1 Diagnostic efficacy
Goerres 2005 evaluated contrast PET-CT and CT efficacy in detecting bone involvement
by oral cancer. Two of the patients tested false positive with PET-CT. SPECT/CT scanning
yielded three false positive results and one false negative. In one patient the result of contrast
CT was false positive.
Table 82.
Test results for each of the methods compared vs. the reference test in Goerres 2005; calculated per patient
Study
PET-CT SPECT/CT CT
TP FP FN TN TP FP FN TN TP FP FN TN
Goerres 2005 12 2 0 20 11 3 1 19 11 0 1 22
195

196
Table 83 presents the diagnostic efficacy parameters as calculated for PET-CT, SPECT/CT
and CT.
Table 83.
Diagnostic efficacy parameters for the technologies compared in Goerres 2005, calculated per patient
Parameter
Se
(95% CI)
Sp
(95% CI)
LR+
(95% CI)
LR-
(95% CI)
Acc
(95% CI)
DOR
(95% CI)
Goerres 2005
PET-CT SPECT/CT CT
100%
(74; 100)
91%
(71; 99)
8,85
(2,73; 28,65)
0,04
(0,003; 0,66)
94%
(80; 99)
205,00
(9,08; 4627,50)
92%
(62; 100)
86%
(65; 97)
6,72
(2,32; 19,51)
0,10
(0,02; 0,64)
88%
(73; 97)
69,67
(6,44; 754,16)
92%
(62; 100)
100%
(85; 100)
40,69
(2,61; 635,61)
0,12
(0,03; 0,53)
97%
(85; 100)
345,00
(13,00; 9155,10)
PET-CT sensitivity was 100% (95% CI: 74; 100), SPECT/CT sensitivity was 92% (95% CI: 62; 100),
and CT sensitivity was 92% (95% CI: 62; 100). That means that PET-CT detected correctly bone
involvement in all cases, whereas CT and SPECT/CT detected lesions in 92% patients
diagnosed with bone involvement. The difference is not statistically significant.
The specificity of PET-CT was 91% (95% CI: 71; 99), the specificity of SPECT/CT was 86% (95%
CI: 65; 97), and the specificity of CT was 100% (95% CI: 85; 100). It means that for all the
patients with no bone involvement the CT result was negative, the results were negative for
PET-CT and SPECT/CT in 91% and 86% patients with no lesions in bones respectively. The
difference is not statistically significant.
The accuracy of PET-CT was 94% (95% CI: 80; 99), the accuracy of SPECT/CT was 88% (95%
CI: 73; 97), and the accuracy of CT was 97% (95% CI: 85; 100). That means that the
proportions of patients diagnosed correctly using PET-CT, SPECT/CT and CT technologies were
94%, 88% and 97% respectively. The difference is not statistically significant.
The positive likelihood ratio as calculated for PET-CT is 8,85 (95% CI: 2,73; 28,65), therefore
the probability of positive results is 8.85 times higher for patients diagnosed with bone
involvement than the probability for patients without involvement. The positive likelihood ratio
for SPECT/CT is 6.72 (95% CI: 2,32; 19,51). That means that the probability of positive results is

6.72 times higher for patients with bone invasion than the probability of positive results for
patients without bone involvement. The positive likelihood ratio as calculated for CT is 40.69
(95% CI: 2,61; 635,61). That means that the probability of positive results is 40,69 times higher
for patients diagnosed with bone invasion than the probability that exists among patients with
no bone invasion.
The negative likelihood ratio as calculated for PET-CT is 0,04 (95% CI: 0,003; 0,66). That
means that the probability of negative results for patients diagnosed with bone involvement
represents 0.04 of the probability that exists for patients with no invasion of bone by oral
cancer. The negative likelihood ratio as calculated for SPECT/CT is 0.10 (95% CI: 0,02; 0,64),
therefore the probability of negative result for patients diagnosed with bone involvement
represents 0.10 of the probability for people with no infiltration. The negative likelihood ratio as
calculated for CT is 0.12 (95% CI: 0,03; 0,53), therefore the probability of negative results for
patients diagnosed with bone involvement represents 0.12 of the probability for patients with
no infiltration.
The diagnostic odds ratio as calculated for PET-CT was 205.00 (95% CI: 9,08; 4627,5). That
means that the probability of positive results is 205 times higher for patients with bones
involvement compared to the probability that exists for patients testing negative for bone
involvement in reference tests. The diagnostic odds ratio of SPECT/CT is 69.67 (95% CI: 6,44;
754,16), which means that the probability of positive results is 69.67 times higher for patients
diagnosed with bone involvement by the reference test than for patients with no infiltration.
The diagnostic odds ratio of CT is 345.00 (95% CI: 13,00; 9155,10), which means that the
probability of positive result 345 times higher for patients testing positive for bone involvement
in reference tests than for patients with no infiltration.
13.2.4.2 Safety
No information on the safety of the diagnostic procedures used was found in the trial
included in this analysis.
13.2.5. Results
As a result of searching through medical databases one primary trial was found
(Goerres 2005) that compared directly the diagnostic efficacy of PET-CT with SPECT/CT and
CT in identifying bone involvement by oral cavity cancer (N = 34). Histopathological
examination following a surgical procedure was used as the reference standard.
The sensitivity of PET-CT was the highest and stood at 100% (95% CI: 74; 100), the sensitivity of
SPECT/CT was 92% (95% CI: 62; 100). The sensitivity of CT was 92% (95% CI: 62; 100). The
specificity of PET-CT was 91% (95% CI: 71; 99), compared to 86% for SPECT/CT (95% CI: 65; 97)
and 100% for CT (95% CI: 85; 100).
197

198
The accuracy of PET-CT scanning was 94% (95% CI: 80; 99), compared to 88% for SPECT/CT
(95% CI: 73; 97) and 97% for CT (95% CI: 85; 100), which represents 94%, 88% and 97%, of
properly diagnosed patients for PET-CT, SPECT/CT and CT respectively. The differences in
accuracy, sensitivity and specificity of PET-CT, CT and SPECT/CT tests in the diagnostics of
local involvement of bones by oral cavity cancer are not statistically significant
13.3. Impact of PET-CT diagnostics on treatment revisions
13.3.1. Results of primary trial search
As a result of searching medical databases, two primary clinical studies were found (Koshy
2005; tab. 157, app. 18.1, Wild 2005; tab. 154, app 18.1), which compared directly the
diagnostic efficacy of PET-CT with traditional methods of clinical assessment and imaging in
the diagnostics of head and neck cancer.
13.3.2. Population characteristics
The retrospective study Wild 2005 included 21 patients with cancers of the nasal cavity,
paranasal sinuses, orbital cavity, pterygopalatine fossa and infratemporal fossa. Patients with
their pterygopalatine fossa or infratemporal fossa tumors restaged were included in the study
only if the tumor was located in the paranasal sinsuses or the nasal cavity. All neoplasm cases
were confirmed histologically prior to imaging. PET-CT scanning was done as additional to CT
or MRI. Included were only those patients, for whom both imaging results and observation
data enabling clinical assessment were available. PET-CT and CT or MRI examinations could
not be separated by treatment procedures. 26 examinations were executed for the purposes
of staging or restaging: 9 were done for disease staging, and 15 patients took 17 restaging
scans. The time interval between a traditional imaging study and PET-CT was below 2 weeks.
PET-CT tests were done twice for five patients.
Koshy 2005 included 36 patients with previously untreated squamous cell carcinoma of the
head and neck, who had taken radiotherapy. PET-CT scanning was executed in all the
patients as part of their planned radiotherapy on the same day as, or a week from, CT
scanning. All the patients with one exception had been recently diagnosed with head and
neck cancer. Routine procedures were followed for the patients, comprising medical check-
up, CT (with contrast) of the head and neck, and chest X-ray. Patients with metastasis from
unknown primary foci underwent endoscopic biopsies or tonsillectomy. Patients with tumors
of nasopharynx and paranasal sinuses had MRI examinations of the head and neck. Patients
with lungs metastasis suspected based on an X-ray study had CT chest tests.

Table 84 presents the characteristics of the population.
Table 84.
Population characteristics
Parameter Koshy 2005 Wild 2005
Size of population 36 21
Median age +/-SD (from - to) [years] 56 (32–80)
Location of primary focus
[persons]
59,1+/-16,4
(16–87)
Female [persons] 8 6
Male [persons] 28 15
Maxillary sinus - 9
Sphenoidal sinus - 3
Orbital cavity or orbital
cavity & ethomid sinus
- 2
Paranasal sinuses 3 -
Nasopharynx 5 -
Nasal cavity - 3
Oropharynx 17 -
Larynx 4 -
Oral cavity 2 -
Lower part of pharynx 2 -
Unknown primary focus 3 -
pterygopalatine fossa and
infratemporal fossa
(restaging)
13.3.3. Intervention description
13.3.3.1 PET-CT imaging
- 4
In Wild 2005, PET-CT imaging was done using a Discovery LS scanner (GE Medical Systems).
After 4 hours’ starving, the patients were given 370 MBq of FDG intravenously. Imaging was
done 1 hour after the contrast medium was administered. Images were taken from head to
pelvic fundus. CT images were used to correct attenuation.
199

200
PET-CT scanning in Koshy 2005 was executed using a Discovery LS unit (GE Medical
Systems) after 4 hours’ starving, 45 to 60 minutes after 370–440 MBq of FDG was given
intravenously to patients immobilized by means of a mask. Corrections of attenuation were
done using CT images. PET-CT images were interpreted with the use of available clinical
information, both by radiology and nuclear medicine specialists. Imaging covered the whole
body.
13.3.3.2 Diagnostic technology compared
In Wild 2005, CT scanning was executed using a Somatom VolumeZoom scanner (Siemens)
with intravenous contrast, from cervical base to collar bones.
All MRI examinations were executed using a 1.5 T GE Signa instrument after contrast was
given intravenously.
In Koshy 2005, CT scanning was done using a GE light speed scanner (General Electric)
after contrast was given intravenously to patients immobilized by means of a mask. The
examination covered the head and neck; only patients with lungs metastasis had chest X-ray
and CT examinations.
Also, patients took medical check-ups, and, in case of nasopharynx or paranasal sinus
tumors, they had MRI examinations of the head and neck (no data on equipment).
13.3.3.3 Reference test
In Wild 2005, all patients with lesions had histological test.
In Koshy 2005, when distant metastasis or synchronous tumors were suspected, the
reference test comprised histological examination and a combination of additional
diagnostic imaging and clinical observation. No diagnostic imaging or clinical observation
data are available.
13.3.4. Results
13.3.4.1 Impact on therapy
Table 85 provides a detailed list of revisions to treatment of head and neck cancer
triggered by PET-CT scanning.

Table 85.
Impact of PET-CT on revisions to head and neck cancer therapy
Changes in treatment
after PET-CT
Chemotherapy in lieu of
radiotherapy and
surgery
Additional therapeutic
surgery
Palliative radiotherapy
with additional
chemotherapy in lieu of
therapeutic
radiotherapy
Koshy 2005 Wild 2005
- 1
- 1
- 1
Additional surgery 1 1
Chemotherapy in lieu of
surgery
Additional
chemotherapy
Discontinuation of
chemotherapy
Changes of
chemotherapy schemes
Adjustment of radiation
area
Adjustment of radiation
doses
- 2
- 1
1 -
2 -
5 2
4 -
In Wild 2005, the area of radiation was adjusted for two patients based on PET-CT findings.
Two patients took chemotherapy instead of surgery; one patient took chemotherapy instead
of radiotherapy and surgery planned before; lesions detected by PET-CT were removed
surgically in two patients; one person took chemotherapy instead of no treatment; one
person was given palliative chemoradiotherapy instead of therapeutic radiotherapy.
In Koshy 2005, some modifications were made to treatment procedures: the radiation area
was adjusted for five patients; the radiation dose was adjusted for four patients; one patient
did not take chemotherapy although it had been planned before; one patient underwent
surgery and radiochemotherapy. Among the patients for who treatment plans were revised,
the disease was upstaged on the TNM scale for five patients, for one the disease was
downstaged and for three it did not change.
Table 86 lists revisions in therapy for patients with head and neck cancer.
201

Table 86.
Revisions in treatment of head an neck cancer based on PET-CT findings
202
Study (N) Changes of treatment Confirmation of treatment
Wild 2005 (21) 9 12
Koshy 2005 (36) 9 27
Changes in the strategy of treatment were made based on PET-CT findings for 43% of
patients in Wild 2005 and for 25% in Koshy 2005.
Graph 27 presents the results of a meta-analysis of Wild 2005 and Koshy 2005 details
relating to therapy revisions.
Graph 27.
Meta-analysis (fixed effects model) of the proportion of patients for head and neck cancer therapy was revised
following PET-CT examination
Wild 2005 0,43 (0,22, 0,66)
Koshy 2005 0,25 (0,12, 0,42)
Result of metaanalysis
The use of PET-CT examination in addition to standard diagnostic methods helped revise
treatment for 32% patients with head and neck cancer (95% CI: 21; 44). Thanks to treatment
revisions, some extra health effects were achieved and unnecessarily burdensome
procedures were avoided.
13.3.4.2 Safety
0,0 0,2 0,4 0,6 0,8
Proportion of patients with treatment revised (95% confidence interval)
Neither of the trials reports on the safety of the diagnostic methods used.
0,32 (0,21, 0,44)

13.3.5. Results
As a result of searching through medical databases two primary studies were found (Wild
2005, Koshy 2005) which compared directly the impact of PET-CT scanning on therapeutic
decisions with standard head and neck cancer staging methods (CT, MRI, medical
examination; N = 57).
Histopathological examination was used as the reference standard in Wild 2005, while in
Koshy 2005, when distant metastasis or synchronous tumors were suspected, histopathological
tests or a combination of additional diagnostic imaging and clinical observation were
executed (no data are available on the reference standard in the remaining patients).
In Wild 2005, PET-CT findings triggered revisions of treatment suggested based on
conventional imaging in 43% patients, while in Koshy 2005 the value was 25%, which
produced the total of 32% cases (95% CI: 21; 44).
203

14. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS.
CONVENTIONAL IMAGING METHODS IN PANCREATIC
CANCER DIAGNOSTICS
204
14.1. Results of primary trial search
As a result of searching through medical databases, one primary prospective clinical trial
was found (Heinrich 2005; tab. 158, app. 18.1). It compares the diagnostic efficacy of PET-CT
with conventional imaging (CT with contrast medium, ERCP, MRI, EUS, diagnostic
laparoscopy) in pancreatic cancer diagnostics.
14.2. Population characteristics
59 patients with suspicions of pancreatic cancer were included in the trial. The diagnostic
efficacy of the imaging methods compared was evaluated with respect to both detecting
the primary focus of pancreatic cancer and T-staging.
Initial characteristics of the population is presented in table 87.
Table 87.
Initial characteristics of patients in Heinrich 2005.
PARAMETER POPULATION
Size of population 59
Median age in years (from-to)
61
(40–80)
Male proportion (%) 50.8%
Patients with primary lesion identified in the head
of the pancreas
Patients with primary lesion identified in the tail of
the pancreas
Patients with test results verified through
histopathological tests
86.4%
13.6%
88.1%
Patients diagnosed with malignant lesions 81.3%
Patients diagnosed with benign lesions 10.2%

The median age of the cohort was 61 (from 40 to 80). 30 men (50.8%) and 29 women
(49.2%) participated in the trial. Cancer involved the head of the pancreas in 51 patients
(86.4%) and the tail of the pancreas in 8 (13.6%) patients.
14.3. Intervention description
14.3.1. PET-CT imaging
The PET-CT examination was conducted by means of a PET-CT Discovery LS scanner
(General Electric Medical Systems, Waukesha, WI), which consisted of a Light Speed Plus
spiral CT scanner and an Advanced NXi PET scanner. The patients were instructed not to eat
4 to 6 hours before the examination. The patients had been given contrast medium orally
before scanning; no iodized contrast medium was administered intravenously. 18F-
fluorodeoxyglucose with the activity of 350 to 450 MBq was used as a marker. First, a CT study
was carried out by taking scans at an exhalation phase, from the tip of the head down to the
pelvic fundus. PET scans were taken immediately after CT scans according to the same
pattern as for CT. The acquisition time for a single scan was 4 minutes.
Table 88 presents a characteristics of the PET-CT scanner used in the examination, and the
procedures applied.
Table 88.
Characteristics of PET-CT scanner and the procedures used in testing.
Type of PET-CT
scanner
Type of PET
radiomarker
Discovery LS F 18 -deoxyglucose
Type of CT
contrast medium
oral contrast
medium; no
intravenous
contrast medium
Scope of
examination
from tip of the
head to pelvic
fundus
Radiomarker
activity [MBq]
350–450 MBq
CT findings were analyzed simultaneously by two or more experienced nuclear medicine
doctors and radiologists. The authors of the trials provide no data on how those were blinded
to the findings of conventional imaging methods.
Interpretation of findings involved locating areas with increased marker uptake as well as
determining the outline of those areas based on fusion PET-CT images. Also, CT images were
analyzed separately in order to identify additional lesions with no marker uptake.
205

206
14.3.2. Diagnostic technology compared
PET-CT findings were compared with the findings of conventional methods.
The following tests were done: CT with contrast medium (1-3 mm section); chest
radiogram; endoscopic ultrasound scanning with fine-needle aspiration biopsy (BAC) of
primary tumor and metastatic focuses; endoscopic retrograde cholangiopancreatography
(ERCP), serial testing of CA 19-9 in blood serum; and diagnostic laparoscopy.
Staging was carried out in stages; at the beginning, each patient had a CT test with
contrast medium as well as PET-CT scanning. If based on the findings the patient was
qualified for surgery, further tests were carried out for pancreatic cancer staging (endoscopic
ultrasonography, CA 19-9 in blood and diagnostic laparoscopy).
The median time between contrast CT and PET-CT was 10 days.
14.3.3. Reference test
Ultrasound findings were verified through observations during surgery and
histopathological test of material removed and bioptates.
Negative test result in patients who had not undergone surgery was validated based on
long-term clinical follow-up. The authors of the research reported that the median duration of
observation was 15 months (scope: 6-18 months) for 7 patients with pancreas lesions not
validated histopathologically. During that period, endoscopic ultrasonography with fine
needle aspiration biopsy, as well as the CT or MRI examinations were repeated to confirm the
benign character of lesions.
14.4. Findings
14.4.1. Tumor detection and analysis
The findings of diagnostic imaging were verified histopathologically for 52 out of 59
patients who had had PET-CT tests.
The number of patients who tested true positive, false positive, false negative and true
negative in PET-CT and contrast CT examinations carried out in a population of patients with
suspected pancreatic cancer is presented in table 89.

Table 89.
Number of patients with TP, FP, FN and TN results in Heinrich 2005: PET-CT vs. contrast CT.
Examination
PET-CT Contrast CT
TP FP FN TN TP FP FN TN
Heinrich 2005 41 4 5 9 bd bd bd bd
Based on the data above, the diagnostic efficacy parameters of PET-CT were calculated
and, along with the parameters reported by the authors for contrast CT, are presented in
table 90.
Table 90.
Diagnostic efficacy parameters of the imaging methods compared: PET-CT vs. contrast CT
Parameter
(95% CI)
Se
(95% CI)
Sp
(95% CI)
Acc
(95% CI)
Diagnostic method
PET-CT CT with contrast medium
89%
(76; 96)
69%
(39; 91)
85%
(73; 93)
Statistical
significance of
difference between
groups compared
93% p = 0,69
21% p = 0,07
bd not found
PET-CT sensitivity in detecting primary tumor is 89% (95% CI: 76; 96) and is lower than the
sensitivity of CT with contrast medium, which is 93%. The difference is not statistically significant
(p = 0.69). That means that the probability of positive PET-CT results for a patient diagnosed
with pancreatic cancer is 4 pp lower compared to CT with contrast medium.
PET-CT specificity in detecting primary tumor is 69% (95% CI: 39; 91) and is higher than the
specificity of CT with contrast medium, which stands at 21%. That means that the probability
of negative results in a patient without pancreatic cancer is 69% for the PET-CT, and is three
times higher compared to CT with contrast medium (21%). The difference is not statistically
significant (p = 0.07).
PET-CT accuracy in detecting primary tumor is 85% (95% CI: 73; 93). The difference
between groups is not statistically significant either.
14.4.2. Staging
The authors of Heinrich 2005 evaluated the diagnostic efficacy of PET-CT imaging with
respect to pancreatic cancer staging.
207

208
Out of 25 patients diagnosed with pancreas adenocarcinoma, who had had a surgery, 24
had metastasis to lymph nodes. The number of true positive results for PET-CT was 3. The
calculated sensitivity of PET-CT in detecting metastasis to lymph nodes is 21.4% (95% CI: 4,7;
50,8).
Out of 46 patients with pancreatic cancer confirmed histopathologically, 16 had distant
metastasis confirmed histopathologically.
PET-CT identified distant metastasis in 13 patients; for 5 of them PET-CT was the only
method that detected distant metastasis located in the liver and retroperitoneal lymph
nodes, abdominal wall, cervical lymph nodes and lungs. In 12 patients, distant metastases
demonstrated an increased marker uptake; in one patient FDG-negative lesions were found
in lungs; and in one patient both FDG-positive and FDG-negative lesions were found in lungs.
The PET-CT technology failed to detect lesions in three patients. No false positive results were
reported.
Conventional methods detected lesions in nine patients; in two, metastasis to liver was
diagnosed incorrectly (one patient with chronic pancreas inflammation and the other with
pancreas adenoma). In 2 patients, lesions were detected only by diagnostic laparoscopy,
while in 5 only by PET-CT.
Table 91 presents the numbers of patients with a true positive, false positive, false negative
and true negative results of PET-CT scanning and contrast CT scanning in the population
diagnosed with distant metastasis of pancreatic cancer.
Table 91.
Number of patients with TP, FP, FN and TN results in M-staging, PET-CT vs. conventional methods
Study
PET-CT Conventional methods
TP FP FN TN TP FP FN TN
Heinrich 2005 13 0 3 43 9 2 7 41
Table 92 presents EBM parameters calculated for the diagnostic methods compared, in a
group of patients diagnosed with distant metastases of pancreatic cancer.

Table 92.
EBM parameters of diagnostic efficacy for the diagnostic methods compared; PET-CT vs. conventional methods
Parameter
Se
(95% CI)
Sp
(95% CI)
LR+
(95% CI)
LR-
(95% CI)
Acc
(95% CI)
DOR
(95% CI)
Diagnostic method
PET-CT Conventional methods
81%
(54; 96)
100%
(92; 100)
69.9
(4.4; 1111.5)
0.2
(0.1; 0.5)
95%
(86; 99)
335.6
(16.3; 6913.9)
56%
(30; 80)
95%
(84; 99)
12,1
(2.9; 50.1)
0,46
(0.3; 0.8)
85%
(73; 93)
26.4
(4.7; 148.5)
Statistical
significance of
differences
between groups
compared
p = 0.22
p = 0.48
-
-
p = 0.08
PET-CT sensitivity in detecting distant metastases is 81% (95% CI: 54; 96) and is higher than
the sensitivity of the conventional imaging methods, which is 56% (95% CI: 30; 80). The
probability of positive results in patients diagnosed with distant metastases is 25 pp higher for
PET-CT than for the conventional methods. The difference in favor of PET-CT is not statistically
significant (p = 0.22).
Specificity also favors PET-CT, for which it stands at 100% (95% CI: 92; 100) and is higher
than the specificity of the conventional imaging methods, which is 95% (95% CI: 84; 99). That
means that the probability of negative results in a patient without distant metastases is 100%,
for PET-CT, which is 5 pp higher than the probability of negative results for the conventional
methods. The differences are not statistically significant (p = 0.48).
The positive likelihood ratio of PET-CT is 69.9 (95% CI: 4.4; 1111.5), and is higher compared to
the conventional methods, for which the value is 12.1 (95% CI: 2.9; 50.1). The probability of
positive PET-CT results in a patient with distant metastasis is almost 70 times higher than the
probability of positive result in a patient without distant metastases.
For the conventional methods, the probability of positive result is more than 12 times higher
in patients with distant metastasis than in patients without metastasis.
The negative likelihood ratio of PET-CT is 0.2 (95% CI: 0.1; 0.5) and is lower compared to the
ratio of the conventional methods, which is 0.46 (95% CI: 0.3; 0.8). For PET-CT, the probability
of negative results in a patient with distant metastasis represents 20% of the probability of
negative results in a patient without distant metastasis.
-
209

210
For the conventional methods, the probability of negative result in a patient with distant
metastasis represents 46% of the probability in a patient without distant metastasis.
The accuracy of PET-CT in detecting distant metastasis is 95% (95% CI: 86; 99) and is higher
than the accuracy of the conventional methods (CT, MRI and USG), which is 85% (95% CI: 73;
93). However, the difference did not reach the level of statistical significance (p = 0.08).
The diagnostic odds ratio in detecting distant metastasis of pancreatic cancer is 335.6
(95% CI: 16.3; 6913.9) with PET-CT, and is higher than the diagnostic odds ratio with the
conventional imaging methods, for which the value is 26.4 (95% CI: 4.7; 148.5).
The authors of the study report that if PET-CT scanning is used after the conventional
methods to detect distant metastasis if pancreatic cancer, diagnostic sensitivity goes up to
88%. The difference is not statistically significant (p = 0.06).
14.4.3. Revisions of oncological procedures
The authors of the study reported that two patients who participated in the trial had a
synchronous rectosigmoid junction cancer diagnosed by PET-CT. Radical palliative
rectosigmoid resection was performed in a patient diagnosed negatively for distant
metastases of pancreatic cancer. Palliative resection of a synchronous rectal tumour was
performed in a patient with pancreatic cancer metastasis in the abdominal wall. None of the
patients above developed clinical symptoms of rectal cancer; for none of them lesions
associated with tumor were identified by physical examination.
Considering these patients, as well as five other patients for who PET-CT was the only
technology to have detected distant metastasis, oncological procedures were revised for six
out of 37 patients in whom pancreas lesions were recognized as resectable.
Table 93 presents the impact of both methods compared on the oncological procedures
for patients with pancreatic cancer (staging).
Table 93.
Probability of revision of oncological procedure in patients diagnosed using the methods compared: PET-CT vs.
conventional methods
Parameter
Probability of revision
(95% CI)
Diagnostic method
PET-CT Conventional methods
33%
(20; 48)
20%
(9; 34)
Statistical significance
of difference between
groups compared
p = 0.03

The odds of revision of oncological procedure for pancreatic cancer patients when PET-CT
scans are used for staging is 33% (95% CI: 20; 48) and is 13 pp higher compared to the
conventional methods. The difference in favor of PET-CT is statistically significant (p = 0.03).
Moreover, PET-CT is more efficacious in determining the type of lesion as it provides a
detailed anatomical imaging of its outline.
14.4.4. Safety
The authors of the study do not report on possible side effects in patients diagnosed by
PET-CT and conventional methods.
14.5. Results
As a result of searching through medical databases one primary clinical trial was found
(Heinrich 2005) that compared directly the diagnostic efficacy of PET-CT with conventional
imaging methods (contrast CT, ERCP, MRI, EUS, diagnostic laparoscopy) in diagnosing primary
lesions and in staging pancreatic cancer (N = 59). The comparison of imaging methods was
verified by histopathological tests of material removed during a surgical procedure or
bioptates, or by long-term clinical observation.
The sensitivity of PET-CT scanning in detecting primary lesions of pancreatic cancer is 89%
(95% CI: 76; 96), which is lower than the sensitivity of contrast CT, which is 93%. PET-CT imaging
has a higher sensitivity rating than contrast CT in detecting pancreatic cancer, the estimated
values being 69% (95% CI: 39; 91) vs. 21%, respectively. The accuracy of PET-CT is 85% (95% CI:
73; 93). No statistically significant differences were observed between the groups for any of
the parameters of efficacy discussed.
In M-staging, PET-CT is characterized by a higher sensitivity than conventional imaging
methods, the estimated values being 81% (95% CI: 54; 96) vs. 56% (95% CI: 30; 80) respectively.
The difference in favor of PET-CT is not statistically significant (p = 0.22). Imaging specificity
favors PET-CT, for which it stands at 100% (95% CI: 92; 100) vs. 95% (95% CI: 84; 99) for the
conventional methods compared. The accuracy of PET-CT in M-staging is 95% (95% CI: 86; 99)
and is higher than the accuracy of the conventional methods (CT, NMR and USG), 85% (95%
CI: 73; 93). The difference, although close to the threshold, did not reach statistical
significance (p = 0.08).
A revision of oncological procedures as a result of PET-CT scanning was reported for 16%
patients (95% CI: 6; 32) with resectable pancreatic cancer. Procedure revision is more likely if
PET-CT scanning is used in clinical staging than if the conventional methods are used, the
211

estimated values being 33% (95% CI: 20; 48) vs. 20% (9; 34) respectively. The difference in
favor of PET-CT is statistically significant (p = 0.03).
212

15. COMPARATIVE EFFICACY ANALYSIS OF PET-CT VS. CT IN
THE STAGING AND EVALUATING RESPONSE TO
TREATMENT OF GASTROINTESTINAL STROMAL TUMOR
15.1. Results of primary trial search
As a result of searching medical databases, one primary clinical study was found (Antoch
2004; tab. 159, app. 18.1) that evaluated the diagnostic efficacy of PET coupled with
roentgen CT in detecting gastrointestinal stromal tumour (GIST).
15.2. Population characteristics
20 patients with gastrointestinal stromal tumor confirmed clinically were included in the
study provided GIST diagnosis was confirmed for them through histopathological examination
of primary tumor or metastasis.
The median age of the patients was 60 (from 39 to 77). Men represented 55% of the
population. The proportion of patients with a primary focus located in the stomach was 60%,
in small intestine – 35%, and in mesentery – 5%.
Results of initial neoplasm staging, and subsequently results of analysis of response to
imatinib treatment over 6 months were an indication for diagnosis.
Scans were taken prior to therapy and again in the first, third and sixth month of it.
The imaging procedures were not available for all the patients at the same time. The total
number of tests was 20 initially, 20 in the first month, 10 in the third month, 9 in the sixth month,
and 20 in the follow-up period, which, along with clinical data, served as a reference test. The
analysis was based on 79 tests altogether.
15.3. Description of intervention
15.3.1. PET-CT imaging
Diagnostic PET-CT imaging was performed by means of a Biograph scanner (Siemens
Medical Solutions) that consisted of a CT scanner (Somatom Emotion; Siemens) and a PET
scanner (ECAT HR+; Siemens).
213

214
The Biograph produced two separate CT and PET images that were assessed individually,
and again after fusion, to evaluate therapeutic efficacy. 18F-fluorodeoxyglucose (FDG) was
used as a marker.
PET imaging was carried out 60 minutes after the average dose of 358 MBq 18F-FDG (±42
MBq) was administered. The patients had been asked not to eat for 4 hours minimum before
the examination. The glucose level in blood was confirmed and blood samples taken before
the marker was administered. PET scanning duration was adjusted to the patients’ weight. For
patients with body weight below 65 kg, emission time was 3 minutes, for 65–85 kg it was 4
minutes, and for patients with body weight above 85 kg it was 5 minutes. For the purposes of
GIST diagnosis all the patients had PET-CT scans of the whole body taken. Imaging (which
included staging) was limited to areas where a tumor had been detected, yet in order to
detect new distant metastasis whole-body scans were taken every 3 months.
Table 94.
PET-CT details
Type of
PET-CT
scanner
Biograph
Manufacturer of PET-CT
scanner
Siemens Medical
Solutions (Hoffman
Estates, USA)
Type of
radiopharmaceutical
Coverage
Radiomarker
activity [MBq]
FDG whole body 358
PET scans were interpreted by two nuclear medicine doctors, and CT data by two
radiologists. They were blinded to the findings of other imaging tests. PET-CT fusion results were
interpreted through consensus examined by the same doctors.
15.3.2. Diagnostic technology compared
PET-CT findings were compared with CT findings (i.e. CT as a component of PET-CT). CT
was carried out using a Somatom Emotion CT scanner (Siemens) which is a part of a Biograph
PET-CT scanner (Siemens Medical Solutions).
Table 95.
CT details
Type of CT scanner CT scanner manufacturer
Contrast type and method of
administration
CT Somatom Emotion Siemens Medical Solutions intravenously and orally

The CT scans carried out to assess the efficacy of therapy was classified in keeping with
the directives of the World Health Organization (WHO) and The Response Evaluation Criteria
in Solid Tumors (RECIST).
15.3.3. Reference test
Clinical observation following the completion of a six-month-long treatment and
observation of response to treatment were used as the reference method. The average time
of observation was 381 days (SD 134). All the clinical data available were collected during
that time, including physical examinations, laboratory examinations, and radiological
imaging procedures (CT, MRI, PET-CT). All the patients had whole-body PET-CT scanning.
The participants were divided into two groups: one consisted of patients who responded
to treatment, the other included patients who did not. The evaluation was done by a team of
a nuclear medicine doctor, a radiologist and an oncologist. They had access to all clinical
and radiological data, and had not taken part in any previous imaging diagnosis.
The patients were classified as responsive or non-responsive to treatment, in keeping with
the criteria of WHO, RECIST as well as EORTC (European Organization for Research and
Treatment of Cancer).
15.4. Findings
15.4.1. Staging
In initial staging, 282 neoplastic lesions were located in 20 patients using PET-CT, but 249
using CT with contrast medium. The differences between the diagnostic methods were
statistically significant (p < 0.0001).
Initially, CT did not detect any lesions in 2 patients (10%), therefore the evaluation of
response to treatment was limited to 18 people for this method.
15.4.2. Response to treatment
The authors of the study analyzed the similarity of PET-CT and CT findings in evaluating
response to treatment vs. the reference method. After 1, 3 and 6 months, PET-CT findings
corresponded to the results of the reference test in terms of statistical significance. In none of
those periods significant agreement was observed for CT findings. Details are presented in
Table 96.
215

Table 96.
Scanning findings vs. reference test
216
Imaging method
CT (WHO)
CT (RECIST)
PET-CT
Scan timing after therapy
(months)
p-value
1 NF
3 NF
6 NF
1 NF
3 NF
6 NF
1 < 0.001
3 0.001
6 0.005
The study also evaluated whether response to treatment was correct in the first, third and
sixth month. Details are presented in Table 97.
Table 97.
Correct response to treatment
Period PET-CT (N = 20) CT (N = 18)
Statistical significance
of tests differences
1 st month 95% 44% p = 0.001
3 rd month 100% 60% NF
6 th month 100% 57% NF
PET-CT helped determine correctly response to treatment in the majority of patients
compared with CT results in each period of observation. The observed differences were
statistically significant in the first month.
15.4.3. Safety
The authors do not report on the side effects of the diagnostic techniques used.
15.5. Results
A single clinical trial was found (Antoch 2004) that compared the diagnostic efficacy of
PET-CT with that of CT imaging in GIST staging and in the evaluation of treatment response in
patients with gastrointestinal stromal tumor (N = 20). Long-term clinical observation was used
as a reference standard.

In primary disease staging, PET-CT imaging is more effective as a diagnostics method than
CT. The difference between the diagnostic methods compared was statistically significant (p
< 0.0001). In terms of response to treatment, significant congruence of results between the
method compared and the reference standard was identified only for PET-CT. When PET-CT
scanning was used, response to treatment was diagnosed correctly in 95%, 100% and 100%
patients in 1, 3 and 6-month follow-up periods respectively. For CT, the respective values were
44%, 60% and 57%. The difference between particular diagnostic methods reached statistical
significance in the 1 st month (p = 0.001).
217

16. COMPARATIVE EFFICACY ANALYSIS OF THE PET-CT AND
CT IN ASSESSING RESIDUAL LESIONS IN COLORECTAL
LIVER METASTASIS
218
16.1. Results of primary trial search
As a result of searching medical databases, one primary prospective clinical study was
found (Veit 2006; tab. 160, app. 18.1) that compares the diagnostic efficacy of PET coupled
with roentgen CT in detecting residual lesions following radiofrequency ablation of colorectal
liver metastases.
16.2. Population characteristics
Included in the trial were 13 patients (11 men, 2 women) aged 55 to 71 (63 on average)
with colorectal cancer and liver metastases confirmed histopathologically, who, due to
contraindications to surgery, were classified for high-current percutaneous radio-frequency
ablation. The patients included in the trial had contraindications to surgical resection of
metastasis (recurring liver metastasis after hepatectomy, cardiologic contraindications to
surgery, functional liver anomaly, or metastasis located close to a blood vessel, which makes
surgery impossible).
16.3. Description of intervention
16.3.1. PET-CT imaging
PET-CT was performed using a Biograph PET-CT system (Siemens Medical Solutions,
Hoffman Estates, IL, USA) which consisted of a CT scanner with dual-slice configuration and a
PET scanner. CT scans were taken at the beginning of the examination. Before whole-body
examination, 140 ml of ionized contrast medium was administered intravenously; 0.2% water
solution of locust bean gum as negative contrast and 2.5% of mannitol were given orally. Prior
to guided examination of the liver, 100 ml of ionised contrast medium was administered.
PET scans were done after CT examination. F18-deoxyglucose was used as marker; activity
of the radiomarker was 350 MBq per dose. The acquisition time for a single scan was adjusted
to the patient’s weight, and was 3 minutes per bed position for a patient with body weight

elow 65 kg, 4 minutes for patients with body weight between 65 and 85, and 5 minutes per
bed position for a patient with body weight above 85 kg.
A description of the equipment used in PET-CT examinations is presented in table 98.
Table 98.
Scanner and PET-CT procedure
Type of PET-CT
scanner
PET-CT Biograph
system
PET marker
Radiomarker
activity [MBq]
18F-deoxyglukose 350
Type of CT
contrast medium
intravenous ionised
contrast medium;
contrast medium
producing
negative
amplification of the
large intestine area
Comments
whole-body examination
before ablation;
guided examination of
the liver within two days
of ablation
All the patients had whole-body PET-CT scans (from cranium to upper thigh) one day
before ablation; follow-up guided examination of the liver was carried out for all the patients
2 days before surgery. For patients excluded from the trial within two days of ablation, follow-
up PET-CT scans had the same coverage as pre-ablation tests (whole body).
The image obtained as a result of PET and CT scan fusion was analyzed. PET-CT findings
were interpreted by two experienced nuclear medicine doctors; in case of discrepancies,
the result was determined by consensus. The doctors had access to the clinical data of the
patients examined, except for CT findings.
In order to detect residual lesions, images obtained using each imaging method before
and after ablation was analyzed.
Focuses of intense glucose metabolism found by PET-CT scanning next to necrosis areas
resulting from ablation were considered indicative of residual lesions. Also, a qualitative and
quantitative evaluation of focuses of increased glucose uptake was done.
16.3.2. Diagnostic technology compared
PET-CT findings were compared to the results from contrast CT obtained at the time of PET-
CT scanning. CT findings were interpreted by two experienced radiologists; if opinions were
divided, the result was agreed by consensus. The radiologists who performed the ablation did
not participate in CT interpretation.
Irregular peripheral contrast amplification as well as multi-nodular edges of a lesion were
considered indicative of residual lesions. When residual lesions were detected, ablation was
repeated during the same session.
219

220
16.3.3. Reference test
Imaging diagnoses were verified based on the findings of liver imaging tests (CT, PET-CT,
MRI) carried out in all patients after the ablation, laboratory tests results and clinical
observation. For two patients results of histopathological test of material from guided biopsy
were available. In six patients, a higher concentration level of colorectal neoplasm markers
was identified.
In case of tumor recurrence, another CT-guided ablation of the recurrence areas was
performed during the follow-up period.
The average follow-up period was 393 days (between 205 and 720).
16.4. Findings
Ablation was performed in 13 patients with colorectal liver metastasis; 11 had a PET-CT
examination immediately after ablation. Two patients (each with one metastasis and one
radio-frequency current ablation) had no follow-up PET-CT examination directly after ablation
due to poor general condition; for these only CT and MRI findings were available.
19 ablation sessions were performed on 11 patients with 16 metastases confirmed
(including repeated ablation). For these patients, 15 PET-CT examinations were performed
within 2 days after the procedure; the remaining 4 examinations were performed to evaluate
treatment effects during the observation period, its median being 58 days. In total, 32 follow-
up PET-CT examinations were performed (including 19 examinations mentioned above).
The authors of the study provide data on the sensitivity and accuracy of both methods in
evaluating residual lesions after radio-frequency ablation of colorectal liver metastases.
Table 99 presents the findings.
Table 99.
Sensitivity and accuracy of the diagnostic methods compared in detecting residual lesions after ablation of
colorectal liver metastasis, PET-CT vs. CT
Parameter
Diagnostic method
PET-CT CT
Sensitivity 65% 44%
Accuracy
68%
47%

PET-CT sensitivity in detecting residual lesions after radio-frequency ablation of colorectal
liver metastasis is 65%, and is higher than CT sensitivity, which is 44%. That means that the
probability of positive result for a patient with residual lesions confirmed in the liver after
ablation is 65% for PET-CT and 44% for CT with contrast medium. The authors do not report on
the statistical significance of the difference.
The accuracy of PET-CT is 68%, and is higher than the accuracy of conventional CT
imaging (47%).
In four patients with five metastases confirmed, residual lesions were detected by PET-CT in
the course of further observation, while CT findings were negative. The ablation procedure
was repeated. The use of PET-CT with these patients allowed revising treatment early on, to
the patients’ benefit (longer disease-free period of life).
16.5. Results
As a result of searching through medical databases, a single primary prospective clinical
trial was found (Veit 2006) that compared directly the diagnostic efficacy of PET-CT and CT
imaging in detecting residual lesions of colorectal liver metastasis following a therapy that
used radio-frequency current ablation (N = 13).
The sensitivity of PET-CT in detecting residual disease is 65%, and is higher than that of CT,
which stands at 44%. The authors provide no data on the statistical significance of the results
above.
The accuracy of PET-CT in detecting residual lesions is 68%, and is higher than the accuracy
of CT, which stands at 47%.
Analysis of imaging methods compared showed that in detecting residual lesions of
colorectal liver metastasis following radiofrequency ablation, a higher efficacy is
demonstrated by PET-CT diagnostics than by CT imaging.
221

17. COMPARATIVE ANALYSIS OF THE EFFICACY OF PET-CT VS
OTHER IMAGING TECHNIQUES (MRI OR CT) IN THE
STAGING OF NEOPLASM IN VARIED LOCATIONS
222
17.1. Neoplasm in varied locations – disease staging (PET-CT vs.
MRI)
17.1.1. Results of trial search
As a result of searching medical databases, two primary prospective trials were
found: Antoch 2003 (tab. 140, app. 18.1), and Schmidt 2005 (tab. 141, app. 18.1),,
which discussed the use of PET-CT in staging neoplasm in varied locations.
For both of these trials, hybrid PET-CT was compared with magnetic resonance
(MRI), and both methods were verified based on a reference test, which was
histopathological examination and/or clinical observation.
17.1.2. Population characteristics
Patients with neoplasm in varied locations participated in all the trials reviewed. Pre-
surgery staging was performed for 84% of the patients included in Antoch 2003, and for
7% in Schmidt 2005. Staging in case of suspected recurrence was performed for 16% of
patients in Antoch 2003 and for 15% in Schmidt 2005. In Schmidt 2005 covered additional
patients with whom the diagnostic methods compared were used for T-staging (10%)
and post-treatment restaging (68%).
In neither of the trials, the patients inclusion or exclusion criteria were specified.
Table 100 provides initial characteristics of patients included in the trials.
Table 100.
Initial characteristics of patients included in trials
Parameter
Size of population
Mean age [years]
Male proportion
lung and bronchial cancers
cancer of unknown
primary origin
head and neck cancer
Antoch 2003
98
58
64%
30%
12%
13%
Schmidt 2005
38
56**
44%**
0%
10,5%
0%
Total
136
57*
58%
22%
12%
9%

Cancer type
(patient
proportion)
melanoma
genitourinary cancers
esophageal cancer
thyroid cancer
mesothelioma
liver cancer
bone cancer
breast cancer
testicular cancer
lymphoma
sarcoma
13%
* average weighted with patient population number participating in 2 studies
**data for 41 patients
8%
6%
6%
6%
10,5%
115 patients were initially included in Antoch 2003, contraindications to imaging were
identified in 17 of them (acute allergic reaction to intravenous contrast medium in 8
patients; in 9 patients contraindications to MRI were identified for reasons such as heart
simulators, metal implants or claustrophobia).
41 patients were included in Schmidt 2005, but only 38 were qualified. The reasons for
excluding two patients were contraindications to MRI, such as heart simulator and
claustrophobia. For one patient, MRI testing was stopped due to strong pain caused by
advanced metastasis to bones.
The total of 136 patients were included in this analysis, with the average age of 56-68
and the male proportion of 44–64%.
17.1.3. Description of intervention
17.1.3.1 PET-CT
Biograph produced by Siemens Medical Solutions (Hoffman Estates, USA) was used for
disease staging in Antoch 2003, and Philips Gemini by Philips Medical Systems was used
in Schmidt 2005.
For both trials included, the radiopharmaceutical used was FDG (fluoro-deoxy-glucose),
with the activity of 350 MBq in Antoch 2003, and 202-372 MBq in Schmidt 2005. The
radiopharmaceutical was applied 60 minutes before PET-CT scanning in both trials. In
Schmidt 2005, FDG was preceded by 20 mg of furosemide and buskopan administered
intravenously.
3%
2%
0%
0%
0%
0%
0%
37%
5%
0%
0%
0%
29%
3%
3%
3%
12%
6%
15%
6%
4%
2%
1%
8%
1%
1%
1%
223

224
Table 101 gives details of the PET-CT tests.
Table 101.
Description of intervention
Trial
Antoch
2003
Schmidt
2005
PET-CT
scanner
type
Biograph
Philips
Gemini
PET-CT scanner
manufacturer
Siemens Medical
Solutions (Hoffman
Estates, USA)
Philips Medical
Systems
Radiopharma
ceutical type
and
administration
method
FDG
intravenously
FDG
Study range
whole body
no data
Radiomarker
activity
[MBq]
350
202–372
In Schmidt 2005, patients could not eat for at least 6 hours before, so the sugar level did
not exceed 120 mg/dL. In Antoch 2003, before giving the radiopharmaceutical, the correct
level of glucose concentration in blood was checked.
In both studies, in order to perform the CT part of PET-CT scanning, the patients received
contrast medium intravenously. In Antoch 2003, large intestine enlargement was achieved by
administering glucose-free barium.
The average PET-CT testing time was 27 minutes (range: 22-39 minutes) in Antoch 2003,
and 103 minutes in Schmidt 2005. The authors of the latter noted that it took 60 minutes to
prepare a patient and 43 minutes to scan.
For both studies, the PET-CT scans were assessed by a radiologist and a nuclear
medicine expert. The assessors were blinded to the results of imaging studies other than PET-
CT.
17.1.3.2 Compared diagnostic test
For the two studies assessed in this part of the analysis (Antoch 2003, Schmidt 2005), PET-CT
scanning was compared with magnetic resonance imaging (MRI).
In Antoch 2003, magnetic resonance was performed using Sonata System 1.5-T (Siemens
Medical Solutions, Erlangen, Germany), and in Schmidt 2005, the Magnetom Avanto 1.5-T
scanner was used (Siemens Medical Solutions).
Table 102 provides a detailed description of the magnetic resonance tests in each trial.

Table 102.
Description of diagnostic tests compared
Study
Antoch 2003
Schmidt 2005
MRI scanner type
Sonata System 1.5-T
Magnetom Avanto
1.5-T
MRI scanner
manufacturer
Siemens Medical
Solutions
Siemens Medical
Solutions
Contrast medium
type and
administration
method
intravenous
contrast medium
intravenous
contrast medium
Study range
whole body
whole body
In Antoch 2003, axial scanning from head to thigh was done, which corresponded to the
area scanned using PET-CT. Initially, the thorax and abdomen were scanned without a
contrast medium used, and than the paramagnetic contrast medium Megnevist (Schering,
Germany) was given intravenously at 3 ml/sec and the dose of 0.2 mmol/kg, and after 12
seconds, seven other scans were performed enhanced by contrast in the following order:
abdomen (arterial phase), thorax, abdomen (portal-venous phase), pelvis, thighs, head and
abdomen (late venous phase).
In Schmidt 2005, the whole body was scanned using parallel acquisition techniques (PAT).
Initially, the head/neck, pelvis, thighs, calves and thorax/abdomen were scanned. After
gadolinum-DTPA was administered at 3 ml/sec with the dose of 2 mmol/ks, and 20 ml of salt
solution was given, the liver, brain and whole abdomen were scanned axially. Another PAT
agent was used for axial imaging of brain, lungs and abdomen, and for sagittal imaging of
spine and frontal imaging of calfs.
The average MRI testing time was 26 minutes (range: 20-34 minutes) in Antoch
2003, and 70 minutes (range: 56-76 minutes) in Schmidt 2005. The authors of the latter noted
that the scanning alone took approx. 55 minutes.
17.1.3.3 Reference test
In both studies, histopathological examination and/or imaging follow-up were the
reference test.
In Antoch 2003, 47% patients underwent tumor resection, and the tumor was assessed
pathologically, therefore only for these patients the accuracy of PET-CT vs. MRI was
evaluated. Similarly, metastases to lymph nodes was verified based on pathological tests for
44% of the patients, and distant metastases for 14%. Follow-up was the reference method
for patients without histopathological verification of N and M features. The average
observation time was 273 days (range: 75–515 days). During that period clinical
assessment, laboratory tests and diagnostic imaging (CT, MRI and/or PET-CT) were done,
225

followed by histopathological diagnostics. Data on the reference test results were
collected by a doctor blinded to the results of PET-CT and MRI scanning.
226
In Schmidt 2005, clinical, histological and radiological tests in the course of 6-month-long
observations were used as reference methods for all pathological changes detected,
especially to verify divergent and questionable data. 14 targeted CT-guided biopsies, Tests
done as part of follow-up included 14 CT scans, 14 PET scans, 16 PET-CT scans, 14 bone
scintigraphies, 10 MRI tests, 1 whole body MRI, 18 X-ray pictures and 5 ultrasound test.
Histological test were done in case a primary tumor or disease recurrence were suspected.
17.1.4. Findings
17.1.4.1 Diagnostic accuracy in detecting primary and recurring carcinomas
This end point was evaluated only in Schmidt 2005. The authors noted that both PET-CT
and MRI helped detect 7 cancer cases, including 3 primary and 4 recurring tumors in 38
patients qualified for the clinical trial.
The number of patients with true positive (TP), false positive (FP), false negative (FN)
and true negative (TN) result of PET-CT and MRI as calculated based on the data
provided by the authors in Schmidt 2005 is presented in table 103.
Table 103.
Number of patients with TP, FP, FN and TN results in detecting cancer in patients with varied location of the disease
using PET-CT and MRI.
TP
FP
PET-CT
FN
7*
0*
0*
*Calculated based on data available
TN
31*
Table 104 presents the diagnostic parameters: sensitivity (Se), specificity (Sp),
accuracy (Acc), Positive likelihood ratio (LR+), negative likelihood ratio (LR-) and
diagnostic odds ratio (DOR) as calculated for the methods compared (PET-CT and MRI).
Table 104.
Accuracy in detecting cancer in patients with the disease in varied location using PET-CT vs MRI .
Parameter
Se (95% CI)
Sp (95% CI)
LR+ (95% CI)
LR- (95% CI)
TP
6*
PET-CT
FP
0*
100% (59; 100)*
100% (89; 100)*
60,00* (3,81; 944,10)*
0,06* (0,00; 0,93)*
MRI
FN
1*
MRI
86% (42; 100)*
TN
31*
100% (89; 100)*
52,00* (3,26; 829,97)*
0,19* (0,04; 0,81)*

Acc (95% CI)
DOR
*Calculated based on data available
100% (91; 100)*
945,00* (17,31; 51595)*
97% (86; 100)*
273,00* (9,97; 7477,05)*
Based on the data above, PET-CT sensitivity is 100% (95% CI: 59; 100), and MRI sensitivity is
86% (95% CI: 42; 100), which means that the probability of positive results for patients with
primary or recurring cancer is 100% and 86% for PET-CT and MRI, respectively.
The specificity of both methods is 100% (95% CI: 89; 100), so the probability of negative
result for healthy patients is 100% for both PET-CT and MRI.
The diagnostic accuracy of PET-CT is 100% (95% CI: 91; 100), and for MRI the value is 97%
(95% CI: 86; 100). No statistically significant differences between the groups were observed
for none of the parameters above.
The positive likelihood ratio for PET-CT is 60,00 (95% CI: 3,81; 944,10), so the probability of
positive results for patients with primary and recurring cancers is 60 times higher than for
healthy patients. The positive likelihood ratio (LR+) for magnetic resonance is 52,00 (95% CI:
3,26; 829,97). It means that the probability of positive results for cancer patients is 52 times
higher than for patients with no cancer detected using the index test.
The negative likelihood ratio (LR-) for PET-CT, is 0.06 (95% CI: 0,00; 0,93), so the probability of
negative results in patients with primary or recurring cancers is 0.06 of that for patients without
cancer. The negative likelihood ratio (LR-) for MRI is 0.19 (0.04; 0.81), so the probability of
negative result for cancer patients is 0.19 of that for patients without the disease.
The diagnostic odds ratio (DOR) calculated for PET-CT is 945 (95% CI: 17,31; 51595), which
means that the probability of positive results is 945 times higher for patients with primary or
recurring cancers than for patients not diagnosed with cancer using the reference test. The
diagnostic odds ratio (DOR) for MRI is 273 (95% CI: 9,97; 7477,05), which means that the
probability of positive results in patients with primary or recurring cancers is 273 times higher
than for patients without such cancers.
In Schmidt 2005, four patients with primary tumors in unknown locations were diagnosed
using PET-CT and MRI in order to identify the locations. However, for none of the patients the
primary origin was detected using the diagnostic methods compared. No primary tumor
was identified in these patients during 6 months-long observations.
17.1.4.2 T-staging
T-status was assessed in both trials included (Antoch 2003, Schmidt 2005).
In all tests, the T-status was assessed based on the TNM staging system created by the
AJCC (American Joint Committee on Cancer). PET-CT and MRI results were verified
histopathologically and based on radiologcal follow-up.
227

228
The consistency of the T-status established using the diagnostic methods
compared with the reference test results as described by the authors is given in
table 105.
Table 105.
Consistency of the T feature with the reference test for patients with neoplasm in varied locations, PET-CT vs MRI
Study
Antoch
2003
N*
46
Correct
staging
(accuracy)
n (%)
37 (80%)
Overstage
4 (9%)
PET-CT
Incorrect staging
n (%)
Understaged
5 (11%)
Schmidt
2005
38 37 (97%) 0 (0%)
1 (3%)
*Number of patients verified against the reference test results
Correct
staging
(accuracy)
n (%)
24 (52%)
37 (97%)
Overstaged
6 (13%)
0 (0%)
MRI
Incorrect staging
n (%)
Based on the data above, for all the tests, the proportion of correctly staged
patients was higher for PET-CT than for magnetic resonance (MRI). PET-CT accuracy
is 80 and 97%, and MRI accuracy is 52% and 97%. Overstaged and understaged
results are 0 and 9% and 3 and 11% respectively for PET-CT, and 0 and 13% and 3
and 35% respectively for MRI.
Understaged
16 (35%)
The authors in Antoch 2003 described PET-CT as demonstrating diagnostic accuracy that is
statistically significantly higher than MRI (p < 0.001). Differences in accuracy between PET-
CT and MRI were not statistically significant in Schmidt 2005.
In Schmidt 2005, the sensitivity and specificity of the methods compared were the same:
86% and 100% respectively.
Graph 28 illustrates a meta-analysis of PET-CT diagnostic accuracy in T-staging. As there
was significant heterogeneity between trials (p = 0.0122) meta-analysis was performed
using the random effects method.
1 (3%)

Graph 28.
Meta-analysis of the diagnostic accuracy of PET-CT in T-staging in patients with neoplasm in varied locations
Antoch 2003 0,80 (0,66, 0,91)
Schmidt 2005 0,97 (0,86, 1,00)
Meta-analysis result [random]
0,6 0,7 0,8 0,9 1,0
Diagnostic accuracy (95% confidence interval)
0,89 (0,68, 1,00)
PET-CT diagnostic accuracy as calculated by meta-analysis of the two trials is 89% (95% CI:
68; 100).
Graph 29 illustrates a meta-analysis of the diagnostic accuracy of T-staging using the
magnetic resonance technology. As there was significant heterogeneity between trials (p <
0.0001) the meta-analysis was performed using the random effects method.
229

Graph 29.
Meta-analysis of the diagnostic accuracy of MRI in T-staging in patients with neoplasm in varied locations
230
The average value of the diagnostic accuracy of magnetic resonance (MRI) in T-staging
is 79% (95% CI: 26; 99).
The average values of diagnostic efficacy calculated for PET-CT and MRI are given in
table 106.
Antoch 2003
Result of meta-analysis
[random]
Schmidt 2005 0,97 (0,86, 1,00)
Table 106.
Average values of PET-CT and MRI accuracy in T-staging in patients with neoplasm in varied locations.
Parameter
Acc (95% CI)
0,0 0,2 0,4 0,6 0,8 1,0
PET-CT
89% (68; 100)
MRI
79% (26; 99)
Based on the data above, the diagnostic accuracy in T-staging is higher for PET-CT than
for magnetic resonance (MRI).
Diagnostic accuracy (95% confidence interval)
Graph 30 illustrates a meta-analysis of the proportion of patients for whom the results of T-
staging using PET-CT or MRI scanning were consistent with the reference test.
0,52 (0,37, 0,67)
0,79 (0,26, 0,99)

Graph 30.
Odds ratio for the consistency between the reference test and T- staging results for patients with neoplasm in varied
locations, PET-CT vs. MRI
Antoch 2003 3,77 (1,37, 10,83)
Schmidt 2005 1,00 (0,01, 80,59)
Meta-analysis result [fixed] 3,29 (1,37, 7,90)
The odds ratio as calculated by meta-analysis is 3.29 (95% CI: 1.37; 7.90), which means
that the probability of T-staging results consistent with reference test results for PET-CT is 3.29
times higher than for magnetic resonance. The result is statistically significant.
In order to obtain one additional case of correct T-staging, it is necessary to use PET-CT
instead of MRI with 7 patients, NNT = 7 (95% CI: 4; 20).
17.1.4.3 N-staging
Disease staging with respect to metastasis to lymph nodes was analyzed in two of the trials
included.
In both studies (Antoch 2003 and Schmidt 2003), disease staging was done based on the
TNM lung cancer staging system developed by the AJCC (American Joint Committee on
Cancer).
In Antoch 2003, the diagnostic accuracy of PET-CT vs. MRI was evaluated for 98 patients,
and the results were verified by the reference test. In Schmidt 2005, 120 lymph nodes from 38
patients were examined, out of which 60 were affected by metastasis.
Table 107 presents the consistency between the N-staging results obtained using the
diagnostic methods compared and the results of the reference test as described by the
authors in both trials.
0,01 0,1 0,2 0,5 1 2 5 10 100
Odds ratio (95% confidence interval)
231

Table 107.
Consistency of N-staging results with the reference test in patients with neoplasm in varied locations, PET-CT vs. MRI
232
Study
Antoch
2003
N*
98
Correct
staging
(accuracy)
n (%)
91 (93%)
PET-CT
Overstaged
5 (5%)
Schmidt
2005
38 37 (97%) 1 (3%)
*Number of patients verified using reference test
Incorrect staging
n (%)
Understaged
2 (2%)
0 (0%)
Correct
staging
(accuracy)
n (%)
77 (79%)
32 (82%)
MRI
Overstaged
13 (13%)
3 (8%)
Incorrect staging
n (%)
Based on the data above, for all the tests evaluated, the proportion of correctly
diagnosed patients was higher for PET-CT than for magnetic resonance (MRI). PET-CT
accuracy is 93% and 97%, and the accuracy of MRI is 79% and 82%. The proportion
of overstaged and understaged cases is 3%–5% and 0%–2% respectively for PET-CT
and 8%–13% and 8% respectively for MRI.
In Antoch 2003, the differences in accuracy between the diagnostic methods
compared were statistically significant (p = 0,001). In Schmidt 2005, the differences
were not statistically significant.
Graph 31 illustrates a meta-analysis of PET-CT accuracy in N-staging.
Graph 31.
Meta-analysis of the diagnostic accuracy of PET-CT in N-staging in patients with neoplasm in varied locations
Antoch 2003 0,93 (0,86, 0,97)
Schmidt 2005 0,97 (0,86, 1,00)
Result of meta-analysis [fixed] 0,94 (0,89, 0,97)
0,85 0,90 0,95 1,00
Diagnostic accuracy (95% confidence interval)
Understaged
8 (8%)
3 (8%)

PET-CT diagnostic accuracy as calculated by meta-analysis of the two studies is 94% (95%
CI: 89; 97).
The results of a meta-analysis of the accuracy of MRI in N-staging are presented in graph
32.
Graph 32.
Meta-analysis of the diagnostic accuracy of MRI in N-staging in patients with neoplasm in varied locations.
Antoch 2003 0,93 (0,86, 0,97)
Schmidt 2005 0,97 (0,86, 1,00)
Meta-analysis result [fixed] 0,94 (0,89, 0,97)
The average MRI diagnostic accuracy as calculated by meta-analysis is 80% (95% CI: 73; 86).
The average values of diagnostic efficacy of N-staging calculated for PET-CT and MRI is
given in table 108.
Table 108.
Average values of PET-CT and MRI accuracy in N-staging in patients with neoplasm in varied locations.
Parameter PET-CT MRI
Acc (95% CI) 94% (89; 97) 80% (73; 86)
Based on the data above, the diagnostic accuracy of PET-CT in the assessment of the
involvement of lymph nodes is higher that that of magnetic resonance (MRI).
Graph 33 illustrates a meta-analysis of the proportion of patients for whom the results
of N-staging using PET-CT vs. MRI scanning were consistent with the reference tests
results.
0,85 0,90 0,95 1,00
Diagnostic accuracy (95% confidence interval)
233

Graph 33.
Odds ratio for the consistency between the reference test and N-staging result in patients with neoplasm in varied
locations, PET-CT vs. MRI
234
Antoch 2003 3,55 (1,35, 10,36)
Schmidt 2005 6,94 (0,76, 327,53)
Meta-analysis results
[fixed]
The odds ratio is 4.00 (95% CI: 1.74; 9.19), so the probability of consistency between the
results of N-staging and the reference test results is 4 times higher for PET-CT than for
magnetic resonance. The result is statistically significant.
In order to obtain one additional case of correct N-staging it is necessary to use PET-CT
instead of MRI with 8 patients with cancer; NNT = 8 (95% CI: 5; 17).
Table 109 presents additional parameters concerning the diagnostic accuracy of the
methods compared: sensitivity (Se) and specificity (Sp), as provided by the authors of the
trials.
Table 109.
The diagnostic accuracy of N-staging in patients with neoplasm in varied locations. PET-CT vs. MRI
Parametr
0,5 1 2 5 10 100 1000
Odds ration (95% confidence interval)
PET-CT MRI
Antoch 2003 Schmidt 2005
Statistical
significance
(PET-CT vs
MRI)
PET-CT MRI
4,00 (1,74, 9,19)
Statistical
significance
(PET-CT vs
MRI)
Se 95% 79% bd 100% 79% bd
Sp 92% 78% bd 95% 95% bd

The diagnostic sensitivity of PET-CT is 95% and 100% and for MRI it is 79% in both trials. The
specificity reported by the authors of both studies is 92% and 95% for PET-CT, and 78%-95% for
magnetic resonance.
The diagnostic parameters calculated based on the number of lymph nodes affected by
metastases was additionally reported in Schmidt 2005. Detailed results are given in table 110.
Table 110.
Diagnostic accuracy evaluation parameters for N-staging using PET-CT vs MRI, as calculated in Schmidt 2005 in
relation to the number of lymph nodes assessed.
Parameter
Se
n/N
Sp
n/N
Number
of lymph
nodes assessed
120
PET-CT
98%
59/60
83%
50/60
MRI
80%
48/60
75%
45/60
Statistical
significance
(PET-CT vs MRI)
no data
Considering the number of lymph nodes invaded by metastases, sensitivity and
specificity are higher for PET-CT than for magnetic resonance, and are 98% and 83%
respectively for PET-CT, and 80% and 75% respectively for MRI.
Schmidt 2005 established that the median size of lymph nodes invaded by
metastasis diagnosed based on PET-CT is 15 mm (SD = 8), and based on MRI it is 18 mm
(SD = 8).
In Schmidt 2005, PET-CT helped diagnose a greater number of lymph nodes in all
size-based groups, and a statistically significantly greater number of small lymph
nodes (below 10 mm). Two large lymph nodes (>20 mm) were additionally located in
the mediastinal and retrotibial regions using this technology.
17.1.4.4 Assessment of distant metastases (M feature)
The assessment of cancer stage based on the TNM system with respect to the
presence of distant metastasis was performed in two studies included in this analysis:
Antoch 2003 and Schmidt 2005.
In Antoch 2003, the diagnostic accuracy of PET-CT was compared with MRI for 98 patients,
and the results were verified using the reference method. In Schmidt 2005, 268 pathological
lesions were assessed in 38 patients, including 191 malignant lesions and 77 benign lesions.
The consistency of the results of M-staging one with the use of the technologies
compared with the reference (index) test as reported by the authors is given in
table 111.
NS
235

Table 111.
Consistency of distant metastasis staging (M feature) with reference test in patients with neoplasm in varied locations,
PET-CT vs MRI
236
Study
Antoch
2003
N*
98
Correct
staging
(accuracy)
n (%)
92 (94%)
PET-CT
Overstaged
3 (3%)
Schmidt
2005
38 37 (97%) 1 (3%)
*Number of patients verified using reference test
Incorrect staging
n (%)
Understaged
3 (3%)
0 (0%)
Correct
staging
(accuracy)
n (%)
91 (93%)
38 (100%)
Overstaged
3 (3%)
0 (0%)
MRI
Incorrect staging
n (%)
Based on the data above the accuracy of PET-CT is 94% and 97%, and the accuracy of
MRI is 93%–100%. Overstaged and understaged results stood at 3% and 0%–3% respectively
for PET-CT, and 0%–3% and 0%–4% for MRI respectively.
In Antoch 2005, slightly higher diagnostic accuracy was reported for PET-CT (94%) as
compared to MRI (93%), but the differences were not statistically significant (p > 0.99). The
differences between groups were not statistically significant in Schmidt 2005 either (p > 0,99).
CT.
Graph 34 illustrates a meta-analysis of the diagnostic accuracy of M-staging using PET-
Graph 34.
Meta-analysis of the diagnostic accuracy of PET-CT in M-staging in patients with neoplasm in varied locations
Antoch 2003 0,94 (0,87, 0,98)
Schmidt 2005 0,97 (0,86, 1,00)
Results of meta-analysis [fixed]
0,86 0,91 0,96 1,01
Diagnostic accuracy (95%) confidence interval)
0,94 (0,90, 0,98)
Understaged
4 (4%)
0 (0%)

The PET-CT diagnostic accuracy calculated by meta-analysis of the two studies is 94% (95%
CI: 90; 98).
Graph 35 illustrates a meta-analysis of the diagnostic accuracy of MRI in M-staging. As
there was significant heterogeneity between trials (p = 0.0359) the meta-analysis was
performed using the random effects method.
Graph 35.
Meta-analysis of the diagnostic accuracy of MRI in M-staging in patients with neoplasm in varied locations
Antoch 2003
0,93 (0,86, 0,97)
Schmidt 2005 1,00 (0,91, 1,00)
Meta-analysis result [random] 0,96 (0,86, 1,00)
0,85 0,90 0,95 1,00
Diagnostic accuracy (95% confidence interval)
Magnetic resonance diagnostic accuracy as calculated by meta-analysis of the two
studies is 96% (95% CI: 86; 100).
Table 112 lists the average values of diagnostic accuracy as calculated for PET-CT and
MRI in M-staging.
Table 112.
Average values of PET-CT and MRI accuracy in M-staging in patients with neoplasm in varied locations.
Parameter
Acc (95% CI)
PET-CT
94% (90; 98)
MRI
96% (86; 100)
Based on the data above, the diagnostic accuracy of PET-CT in M-staging is lower than
the diagnostic accuracy of MRI.
Graph 36 illustrates a meta-analysis of the proportion of patients for whom M-staging
using PET-CT vs. MRI gave results consistent with the index test.
237

Graph 36.
Odds ratio for the consistency of M-staging results with the reference test in patients with neoplasm in varied
locations, PET-CT vs MRI
238
Antoch 2003 1,18 (0,33, 4,42)
Schmidt 2005 0,32 (0,00, 39,00)
Meta-analysis result [fixed]
0,2 0,5 1 2 5 10 100
Odds ratio (95%
confidence interval)
1,00 (0,34, 2,95)
The odds ratio calculated by meta-analysis is 1.00 (95% CI: 0,34; 2,95). It means that the
probability of the results of M-staging being consistent with the reference method is
identical for both of the diagnostic technologies compared, and the result is not
statistically significant.
The parameters of the diagnostic efficacy of the methods compared (accuracy,
specificity and sensitivity) presented in the trials are listed in table 113. In Antoch 2003, the
authors provide efficacy data for both methods in detecting metastasis in individual organs.
Table 113.
Evaluation of the efficacy of PET-CT and MRI in detecting distant metastasis in patients with neoplasm in
varied locations.
Parameter
Se
Metastasis
location
lungs
liver
bones
other organs
total
lungs
liver
bones
PET-CT
n/N (%)
(89%)
(86%)
(62%)
(73%)
(93%)
(94%)
(96%)
(96%)
Antoch 2003
MRI
n/N (%)
(82%)
(93%)
(85%)
(67%)
(90%)
(94%)
(95%)
(92%)
Statistical
significance
PET-CT vs MRI
no data
no data
no data
no data
NS
no data
no data
no data
PET-CT
n/N (%)
no data
no data
no data
no data
(100%)
no data
no data
no data
Schmidt 2005
MRI
n/N (%)
no data
no data
no data
no data
(100%)
no data
no data
no data
Statistical
significance
PET-CT vs MRI
no data
no data
no data
no data
NS
no data
no data
no data

Sp
Acc
other organs
total
lungs
liver
bones
other organs
total
(73%)
(95%)
(89%)
(95%)
(92%)
(95%)
92/98
(94%)
(67%)
(95%)
(82%)
(95%)
(91%)
(93%)
91/98
(93%)
no data
NS
no data
no data
no data
no data
p > 0,99
no data
(98%)
no data
no data
no data
no data
97%
no data
(100%)
no data
no data
no data
no data
100%
no data
NS
no data
no data
no data
no data
p > 0,99
The sensitivity of PET-CT for individual organs was 93-100%, and that of magnetic
resonance was 90-100%. PET-CT specificity is 95% and 98% and MRI specificity was 95%–
100%.
Based on Antoch 2003, PET-CT sensitivity is higher compared to MRI in detecting
metastasis to lungs (89% vs. 82%), organs total (93% vs. 90%) and organs other than lungs,
liver and bones (73% vs. 67%); in detecting metastasis to liver and bones, PET-CT sensitivity
is lower than that of MRI, and was 86% vs. 93% for liver, and 62% vs. 85% for bones.
The specificity and accuracy of PET-CT scanning were higher or equal to the respective
parameters of MRI in detecting metastasis in all the organs scanned.
Schmidt 2005 reported additional diagnostic parameters calculated based on the
number of pathological lesions. Detailed results are presented in table 114.
Table 114.
Parameters of diagnostic efficacy in M-staging with the use of PET-CT and MRI, calculated in Schmidt 2005 based on
the number of pathological changes.
Parameter
Se
n/N
Sp
n/N
Acc
Number
of confirmed
pathological
changes
268
PET-CT
82%
157/191
82%
63/77
MRI
96%
184/191
82%
63/77
With respect to the number of organs affected by metastases, PET-CT sensitivity is
lower compared to MRI (82% vs. 96%), and specificity is the same for both (82%).
82%
92%
Statistical
significance
(PET-CT vs MRI)
no data
PET-CT was more accurate compared to MRI in detecting metastasis to lungs (37 vs. 36)
and to soft tissues (6 vs. 3), and MRI was more accurate compared to PET-CT in
detecting metastasis to liver (71 vs. 62) and bones (76 vs. 50).
Metastases with the median size was 14 mm (SD = 13 mm, n = 40) were detected using
PET-CT, and for MRI the median size of metastases was 12 mm (SD = 11, n = 61).
NS
no
dat
a
239

240
17.1.4.5 TNM staging system
In Antoch 2003 and Schmidt 2005, the stage of disease was assessed based on the TNM
staging system created by the AJCC (American Joint Committee on Cancer).
Table 115 provides detailed results concerning the consistency between the
diagnostic methods evaluated, and the reference test, as described by the authors of
each study.
Table 115.
Consistency between the reference test and cancer staging results (TNM feature) in patients with neoplasm in varied
locations, PET-CT vs. MRI
Study
Antoch
2003
N
98
Correct
staging
(accuracy)
n (%)
75 (77%)
PET-CT
Overstaged
11 (11%)
Schmidt
2005
38 36* (96%) no data
*Calculated based on data available
Incorrect staging
n (%)
Understaged
12 (12%)
no data
Correct
staging
(accuracy)
n (%)
53 (54%)
35* (91%)
MRI
Overstaged
19 (19%)
no data
Incorrect staging
n (%)
Based on the data above, the proportion of correctly staged patients was higher
for PET-CT than for magnetic resonance (MRI) in both studies. PET-CT accuracy is of 77
and 96%, and the accuracy of MRI is 54% and 91%. Antoch 2005 reports that the
differences in diagnostic accuracy of the testing technologies compared were
statistically significant. The differences in Schmidt 2005 were not statistically significant.
Understaged
26 (27%)
no data
In Antoch 2003, the proportion of overstaged and understaged results was 11% and 12%
respectively for PET-CT. and 19% and 27% respectively for MRI.
Graph 37 illustrates a meta -analysis of the accuracy of clinical TNM-staging for PET-CT. As
there was significant heterogeneity between trials (p = 0.0072), the meta-analysis was
performed using the random effects method.

Graph 37.
Meta-analysis of the diagnostic accuracy of PET-CT in cancer staging in patients with neoplasm in varied locations
Antoch 2003 0,77 (0,67, 0,85)
Schmidt 2005 0,95 (0,82, 0,99)
Meta-analysis result [random] 0,86 (0,65, 0,98)
The diagnostic accuracy of PET-CT in TNM-staging as calculated by meta-analysis of two
studies is 86% (95% CI: 65; 98).
0,6 0,7 0,8 0,9 1,0
Diagnostic accuracy (95% confidence interval)
Graph 38 illustrates a meta-analysis of the diagnostic accuracy of magnetic resonance in
cancer staging. As there was significant heterogeneity between trials, the meta-analysis
was performed using the random effects method (p < 0,0001).
241

Graph 38.
Meta-analysis of the diagnostic accuracy of MRI in cancer staging in patients with neoplasm in varied locations.
Meta-analysis result
[random]
242
Antoch 2003 0,54 (0,44, 0,64)
Schmidt 2005 0,92 (0,79, 0,98)
The diagnostic accuracy of MRI in cancer staging (TNM feature) as calculated by meta-
analysis of the two studies is 75% (95% CI: 33; 99).
The average values of the diagnostic accuracy of PET-CT and MRI in cancer staging (TNM)
are presented in table 116.
Table 116.
Average values of PET-CT and MRI accuracy in TNM-staging in patients with neoplasm in varied locations.
Parameter
Acc (95% CI)
0,0 0,2 0,4 0,6 0,8 1,0
PET-CT
86% (65; 98)
MRI
75% (33; 99)
Based on the data above, the diagnostic accuracy of PET-CT in cancer staging (TNM) is
higher compared to magnetic resonance (MRI).
Diagnostic accuracy (95% confidence interval)
0,75 (0,33, 0,99)
Graph 39 illustrates a meta-analysis of the proportion of patients for whom the results
of cancer staging using PET-CT or MRI scanning were consistent with the reference test.

Graph 39.
Odds ratio for the consistency of TNM-staging results with the reference test in patients with neoplasm in varied
locations, PET-CT vs MRI
Antoch 2003 2,77 (1,44, 5,38)
Schmidt 2005 1,54 (0,17, 19,41)
Meta-analysis result
[fixed]
0,1 0,2 0,5 1 2 5 10 100
The odds ratio as calculated by meta-analysis amounts to 2,61 (95% CI: 1.46; 4.67), so the
probability of cancer staging results being consistent with the reference test for PET-CT is 2.61
times higher than for MRI. The result is statistically significant.
In order to obtain one additional case of correct cancer staging it is necessary to use PET-CT
instead of MRI with 6 patients, NNT = 6 (95% CI: 4; 15).
17.1.4.6 Impact on therapy
Information on how the use of PET-CT instead of classical imaging methods (MRI) causes
therapy tp be changed is provided only in one of the studies analyzed (Antoch 2003).
The results presented by the authors of the study are given in table 117.
Table 117.
Influence of PET-CT vs MRI scanning results on therapy changes in patients with neoplasm in varied locations
Therapeutic decision
Other therapeutic decisions; total
Palliative treatment instead of operation
Operation instead of palliative treatment
Neoadjuvant therapy instead of operation
Limited surgery instead of extensive surgery
Odds ratio (95% confidence interval)
PET-CT instead of MRI
n/N (%)
12/98 (12%)
4/98 (4%)
5/98 (5%)
1/98 (1%)
2/98 (2%)
2,61 (1,46, 4,67)
MRI instead of PET-CT
n/N (%)
2/98 (2%)
1/98 (1%)
1/98 (1%)
0/98 (0%)
0/98 (0%)
Staging the disease with the use of PET-CT instead of MRI resulted in a different
243

ecommendation for further treatment in the case of 12 patients (12%), and when magnetic
resonance was used instead of PET-CT therapeutic decision in were changed for 2 patients
(2%).
244
17.1.4.7 Safety
No information on the safety of the diagnostic procedures applied is given in either of the
studies under analysis.
17.1.5. Results
Two primary clinical trials (Antoch 2003 and Schmidt 2005) were found, where the diagnostic
efficacy of PET-CT in the staging of neoplasms in varied locations was directly compared to
magnetic resonance imaging – MRI (N=136). Both trials were qualified based on a reference
methods, which in this part of the study were histopathological examination and/or clinical
follow-up.
A single-trial-based rating of the efficacy of primary and secondary neoplasm detection
showed that the sensitivity of PET-CT is higher in comparison to magnetic resonance imaging:
100% (95% CI: 59; 100) vs. 86% (95% CI: 42; 100). The specificity of both methods was 100%. The
differences between groups were not statistically significant.
For T-staging, the diagnostic accuracy established by meta-analysis of two trials was 89% (95%
CI: 68; 100) for PET-CT and 79% (95% CI: 26; 99) for MRI. Calculated by meta-analysis, the odds
ratio for T-staging results being consistent with the reference test using PET-CT versus MRI, is 3.29
(95% CI: 1.37; 7.90), and the value is statistically significant; NNT=7 (95% CI: 4; 20).
Analysis showed that the PET-CT method was more accurate compared to MRI in the
assessment of the involvement of lymph nodes by cancer metastasis (N status). The accuracy
established by meta-analysis is 94% (95% CI: 89; 97) for PET-CT, as compared to 80% for MRI (95%
CI: 73; 86). The odds of the staging results for the involvement of lymph nodes by cancer
metastasis being consistent with the reference test were four times higher for the PET-CT method
than for magnetic resonance. The result is statistically significant; OR = 4.00 (95% CI: 1.74; 9.19);
NNT = 8 (95% CI: 5; 17). The diagnostic sensitivity reported by the authors is 95% and 100% for PET-
CT, and is 79% for MRI, while specificity is 92%-95% for PET-CT and 78%-95% for MRI.
Established by meta-analysis of two trials, the diagnostic accuracy of PET-CY vs. CT in distant
metastasis staging (M status) is 94% (95% CI: 90; 98) for PET-CT and 96% (95% CI: 86; 100) for
magnetic resonance. The odds of obtaining reference method-consistent staging results for
distant metastasis using the PET-CT method are the same as the odds for magnetic resonance:
OR = 1.00 (95% CI: 0.34; 2.95). The result is statistically significant. Based on two trials included in
this analysis, sensitivity is 93% and 100% for PET-CT and 90% and100% for MRI. Specificity is 95% and

98% for PET-CT and 95% and 100% for MRI.
A review of the diagnostic accuracy of the methods in total staging of cancer (TNM staging)
was conducted by meta-analysis of two trials, which showed that the accuracy is higher for PET-
CT than for MRI. The values are 86% (95% CI: 65; 98) and 75% (95% CI: 33; 99) respectively. The
odds of obtaining results consistent with reference test are 2.61 times higher for PET-CT than for
MRI. The result is statistically significant; OR = 2.61 (95% CI: 1.46; 4.67); NNT = 6 (95% CI: 4; 15).
The use of PET-CT instead of MRI in the staging of cancer was conducive to changes in
therapeutic recommendations in 12% of patients suffering from cancer with varied locations,
while the use of MRI instead of PET-CT was conducive to changes in therapeutic
recommendations in 2% of patients
In patients with various cancer locations, the PET-CT method shows higher diagnostic efficacy
in comparison to MRI in detecting primary and secondary neoplasm, as well as in the staging of
tumor (T-status), lymph nodes involvement (N-status), and distant metastases (M-status) and
combined staging (TNM staging).
245

246
17.2. Neoplasm in varied locations: disease staging(PET-CT
versus CT)
17.2.1. Results of trial search
As a result of searching medical databases only one primary retrospective study was
found (Antoch 2004;tab. 139, app. 18.1), where PET-CT scanning was compared directly
with CT in staging neoplasm in varied locations.
Both methods were verified based on a reference test (histologic study and/or clinical
observation).
17.2.2. Population characteristics
Included in the trial under analysis were patients with suspected malignant tumor or
with confirmed cancer.
Staging was performed for 112 patients (43%), and post-treatment restaging for 148
patients (57%).
Table 118 provides initial characteristics of patients included in Antoch 2004.
Table 118.
Initial characteristics of patients with neoplasm in varied locations included in Antoch 2004.
Cancer type
(proportion of patients)
Parameter
Population number
Median age
[years]
Male proportion
lung cancer
head and neck cancer
esophageal cancer
liver cancer
thyroid cancer
cancer of unknown primary origin
genitourinary cancer
soft tissues or bone cancer
breast cancer
adrenal cancer
pleural cancer
Antoch 2004
260
56
26%
22%
18%
17%
9%
9%
8%
7%
4%
2%
2%
2%

Excluded from the trial were patients with no prior disease staging using the TNM system
or clinical data such as histopathological examination of primary tumor or at least 6-
months-long clinical observation.
Out of 400 patients initially included in the study, 140 patients were excluded for the
reasons above (120 patients for insufficient follow-up, and 20 for unavailability of TNM-
staging). Ultimately, 260 patients were included in the trial. 55 were given treatment
during or after PET-CT scanning. The authors noted that 123 untreated patients included in
the trial had had typical indications (as defined by the National Coverage Analysis, USA) 16
for PET scanning, refunded by the Centers of Medicare and Medicaid Services, USA.
The median age of the participants in the trial was 56, and the male proportion was 26%.
17.2.3. Description of intervention
17.2.3.1 PET-CT
In Antoch 2004, the Biograph system produced by Siemens Medical Solutions
(Hoffman Estates, USA) was used for disease staging. The system consisted of a single-
slice spiral CT and a full-ring PET.
Whole body scans (from head to upper thigh) were taken using PET-CT for 212 patients
(82%), and for the remaining 48 patients (18%) smaller areas were scanned. FDG (fluoro-
deoxy-glucose) with the activity of 350 MBq was given as a radiopharmaceutical 60
minutes prior to PET-CT tests. Glucose concentration in blood was checked before
administering FDG.
Table 119 contains a detailed description of the PET-CT tests.
Table 119.
Description of the intervention in Antoch 2004.
PET-CT scanner
type
Biograph
PET-CT scanner
manufacturer
Siemens Medical
Solutions (Hoffman
Estates, USA)
Radiopharmaceutical
type and
administration method
FDG intravenous
Study range
whole body (82%)
smaller area
(12%)
Radiomarker
activity
[MBq]
In Antoch 2004, FDG was given intravenously to all patients without contraindication
for the purposes of PET-CT scanning.
Two radiologists and two nuclear medicine consultants assessed the PET-CT images.
PET-CT as well as CT scans were carried out using the same PET-CT machine, however PET-CT
16 National Coverage Determinations: Positron Emission Tomography (PET) Scans, Centers for
Medicare and Medicaid Services. http://cms.hhs.gov/mcd/viewdecisionmemo.asp?id=85
350
247

scans were analyzed 12 weeks after the assessment of CT images. Identical criteria were used
for the assessment of cancer malignancy using CT and PET-CT, and all assessors had the
same information available for all patients.
248
17.2.3.2 Diagnostic trial compared
Antoch 2004 compared PET-CT with CT using a single slice-spiral CT that was an
integral part of PET-CT system.
Table 120 provides a detailed description of the CT tests performed in Antoch 2004.
Table 120.
Description of the diagnostic CT tests performed in Antoch 2004
CT scanner type
no data
CT scanner manufacturer
Siemens Medical
Solutions
Contrast medium type
and administration
method
intravenous contrast
medium
Scope of test
whole body (82%)
smaller area (18%)
In Antoch 2004, whole body scans that corresponded to the coverage of the PET-CT
tests (from head to upper thigh) were performed for 82% of patients, and for 18% smaller
areas were scanned.
17.2.3.3 Reference test
In Antoch 2004, histopathological examination and/or clinical observation were the
reference test. In line with the AJCC classification (American Joint Committee on Cancer),
cancer staging was done by a medical board consisting of a nuclear medicine consultant
and a radiologist. All clinical and radiological data for all the patients were provided to the
medical board. The medical board members had not participated in disease staging based
on the imaging techniques compared. Cancer staging was based on histopathological tests
and data obtained through observation, including clinical examinations, laboratory tests,
radiological procedures and histopathological tests that followed a surgery carried out later.
For 77 patients (30%), their tumors were resected and T-staged so for these patients
only the diagnostic efficacy of the procedures compared was evaluated. The involvement
of lymph nodes (N feature) and the presence of distant metastases (M feature) were
identified following a surgery for 71 (28%) and 57 (22%) patients respectively. However, the
imaging methods were compared with respect to these two features for 260 trial
participants. The average time observation, which was the reference method for N- and M-
staging, was 311 days (SD = 125 days). This relatively short observation time was caused by
the patient's death due to cancer.

17.2.4. Findings
17.2.4.1 T-staging
T-staging was done based on the TNM staging system designed by the AJCC
(American Joint Committee on Cancer). PET-CT and CT method results were verified
histopathologicaly. The total of 77 patients were analyzed following tumor resections.
The consistency between the T-staging done using the diagnostic methods compared
and the reference test as described in Antoch 2004 is presented in table 121.
Table 121.
Consistency of T-staging with the reference test in patients with neoplasm in varied locations in Antoch 2004, PET-CT
vs CT
N*
Correct staging
(accuracy)
n (%)
PET-CT
Overstaged
Incorrect staging
n (%)
Understaged
77 63 (82%) 6 (8%**) 8 (10%**)
*Number of patients verified using the reference test
**Calculated based on data available
Correct staging
(accuracy)
n (%)
51 (66%)
CT
Overstaged
11 (14%**)
Incorrect staging
n (%)
Understaged
15 (19.5%**)
Based on the results in Antoch 2004, the proportion of correctly staged patients was
higher for PET-CT than for CT and the result was statistically significant (p = 0.0018). PET-CT
accuracy is 82% (95% CI: 71; 90), and CT accuracy is 66% (95% CI: 55; 77). Overstaged and
understaged results represented 8% and 10% of total results respectively for PET-CT, 14%
and 19,5% respectively for CT,.
Calculated based on the results above, the odds ratio for the consistency of T-staging
with the reference test for patients with neoplasm in varied locations is 2.29 (95% CI: 1.03;
5.25). It means that the probability of consistency between T-staging and the reference
test is 2.29 times higher for PET-CT than for CT. The result is statistically significant.
In order to obtain one additional case of correct T-staging it is necessary to use PET-CT
instead of CT with 7 patients, NNT = 7 (95% CI: 4; 59).
17.2.4.2 N-staging
In Antoch 2004, N-staging was based on the TNM lung cancer staging system designed
by AJCC (American Joint Committee on Cancer).
Antoch 2004 evaluated the diagnostic accuracy of PET-CT in comparison with CT in 260
patients; in 72 of them the results were verified histopathologically, and for the remaining
participants, clinical observation was reference test.
The consistency between the N-staging results of the diagnostic methods compared
and the reference test in Antoch 2004 is presented in table 122.
249

Table 122.
Consistency between the reference test and N-staging results in patients with carcinomas in varied locations, PET-CT
vs CT
N*
250
Correct staging
(accuracy)
n (%)
PET-CT
Overstaged
Incorrect staging
n (%)
Understaged
260 240 (92%) 12 (5%**) 8 (3%**)
*Number of patients verified using the reference test
**Calculated based on data available
Correct staging
(accuracy)
n (%)
197 (76%)
CT
Overstaged
27 (10%**)
Incorrect staging
n (%)
Understaged
36 (14%**)
Based on the data above, the proportion of correctly staged patients was higher for
PET-CT than for CT. The diagnostic accuracy for PET-CT is 92% (95% CI: 88; 95), and the
diagnostic accuracy for CT is 76% (95% CI: 70; 81). Overstaged and understaged results
represented 5% and 3% of results total respectively for PET-CT, and 10% and 14%
respectively for CT.
The authors of Antoch 2004 noted that the differences in accuracy between the
diagnostic methods compared was statistically significant (p < 0,0001).
The odds ratio calculated based on the results in Antoch 2004 is 3.84 (95% CI: 2.19;
6.93) so the probability of obtaining consistency between the reference test and N-
staging using PET-CT is almost four times higher than the odds ratio for CT.
In order to obtain one additional N-staging consistent with the reference test it is necessary
to use PET-CT instead of CT with 7 patients with neoplasm in varied locations; NNT = 7 (95% CI:
5; 10).
17.2.4.3 Assessment of distant metastasis
Antoch 2004 cancer staging was done based on the TNM system with respect to distant
metastasis.
The authors of the trial evaluated the diagnostic accuracy of PET-CT as compared to CT in
260 patients, and histopathological tests were done for 57 patients, while for the remaining
patients clinical observation was used as reference test.
The consistency between the reference test and the M-staging results obtained using the
diagnostic methods compared as described by the authors of the trial are given in table
123.

Table 123.
Consistency between the reference test and M-staging in patients with neoplasm in varied locations, PET-CT vs. CT
N*
Correct staging
(accuracy)
n (%)
PET-CT
Overstaged
Incorrect staging
n (%)
Understaged
260 248 (95%) 4 (1,5%**) 8 (3%**)
*Number of patients verified using the reference test
**Calculated based on data available
Correct staging
(accuracy)
n (%)
230 (88%)
CT
Overstaged
7 (3%**)
Incorrect staging
n (%)
Understaged
23 (9%**)
In Antoch 2004, a higher diagnostic accuracy was observed for PET-CT study as
compared to CT, and the differences were statistically significant (p = 0.0001). Based on
the data above, PET-CT accuracy is 95% (95% CI: 92; 98), and CT accuracy is 88% (95%
CI: 84; 92). The proportions of overstaged and understaged results represented 1.5% and
3% of results total respectively for PET-CT, and 3% and 9% respectively for CT.
The odds ratio calculated based on the results of a single trial is 2.70 (95% CI: 1,30;
5,92), which means that the probability of obtaining M-staging results consistent with
the reference tests is 2.7 times higher for PET-CT than for CT, and the result is statistically
significant.
In order to obtain one additional case of correct M-staging it is necessary to use PET-CT
scanning instead of CT with 15 patients, NNT = 15 (95% CI: 7; 44).
The parameters of the diagnostic efficacy of the methods compared (accuracy,
specificity and sensitivity) presented in the trial are listed in table 124. In Antoch 2004, the
authors additionally provided data on the efficacy of both methods in detecting metastasis in
individual organs.
Table 124.
Evaluation of the efficacy of PET-CT and CT in detecting metastasis in patients with neoplasm in varied locations
Parameter
Se (95% CI)
Sp (95% CI)
Acc (95% CI)
Location of metastases
lungs
liver
bones
total
lungs
liver
bones
total
lungs
liver
PET-CT
92% (83; 97)
95% (86; 99)
81% (62; 94)
94% (88; 97)
93% (88; 96)
97% (93; 99)
99% (97; 100)
97% (92; 99)
93% (no data)
97% (no data)
CT
83% (72; 91)
86% (75; 94)
48% (29; 68)
82% (74; 88)
91% (85; 95)
95% (90; 98)
98% (95; 99)
95% (89; 98)
89% (no data)
93% (no data)
251

252
bones
total
97% (no data)
95% (92; 98)
93% (no data)
88% (84; 92)
The sensitivity of PET-CT for individual organs was 94%, and that of CT was 82%. PET-CT
specificity is within the range of 97%, and MRI specificity was 95%.
Based on Antoch 2004, the diagnostic specificity, sensitivity and accuracy of PET-CT
scanning were higher compared to CT in detecting metastasis to lungs, liver and bones, as
well as to all organs total.
Antoch 2004 presented additional diagnostic parameters calculated for a population
of untreated patients (n = 123) with typical indications for PET scanning refunded by the
Centers of Medicare and Medicaid Services, USA.
Table 125.
Parameters of the diagnostic efficacy of M-staging using PET-CT and CT in patients with typical indications for PET in
Antoch 2004.
Parameter
Se (95% CI)
Sp (95% CI)
Acc (95% CI)
PET-CT
97% (90; 100)
96% (87; 100)
97% (no data)
CT
84% (73; 92)
95% (85; 99)
89% (no data)
Statistical
significance
(PET-CT vs CT)
no data
no data
no data
With respect to patients with typical indications for PET, the sensitivity, specificity and
diagnostic accuracy of PET-CT were higher compared to CT and stood at 97% vs. 84%,
96% vs. 95%, 97% vs. 89% respectively. The trial provides no information on the statistical
significance of the differences between the methods compared.
17.2.4.4 TNM staging system
In Antoch 2004, disease staging was done based on the TNM system designed by the
AJCC (American Joint Committee on Cancer).
Detailed data on the consistency between the reference (index) test and the diagnostic
technologies under assessment as described by the authors are given in table 126.

Table 126.
Consistency between the reference test and cancer staging in patients with neoplasm in varied locations, PET-CT vs.
CT
N
Correct staging
(accuracy)
n (%)
PET-CT
Overstaged
260 218 (84%) 18 (7%)
*Calculated based on data available
Incorrect staging
n (%)
Understaged
24 (9%)
Correct staging
(accuracy)
n (%)
163 (63%)
CT
Overstaged
36 (14%)
Incorrect staging
n (%)
Understaged
61 (23,5%)
Based on the data above, the proportion of correctly staged patients was higher for
PET-CT than for CT. The accuracy of PET-CT was 84% (95% CI: 79; 88), and the accuracy
of CT was 63% (95% CI: 57; 69). Antoch 2004 reports that the differences in diagnostic
accuracy between the scanning technologies were statistically significant (p < 0.0001).
In Antoch 2004, the proportions of overstaged and understaged results were 7% and 9%
respectively for PET-CT, and 14% and 23.5% respectively for CT.
As calculated based on the data above, the odds ratio is 3.09 (95% CI: 2.00; 4.80),
so the probability of cancer staging consistent with the reference test is more than
three times higher for PET-CT than for CT. The difference is statistically significant.
In order to obtain one additional case of correct cancer staging it is necessary to use PET-
CT instead of CT with 5 patients, NNT = 5 (95% CI: 4; 8).
17.2.4.5 Impact on therapy
Antoch 2004 reports on how the use of PET-CT scanning instead of CT caused the
therapeutic procedure to be changed.
Clinically significant impact on treatment was defined in the trial as a change of
recommendation from surgery to palliative treatment, from neoadjuvant to surgery, and
from palliative to neoadjuvant treatment.
The results reported in Antoch 2004 are given in table 127.
Table 127.
Influence of the diagnostic methods compared on therapy in patients with neoplasm in varied locations, PET-CT vs.
CT
Therapeutic decision
Other therapeutic decisions; total
*Calculated based on data available
PET-CT instead of CT
n/N (%)
39/260 (15%*)
CT instead of PET-CT
n/N (%)
2/260 (0,8%*)
Staging the disease using PET-CT scanning instead of CT led to different
recommendations for further treatment in the case of 39 patients (15%), and the use of CT
instead of PET-CT resulted in changing the therapy for 2 patients (0.8%).
253

254
17.2.4.6 Safety
No information on the safety of the diagnostic procedures used was found in the trial
under analysis.
17.2.5. Results
One primary, retrospective clinical trial (Antoch 2004) was identified, where the diagnostic
efficacy of PET-CT in the staging of neoplasm with varied locations was compared directly with
CT (N=260). Both testing methods were verified against the reference methods, i.e.
histopathological examination and/or clinical follow-up.
For T-staging, the diagnostic accuracy was 82% (95% CI: 71; 90) for PET-CT, and 66% (95% CI:
55; 77) for CT. The differences between the groups under discussion are statistically significant (p
= 0.0018). The odds of obtaining a T-status consistent with the reference method is 2.29 times
higher for PET-CT versus CT. The result is statistically significant; OR = 2.29 (95% CI: 1.03; 5.25), NNT =
7 (95% CI: 4; 59).
Analysis showed that the PET-CT method is statistically significantly more accurate than CT in
the staging of the involvement of lymph nodes (N status). The diagnostic accuracy is 92% (95%
CI: 88; 95) for PET-CT and 76% (95% CI: 70; 81) for CT. The odds of obtaining lymph nodes
involvement staging results consistent with the reference test is nearly four times higher for the
PET-CT procedure versus CT. The result is statistically significant; OR = 3.84 (95% CI: 2.19; 6.93), NNT
= 7 (95% CI: 5; 10).
The diagnostic accuracy of the methods compared in the staging of distant metastases (M
status) is 95% (95% CI: 92; 98) for PET-CT and 88% (95% CI: 84; 92) for CT, and the differences
between the methods are statistically significant (p=0.0001). The odds of M-staging results being
consistent with the reference method is 2.7 times higher for PET-CT versus CT. The result is
statistically significant; OR = 2.70 (95% CI: 1.30; 5.92), NNT = 15 (95% CI: 7; 44).
Sensitivity, specificity and accuracy are higher for PET-CT compared to CT, including in staging
metastases to lungs, liver and bones, as well as organs total.
Analysis showed that the diagnostic accuracy of the methods under assessment in cancer
staging (TNM staging) is higher when the PET-CT method is used compared to CT. The accuracy
of PET-CT is 84% (95% CI: 79; 88), and for CT it is 63% (95% CI: 57; 69). The odds of obtaining staging
results consistent with the reference standard is more than three times higher for PET-CT
compared to CT. The result is statistically significant, OR = 3,09 (95% CI 2.00; 4.80), NNT = 5 (95% CI:
4; 8).
Using PET-CT instead of CT in disease staging led to a different recommendation for further
treatment in 15% patients. Using CT instead of PET-CT caused therapeutic decisions to be

changed for 0.8% patients
17.3. Cancers of unknown primary origin: diagnostic efficacy
17.3.1. Results of trial search
Two primary clinical trials were found: Freudenberg 2005 (tab. 142, app. 18.1), Gutzeit
2005 (tab. 143, app. 18.1) that compared directly the diagnostic efficacy of the PET-CT
method with CT in locating focuses of primary carcinoma in metastatic patients.
The scanning methods compared were verified based on reference tests:
histopathological examination and/or clinical observation in Freudenberg 2005, and
histopathological examination in Gutzeit 2005.
As the trials were executed at the same health center (University Hospital Essen), and the
patients recruitment periods coincided, the fact that the population of Freudenberg 2005
represented a subgroup of Gutzeit 2005 population was taken into account. However, in view
of differences in cancer scanning methodology as reported in the trials, and differences in
final trial results, the populations in the two trials included in this analysis are deemed
disparate.
17.3.2. Population characteristics
Patients with metastasis of unknown origin participated in the two trials.
In Freudenberg 2005, patients with metastasis to neck lymph nodes participated, while in
Gutzeit 2005, and patients with metastasis both to neck and outside neck participated.
Patients with metastasis confirmed histologically or cytologically as well as patients
with the disease staged clinically, endoscopically, sonographically or radiologically
were included in Freudenberg 2005. CT of the neck or head had not been done for any
of the patients.
In Gutzeit 2005 study, metastases to neck lymph nodes were detected in 40% of
patients and metastasis to other body parts in 60% of patients. A histological test of at
least one metastasis spot was done for each patient. All patients were interviewed, and
results of detailed medical examinations, laboratory tests, imaging tests and endoscopic
procedures were collected.
Neither of the trials provided detailed patient inclusion or exclusion criteria.
Table 128 contains initial characteristics of patients included in each trial.
255

Table 128.
Initial characteristics of patients included in trials.
256
Histology
(patient proportion)
Parameter
Size of population
Mean age [years]
Male proportion
adenocarcinoma
squamous cell
carcinoma
Freudenberg
2005
21
64
76%
19%
67%
anaplastic carcinoma
14%
* average weighted by the number of patients participating in the two trials
Gutzeit
2005
21 and 45 patients were included in Freudenberg 2005 and Gutzeit 2005 trials
respectively. The total of 66 patients were included in the analysis with the mean age of 59-
64 and the male proportion of 58–76%. In Freudenberg 2005, squamous cell carcinoma was
identified in most patients, while in Gutzeit 2005, metastases had the form of
adenocarcinoma in most patients.
17.3.3. Description of intervention
17.3.3.1 PET-CT
The Biograph system produced by Siemens Medical Solutions (Hoffman Estates, USA)
was used for disease staging in both trials included in analysis. The system consisted of a
dual-slice spiral computed tomograph (CT) and full-ring PET tomograph with BGO
detectors.
FDG (fluoro-deoxy-glucose) was used as radiopharmaceutical in both trials, its activity
ranging from 350 MBq in Gutzeit 2005, to 360 MBq in Freudenberg 2005. The
radiopharmaceutical was administered 60 minutes prior to PET-CT scanning in both studies.
Patients could not eat for at least 4 hours before the radiopharmaceutical was given in
Gutzeit 2005, and for 10 hours in Freudenberg 2005. In both studies, the level of glucose
concentration was tested.
In Gutzeit 2005, whole body scans were done, and in Freudenberg 2005, scans of head
and neck were taken, followed after 70-75 minutes by additional whole body scans (from
thorax to pelvis).
Table 129 contains a detailed description of the PET-CT tests.
45
59
58%
56%
33%
11%
Total
66
61*
64%
44%
44%
12%

Table 129.
Description of intervention
Study
Freudenberg
2005
Gutzeit
2005
PET-CT
scanner
type
Biograph
Biograph
PET-CT scanner
manufacturer
Siemens Medical
Solutions (Hoffman
Estates, USA)
Siemens Medical
Solutions (Hoffman
Estates, USA)
Radiopharmaceu
tical type and
administration
method
FDG
intravenous
FDG
intravenous
Study range
head and
neck; whole
body
whole body
Radiomarker
activity [MBq]
PET-CT images included in the analysis were assessed by two nuclear medicine
consultants and two radiologists blinded to the results of other imaging studies.
I Gutzeit 2005 noted that the medical assessors had 2 years’ experience with PET-CT. In
order to avoid mistakes in locating primary tumors, the time interval between scan reading
sessions for particular imaging methods was 4 weeks, and the images were analyzed in a
random order.
17.3.3.2 Diagnostic test compared
In the two trials under analysis (Freudenberg 2005, Gutzeit 2005), PET-CT scanning was
compared with CT.
In both clinical trials, CT imaging was done as part of PET-CT scanning, and the
computed tomograph was an integral component of the hybrid scanner. For both studies
the spiral computed tomograph Somatom Emotion produced by Siemens Medical
Solutions was used.
Table 130 contains a detailed description of Ct tests in each study.
Table 130.
Description of the diagnostic tests compared
Study
Freudenberg
2005
CT scanner type
Somatom Emotion
CT scanner
manufacturer
Siemens Medical
Solutions
Contrast medium type
and administration
method
Xenetix 300
contrasts medium,
intravenous
360
350
Study range
head and neck
whole body
257

258
Gutzeit 2005
Somatom Emotion
Siemens Medical
Solutions
Xenetix 300
contrasts medium,
intravenous
whole body
In order to perform CT as part of PET-CT testing, iodinated Xenetix 300 (Guerbet GmbH,
Sulzbach, Germany) was given intravenously as contrast medium with 300 mg/ml of iodine
in both trials. 140 ml was given in Gutzeit 2005 while in Freudenberg 2005, 60 ml was given
for head and neck scanning, and 90 ml for whole body scanning.
Intestine outline was achieved by administering 1000 ml of barium sulfate or 1500 ml of
0.2% solution of locust bean gum, and 2.5% solution of mannitol.
A blind analysis of CT images was done by two radiologists.
17.3.3.3 Reference test
The reference method in Freudenberg 2005 was histopathological examination and
clinical follow-up, while in Gutzeit 2005, results were verified histologically.
In Freudenberg 2005, histopathological examination was performed for 67% patients, and
results verification based on clinical follow-up (at least 9 months) was performed for 33% of the
patients included in analysis. During the follow-up, panendoscopy with biopsy of the most
probable locations of primary tumor and USG was performed for 33% patients; CT and/or MRI
was performed for 29% patients; and diagnostic removal of tonsils (tonsillectomy) with
additional biopsy were performed for 19% patients.
Gutzeit 2005 provides no detailed description of the reference test.
17.3.4. Findings
17.3.4.1 Diagnostic accuracy in detecting primary cancer of unknown origin
In both studies included in this analysis (Freudenberg 2005, Gutzeit 2005), the efficacy of
detecting carcinomas of unknown location using PET-CT scans compared to CT for metastasis
patients was evaluated.
In Freudenberg 2005, the location of primary carcinoma was histologically confirmed in
14 out of 21 patients with metastasis to neck. Out of that number, 4 patients were
diagnosed with oral cavity cancer, 3 with bronchial cancer, 2 with laryngeal cancer and
non-Hodgkin lymphoma, and single patients were diagnosed with esophageal, thyroid and
salivary gland cancers. In 7 patients no primary tumor was detected using any of the
diagnostic methods or during the follow-up period since they took combined radio-
chemotherapy.

In Gutzeit 2005, the total of 17 primary tumors were diagnosed: 8 lung cancer cases, 3
breast cancers, 2 gastric cancers, 2 mandible adenocarcinomas, one tongue base
cancer and 1 esophageal cancer.
The number of patients with true positive (TP), false positive (FP), false negative (FN)
results of PET-CT and CT is given in table 131. Patients without primary tumor located using
either PET-CT or the reference method are included under false negative.
Table 131.
Number of metastasis patients with TP, FP, FN and TN results in the diagnostics of primary tumor using PET-CT
and CT
Study
Freudenberg 2005
Gutzeit 2005
Population
neck area
metastasis
neck area
metastasis
metastasis
outside neck
total metastasis
*Calculated based on data available
TP
12
6
9
15
PET-CT
Gutzeit 2005 noted that the reason for three false positive results for PET-CT scans were
colitis, inflammation of esophagus and lung infarction.
PET-CT and CT sensitivity eating for each study are given in table 132.
Table 132.
PET-CT sensitivity vs. CT sensitivity in detecting primary carcinomas of unknown locations
Study
Freudenberg
2005
Gutzeit 2005
Population
neck area
metastasis
neck area
metastasis
metastasis
outside neck
total
*Calculated based on data available
PET-CT
Se (95% CI)
n/N
57% (34; 78)*
12/21
35% (14; 62)*
6/17
36% (18; 57)*
9/25
36% (22; 52)*
15/42
FP
0
1
2
3
FN
9*
11
16
27
CT
TP
5
4
4
8
Se (95% CI)
n/N
28% (10; 53)*
5/18
25% (7; 52)*
4/16
15% (4; 35)*
4/26
19% (9; 34)*
8/42
The authors of Freudenberg 2005 found that the sensitivity of PET-CT is significantly different
CT
FP
3
2
1
3
FN
13*
12
22
34
Statistical
significance
(PET-CT vs CT)
p = 0,03
than that on CT (p=0.03). In Gutzeit 2005, PET-CT sensitivity was higher compared to CT, but the
NS
NS
NS
259

260
differences were not statistically significant.
Graph 40 illustrates PET /CT diagnostic accuracy for patients with distant metastasis to the
neck area as calculated by meta-analysis of the two trials discussed.
Graph 40.
Meta-analysis of PET-CT diagnostic sensitivity in patients with metastasis to neck area
PET-CT study sensitivity as calculated by meta-analysis of two trials for patients with
metastasis to the neck area is 47% (95% CI: 31; 64), which means that if hybrid PET-CT is used
the probability of primary carcinoma detection in patients with metastasis to the neck area
is 47%.
Freudenberg 2005 0,57 (0,34, 0,78)
Meta-analysis result
[fixed]
Gutzeit 2005 0,35 (0,14, 0,62)
Graph 41 illustrates a meta-analysis of the diagnostic sensitivity of CT in patients with
metastasis to the neck area.
0,0 0,2 0,4 0,6 0,8
Diagnostic sensitivity (95% confidence
interval)
0,47 (0,31, 0,64)

Graph 41.
Meta-analysis of CT diagnostic sensitivity in patients with metastasis to the neck area.
The average diagnostic sensitivity of CT is 26% (95% CI: 13; 44), which means that if CT is
used the probability of primary carcinoma detection in patients with metastasis to the
neck area is 26%.
The average values of diagnostic sensitivity for PET-CT and CT are listed in table 133.
Table 133.
Average values of PET-CT and CT sensitivity in primary carcinoma detection in patients with metastasis to the neck
area.
Parameter
Se (95% CI)
PET-CT
47% (31; 64)
CT
26% (13; 44)
Based on the data above, the diagnostic sensitivity of PET-CT in primary carcinoma
detection in patients with metastasis to the neck area is almost two times higher than that of
CT.
Freudenberg 2005 0,28 (0,10, 0,53)
Gutzeit 2005 0,25 (0,07, 0,52)
Meta-analysis result {fixed] 0,26 (0,13, 0,44)
0,0 0,2 0,4 0,6
Diagnostic sensitivity (95% confidence interval)
The odds ratio for primary carcinoma detection in patients with metastasis to the neck
area as calculated by meta-analysis using PET-CT or CT is presented in graph 42.
261

Graph 42.
Odds ratio for primary carcinoma detection in patients with metastasis to the neck area
262
Freudenberg 2005 4,27 (0,96, 20,24)
The odds ratio as calculated by meta-analysis of the two trials is 2.87 (95% CI: 1.08; 7.63),
so the probability of locating primary carcinoma in patients with metastasis to the neck area
is almost three times higher for PET-CT than for CT, and the result is statistically significant.
In order to obtain one additional case of primary carcinoma detection it is necessary to use
PET-CT instead of CT with 5 patients with metastasis to the neck area, NNT = 5 (95% CI: 3; 35).
Based on Gutzeit 2005 results, in patients with metastasis to the neck area, the sensitivity of
PET-CT is 36% (95% CI: 18; 57), and the sensitivity of CT is 15% (95% CI: 4; 35).
The odds ratio for primary carcinoma detection in patients with metastasis to the neck
area as calculated based on a single study is 3.09 (95% CI: 0.69; 15.93). It means that for
PET-CT, the probability of primary carcinoma detection is over three times higher than for
CT, but the result is not statistically significant.
Based on the results of a single trial, the diagnostic sensitivity of PET-CT was higher as
compared to CT in locating primary carcinoma in the total population with metastasis to the
neck area and outside the neck area, and was 36% (95% CI: 22; 52) vs. 19% (95% CI: 9; 34).
used.
Gutzeit 2005 1,75 (0,32, 10,43)
Meta-analysis result [fixed] 2,87 (1,08, 7,63)
17.3.4.2 Safety
0,2 0,5 1 2 5 10 100
The trials under analysis provide no information on the safety of the diagnostic procedures
17.3.5. Results
Odds ratio (95% confidence interval)
Two primary clinical trials were found that compared directly the diagnostic efficacy of PET-CT

with that of CT in locating primary neoplasm in metastasis patients. Both testing methods were
verified against the reference test (histopathological examination and/or clinical observation).
Based on a meta-analysis, for patients with metastasis to the neck area the diagnostic
sensitivity of PET-CT is higher than the values established for CT: 47% (95% CI: 31; 64) vs. 26% (95%
CI: 13; 44). Another meta-analysis showed that the odds of determining the location of primary
neoplasm in a population of patients with metastasis in the neck area using PET-CT was almost
three times higher compared to CT, and the result was statistically significant; OR = 2.87 (95% CI:
1.08; 7.63), NNT = 5 (95% CI: 3; 35).
A single-trial analysis of the diagnostic efficacy of the technologies compared in locating
primary tumor in patients with cancer metastases outside the neck indicated no statistically
significant differences between PET-CT and CT. The diagnostic sensitivity of the PET-CT method
was higher in versus CT, and stood at 36% (95% CI: 18; 57) vs. 15% (95% CI: 4; 35).
The results of a single trial also warranted the claim that the diagnostic sensitivity of PET-CT
proved higher than the sensitivity of CT in locating cancer focuses in the total population of
patients with cancer metastases both in and outside the neck, and was 36% (95% CI: 22; 52) for
PET-CT vs. 19% (95% CI: 9; 34) for CT.
263

18. APPENDICES
264
18.1. Tool for quality assessment of studies
Table 134.
Antoch 2003 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e. the
index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail to
permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without knowledge
of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+

Table 135.
Lardinois 2003 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e. the
index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail to
permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without knowledge
of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
14 Were withdrawals from the study explained? +
Answer
Yes No Unclear
+
+
+
+
+
+
+
+
+
+
+
265

Table 136.
Cerfolio 2005 quality assessment: QUADAS checklist
1
266
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail to
permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without knowledge
of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
14 Were withdrawals from the study explained? +
Answer
Yes No Unclear
+
+
+
+
+
+
+
+
+
+
+

Table 137.
Shim 2005 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without knowledge
of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
267

Table 138.
Antoch 2004 quality assessment: QUADAS checklist (mixed)
1
268
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
14 Were withdrawals from the study explained? +
Answer
Yes No Unclear
+
+
+
+
+
+
+
+
+
+
+

Table 139.
Antoch 2003 quality assessment: QUADAS checklist (mixed)
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
14 Were withdrawals from the study explained? +
Answer
Yes No Unclear
+
+
+
+
+
+
+
+
+
+
+
269

Table 140.
Schmidt 2005 quality assessment: QUADAS checklist
1
270
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
14 Were withdrawals from the study explained? +
Answer
Yes No Unclear
+
+
+
+
+
+
+
+
+
+
+

Table 141.
Freudenberg 2005 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
271

Table 142.
Gutzeit 2005 quality assessment: QUADAS checklist
1
272
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+

Table 143.
Freudenberg 2003 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported?
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
+
273

Table 144.
Schaefer 2004 quality assessment: QUADAS checklist
1
274
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported?
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
+

Table 145.
Cerfolio 2005 quality assessment: QUADAS checklist (esopaegal and gastric cancer)
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported?
14 Were withdrawals from the study explained? +
Answer
Yes No Unclear
+
+
+
+
+
+
+
+
+
+
+
+
275

Table 146.
Kula 2005 quality assessment: QUADAS checklist
1
276
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported?
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
+

Table 147.
Grisaru 2004 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported?
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
+
277

Table 148.
Hauth 2005 quality assessment: QUADAS checklist
1
278
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e. the
index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail to
permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without knowledge
of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+

Table 149.
Makhija 2001 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e. the
index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail to
permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without knowledge
of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
279

Table 150.
Nahas 2005 quality assessment: QUADAS checklist
1
280
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported?
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
+

Table 151.
Freudenberg 2004 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
281

Table 152.
Zimmer 2003 quality assessment: QUADAS checklist
1
282
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+

Table 153.
Wild 2006 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
283

Table 154.
Branstetter 2005 quality assessment: QUADAS checklist
1
284
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+

Table 155.
Goerres 2005 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
285

Table 156.
Koshy 2005 quality assessment: QUADAS checklist
1
286
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+

Table 157.
Heinrich 2005 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+
287

Table 158.
Antoch 2004 quality assessment: QUADAS checklist
1
288
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
Answer
Yes No Unclear
14 Were withdrawals from the study explained? +
+
+
+
+
+
+
+
+
+
+
+

Table 159.
Veit 2006 quality assessment: QUADAS checklist
1
Quality criteria
Was the spectrum of patients representative of the patients who
will receive the test in practice?
2 Were selection criteria clearly described? +
3
4
5
6
7
8
9
10
11
12
Is the reference standard likely to correctly classify the target
condition?
Is the time period between reference standard and index test
short enough to be reasonably sure that the target condition did
not change between the two tests?
Did the whole sample or a random selection of the sample,
receive verification using a reference standard?
Did patients receive the same reference standard regardless of
the index test result?
Was the reference standard independent of the index test (i.e.
the index test did not form part of the reference standard)?
Was the execution of the index test described in sufficient detail
to permit replication of the test?
Was the execution of the reference standard described in
sufficient detail to permit its replication?
Were the index test results interpreted without knowledge of the
results of the reference standard?
Were the reference standard results interpreted without
knowledge of the results of the index test?
Were the same clinical data available when test results were
interpreted as would be available when the test is used in
practice?
13 Were uninterpretable/ intermediate test results reported? +
14 Were withdrawals from the study explained? +
Answer
Yes No Unclear
+
+
+
+
+
+
+
+
+
+
+
289

290
18.2. Detailed search results
Table 160.
Result of the serach in Cochrane database
ID Strategy
Serach
result
#1 MeSH descriptor Positron-Emission Tomography, this term only in MeSH products 122
#2 MeSH descriptor Tomography, Emission-Computed, this term only in MeSH products 673
#3 PET OR positron emission tomography in All Fields in all products 1288
#4 (#1 OR #2 OR #3) 1407
#5 MeSH descriptor Tomography, X-Ray Computed, this term only in MeSH products 1571
#6 MeSH descriptor Tomography, Spiral Computed, this term only in MeSH products 66
#7 CT OR computed tomography in All Fields in all products 17330
#8 (#5 OR #6 OR #7) 17330
#9
dual OR integral OR integration OR combination OR combined OR fusion OR fused
OR hybrid OR coincidental OR combining OR coincidence OR coregistered in All
Fields in all products
#10 (#4 AND #8) 271
#11 (#4 AND #9) 257
#12 (#10 OR #11) 421
83610
#13 MeSH descriptor Neoplasms, this term only in MeSH products 2707
#14 MeSH descriptor Medical Oncology, this term only in MeSH products 74
#15 (#13 OR #14) 2750
#16 (#12 AND #15) 22

Table 161.
Results of the serach in Pubmed data basis
ID Strategy
Serach
result
#1 "Positron-Emission Tomography"[MeSH] OR "Tomography, Emission-Computed"[MeSH] 39914
#2 PET OR positron emission tomography 29430
#3 (#1 OR #2) 50482
#4 ("Tomography, Spiral Computed"[MeSH] OR "Tomography, X-Ray Computed"[MeSH]) 167516
#5 CT OR computed tomography 243809
#6 (#4 OR #5) 243809
#7
dual OR integral OR integration OR combination OR combined OR fusion OR fused
OR hybrid OR coincidental OR combining OR coincidence OR coregistered
1061412
#8 (#3 AND #6) 12708
#9 (#3 AND #7) 6428
#10 (#8 OR #9) 16819
#11 #8 OR #9 Limits: Humans 15079
#12 #8 OR #9 Limits: English, Polish, Humans 12889
#13 #8 OR #9 Limits: English, Polish, Publication Date from 1998/01/01, Humans 7786
#14 "Neoplasms"[MeSH] Limits: English, Polish, Publication Date from 1998/01/01, Humans 418359
#15 "Neoplasms"[MeSH] 1744479
#16 "Medical Oncology"[MeSH] 6670
#17 (#15 OR #16) 1747280
#18 (#10 AND #17) 5240
#19 #10 AND #17 Limits: English, Polish, Publication Date from 1998/01/01, Humans 3233
291

Table 162.
Results of serach in Embase database
ID Strategy Serach result
1 positron emission tomography.mp. OR exp Positron Emission Tomography 27340
2
292
Emission Computed Tomography.mp. OR exp Computer Assisted Emission
Tomography
3 PET.mp. 19613
4 (1 OR 2 OR 3) 36988
5
(dual OR integral OR integration OR combination OR combined OR fusion OR
fused OR hybrid OR coincidental OR combining OR coincidence OR
coregistered).mp. [mp=title, abstract, subject headings, heading word, drug
trade name, original title, device manufacturer, drug manufacturer name]
6301
615862
6 (4 AND 5) 4268
7 exp Computer Assisted Tomography 183410
8 CT.mp 82030
9 (7 OR 8) 205988
10 (4 AND 9) 13380
11 (6 OR 10) 15661
12 limit 11 to human 13700
13 limit 12 to yr="1999 - 2006" 9119
14 exp NEOPLASM 990525
15 (11 AND 14) 5231
16 limit 15 to (human and yr="1998 - 2006") 4213
Table 163.
MeSH terms used for the search strategy
Term [MeSH]
Positron-Emission Tomography
Tomography, Emission-Computed
Synonyms
Positron Emission Tomography
PET Scan
PET Scans
Scan, PET
Scans, PET
Tomography, Positron-Emission
Tomography, Positron Emission
Tomography, Emission Computed
CAT Scan, Radionuclide
CAT Scans, Radionuclide
Radionuclide CAT Scan
Radionuclide CAT Scans
Scan, Radionuclide CAT
Scans, Radionuclide CAT
Computed Tomographic Scintigraphy
Tomographic Scintigraphy, Computed
Computerized Emission Tomography

Emission-Computed Tomography
Emission Computed Tomography
Scintigraphy, Computed Tomographic
Tomography, Computerized Emission
Emission Tomography, Computerized
Radionuclide-Computed Tomography
Radionuclide Computed Tomography
Radionuclide Tomography, Computed
Computed Radionuclide Tomography
Tomography, Computed Radionuclide
Tomography, Radionuclide-Computed
Tomography, Radionuclide Computed
Tomography, Spiral Computed Computed Tomographies, Spiral
Computed Tomography, Spiral
Spiral Computed Tomographies
Tomographies, Spiral Computed
Helical Computed Tomography
Computed Tomographies, Helical
Computed Tomography, Helical
Helical Computed Tomographies
Tomographies, Helical Computed
Helical CT
CT, Helical
CTs, Helical
Helical CTs
Spiral Computed Tomography
Spiral CT
CT, Spiral
CTs, Spiral
Spiral CTs
Spiral Volumetric CT
CT, Spiral Volumetric
CTs, Spiral Volumetric
Spiral Volumetric CTs
Volumetric CT, Spiral
Volumetric CTs, Spiral
Tomography, Helical Computed
Tomography, Spiral Volumetric Computed
Tomography, X-Ray Computed • Computed Tomographies, X-Ray
• Computed Tomography, X-Ray
• Tomographies, X-Ray Computed
• X-Ray Computed Tomographies
• X-Ray Computed Tomography
• Computerized Tomography, X Ray
• Computerized Tomography, X-Ray
• Computerized Tomographies, X-Ray
• Tomographies, X-Ray Computerized
• Tomography, X-Ray Computerized
• X-Ray Computerized Tomographies
• X-Ray Computerized Tomography
293

294
• CT X Ray
• CT X Rays
• X Ray, CT
• X Rays, CT
• Tomodensitometry
• Tomodensitometries
• CAT Scan, X Ray
• CAT Scan, X-Ray
• CAT Scans, X-Ray
• Scan, X-Ray CAT
• Scans, X-Ray CAT
• X-Ray CAT Scan
• X-Ray CAT Scans
• Tomography, Xray Computed
• Computed Tomographies, Xray
• Computed Tomography, Xray
• Tomographies, Xray Computed
• Xray Computed Tomographies
• Xray Computed Tomography
• Tomography, X Ray Computed
• X Ray Tomography, Computed
• X-Ray Tomography, Computed
• Computed X-Ray Tomographies
• Computed X-Ray Tomography
• Tomographies, Computed X-Ray
• Tomography, Computed X-Ray
• X-Ray Tomographies, Computed
• Cine-CT
• Cine CT
• Tomography, Transmission Computed
• Computed Tomographies, Transmission
• Computed Tomography, Transmission
• Tomographies, Transmission Computed
• Transmission Computed Tomographies
• Transmission Computed Tomography
• Electron Beam Computed Tomography
• Electron Beam Tomography
• Beam Tomographies, Electron
• Beam Tomography, Electron
• Electron Beam Tomographies
• Tomographies, Electron Beam
• Tomography, Electron Beam

Neoplasms Neoplasm
Tumors
Tumor
Benign Neoplasms
Neoplasms, Benign
Benign Neoplasm
Neoplasm, Benign
Carcinoma
Carcinomas
Medical Oncology Oncology, Medical
295

19. LITERATURE USED IN THE ANALYSIS
296
19.1. Lung cancer
1. Antoch G, Stattaus J, Nemat AT, Marnitz S, Beyer T, Kuehl H, Bockisch A, Debatin JF,
Freudenberg LS. Non-Small Cell Lung Cancer: Dual-Modality PET-CT in Preoperative Staging.
Radiology 2003; Vol. 229 (2): pp 526–533.
2. Lardinois D, Weder W, Hany TF, Kamel EM, Korom S, Seifert B, von Schulthess GK, Steinert HC.
Staging of non-small-cell lung cancer with integrated positron-emission tomography and
computed tomography. N Engl J Med 2003; 348: pp 2500–2507.
3. Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of
patients with NSCLC: A prospective trial. Ann Thora Surg 2005; Vol. 80 (4): pp 1207–1214.
4. Shim SS, Lee KS, Kim BT, Chung MJ, Lee EJ, Han J, Choi JY, Kwon OJ, Shim YM, Kim S. Non-small
cell lung cancer: prospective comparison of integrated FDG PET-CT and CT alone for
preoperative staging. Radiology 2005 Sep; 236 (3): pp 1011–1019. Epub 2005 Jul 12.
19.2. Neoplasm in varied locations
1. Antoch G, Saoudi N, Kuehl H, Dahmen G, Mueller SP, Beyer T, Bockisch A, Debatin JF,
Freudenberg LS. Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose
positron emission tomography and computed tomography (FDG-PET-CT) for tumor staging in
solid tumors: comparison with CT and PET. J Clin Oncol 2004; Vol. 1; 22 (21): pp 4357–4368.
2. Antoch G, Vogt FM, Freudenberg LS, Nazaradeh F, Goehde SC, Barkhausen J, Dahmen G,
Bockisch A, Debatin JF, Ruehm SG. Whole-body dual-modality PET-CT and whole-body MRI for
tumor staging in oncology. JAMA 2003; Vol. 24; 290 (24): pp 3199–3206.
3. Schmidt GP, Baur-Melnyk A, Herzog P, Schmid R, Tiling R, Schmidt M, Reiser MF, Schoenberg SO.
High-resolution whole-body magnetic resonance image tumor staging with the use of parallel
imaging versus dual-modality positron emission tomography-computed tomography:
experience on a 32-channel system. Invest Radiol 2005; Vol. 40 (12): pp 743–753.
4. Freudenberg LS, Fischer M, Antoch G, Jentzen W, Gutzeit A, Rosenbaum SJ, Bockisch A, Egelhof
T. Dual modality of 18F-fluorodeoxyglucose-positron emission tomography/computed
tomography in patients with cervical carcinoma of unknown primary. Med Princ Pract 2005;
Vol. 14 (3): pp 155–160.
5. Gutzeit A, Antoch G, Kuhl H, Egelhof T, Fischer M, Hauth E, Goehde S, Bockisch A, Debatin J,
Freudenberg L. Unknown primary tumors: detection with dual-modality PET-CT – initial
experience. Radiology 2005; Vol. 234 (1): pp 227–234. Epub 2004 Nov 24.
19.3. Lymphomas
1. Freudenberg LS, Antoch G, Schütt P, Beyer T, Jentzen W, Müller SP, Görges R, Nowrousian MR,
Bockisch A, Debatin JF. FDG-PET-CT in re-staging of patients with lymphoma. Eur J Nucl Med Mol
Imaging 2004; 31 (3): pp 325–329.
2. Schaefer NG, Hany TF, Taverna C, Seifert B, Stumpe KD, von Schulthess GK, Goerres GW. Non-
Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and
restaging – do we need contrast-enhanced CT? Radiology 2004 Sep; 232 (3): pp 823–829.

19.4. Esophageal cancer
1. Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA, Eloubeidi MA. The accuracy of endoscopic
ultrasonography with fine-needle aspiration, integrated positron emission tomography with
computed tomography, and computed tomography in restaging patients with esophageal
cancer after neoadjuvant chemoradiotherapy. J Thorac Cardiovasc Surg 2005; Vol. 129 (6): pp
1232–1241.
2. Kula Z, Pietrzak T, Kobus-Błachnio K, Zuchora Z. Combined positron emission tomography and
computed tomography (PET-CT) imaging in staging esophageal cancer – analysis of 12 casas.
Współczesna Onkologia 2005; vol. 9 (8): pp 336–341.
19.5. Cancer in the female genitals
1. Grisaru D, Almog B, Levine C, Metser U, Fishman A, Lerman H, Lessing JB, Even-Sapir E. The
diagnostic accuracy of 18F-fluorodeoxyglucose PET-CT in patients with gynecological
malignancies. Gynecol Oncol 2004 Sep; 94 (3): pp 680–684.
19.6. Ovarian cancer
1. Hauth EA, Antoch G, Stattaus J, Kuehl H, Veit P. Evaulation of integrated whole-body PET/ CT in
detection of recurrent ovarian cancer. Eur J Radiol 2005 Nov; 56 (2): pp 263–268.
2. Makhija S, Howden N, Edwards R, Kelley J, Townsed DW, Meltzer CC. Positron emission
tomography/computed tomography imaging for the detection of recurrent ovarian and
fallopian tube carcinoma; a retrospective review. Gynecol Oncol 2002 Apr; 85 (1): pp 53–58.
19.7. Thyroid gland cancer
1. Nahas Z, Goldenberg D, Fakhry C, Ewertz M, Zeiger M, Ladenson PW, Wahl R, Tufano RP. The role
of positron emission tomography/computed tomography in the management of recurrent
papillary thyroid carcinoma. Laryngoscope 2005 Feb; 115 (2): pp 237–243.
2. Freudenberg LS, Antoch G, Jentzen W, Pink R, Knust J, Gorges R, Muller SP, Bockisch A, Debatin
JF, Brandau W. Value of 124I -PET-CT in staging of patients with differentiated thyroid cancer. Eur
Radiol 2004; Vol. 14 (11): pp 2092–2098.
3. Zimmer LA, McCook B, Meltzer C, Fukui M, Bascom D, Snyderman C, Townsend DW, Johnson JT.
Combined positron emission tomography/computed tomography imaging of recurrent thyroid
cancer. Otolaryngology – Head & Neck Surgery 2003; Vol. 128 (2): pp 178–184. Date of
Publication: 01 FEB 2003.
19.8. Head and neck cancer
1. Wild D, Eyrich GK, Ciernik IF, Stoeckli SJ, Schuknecht B, Goerres GW. In-line 18Ffluorodeoxyglucose
positron emission tomography with computed tomography (PET-CT) in
patients with carcinoma of the sinus/nasal area and orbit. Journal of Cranio-Maxillo-Facial
Surgery 2006; Vol. 34 (1): pp 9–16.
2. Branstetter IV BF, Blodgett TM, Zimmer LA, Snyderman CH, Johnson JT, Raman S, Meltzer CC.
Head and neck malignancy: Is PET-CT more accurate than PET or CT alone?. Radiology 2005;
Vol. 235 (2): pp 580–586.
297

298
3. Goerres GW, Schmid DT, Schuknecht B, Eyrich GK. Bone invasion in patients with oral cavity
cancer: Comparison of conventional CT with PET-CT and SPECT/CT. Radiology 2005; Vol. 237 (1):
pp 281–287.
4. Koshy M, Paulino AC, Howell R, Schuster D, Halkar R, Davis LW. F-18 FDG PET-CT fusion in
radiotherapy treatment planning for head and neck cancer. Head & Neck 2005; Vol. 27 (6): pp
494–502.
19.9. Pancreatic cancer
1. Heinrich S, Goerres GW, Schafer M, Sagmeister M, Bauerfeind P, Pestalozzi BC, Hany TF, von
Schulthess GK, Clavien P. Positron emission tomography/computed tomography influences on
the management of resectable pancreatic cancer and its cost-effectiveness. Ann Surg 2005;
Vol. 242 (2): pp 235-243.
19.10. Sarcomas
1. Antoch G, Kanja J, Bauer S, Kuehl H, Renzing-Koehler K, Schuette J, Bockisch A, Debatin JF,
Freudenberg LS. Comparison of PET, CT, and dual-modality PET-CT imaging for monitoring of
imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 2004 Mar;
45 (3): pp 357–365.
19.11. Colon cancer
1. Veit P, Antoch G, Stergar H, Bockisch A, Forsting M, Kuehl H. Detection of residual tumor after
radiofrequency ablation of liver metastasis with dual-modality PET-CT: Initial results. Eur Radiol
2006; Vol. 16 (1): pp 80–87.

299

20. TRIALS EXCLUDED FROM THE ANALYSIS
1. Abe K, Sasaki M, Kuwabara Y, Koga H, Baba S, Hayashi K, Takahashi N, Honda H. Comparison of
18 FDG-PET with 99m Tc-HMDP scintigraphy for the detection of bone metastases in patients with breast
cancer. Ann Nucl Med 2005; Vol. 19 (7): pp 573–579. (absence of assessed intervention)
2. Aberle DR, Chiles C, Gatsonis C, Hillman BJ, Johnson CD, McClennan BL, Mitchell DG, Pisano ED,
Schnall MD, Sorensen AG. Imaging and cancer: research strategy of the American College of
Radiology Imaging Network. Radiology 2005; Vol. 235 (3): pp 741–751. (secondary trial)
3. Acker MR, Burrell SC. Utility of 18F-FDG PET in evaluating cancers of lung. J Nucl Med Technol 2005
Jun; 33 (2): pp 69–74; quiz 75–77. (secondary trial)
4. Aigner RM, Schultes G, Wolf G, Yamashita Y, Sorantin E, Karcher H. F-18-FDG PET: early postoperative
period of oro-maxillo-facial flaps. Nuclearmedizin 2003; Vol. (42): pp 210–214. (inadequate
population)
5. Aizer-Dannon A, Bar-Am A, Ron IG, Flusser G, Even-Sapir E. Fused functional-anatomic images of
metastatic cancer of cervix obtained by a combined gamma camera and an X-ray tube hybrid
system with an illustrative case and review of the 18 F-fluorodeoxyglukose literature. Gynecol Oncol
2003 Aug; 90 (2): pp 453–457. (casuistic description)
6. Akeboshi M, Yamakado K, Nakatsuka A, Hataji O, Taguchi O, Takao M, Takeda K. Percutaneous
radiofrequency ablation of lung neoplasms: initial therapeutic response. J Vasc Interv Radiol 2004
May; 15 (5): pp 463–470. (absence of assessed intervention)
7. Alavi A, Lakhani P, Mavi A, Kung JW, Zhuang H. PET: A revolution in medical imaging. Radiol Clin
N Am 2004; Vol. 42 (6): pp 983–1001. (secondary trial)
8. Allen-Auerbach M, Quon A, Weber WA, Obrzut S, Crawford T, Silverman DH, Ratib O, Phelps ME,
Czernin J. Comparison between 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and
positron emission tomography/computed tomography hardware fusion for staging of patients with
lymphoma. Mol Imaging Biol 2004 Nov-Dec; 6 (6): pp 411–416. (absence of assessed intervention)
9. Ambrosini V, Rubello D, Nanni C, Farsad M, Castellucci P, Franchi R, Fabbri M, Rampin L, Crepaldi G,
Al-Nahhas A, Fanti S. Additional value of hybrid PET-CT fusion imaging vs. conventional CT scan
alone in the staging and management of patients with malignant pleural mesothelioma. Nucl Med
Rev 2005; Vol. 8 (2): pp 111–115. (absence of reference method)
10. Amit A, Beck D, Lowenstein L, Lavie O, Bar Shalom R, Kedar Z, Israel O. The role of hybrid PET-CT in
the evaluation of patients with cervical cancer. Gynecol Oncol 2006; Vol. 100 (1): pp 65–69.
(absence of the classical comparative method)
11. An Y-S, Yoon J-K, Lee M-H, Joh C-W, Yoon S-N. False negative F-18 FDG PET-CT in nonsmall cell lung
cancer bone metastases. J Nucl Med 2005; Vol. 30 (3): pp 203–204. (casuistic description)
12. Anderson GS, Brinkmann F, Soulen MC, Alavi A, Zhuang H. FDG positron emission tomography in the
surveillance of hepatic tumors treated with radiofrequency ablation. Clin Nucl Med 2003 Mar; 28
(3): pp 192–197. (absence of assessed intervention)
13. Annovazzi A, Peeters M, Maenhout A, Signore A, Dierckx R, Van de Wiele C. 18-Fluorodeoxyglucose
positron emission tomography in nonendocrine neoplastic disorders of the gastrointestinal tract.
Gastroenterology 2003; Vol. 125 (4): pp 1235–1245. (secondary trial)
14. Anonymous. Recent advances and future perspectives in the management of lung cancer. Curr
Probl Surg 2005; Vol. 42 (8): pp 548–610. (secondart trial)
15. Antoch G, Freudenberg LS, Beyer T, Bockisch A, Debatin JF. To enhance or not to enhance? 18F-
FDG and CT contrast agents in dual-modality. J Nucl Med 2004 Jan; 45 (Suppl 1): pp 56S–65S.
(secondary trial)
16. Aquino SL, Asmuth JC, Moore RH, Weise SB, Fischman AJ. Improved image interpretation with
registered thoracic CT and positron emission tomography data sets. AJR Am J Roentgenol 2002 Apr;
178 (4): pp 939–944. (absence of assessed intervention)
300

17. Bachaud JM, Marre D, Dygai I, Caselles O, Hamelin D, Begue M, Laprie A, Zerdoud S, Gancel M,
Courbon F. The impact of 18F-fluorodeoxyglucose positron emission tomography on the 3D
conformal radiotherapy planning in patients with non-small cell lung cancer. Cancer Radiotherapie
2005; Vol. 9 (8): pp 602–609. (article in French)
18. Bagheri B, Maurer AH, Cone L, Doss M, Adler L. Characterization of the normal adrenal gland with
18F-FDG PET-CT. J Nucl Med 2004 Aug; 45 (8): pp 1340–1343. (absence of assessed intervention)
19. Bar-Shalom R, Gaitini D, Keidar Z, Israel O. Non-malignant FDG uptake in infradiaphragmatic
adipose tissue: a new site of physiological tracer biodistribution characterised by PET-CT. Eur J Nucl
Med Mol Imaging 2004 Aug; 31 (8): pp 1105–1113. Epub 2004 Mar 9. (absence of assessed
intervention)
20. Bar-Shalom R, Guralnik L, Tsalic M, Leiderman M, Frenkel A, Gaitini D, Ben-Nun A, Keidar Z, Israel O.
The additional value of PET-CT over PET in FDG imaging of oesophageal cancer. European Eur
J Nucl Med Mol Imaging 2005; Vol. 32 (8): pp 918–924. (absence of assessed intervention)
21. Bar-Shalom R, Yefremov N, Guralnik L, Gaitini D, Frenkel A, Kuten A, Altman H, Keidar Z, Israel O.
Clinical performance of PET-CT in evaluation of cancer: additional value for diagnostic imaging and
patient management. J Nucl Med 2003; Vol. 44 (8): pp 1200–1209. (absence of comparative
diagnostic test)
22. Belohlavek O, Klener J, Vymazal J, Dbaly V, Tovarys F. The diagnostics of recurrent gliomas using
FDG-PET: Still questionable. Nuclear Medicine Review 2002; Vol. 5 (2): pp 127–130. (absence of
assessed intervention)
23. Benchaou M, Lehmann W, Slosman DO, Becker M, Lemoine R, Rufenacht D, Donath A. The role of
FDG-PET in the preoperative assessment of N-staging in head and neck cancer. Acta Otoaryngol
1996; Vol. 116 (2): pp 332–335. (absence of assessed intervention)
24. Berlangieri SU, Brizel DM. Scher RL, Schifter T, Hawk TC, Hamblen S, Coleman RE, Hoffman JM. Pilot
study of positron emission tomography in patients with advanced head and neck cancer receiving
radiotherapy and chemotherapy. Head & Neck 1994; Vol. 16 (4): pp 340–346. (absence of assessed
intervention)
25. Berthelsen AK, Holm S, Loft A, Klausen TL, Andersen F, Hojgaard L. PET-CT with intravenous contrast
can be used for PET attenuation correction in cancer patients. Eur J Nucl Med Mol Imaging 2005;
Vol. 32 (10): pp 1167–1175. (absence of reference method)
26. Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, Jerin J, Young J, Byars L, Nutt R.
A combined PET-CT scanner for clinical oncology. J Nucl Med 2000; Vol. 41 (8): pp 1369–1379.
(absence of assessed intervention)
27. Bienert M, McCook B, Carr BI, Geller DA, Sheetz M, Tutor C, Amesur N, Avril N. 90 Y microsphere
treatment of unresectable liver metastases: Changes in 18 F-FDG uptake and tumour size on PET-CT.
Eur J Nucl Med Mol Imaging 2005; Vol. 32 (7): pp 778–787. (absence of end-points)
28. Blake MA, Slattery JMA, Kalra MK, Halpern EF, Fischman AJ, Mueller PR, Boland GW. Adrenal lesions:
Characterization with fused PET-CT image in patients with proved or suspected malignancy – Initial
experience. Radiology 2006; Vol. 238 (3): pp 970–977. (absence of comparative method)
29. Blake MA, Sweeney AT, Kalra MK, Maher MM. Collision adrenal tumors on PET/ CT. AJR Am J
Roentgenol 2004; Vol. 183 (3): pp 864–865. (casuistic description)
30. Blomqvist L, Torkzad MR. Whole-Body Imaging with MRI or PET-CT: The Future for Single-Modality
Imaging in Oncology. J Am Med Association 2003; Vol. 290 (24): pp 3248–3249. Date of Publication:
24 DEC 2003. (secondary trial)
31. Bockisch A, Brandt-Mainz K, Gorges R, Muller St, Stattaus J, Antoch G. Diagnosis in medullary thyroid
cancer with [ 18 F] FDG-PET and improvement using a combined PET-CT scanner. Acta Medica
Austriaca 2003; Vol. 30 (1): pp 22–25. (secondary trial)
32. Bradley JD, Dehdashti F, Mintun MA, Govindan R, Trinkaus K, Siegel BA. Positron emission
tomography in limited-stage small-cell lung cancer: a prospective study. J Clin Oncol 2004 Aug 15;
22 (16): pp 3248–3254. (absence of assessed intervention)
33. Bradley JD, Perez CA, Dehdashti F, Siegel BA. Implementing biologic target volumes in radiation
treatment planning for non-small cell lung cancer. J Nucl Med 2004 Jan; 45 Suppl 1: pp 96S–101S.
(secondary trial)
301

34. Braun V, Dempf S, Weller R, Reske S-N, Schachenmayr W, Richter HP. Cranial neuronavigation with
direct integration of 11 C methionine positron emission tomography (PET) data – Results of a pilot
study in 32 surgical cases. Acta Neurochirurgica 2002; Vol. 144 (8): pp 777–782. (absence of
assessed intervention)
35. Brianzoni E, Rossi G, Ancidei S, Berbellini A, Capoccetti F, Cidda C, D'Avenia P, Fattori S, Montini GC,
Valentini G, Proietti A. Radiotherapy planning: PET-CT scanner performances in the definition of
gross tumour volume and clinical target volume. Eur J Nucl Med Mol Imaging 2005; Vol. 32 (12): pp
1392–1399. (absence of comparative diagnostic test)
36. Brink I, Klenzner Th, Krause Th, Mix M, Ross UH, Moser E, Nitzsche EU. Lymph node staging in
extracranial head and neck cancer with FDG PET – Appropriate uptake period and sizedependence
of the results. Nuklearmedizin 2002; Vol. 41 (2): pp 108–113. (absence of assessed
diagnostic method)
37. Bristow RE, del Carmen MG, Pannu HYK, Cohade C, Zhurak ML, Fishman EK, Wahl RL, Montz FJ.
Clinically occult recurrent ovarian cancer: patient selection for secondary cytoreductive surgery
using combined PET-CT. Gynecol Oncol 2003 Sep; 90 (3): pp 519–528. (absence of comparative
diagnostic method)
38. Brun E, Kjellen E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, Wennerberg J, Strand SE. FDG PET studies
during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
Head & Neck 2002; Vol. 24 (2): pp 127–135. (absence of assessed intervention)
39. Buell U, Wieres FJ, Schneider W, Reinartz P. 18 FDG-PET in 733 consecutive patients with or without
side-by-side CT evaluation: Analysis of 921 lesions. Nuklearmedizin 2004; Vol. 43 (6): pp 210–216.
(absence of assessed intervention)
40. Caldwell CB, Mah K, Skinner M, Danjoux CE. Can PET provide the 3D extent of tumor motion for
individualized internal target volumes? A phantom study of the limitations of CT and the promise of
PET. Int J Radiat Oncol Biol Phys 2003 Apr 1; 55 (5): pp 1381–1393. (inadequate population)
41. Calvo FA, Domper M, Matute R, Martinez-Lazaro R, Arranz JA, Desco M, Alvarez E, Carreras JL. 18F-
FDG positron emission tomography staging and restaging in rectal cancer treated with
preoperative chemoradiation. Int J Radiat Oncol Biol Phys. 2004 Feb 1; 58 (2): pp 528–535. (absence
of assessed intervention)
42. Castillo E, Lawler LP. Diagnostic radiology and nuclear medicine. J Surg Oncol 2005 Dec 1; 92 (3): pp
191–202. (secondary trial)
43. Cerfolio RJ, Ojha B, Bryant AS, Raghuveer V, Mountz JM, Bartolucci AA. The accuracy of integrated
PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung
cancer. Ann Thorac Surg 2004 Sep; 78 (3): pp 1017–1023. (absence of assessed intervention)
44. Chaiken L, Rege S, Hoh C, Choi Y, Jabour B, Juillard G, Hawkins R, Parker R. Positron emission
tomography with fluorodeoxyglucose to evaluate tumor response and control after radiation
therapy. Int J Radiat Oncol Biol Phys 1993; Vol. 27 (2): pp 455–464. (absence of assessed diagnostic
method)
45. Chander S, Ergun EL. Positron Emission Tomographic-Computed Tomographic imaging of uterine
sarcoma. Clin Nucl Med 2003; Vol. 28 (5): pp 443–444. (secondary trial)
46. Charron M, Beyer T, Bohnen NN, Kinahan PE, Dachille M. Jerin J, Nutt R, Meltzer CC, Villemagne V,
Townsend DW. Image analysis in patients with cancer studied with a combined PET and CT scanner.
Clin Nucl Med 2000; Vol. 25 (11): pp 905–910. (absence of assessed intervention)
47. Chen J, Cheong JH, Yun MJ, Kim J, Lim JS, Hyung WJ, Noh SH. Improvement in preoperative staging
of gastric adenocarcinoma with positron emission tomography. Cancer 2005 Jun 1; 103 (11): pp
2383–2390. (absence of assessed intervention)
48. Chen Y-K, Ding H-J, Su C-T, Shen Y-Y, Chen L-K, Liao AC, Hung T-Z, Hu F-L, Kao C-H. Application of
PET and PET-CT imaging for cancer screening. Anticancer Research 2004; Vol. 24 (6): pp 4103–4108.
(only slight perecentage of patients had PET-CT test and there was no reference test)
49. Cheng EY. Surgical management of sarcomas. Hematol Oncol Clin N Am 2005; Vol. 19 (3): pp 451–
470. (secondary trial)
50. Chessin DB, Kiran RP, Akhurst T, Guillem JG. The emerging role of 18F-fluorodeoxyglucose positron
emission tomography in the management of primary and recurrent rectal cancer. J Am Coll Surg
2005 Dec; 201 (6): pp 948–956. (secondary trial)
302

51. Chin BB, Chang PPL. Gastrointestinal malignancies evaluated with 18 F-fluoro-2-deoxyglucose
positron emission tomography. Best Practice & Research in Clinical Gastroenterology 2006; Vol. 20
(1): pp 3–21. (secondary trial)
52. Cho D, Kocher O, Parker JA, Halmos B. Multiple positron-emission tomography false positives in
a patient with malignant melanoma. Clinical Oncology (Royal College of Radiologists) 2006; Vol. 18
(1): pp 87–88. (casuistic description)
53. Cho Sm, Ha HK, Byun JY, Lee JM. Usefulness of FDG PET for assessemant of early recurrent eithelial
ovarian cancer. AJR Am J Roentgenol 2002 Aug; 179 (2): pp 391–395. (absence of assessed
intervention)
54. Choi JY, Lee KS, Kwon OJ, Shim YM, Baek CH, Park K, Lee KH, Kim BT. Improved detection of second
primary cancer using integrated [18F] fluorodeoxyglucose positron emission tomography and
computed tomography for initial tumor staging. J Clin Oncol 2005; Vol. 20; 23 (30): pp 7654–7659.
(absence of assessed diagnostic test)
55. Choi MY, Lee KM, Chung JK, Lee DS, Jeong JM, Park JG, Kim JH, Lee MC. Correlation between
serum CEA level and metabolic volume as determined by FDG PET in postoperative patients with
recurrent colorectal cancer. Ann Nucl Med 2005 Apr; 19 (2): pp 123–129. (absence of assessed
intervention)
56. Ciernik IF, Dizendorf E, Baumert BG, Reiner B, Burger C, Davis JB, Lutolf UM, Steinert HC, Von
Schulthess GK. Radiation treatment planning with an integrated positron emission and computer
tomography (PET-CT): a feasibility study. Int J Radiat Oncol Biol Phys 2003; Vol. 1; 57 (3): pp 853–863.
(absence of reference method)
57. Civantos FJ, Gomez C, Duque C, Pedroso F, Goodwin WJ, Weed DT, Arnold D, Moffat F. Sentinel
node biopsy in oral cavity cancer: correlation with PET scan and immunohistochemistry. Head Neck
2003 Jan; 25 (1): pp 1–9. (absence of assessed intervention)
58. Cohade C, Osman M, Leal J, Wahl RL. Direct comparison of 18 F-FDG PET and PET-CT in patients with
colorectal carcinoma. J Nucl Med 2003; Vol. 44 (11): pp 1797–1803. (absence of the classical
comparative method)
59. Cohade C, Osman M, Marshall L, Wahl R. PET-CT: accuracy of PET and CT spatial registration of lung
lesions. Eur J Nucl Med Mol Imaging 2003; Vol. 30 (5): pp 721–726. Epub 2003 Mar 1. (absence of
refrence test)
60. Cohade C, Osman M, Nakamoto Y, Marshall L, Links J, Fishman E, Wahl R. Initial experience with oral
contrast in PET-CT: phantom and clinical studies. J Nucl Med 2003; Vol. 44: pp 412–416. (inadequate
population)
61. Cohade C, Wahl RL. Applications of positron emission tomography/computed tomography image
fusion in clinical positron emission tomography-clinical use, interpretation methods, diagnostic
improvements. Semin Nucl Med 2003 Jul; 33 (3): pp 228–237. (secondary trial)
62. Collins BT, Gardner LJ, Verma AK, Lowe VJ, Dunphy FR, Boyd JH. Correlation of fine needle
aspiration biopsy and fluoride-18 fluorodeoxyglucose positron emission tomography in the
assessment of locally recurrent and metastatic head and neck neoplasia. Acta Cytologica 1998;
Vol. 42 (6): pp 1325–1329. (absence of assessed intervention)
63. Comans EF, Miles KA, Schirrmeister H. Staging of non-small-cell lung cancer with integrated PET and
CT. N Engl J Med 2003 Sep 18; 349 (12): pp 1188–1190; author reply pp 1188–1190. (letters)
64. D'Amico TA, Wong TZ, Harpole DH, Brown SD, Coleman RE. Impact of computed tomographypositron
emission tomography fusion in staging patients with thoracic malignancies. Ann Thorac
Surg 2002; Vol. 74 (1): pp 160–163. (absence of the classical comparative method)
65. Dehdashti F, Siegel BA. Neoplasms of the esophagus and stomach. Semin Nucl Med 2004; Vol. 34
(3): pp 198–208. (secondary trial)
66. Delbeke D, Martin WH. PET and PET-CT for evaluation of colorectal carcinoma. Semin Nucl Med
2004; Vol. 34 (3): pp 209–223. (secondary trial)
67. Deniaud-Alexandre E, Touboul E, Lerouge D, Grahek D, Foulquier JN, Petegnief Y, Gres B, El Balaa H,
Keraudy K, Kerrou K, Montravers F, Milleron B, Lebeau B, Talbot JN. Impact of computed
tomography and 18F-deoxyglucose coincidence detection emission tomography image fusion for
optimization of conformal radiotherapy in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys
2005 Dec 1; 63 (5): pp 1432–1441. Epub 2005 Aug 25. (absence of assessed intervention)
303

68. Desai DC, Zervos EE, Arnold MW, Burak WE Jr, Mantil J, Martin EW Jr. Positron emission tomography
affects surgical management in recurrent colorectal cancer patients. Ann Surg Oncol 2003 Jan-
Feb; 10 (1): pp 59–64. (absence of assessed intervention)
69. Di Martino E, Nowak B, Krombach GA, Sellhaus B, Hausmann R, Cremerius U, Bull U, Westhofen M.
Results of pretherapeutic lymph node diagnosis in head and neck cancer: Clinical value of 18fluorodeoxyglucose
positron emission tomography (PET). Laryngo- Rhino- Otol 2000; Vol. 79 (4): pp
201–206. (article in German)
70. Diaz-Montes TP, Jacene HA, Wahl RL, Bristow RE. Combined FDG-positron emission tomography and
computed tomography for the detection of ovarian cancer recurrence in an inguinal hernia sac.
Gynecol Oncol 2005; Vol. 98 (3): pp 510–512. (casuistic description)
71. Dos Santos DT, Pereira Lima EN, Chojniak R, Cavalcanti MG. Topographic metabolic map of head
and neck squamous cell carcinoma using 18F-FDG PET and CT image fusion. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 2005; Vol. 100 (5): pp 619–625. (absence of the classical comparative
method)
72. Dresel S, Grammerstorff J, Schwenzer K, Brinkbaumer K, Schmid R, Pfluger T, Hahn K. [18F] FDG
imaging of head and neck tumours: comparison of hybrid PET and morphological methods. Eur J
Nucl Med Mol Imaging 2003 Jul; 30 (7): pp 995–1003. Epub 2003 May 9. (absence of assessed
diagnostic method)
73. Dresell S, Schwenzer K, Brinkbaumer K, Schmid R, Szeimies U, Popperl G, Hahn K. [F-18] FDG imaging
of head and neck tumors: Comparison of Hybrid PET, dedicated PET and CT. Nuklearmedizin 2001;
Vol. 40 (5): pp 172–178. (article in German)
74. Eary JF, O'Sullivan F, Powitan Y, Chandhury KR, Vernon C, Bruckner JD, Conrad EU. Sarcoma tumor
FDG uptake measured by PET and patient outcome: a retrospective analysis. Eur J Nucl Med Mol
Imaging 2002 Sep; 29 (9): pp 1149–1154. Epub 2002 Jun 19. (absence of assessed intervention)
75. Eifel PJ. Accurate diagnosis of regional metastasis from cervical cancer: Is PET the answer?. Int
J Radiat Oncol Biol Phys 2004; Vol. 59 (3): pp 637–638. Date of Publication: 01 JUL 2004. (secondary
trial)
76. Ell PJ. PET-CT in oncology: A major technology for cancer care. Chang Gung Med J 2005; Vol. 28
(5): pp 274–283. (secondary trial)
77. Erasmus JJ, Truong MT, Smythe WR, Munden RF, Marom EM, Rice DC, Vaporciyan AA, Walsh GL,
Sabloff BS, Broemeling LD, Stevens CW, Pisters KM, Podoloff DA, Macapinlac HA. Integrated
computed tomography-positron emission tomography in patients with potentially resectable
malignant pleural mesothelioma: Staging implications. J Thorac Cardiovasc Surg 2005; Vol. 129 (6):
pp 1364–1370. (absence of comparative diagnostic method)
78. Erdi YE, Nehmeh SA, Pan T, Pevsner A, Rosenzweig KE, Mageras G, Yorke ED, Schoder H, Hsiao W,
Squire OD, Vernon P, Ashman JB, Mostafavi H, Larson SM, Humm JL. The CT motion quantitation of
lung lesions and its impact on PET-measured SUVs. J Nucl Med 2004 Aug; 45 (8): pp 1287–1292.
(absence of the end-points for assessment of diagnostic efficacy)
79. Erdi YE, Rosenzweig K, Erdi AK, Macapinlac HA, Hu Y-C, Braban LE, Humm JL, Squire OD, Chui C-S,
Larson SM, Yorke ED. Radiotherapy treatment planning for patients with non-small cell lung
cancer using positron emission tomography (PET). Radiother Oncol 2002 Jan; 62 (1): pp 51–60.
(fusion of PET-CT images)
80. Eschmann SM, Bitzer M, Paulsen F, Friedel G, Besenfelder H, Horger M, Reimold M, Dittmann H,
Pfannenberg AC, Bares R. The benefit of functional-anatomical imaging with [18F]
fluorodeoxyglucose utilizing a dual-head coincidence gamma camera with an integrated Xray
transmission system in non-small cell lung cancer. Nucl Med Commun 2004 Sep; 25 (9): pp 909–
915. (absence of assessed intervention)
81. Eubank WB, Mankoff DA, Schmiedl UP, Winter TC 3rd, Fisher ER, Olshen AB, Graham MM, Eary JF.
Imaging of oncologic patients: benefit of combined CT and FDG PET in the diagnosis of
malignancy. AJR Am J Roentgenol 1998; Vol. 171 (4): pp 1103–1110. (absence of assessed
intervention)
82. Even-Sapir E, Metser U, Flusser G, Zuriel L, Kollender Y, Lerman H, Lievshitz G, Ron I, Mishani E.
Assessment of malignant skeletal disease: initial experience with 18F-fluoride PET-CT and comparison
between 18F-fluoride PET and 18F-fluoride PET-CT. J Nucl Med 2004; Vol. 45 (2): pp 272–278.
(absence of the classical comparative method)
304

83. Even-Sapir E, Parag Y, Lerman H, Gutman M, Levine C, Rabau M, Figer A, Metser U. Detection of
recurrence in patients with rectal cancer: PET-CT after abdominoperineal or anterior resection.
Radiology 2004; Vol. 232 (3): pp 815–822. Epub 2004 Jul 23. (absence of the classical comparative
method)
84. Farsad M, Schiavina R, Castellucci P, Nanni C, Corti B, Martorana G, Canini R, Grigioni W, Boschi S,
Marengo M, Pettinato C, Salizzoni E, Monetti N, Franchi R, Fanti S. Detection and localization of
prostate cancer: correlation of (11)C-choline PET-CT with histopathologic step-section analysis. J
Nucl Med 2005; Vol. 46 (10): pp 1642–1649. (absence of comparative diagnostic test)
85. Ferris RL, Branstetter BF, Nayak JV. Diagnostic utility of positron emission tomography-computed
tomography for predicting malignancy in cystic neck masses in adults. Laryngoscope 2005; Vol. 115
(11): pp 1979–1982. (casuistic description)
86. Finger PT, Kuril M, Reddy S, Tena LB, Pavlick AC. Whole body PET-CT for initial staging of choroidal
melanoma. Br J Ophthalmol 2005; Vol. 89 (10): pp 1270–1274. (absence of the classical comparative
method)
87. Finger PT, Kurli M, Wesley P, Tena LB, Kerr KR, Pavlick AC. Whole body PET-CT imaging for detection
of metastatic choroidal melanoma. Br J Ophthalmol 2004; Vol. 88 (8): pp 1095–1097. (casuistic
description)
88. Fogarty GB, Peters LJ, Stewart J, Scott C, Rischin D, Hicks RJ. The usefulness of fluorine 18-labelled
deoxyglucose positron emission tomography in the investigation of patients with cervical
lymphadenopathy from an unknown primary tumor. Head & Neck 2003; Vol. 25 (2): pp 138–145.
Date of Publication: 01 FEB 2003. (absence of assessed intervention)
89. Francis DL, Visvikis D, Costa DC, Arulampalam TH, Townsend C, Luthra SK, Taylor I, Ell PJ. Potential
impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F] fluoro-2-deoxy-D-glucose in positron emission
tomography for colorectal cancer. Eur J Nucl Med Mol Imaging 2003 Jul; 30 (7): pp 988–994. Epub
2003 May 9. (absence of the classical comparative method)
90. Frank SJ, Chao KS, Schwartz DL, Weber RS, Apisarnthanarax S, Macapinlac HA. Technology insight:
PET and PET-CT in head and neck tumor staging and radiation therapy planning. Nat Clin Pract
Oncol 2005; Vol. 2 (10): pp 526–533. (secondary trial)
91. Freudenberg LS, Antoch G, Görges R, Knust EJ, Beyer T, Brandau W, Bockisch A, Debatin JF. 124 I-PET-
CT in metastatic follicular thyroid carcinoma. Eur J Nucl Med 2002; Vol. 29: p 1106. (casuistic
desription)
92. Freudenberg LS, Antoch G, Görges R, Knust EJ, Beyer T, Debatin JF. Combined PET-CT with Iodine-
124 in Diagnosis of Mediastinal Micrometastases in Thyroid Carcinoma. Int J Radiol 2002; Vol. 2
Number 2. (casuistic desription)
93. Freudenberg LS, Antoch G, Görges R, Knust EJ, Pink R, Jentzen W, Debatin JF, Brandau W, Bockisch
A, Stattaus J. Combined PET-CT with iodine-124 in diagnosis of spread metastatic thyroid carcinoma:
a case report. Eur Radiol 2003 Dec; 13 (Suppl 4): pp L19–23. (casuistic description)
94. Freudenberg LS, Schueler AO, Beyer T, Antoch G, Kuhl H, Bornfeld N, Bockisch A, Egelhof T. Wholebody
fluorine-18 fluordeoxyglucose positron emission tomography/computed tomography (FDG-
PET-CT) in staging of advanced uveal melanoma. Surv Ophthalmol 2004; Vol. 49 (5): pp 537–540.
(casuistic description)
95. Fukui MB, Blodgett TM, Meltzer CC. PET-CT imaging in recurrent head and neck cancer. Semin
Ultrasound CT MR 2003; Vol. 24 (3): pp 157–163. (secondary trial)
96. Fukunaga H, Sekimoto M, Tatsumi M, Ikenaga M, Ohue M, Seshimo I, Higuchi I, Takayama O, Yasui
M, Ikeda M, Yamamoto H, Monden M. Clinical relevance of fusion images using (18)F-2-fluoro-2deoxy-D-glucose
positron emission tomography in local recurrence of rectal cancer. Int J Oncol
2002 Apr; 20 (4): pp 691–695. (absence of assessed intervention)
97. Goerres GW, Burger C, Kamel E, Seifert B, Kaim AH, Buck A, Buehler TC, von Schulthess GK.
Respiration-induced attenuation artifact at PET-CT: technical considerations. Radiology 2003 Mar;
226 (3): pp 906–10. (absence of end-points)
98. Goerres GW, Haenggeli CA, Allaoua M, Albrecht SR, Dulguerov P, Becker M, Allal AS, Lehmann W,
Slosman DO. Directcomparison off-18-FDG PET and ultrasound in the follow-up of patients with
squamous cell cancer of the head and neck. Nuklearmedizin 2000; Vol. 39 (8): pp 246–250.
(absence of assessed diagnostic method)
305

99. Goerres GW, Kamel E, Heidelberg T-N, Schwitter MR, Burger C, von Schulthess GK. PET-CT image coregistration
in the thorax: influence of respiration. Eur J Nucl Med Mol Imaging 2002 Mar; 29 (3): pp
351–360. (absence of the end-points for assessment of diagnostic efficacy)
100. Goerres GW, Kamel E, Seifert B, Burger C, Buck A, Hany T, von Schulthess GK. Accuracy of image
coregistration of pulmonary lesions in patients with non-small cell lung cancer using an integrated
PET-CT system. J Nucl Med 2002 Nov; 43 (11): pp 1469–1575. (absence of the end-points for
assessment of diagnostic efficacy)
101. Goerres GW, Schmid DT, Gratz KW, von Schulthess GK, Eyrich GK. Impact of whole body positron
emission tomography on initial staging and therapy in patients with squamous cell carcinoma of the
oral cavity. Oral Oncol 2003 Sep; 39 (6): pp 547–551. (combined assessment of the results for PET and
PET-CT)
102. Goerres GW, Stoeckli SJ, von Schulthess GK, Steinert HC. FDG PET for mucosal malignant melanoma
of the head and neck. Laryngoscope 2002 Feb; 112 (2): pp 381–385. (absence of assessed
intervention)
103. Goerres GW, Stupp R, Barghouth G, Hany TF, Pestalozzi B, Dizendorf E, Schnyder P, Luthi F, von
Schulthess GK, Leyvraz S. The value of PET, CT and in-line PET-CT in patients with gastrointestinal
stromal tumours: long-term outcome of treatment with imatinib mesylate. Eur J Nucl Med Mol
Imaging 2005 Feb; 32 (2): pp 153–162. Epub 2004 Sep 4. (absence of end-points)
104. Goerres GW, von Schulthess GK, Steinert HC. Why most PET of lung and head-and-neck cancer will
be PET-CT. J Nucl Med 2004 Jan; 45 Suppl 1: pp 66S-71S. (review)
105. Green D, Johnson IR. Magnetic resonance imaging for gynaecological masses. Reviews in
Gynaecological Practice 2004; Vol. 4 (2): pp 132–140. (secondary trial)
106. Greven KM, Williams III DW, McGuirt WF Sr, Harkness BA, D'Agostino RB Jr, Keyes JW Jr, Watson NE Jr.
Serial positron emission tomography scans following radiation therapy of patients with head and
neck cancer. Head & Neck 2001; Vol. 23 (11): pp 942–946. (absence of assessed intervention)
107. Grigsby PW, Siegel BA, Dehdashti F. Lymph node staging by positron emission tomography in
patients with carcinoma of the cervix. Journal of Clinical Oncology 2002; Vol. 19 (17): pp 3745–3749.
Date of Publication: 01 SEP 2001. (absence of assessed intervention)
108. Grisaru D, Almog B, Levine C, Metser U, Fishman A, Lerman H, Lessing JB, Even-Sapir E. The
diagnostic accuracy of 18 F-Fluorodeoxyglucose PET-CT in patients with gynecological malignancies.
Gynecol Oncol 2004; Vol. 94 (3): pp 680–684.
109. Grosu A-L, Lachner R, Wiedenmann N, Stark S, Thamm R, Kneschaurek P, Schwaiger M, Molls M,
Weber WA. Validation of a method for automatic image fusion (BrainLAB System) of CT data and
11 C-methionine-PET data for stereotactic radiotherapy using a LINAC: First clinical experience. Int J
Radiat Oncol Biol Phys 2003; Vol. 56 (5): pp 1450–1463. Date of Publication: 01 AUG 2003. (absence
of assessed intervention)
110. Gulec SA, Beller M, Edwards K, Lizotte P, O'Day S. Case 3. Positron emission tomography-computed
tomography diagnosis of metastatic melanoma with intussusception. J Clin Oncol 2004; Vol. 22 (23):
pp 4802–4803. (casuistic description)
111. Gutman F, Alberini JL, Wartski M, Vilain D, Le Stanc E, Sarandi F, Corone C, Tainturier C, Pecking AP.
Incidental colonic focal lesions detected by FDG PET-CT. AJR Am J Roentgenol 2005 Aug; 185 (2):
pp 495–500. (absence of the classical comparative method)
112. Ha PK, Hdeib A, Goldenberg D, Jacene H, Patel P, Koch W, Califano J, Cummings CW, Flint PW,
Wahl R, Tufano RP. The role of positron emission tomography and computed tomography fusion in
the management of early-stage and advanced-stage primary head and neck squamous cell
carcinoma. Arch Otolaryngol Head Neck Surg 2006 Jan; 132 (1): pp 12–16. (absence of reference
method)
113. Haberkorn U, Strauss LG, Dimitrakopoulou A, Seiffert E, Oberdorfer F, Ziegler S, Reisser C, Doll J, Helus
F, Van Kaick G. Fluorodeoxyglucose imaging of advanced head and neck cancer after
chemotherapy. J Nucl Med 1993; Vol. 34 (1): pp 12–17. (absence of assessed intervention)
114. Haberkorn U, Strauss LG, Reisser C, Haag D, Dimitrakopoulou A, Ziegler S, Oberdorfer F, Rudat V, Van
Kaick G. Glucose uptake, perfusion and cell proliferation in head and neck tumors: relation of
positron emission tomography to flow cytomery. J Nucl Med 1991; Vol. 32 (8): pp 1548–1555.
(absence of assessed intervention)
306

115. Halfpenny W, Hain SF, Biassoni L, Maisey MN, Sherman JA, McGurk M. FDG-PET. A possible prognostic
factor in head and neck cancer. Br J Cancer 2002; Vol. 86 (4): pp 512–516. Date of Publication: 12
FEB 2002. (absence of assessed diagnostic method)
116. Halpern BS, Schiepers C, Weber WA, Crawford TL, Fueger BJ, Phelps ME, Czernin J. Presurgical
staging of non-small cell lung cancer: Positron emission tomography, integrated positron emission
tomography/CT, and software image fusion. Chest 2005; Vol. 128 (4): pp 2289–2297. (absence of
comparative diagnostic method)
117. Hany TF, Heuberger J, von Schulthess GK. Iatrogenic FDG foci in the lungs: a pitfall of PET image
interpretation. Eur Radiol 2003 Sep; 13 (9): pp 2122–2127. Epub 2002 Oct 17. (casuistic description)
118. Hany TF, Steinert HC, Goerres GW, Buck A, von Schulthess GK. PET diagnostic accuracy:
improvement with in-line PET-CT system: initial results. Radiology 2002 Nov; 225 (2): pp 575–581.
(absence of the classical comparative method)
119. Havrilesky LJ, Kulasingam SL, Matchar DB, Myers ER. FDG-PET for management of cervical and
ovarian cancer. Gynecol Oncol 2005; Vol. 97 (1): pp 183–191. (absence of assessed intervention)
120. Hayashi K, Abe K, Yano F, Watanabe S, Iwasaki Y, Kosuda S. Should mediastinoscopy actually be
incorporated into the FDG PET strategy for patients with non-small cell lung carcinoma?. Ann Nucl
Med 2005 Jul; 19 (5): pp 393–398. (absence of assessed intervention)
121. Heller MT, Meltzer C, Fukui M, Rosen C, Chander S, Martinelli M, Townsend DW. Superphysiologic FDG
uptake in the non-paralyzed vocal cord: resolution of a false-positive PET result with combined PET-
CT imaging. Clin Pos Imag 2000; Vol. 3 (5): pp 207–211. (casuistic description)
122. Hensing TA. Clinical evaluation and staging of patients who have lung cancer. Hematol Oncol Clin
N Am 2005; Vol. 19 (2): pp 219–235. (secondary trial)
123. Heron DE, Andrade RS, Flickinger J, Johnson J, Agarwala SS, Wu A, Kalnicki S, Avril N. Hybrid PET-CT
simulation for radiation treatment planning in head-and-neck cancers: a brief technical report. Int J
Radiat Oncol Biol Phys 2004 Dec 1; 60 (5): pp 1419–1424. (absence of assessed intervention)
124. Hicks RJ, Mac Manus MP, Seymour JF. Initial staging of lymphoma with positron emission
tomography and computed tomography. Semin Nucl Med 2005 Jul; 35 (3): pp 165–175. (secondary
trial)
125. Ho CL. Clinical PET imaging – An asian perspective. Ann Acad Med Singapore 2004; Vol. 33 (2): pp
155–165. (secondary trial)
126. Ho YH, Ooi LLPJ. Recent advances in the total management of colorectal cancer. Ann Acad Med
Singapore 2003; Vol. 32 (2): pp 143–144. (secondary trial)
127. Hoskin PJ. PET in lymphoma: what are the oncologist's needs?. Eur J Nucl Med Mol Imaging 2003
Jun; 30 (Suppl 1): pp S37–41. Epub 2003 Apr 4. (secondary trial)
128. Hosten N, Lemke AJ, Wiedenmann B, Bohmig M, Rosewicz S. Combined imaging techniques for
pancreatic cancer. Lancet 2000; Vol. 9; 356 (9233): pp 909–910. (secondary trial)
129. Hustinx R. PET imaging in assessing gastrointestinal tumors. Radiol Clin N Am 2004; Vol. 42 (6): pp
1123–1139. (secondary trial)
130. Ioannidis JP, Lau J. 18 F-FDG PET for the diagnosis and grading of soft-tissue sarcoma: a meta-analysis.
J Nucl Med 2003 May; 44 (5): pp 717–724. (absence of assessed intervention)
131. Ishimori T, Patel PV, Wahl RL. Detection of unexpected additional primary malignancies with PET-CT.
J Nucl Med 2005; Vol. 46 (5): pp 752–757. (absence of comparative diagnostic test)
132. Israel O, Mor M, Gaitini D, Keidar Z, Guralnik L, Engel A, Frenkel A, Bar-Shalom R, Kuten A. Combined
functional and structural evaluation of cancer patients with a hybrid camera-based PET-CT system
using 18 F-FDG. J Nucl Med 2002; Vol. 43 (9): pp 1129–1136. (absence of combined resylts for PET-CT)
133. Israel O, Mor M, Guralnik L, Hermoni N, Gaitini D, Bar-Shalom R, Keidar Z, Epelbaum R. Is 18F-FDG PET-
CT useful for imaging and management of patients with suspected occult recurrence of cancer. J
Nucl Med 2004; Vol. 45 (12): pp 2045–2051. (absence of the classical comparative method)
134. Israel O, Yefremov N, Bar-Shalom R, Kagana O, Frenkel A, Keidar Z, Fischer D. PET-CT detection of
unexpected gastrointestinal foci of 18F-FDG uptake: incidence, localization patterns, and clinical
significance. J Nucl Med 2005 Vol. 46 (5): pp 758–762. (absence of comparative diagnostic test)
307

135. Jadvar H, Alavi A, Mavi A, Shulkin BL. PET in pediatric diseases. Radiol Clin N Am 2005; Vol. 43 (1): pp
135–152. (secondary trial)
136. Jadvar H, Conti PS. The reproductive tract. Semin Nucl Med 2004; Vol. 34 (4): pp 262–273.
(secondary trial)
137. Jadvar H, Gamie S, Ramanna L, Conti PS. Musculoskeletal system. Semin Nucl Med 2004 Oct; 34 (4):
pp 254–261. (secondary trial)
138. Jana S, Zhang T, Milstein DM, Isasi CR, Blaufox MD. FDG-PET and CT characterization of adrenal
lesions in cancer patients. Eur J Nucl Med Mol Imaging 2006; Vol. 33 (1): pp 29–35. (combined
assessment of the results for PET and PET-CT)
139. Jaskowiak CJ, Bianco JA, Perlman SB, Fine JP. Influence of reconstruction iterations on 18 F-FDG PET-
CT standardized uptake values. J Nucl Med 2005; Vol. 46 (3): pp 424–428. (absence of comparative
diagnostic test)
140. Jerusalem G, Hustinx R, Beguin Y, Fillet G. The value of positron emission tomography (PET) imaging
in disease staging and therapy assessment. Ann Oncol 2002; Vol. 13 (Suppl. 4): pp 227–234.
(secondary trial)
141. Kalff V, Hicks RJ, Ware RE, Hogg A, Binns D, McKenzie AF. The clinical impact of (18)F-FDG PET in
patients with suspected or confirmed recurrence of colorectal cancer: a prospective study. J Nucl
Med 2002 Apr; 43 (4): pp 492–499. (absence of assessed intervention)
142. Kalra MK, Maher MM, Boland GW, Saini S, Fischman AJ. Correlation of positron emission tomography
and CT in evaluating pancreatic tumors: Technical and clinical implications. AJR Am J Roentgenol
2003; Vol. 181 (2): pp 387–393. Date of Publication: 01 AUG 2003. (secondary trial)
143. Kamel EM, Goerres GW, Burger C, von Schulthess GK, Steinert HC. Recurrent laryngeal nerve palsy in
patients with lung cancer: Detection with PET-CT image fusion – Report of six cases. Radiology 2002;
Vol. 224 (1): 153–156. (fuzja obrazów PET-CT u 4 pacjentów)
144. Kamel EM, Hany TF, Burger C, Treyer V, Lonn AHR, Von Schulthess GK, Buck A. CT vs 68 Ge attenuation
correction in a combined PET-CT system: Evaluation of the effect of lowering the CT tube current.
Eur J Nucl Med 2002; Vol. 29 (3): pp 346–350. (absence of comparative diagnostic test)
145. Kamel EM, Thumshirn M, Truninger K, Schiesser M, Fried M, Padberg B, Schneiter D, Stoeckli SJ, von
Schulthess GK, Stumpe KD. Significance of incidental 18F-FDG accumulations in the gastrointestinal
tract in PET-CT: correlation with endoscopic and histopathologic results. J Nucl Med 2004 Nov; 45
(11): pp 1804–1810. (absence of the classical comparative method)
146. Kamel EM, Zwahlen D, Wyss MT, Stumpe KD, von Schulthess GK, Steinert HC. Whole-body 18 F-FDG PET
improves the management of patients with small cell lung cancer. Source. J Nucl Med 2003; Vol. 44
(12): pp 1911–1917. (absence of assessed intervention)
147. Kamel IR, Cohade C, Neyman E, Fishman EK, Wahl RL. Incremental value of CT in PET-CT of patients
with colorectal carcinoma. Abdominal Imaging 2004; Vol. 29 (6): pp 663–668. (absence of the
classical comparative method)
148. Kapoor V, Fukui MB, McCook BM. Role of 18FFDG PET-CT in the treatment of head and neck
cancers: principles, technique, normal distribution, and initial staging. AJR Am J Roentgenol 2005
Feb; 184 (2): pp 579–587. (secondary trial)
149. Kaste SC. Issues specific to implementing PET-CT for pediatric oncology: What we have learned
along the way. Pediatr Radiol 2004; Vol. 34 (3): pp 205–213. (secondary trial)
150. Kato H, Miyazaki T, Nakajima M, Fukuchi M, Manda R, Kuwano H. Value of positron emission
tomography in the diagnosis of recurrent oesophageal carcinoma. Br J Surg 2004; Vol. 91 (8): pp
1004–1009. (absence of assessed intervention)
151. Kato H, Miyazaki T, Nakajima M, Takita J, Kimura H, Faried A, Sohda M, Fukai Y, Masuda N, Fukuchi
M, Manda R, Ojima H, Tsukada K, Kuwano H, Oriuchi N, Endo K. The incremental effect of positron
emission tomography on diagnostic accuracy in the initial staging of esophageal carcinoma.
Cancer 2005; Vol. 103 (1): pp 148–156. (absence of assessed intervention)
152. Katzel JA, Heiba SI. PET-CT F-18 FDG scan accurately identifies osteoporotic fractures in a patient
with known metastatic colorectal cancer. Clin Nucl Med 2005; Vol. 30 (10): pp 651–654. (casuistic
description)
308

153. Kayani I, Groves AM, Ell PJ, George PJ, Bomanji J. Imaging bronchial carcinoma in situ: possible roles
for combined positron emission tomography (PET)-CT. Lancet Oncol 2005 Mar; 6 (3): p 190. (casuistic
description)
154. Kayani I, Groves AM, Syed R, Bomanji J. Combined F-18 FDG positron emission tomography
/computed tomography in the diagnosis of colonic polyps: The potential and limitations of the
technique. Clin Nucl Med 2005; Vol. 30 (2): pp 116–117. (casuistic description)
155. Keidar Z, Haim N, Guralnik L, Wollner M, Bar-Shalom R, Ben-Nun A, Israel O. PET-CT using 18F-FDG in
suspected lung cancer recurrence: diagnostic value and impact on patient management. J Nucl
Med 2004 Oct; 45 (10): pp 1640–1646. (absence of comparative diagnostic test)
156. Keyes JW, Chen MYM, Watson NE, Greven KM, McGuirt WF, Williams III DW. FDG pet evaluation of
head and neck cancer: Value of imaging the thorax. Head & Neck 2000; Vol. 22 (2): pp 105–110.
(absence of assessed intervention)
157. Kim J-H, Czernin J, Allen-Auerbach MS, Halpern BS, Fueger BJ, Hecht JR, Ratib O, Phelps ME, Weber
WA. Comparison between 18 F-FDG PET, in-line PET-CT, and software fusion for restaging of recurrent
colorectal cancer. J Nucl Med 2005; Vol. 46 (4): pp 587–595. (absence of the classical comparative
method)
158. Kinahan P, Townsend D, Beyer T, Sashin D. Attenuation correction for a combined 3D PET-CT
scanner. Med Phys 1998; Vol. 25 (10): pp 2046–2053. (absence of assessed intervention)
159. Kluetz PG, Meltzer CC, Villemagne VL, Kinahan PE, Chander S, Martinelli MA, Townsend DW.
Combined PET-CT Imaging in Oncology: Impact on Patient Management. Clin Positron Imaging
2000; Vol. 3, No. 6: pp 223–230. (casuistic description)
160. Kole AC, Plukker JT, Nieweg OE, Vaalburg W. Positron emission tomography for staging of
oesophageal and gastroesophageal malignancy. Br J Cancer 1998 Aug; 78 (4): pp 521–527.
(absence of assessed intervention)
161. Konski A, Doss M, Milestone B, Haluszka O, Hanlon A, Freedman G, Adler L. The integration of 18fluoro-deoxy-glucose
positron emission tomography and endoscopic ultrasound in the treatmentplanning
process for esophageal carcinoma. Int J Radiat Oncol Biol Phys 2005; Vol. 61 (4): pp 1123–
1128. (absence of assessed intervention)
162. Kostakoglu L, Goldsmith SJ. 18F-FDG PET evaluation of the response to therapy for lymphoma and
for breast, lung, and colorectal carcinoma. J Nucl Med 2003 Feb; 44 (2): pp 224–239. (secondary
trial)
163. Koyama K, Okamura T, Kawabe J, Ozawa N, Torii K, Umesaki N, Miyama M, Ochi H, Yamada R.
Evaluation of 18 F-FDG PET with bladder irrigation in patients with uterine and ovarian tumors. J Nucl
Med 2003; Vol. 44 (3): pp 353–358. (absence of assessed intervention)
164. Kresnik E, Kogler D, Gallowitsch H-J, Mikosch P, Wieser S, Igerc I, Gomez I, Kumnig G, Lind P. Head
and neck tumors. Current evaluation with 18 F-FDG-PET compared with conventional methods.
Internistische Praxis 2003; Vol. 43 (2): pp 301–309. (article in German)
165. Krishnasetty V, Fischman AJ, Halpern EL, Aquino SL. Comparison of alignment of computerregistered
data sets: combined PET-CT versus independent PET and CT of the thorax. Radiology
2005; Vol. 237 (2): pp 635–639. (inadequate population)
166. Kuhnel G, Horn L-C, Fischer U, Hesse S, Seese A, Georgi P, Kluge R. 18 F-FDG-Positron-Emission-
Tomography in patients with uterine cervical cancer: Preliminary results. Zentralblatt fur Gynakologie
2001; Vol. 123 (4): pp 229–235. (article in German)
167. Kula Z, Szefer J, Pietrzak T, Zuchora Z. An attempt at assessing the efficacy of combined positron
emision tomography and computed tomography (PET-CT) imaging in the diagnosis of pancreatic
carcinoma – Own experiences. Nowotwory 2005; Vol. 55 (5): pp 373–379. (absence of the
unambiguous results)
168. Kula Z, Szefer J, Pietrzak T, Zuchora Z. Our first experience with combined positron emission
tomography and computed tomography (PET-CT) in patients with gastric cancer. Współczesna
Onkologia 2005; Vol. 9 (4): pp 213–217. (absence of assessed intervention)
169. Kumar R, Alavi A. PET imaging in gynecologic malignancies. Radiol Clin N Am 2004; Vol. 42 (6): pp
1155–1167. (secondary trial)
170. Kunkler I. Cure, palliation, and cost in cancer care. Lancet Oncol 2004; Vol. 5 (12): p 709.
(secondary trial)
309

171. Kurli M, Reddy S, Tena LB, Pavlick AC, Finger PT. Whole body positron emission
tomography/computed tomography staging of metastatic choroidal melanoma. Am J Ophthalmol
2005 Aug; 140 (2): pp 193–199. (absence of the results in application of reference method)
172. Kwon RS, Sahani DV, Brugge WR. Gastrointestinal cancer imaging: Deeper than the eye can see.
Gastroenterology 2005; Vol. 128 (6): pp 1538–1553. (secondary trial)
173. Ladabaum U. Positron emission tomography: The gastroenterologists's perspective. Gastrointestinal
Endoscopy 2002; Vol. 55 (7 II): pp S64–S66. (secondary trial)
174. Lamoreaux WT, Grigsby PW, Dehdashti FD, Zoberi I, Powell MA, Gibb RK, Rader JS, Mutch DG, Siegel
BA. FDG-PET evaluation of vaginal carcinoma. Int J Radiat Oncol Biol Phys 2005; Vol. 62 (3): pp 733–
737. (absence of separated results for PET and PET-CT)
175. Lardinois D, Weder W, Roudas M, von Schulthess GK, Tutic M, Moch H, Stahel RA, Steinert HC.
Etiology of solitary extrapulmonary positron emission tomography and computed tomography
findings in patients with lung cancer. J Clin Oncol 2005 Oct 1; 23 (28): pp 6846–6853. (absence of
comparative diagnostic test)
176. Larson SM, Nehmeh SA, Erdi YE, Humm JL. PET-CT in non-small-cell lung cancer: Value of respiratorygated
PET. Chang Gung Med J 2005; Vol. 28 (5): pp 306–314. (secondary trial absence of assessed
intervention)
177. Lau WF, Binns DS, Ware RE, Ramdave S, Cachin F, Pitman AG, Hicks RJ. Clinical experience with the
first combined positron emission tomography/computed tomography scanner in Australia. Med J
Aust 2005; Vol. 21; 182 (4): pp172–176. (secondary trial)
178. Lavrenkov K, Partridge M, Cook G, Brada M. Positron emission tomography for target volume
definition in the treatment of non-small cell lung cancer. Radiother Oncol 2005; Vol. 77 (1): pp 1–4.
(secondary trial)
179. Lejeune C, Bismuth MJ, Conroy T, Zanni C, Bey P, Bedenne L, Faivre J, Arveux P, Guillemin F. Use of
a decision analysis model to assess the cost-effectiveness of 18F-FDG PET in the management of
metachronous liver metastases of colorectal cancer. J Nucl Med 2005 Dec; 46 (12): pp 2020–2028.
(secondary trial)
180. Lerman H, Metser U, Grisaru D, Fishman A, Lievshitz G, Even-Sapir E. Normal and abnormal 18F-FDG
endometrial and ovarian uptake in pre- and postmenopausal patients: assessment by PET-CT.
J Nucl Med 2004 Feb; 45 (2): pp 266–271. (absence of the classical method and end-points of
diagnostic efficacy assessment)
181. Leskinen-Kallio S, Lindholm P, Lapela M, Joensuu H, Nordman E. Imaging of head and neck tumors
with positron emission tomography and [ 11 C]methionine. Int J Radiat Oncol Biol Phys 1994; Vol. 30
(5): pp 1195–1199. (absence of assessed diagnostic method)
182. Lim JWM, Tang CL, Keng GHW. False positive F-18 fluorodeoxyglucose combined PET-CT scans from
suture granuloma and chronic inflammation: Report of two cases and review of literature. Ann
Acad Med Singapore 2005; Vol. 34 (7): pp 457–460. (casuistic description)
183. Lind P, Igerc I, Beyer T, Reinprecht P, Hausegger K. Advantages and limitations of FDG PET in the
follow-up of breast cancer. Eur J Nucl Med Mol Imaging 2004 Jun; 31 (Suppl 1): pp S125–134. Epub
2004 Apr 15. (secondary trial)
184. Lind P, Kumnig G, Heinisch M, Gallowitsch HJ, Mikosch P, Kresnik E, Gomez I, Unterweger O. F-18-FDG
positron emission tomography in oncology. Tagliche Praxis 2003; Vol. 44 (3): pp 503–520. (article in
German)
185. Lowe VJ, Dunphy FR, Varvares M, Kim H, Wittry M, Dunphy CH, Dunleavy T, McDonough E, Minster J,
Fletcher JW, Boyd JH. Evaluation of chemotherapy response in patients with advanced head and
neck cancer using [F-18] fluorodeoxyglucose positron emission tomography. Head & Neck 1997;
Vol. 19 (8): pp 666–674. (absence of assessed intervention)
186. Lytras D, Connor S, Bosonnet L, Jayan R, Evans J, Hughes M, Garvey CJ, Ghaneh P, Sutton R,
Vinjamuri S, Neoptolemos JP. Positron emission tomography does not add to computed
tomography for the diagnosis and staging of pancreatic cancer. Dig Surg 2005; Vol. 22 (1–2): pp 55–
61. (absence of assessed intervention)
187. Ma S-Y, See L-C, Lai C-H, Chou H-H, Tsai C-S, Ng K-K, Hsueh S, Lin W-J, Chen J-T, Yen T-C. Delayed 18 F-
FDG PET for detection of paraaortic lymph node metastases in cervical cancer patients. J Nucl Med
2003; Vol. 44 (11): pp 1775–1783. (absence of assessed intervention)
310

188. Macapinlac HA. FDG PET and PET-CT imaging in lymphoma and melanoma. Cancer J 2004 Jul-Aug;
10 (4): pp 262–270. (secondary trial)
189. Macapinlac HA. FDG-PET in the evaluation of cervical cancer. Gynecol Oncol 2005; Vol. 99
(3 Suppl.): pp S171–S172. (secondary trial)
190. Macapinlac HA. The utility of 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography and
combined positron emission tomography and computed tomography in lymphoma and
melanoma. Mol Imaging Biol 2004 Jul-Aug; 6 (4): pp 200–207. (secondary trial)
191. Magnani P, Carretta A, Rizzo G, Fazio F, Vanzulli A, Lucignani G, Zannini P. FDG/PET and spiral CT
image fusion for medistinal lymph node assessment of patients with small cell lung cancer. J
Cardiovasc Surg (Torino) 1999 Oct; 40 (5): pp 741–748. (absence of assessed intervention)
192. Mahoney EJ, Spiegel JH. Evaluation and management of malignant cervical lymphadenopathy
with an unknown primary tumor. Otolaryngol Clin N Am 2005; Vol. 38 (1): pp 87–97. (secondary trial)
193. Manavis J, Sivridis L, Koukourakis MI. Nasopharyngeal carcinoma: the impact of CT-scan and of MRI
on staging, radiotherapy treatment planning, and outcome of the disease. Clin Imaging 2005 Mar-
Apr; 29 (2): pp 128–133. (secondary trial)
194. Martinez-Roman S, Ramirez PT, Oh J, Viciedo MG, MacApinlac HA. Combined positron emission
tomography and computed tomography for the detection of recurrent ovarian mucinous
adenocarcinoma. Gynecol Oncol 2005; Vol. 96 (3): pp 888–891. (absence of assessed intervention)
195. Mattes D, Haynor DR, Vesselle H, Lewellen TK, Eubank W. PET-CT image registration in the chest using
free-form deformations. IEEE Trans Med Imaging 2003 Jan; 22 (1): pp 120–128. (absence of endpoints)
196. Matthies A, Ezziddin S, Ulrich E-M, Palmedo H, Biersack H-J, Bender H, Guhlke S. Imaging of prostate
cancer metastases with 18 F-fluoroacetate using PET/ CT. Eur J Nucl Med Mol Imaging 2004; Vol. 31
(5): p 797. (absence of assessed intervention)
197. McCarville MB, Christie R, Daw NC, Spunt SL, Kaste SC. PET-CT in the evaluation of childhood
sarcomas. AJR Am J Roentgenol 2005 Apr; 184 (4): pp 1293–1304. (casuistic description)
198. McCollum AD, Burrell SC, Haddad RI, Norris CM, Tishler RB, Case MA, Posner MR, Van Den Abbeele
AD. Positron emission tomography with 18 F-fluorodeoxyglucose to predict pathologic response after
induction chemotherapy and definitive chemoradiotherapy in head and neck cancer. Head &
Neck 2004; Vol. 26 (10): pp 890–896. (absence of assessed intervention)
199. Menda Y, Graham MM. Update on 18F-fluorodeoxyglucose/positron emission tomography and
positron emission tomography/computed tomography imaging of squamous head and neck
cancers. Semin Nucl Med 2005; Vol. 35 (4): pp 214–219. (secondary trial)
200. Metser U, Golan O, Levine CD, Even-Sapir E. Tumor lesion detection: When is integrated positron
emission tomography/computed tomography more accurate than side-by-side interpretation of
positron emission tomography and computed tomography? J Comput Assist Tomogr 2005; Vol. 29
(4): pp 554–559. (PET-CT compared to PET)
201. Metser U, Goor O, Lerman H, Naparstek E, Even-Sapir E. PET-CT of extranodal lymphoma. AJR Am J
Roentgenol 2004 Jun; 182 (6): pp 1579–1586. (secondary trial)
202. Metser U, Lerman H, Blank A, Lievshitz G, Bokstein F, Even-Sapir E. Malignant involvement of the
spine: assessment by 18F-FDG PET-CT. J Nucl Med 2004; Vol. 45 (2): pp 279–284. (absence of results
for the reference methods)
203. Metser U, Miller E, Kessler A, Lerman H, Lievshitz G, Oren R, Even-Sapir E. Solid splenic masses:
Evaluation with 18 F-FDG PET-CT. J Nucl Med 2005; Vol. 46 (1): pp 52–59. (absence of comparative
diagnostic test)
204. Miller E, Lerman H, Gutman M, Figer A, Livshitz G, Even-Sapir E. The clinical impact of camera-based
positron emission tomography imaging in patients with recurrent colorectal cancer. Invest Radiol
2004 Jan; 39 (1): pp 8–12. (absence of assessed intervention)
205. Mitchell JC, Grant F, Evenson AR, Parker JA, Hasselgren PO, Parangi S. Preoperative evaluation of
thyroid nodules with 18FDG-PET-CT. Surgery 2005 Dec; 138 (6): pp 1166–1174; discussion: pp 1174–
1175. (absence of the classical comparative method)
206. Moadel RM, Blaufox MD, Freeman LM. The role of positron emission tomography in gastrointestinal
imaging. Gastroenterol Clin N Am 2002; Vol. 31 (3): pp 841–861. (secondary trial)
311

207. Modi D, Fulham MJ, Mohamed A, McCaughan BC. Intraluminal FDG uptake in a rectal polyp
detected with PET CT: Identification of an unsuspected synchronous primary bowel tumor. Clin Nucl
Med 2005; Vol. 30 (3): pp 180–181. (casuistic description)
208. Moureau-Zabotto L, Touboul E, Lerouge D, Deniaud-Alexandre E, Grahek D, Foulquier J-N, Petegnief
Y, Gres B, El Balaa H, Kerrou K, Montravers F, Keraudy K, Tiret E, Gendre J-P, Grange J-D, Houry S,
Talbot J-N. Impact of CT and 18 F-deoxyglucose positron emission tomography image fusion for
conformal radiotherapy in esophageal carcinoma. Int J Radiat Oncol Biol Phys 2005; Vol. 63 (2): pp
340–345. (absence of assessed intervention)
209. Mukherji SK, Wolf GT. Evaluation of head and neck squamous cell carcinoma after treatment. AJNR
Am J Neuroradiol 2003; Vol. 24: pp 1743–1746. (secondary trial)
210. Mumber M, Greven K, Haygood T. Pelvic insufficiency fractures associated with radiation atrophy:
clinical recognition and diagnostic evaluation. Skeletal Radiol 1997 Feb; 26 (2): pp 94–99. (casuistic
description)
211. Nakahara T, Fujii H, Ide M, Mochizuki Y, Takahashi W, Yasuda S, Shohtsu A, Kubo A. F-18 FDG uptake
in endometrial cancer. Clin Nucl Med 2001 Jan; 26 (1): pp 82–83. (casuistic description)
212. Nakamoto Y, Cohade C, Tatsumi M, Hammoud D, Wahl RL. CT appearance of bone metastases
detected with FDG PET as part of the same PET-CT examination. Radiology 2005; Vol. 237 (2): pp
627–634. (absence of assessed intervention)
213. Nakamoto Y, Osman M, Cohade C, Marshall LT, Links JM, Kohlmyer S, Wahl RD. PET-CT: comparison
of quantitative tracer uptake between germanium and CT transmission attenuation-corrected
images. J Nucl Med 2002 Sep; 43 (9): pp 1137–1143. (absence of the clinical anf diagnostic
assessment, absence of reference method)
214. Nanni C, Rubello D, Castellucci P, Farsad M, Franchi R, Toso S, Barile C, Rampin L, Nibale O, Fanti S.
Role of 18 F-FDG PET-CT imaging for the detection of an unknown primary tumour: Preliminary results
in 21 patients. Eur J Nucl Med Mol Imaging 2005; Vol. 32 (5): pp 589–592. (absence of the classical
comparative method)
215. Nanni C, Rubello D, Farsad M, De Iaco P, Sanovivini M, Erba P, Rampin L, Mariani G, Fanti S. FDG-PET
CT in evaluation of recurrent ovarian cancer: a prospective study on forty one patients. Eur J Surg
Oncol 2005 Sep; 31 (7): pp 792–797. (absence of comparative diagnostic method)
216. Nehmeh SA, Erdi YE, Pan T, Pevsner A, Rosenzweig KE, Yorke E, Mageras GS, Schoder H, Vernon P,
Squire O, Mostafavi H, Larson SM, Humm JL. Four-dimensional (4D) PET-CT imaging of the thorax.
Medical Physics 2004; Vol. 31 (12): pp 3179–3186. (secondary trial)
217. Nehmeh SA, Erdi YE, Pan T, Yorke E, Mageras GS, Rosenzweig KE, Schoder H, Mostafavi H, Squire O,
Pevsner A, Larson SM, Humm JL. Quantitation of respiratory motion during 4D-PET-CT acquisition.
Med Phys 2004 Jun; 31 (6): pp 1333–1338. (absence of end-points for assessment of diagnostic
efficacy)
218. Nestle U, Hellwig D, Fleckenstein J, Walter K, Ukena D, Rube C, Kirsch CM, Baumann M. Comparison
of early pulmonary changes in 18FDG-PET and CT after combined radiochemotherapy for
advanced non-small-cell lung cancer: a study in 15 patients. Front Radiat Ther Oncol 2002; 37: pp
26–33. (absence of assessed intervention)
219. Nguyen BD, Fletcher GP, Patel AC. PET-CT imaging of conus medullaris metastasis from lung cancer.
Clin Nucl Med 2005; Vol. 30 (4): pp 253–256. (casuistic description)
220. Nomayr A, Romer W, Hothorn T, Pfahlberg A, Hornegger J, Bautz W, Kuweit T. Anatomical accuracy
of lesion localization: Retrospective interactive rigid image registration between 18 F-FDG-PET and Xray
CT. Nuklearmedizin 2005; Vol. 44 (4): pp 149–155. (absence of assessed intervention)
221. Okada J, Yoshikawa K, Imazeki K, Minoshima S, Uno K, Itami J, Kuyama J, Maruno H, Arimizu N. The
use of FDG-PET in the detection and management of malignant lymphoma: Correlation of uptake
with prognosis. J Nucl Med 1991; Vol. 32 (4): pp 686–691. (absence of assessed intervention)
222. Ollenberger GP. Staging of lung cancer with integrated PET and CT. N Engl J Med 2004 Jan 1; 350
(1): pp 86–87; author reply 86–87. (letter)
223. Ong SC, Ng DC, Sundram FX. Initial experience in use of fluorine-18-fluorodeoxyglucose positron
emission tomography/computed tomography in thyroid carcinoma patients with elevated serum
thyroglobulin but negative iodine-131 whole body scans. Singapore Med J 2005 Jun; 46 (6): pp 297–
301. (absence of verification of study results in application of reference test)
312

224. Osman MM, Cohade C, Fishman EK, Wahl RL. Clinically significant incidental findings on the
unenhanced CT portion of PET-CT studies: frequency in 250 patients. J Nucl Med 2005; Vol. 46 (8): pp
1352–1355. (absence of reference test)
225. Osman MM, Cohade C, Nakamoto Y, Marshall L, Leal J, Wahl R. Clinically significant inaccurate
localization of lesions with PET-CT: frequency in 300 patients. J Nucl Med 2003 Feb; 44 (2): pp 240–
243. (absence of the classical comparative method)
226. Osman MM, Cohade C, Nakamoto Y, Wahl RL. Respiratory motion artifacts on PET emission images
obtained using CT attenuation correction on PET-CT. Eur J Nucl Med Mol Imaging 2003 Apr; 30 (4):
pp 603–606. Epub 2003 Jan 21. (absence of end-points for assessment of diagnostic efficacy)
227. Otsuka H, Graham MM, Kogame M, Nishitani H. The impact of FDG-PET in the management of
patients with salivary gland malignancy. Ann Nucl Med 2005; Vol. 19 (8): pp 691–694. (absence of
assessed diagnostic method)
228. Oudoux A, Rousseau T, Bridji B, Resche I, Rousseau C. Interest of F-18 fluorodeoxyglucose positron
emission tomography in the evaluation of vaginal malignant melanoma. Gynecol Oncol 2004; Vol.
95 (3): pp 765–768. (casuistic description)
229. Pacak K, Ilias I, Chen CC, Carrasquillo JA, Whatley M, Nieman LK. The Role of [ 18 F]
Fluorodeoxyglucose Positron Emission Tomography and [ 11 In]-Diethylenetriaminepentaacetate-D-
Phe-Pentetreotide Scintigraphy in the Localization of Ectopic Adrenocorticotropin-Secreting Tumors
Causing Cushing's Syndrome. J Clin Endocrinol Metab 2004; Vol. 89 (5): pp 2214–2221. (absence of
assessed intervention)
230. Pannu HK, Cohade C, Bristow RE, Fshman EK, Wahl RL. PET-CT detection of abdominal recurence of
ovarian cancer: radiologic-surgical correlation. Abdom Imaging 2004 May-Jun; 29 (3): pp 398–403.
(absence of comparative diagnostic method)
231. Pardo FS, Aronen HJ, Fitzek M, Kennedy DN, Efird J, Rosen BR, Fischman AJ. Correlation of FDG-PET
interpretation with survival in a cohort of glioma patients. Anticancer Research 2004; Vol. 24 (4): pp
2359–2365. (absence of assessed intervention)
232. Park D, Kim K, Park S, Lee B, Choi C, Chin S. Diagnosis of recurrent uterine cervical cancer:
computed tomography versus positron emission tomography. Korean J Radiol 2000 Jan-Mar; 1 (1):
pp 51–55. (absence of assessed intervention)
233. Patel PV, Cohade C, Chin BB. PET-CT localizes previously undetectable metastatic lesions in
recurrent fallopian tube carcinoma. Gynecol Oncol 2002; Vol. 87: pp 323–326. (casuistic
description)
234. Paulino AC, Koshy M, Howell R, Schuster D, Davis LW. Comparison of CT- and FDG-PET-defined gross
tumor volume in intensity-modulated radiotherapy for head-and-neck cancer. Int J Radiat Oncol
Biol Phys 2005 Apr 1; 61 (5): pp 1385–1392. (absence of the classical comparative method)
235. Pelosi E, Messa C, Sironi S, Picchio M, Landoni C, Bettinardi V, Gianolli L, Del Maschio A, Gilardi MC,
Fazio F. Value of integrated PET-CT for lesion localisation in cancer patients: A comparative study.
Eur J Nucl Med Mol Imaging 2004; Vol. 31 (7): pp 932–939. (absence of the classical comparative
method)
236. Perrotin C, Lemeunier P, Grahek D, Molina T, Petino A, Alifano M, Bellenot F, Magdeleinat P, Talbot J-
N, Regnard J-F. Results of FDG-PET scanning in the pre-operative staging of broncho-pulmonary
tumours. Revue des Maladies Respiratoires 2005; Vol. 22 (4): pp 579–585. (article in French)
237. Phongkitkarun S, Varavithya V, Kazama T, Faria SC, Mar MV, Podoloff DA, Macapinlac HA.
Lymphomatous involvement of gastrointestinal tract: Evaluation by positron emission tomography
with 18 F-fluorodeoxyglucose. World J Gastroenterol 2005; Vol. 11 (46): pp 7284–7289. Date of
Publication: 14 DEC 2005. (absence of assessed intervention)
238. Picchio M, Sironi S, Messa C, Mangili G, Landoni C, Gianolli L, Zangheri B, Vigano R, Aletti Gde M, De
Cobelli F, Del Maschio A, Ferrari A, Fazio F. Advanced ovarian carcinoma: usefulness of [(18)F]FDG-
PET in combination with CT for lesion detection after primary treatment. Q J Nucl Med 2003 Jun; 47
(2): pp 77–84. (absence of assessed intervention)
239. Poöttgen C, Levegrϋn S, Theegarten D, Marnitz S, Grehl S. Value of 18 F-fluoro-2-deoxy-D-glucosepositron
emission tomography/computed tomography in non-small-cell lung cancer for prediction
of pathologic response and times to relapse after neoadjuvant chemoradiotherapy. Clin Cancer
Res 2006; Vol. 12 (1): pp 97–106. (absence of end-points for assessment of diagnostic efficacy)
313

240. Poppe K, Lahoutte T, Everaert H, Bossuyt A, Velkeniers B. The utility of multimodality imaging in
anaplastic thyroid carcinoma. Thyroid 2004 Nov; 14 (11): pp 981–982. (casuistic description)
241. Raanani P, Shasha Y, Perry C, Metser U, Naparstek E, Apter S, Nagler A, Polliack A, Ben-Bassat I,
Even-Sapir E. Is CT scan still necessary for staging in Hodgkin and non-Hodgkin lymphoma patients in
the PET-CT era?. Ann Oncol 2006; Vol. 17 (1): pp 117–122. (absence of reference test)
242. Reddy S, Kurli M, Tena LB, Finger PT. PET-CT imaging: detection of choroidal melanoma. Br J
Ophthalmol 2005; Vol. 89 (10): pp 1265–1269. (absence of the classical comparative method)
243. Rege S, Maass A, Chaiken L, Hoh CK, Choi Y, Lufkin R, Anzai Y, Juillard G, Maddahi J, Phelps ME. Use
of positron emission tomography with fluorodeoxyglucose in patients with extracranial head and
neck cancers. Cancer 1994; Vol. 73 (12): pp 3047–3058. (absence of assessed diagnostic method)
244. Reinartz P, Wieres FJ, Schneider W, Schur A, Buell U. Side-by-side reading of PET and CT scans in
oncology: which patients might profit from integrated PET-CT?. Eur J Nucl Med Mol Imaging 2004;
Vol. 31 (11): pp 1456–1461. (absence of assessed intervention)
245. Reinhardt MJ, Strunk H, Gerhardt T, Roedel R, Jaeger U, Bucerius J, Sauerbruch T, Biersack HJ,
Dumoulin FL. Detection of Klatskin's tumor in extrahepatic bile duct strictures using delayed 18F-FDG
PET-CT: preliminary results for 22 patient studies. J Nucl Med 2005; Vol. 46 (7): pp 1158–1163.
(absence of the classical comparative method)
246. Reinhardt MJ, Wiethoelter N, Matthies A, Joe AY, Strunk H, Jaeger U, Biersack H-J. PET recognition of
pulmonary metastases on PET-CT imaging: Impact of attenuation-corrected and non-attenuationcorrected
PET images. Eur J Nucl Med Mol Imaging 2006; Vol. 33 (2): pp 134–139. (absence of the
classical comparative method)
247. Ribom D, Smits A. Baseline 11 C-methionine PET reflects the natural course of grade 2
oligodendrogliomas. Neurological Research 2005; Vol. 27 (5): pp 516–521. (absence of assessed
intervention)
248. Rizzo G, Cattaneo GM, Castellone P, Castiglioni I, Ceresoli GL, Messa C, Landoni C, Gilardi MC,
Arienti R, Cerutti S, Fazio F. Multi-modal medical image integration to optimize radiotherapy
planning in lung cancer treatment. Ann Biomed Eng 2004 Oct; 32 (10): pp 1399–1408. (absence of
assessed intervention)
249. Roman CD, Martin WH, Delbeke D. Incremental value of fusion imaging with integrated PET-CT in
oncology. Clin Nucl Med 2005; Vol. 30 (7): pp 470–477. (absence of the classical comparative
method)
250. Rosa F, Meimarakis G, Stahl A, Bumm R, Hahn K, Tatsch K, Dresel S. Colorectal cancer patients
before resection of hepatic metastases. Impact of (18)F-FDG PET on detecting extrahepatic
disease. Nuklearmedizin 2004 Aug; 43 (4): pp 135–140. (absence of assessed intervention)
251. Rosenbaum SJ, Stergar H, Antoch G, Veit P, Bockisch A, Kuhl H. Staging and follow-up of
gastrointestinal tumors with PET-CT. Abdominal Imaging 2006; Vol. 31 (1): pp 25–35. (secondary trial)
252. Ruf J, Hanninen EL, Oettle H, Plotkin M, Pelzer U, Stroszczynski C, Felix R, Amthauer H. Detection of
recurrent pancreatic cancer: Comparison of FDG-PET with CT/MRI. Pancreatology 2005; Vol. 5 (2–3):
pp 266–272. (absence of assessed intervention)
253. Safa AA, Tran LM, Rege S, Brown CV, Mandelkern MA, Wang MB, Sadeghi A, Juillard G. The role of
positron emission tomography in occult primary head and neck cancers. Cancer Journal From
Scientific American 1999; Vol. 5 (4): pp 214–218. (absence of assessed intervention)
254. Sakamoto H, Nakai Y, Ohashi Y, Okamura T, Ochi H. Positron emission tomographic imaging of head
and neck lesions. Eur Arch Otorhinolaryngol 1997; Vol. 254 (SUPPL. 1): pp S123-S126. (absence of
assessed intervention)
255. Sakurai H, Suzuki Y, Nonaka T, Ishikawa H, Shioya M, Kiyohara H, Katoh H, Nakayama Y, Hasegawa
M, Nakano T. FDG-PET in the detection of recurrence of uterine cervical carcinoma following
radiation therapy-tumor volume and FDG uptake value. Gynecol Oncol 2006; Vol. 100 (3): pp 601–
607. (absence of assessed intervention)
256. Santos Dellea MM. Malignant Pleural Mesothelioma: Response Evaluation with Integrated PET-CT
Imaging. Radiological Society of North America 2004: p 648. (conference report)
257. Sarinas PSA, Chitkara RK. PET and SPECT in the management of lung cancer. Curr Opin Pulm Med
2002; Vol. 8 (4): pp 257–264. (secondary trial)
314

258. Scarfone C, Lavely WC, Cmelak AJ, Delbeke D, Martin WH, Billheimer D, Hallahan DE. Prospective
feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET
and CT imaging. J Nucl Med 2004 Apr; 45 (4): pp 543–552. (absence of assessed intervention)
259. Schaffler GJ, Groell R, Schoellnast H, Kriegl D, Ruppert-Kohlmaier A, Schwarz T, Aigner RM. Digital
image fusion of CT and PET data sets – clinical value in abdominal/pelvic malignancies. J Comput
Assist Tomogr 2000; Vol. 24 (4): pp 644–647. (absence of assessed intervention)
260. Scheidhauer K, Walter C, Seemann MD. FDG PET and other imaging modalities in the primary
diagnosis of suspicious breast lesions. Eur J Nucl Med Mol Imaging 2004 Jun; 31 (Suppl 1): pp S70–79.
Epub 2004 May 6. (secondary trial)
261. Scher B, Seitz M, Reiser M, Hungerhuber E, Hahn K, Tiling R, Herzog P, Reiser M, Schneede P, Dresel S.
18F-FDG PET-CT for staging of penile cancer. J Nucl Med 2005; Vol. 46 (9): pp 1460–1465. (absence
of comparative diagnostic test)
262. Schiepers C. PET-CT in colorectal cancer. J Nucl Med 2003; Vol. 44 (11): pp 1804–1805. (secondary
trial)
263. Schiepers C. Positron emission tomography: A coming of age?. Eur J Intern Med 2004; Vol. 15 (3): pp
143–146. (secondary trial)
264. Schmid DT, John H, Zweifel R, Cservenyak T, Westera G, Goerres GW, von Schulthess GK, Hany TF.
Fluorocholine PET-CT in patients with prostate cancer: initial experience. Radiology 2005 May; 235
(2): pp 623–628. (absence of comparative diagnostic test)
265. Schmidt M, Schmalenbach M, Jungehulsing M, Theissen P, Dietlein M, Schroder U, Eschner W,
Stennert E, Schicha H. 18 F-FDG PET for detecting recurrent head and neck cancer, local lymph node
involvement and distant metastases: Comparison of qualitative visual and semiquantitative analysis.
Nuklearmedizin 2004; Vol. 43 (3): pp 91–101. (absence of assessed intervention)
266. Schmucking M, Baum RP, Bonnet R, Junker K, Müller K-M. Correlation of histologic results with PET
findings for tumor regression and survival in locally advanced non-small cell lung cancer after
neoadjuvant treatment. Pathologe 2005; Vol. 26 (3): pp 178–190. (article in German)
267. Schoder H, Erdi YE, Larson SM, Yeung HWD. PET-CT: a new imaging technology in nuclear medicine.
Eur J Nucl Med Mol Imaging 2003; Vol. 30 (10): pp 1419–1437. (secondary trial)
268. Schoder H, Herrmann K, Gonen M, Hricak H, Eberhard S, Scardino P, Scher HI, Larson SM. 2-[ 18 F]
fluoro-2-deoxyglucose positron emission tomography for the detection of disease in patients with
prostate-specific antigen relapse after radical prostatectomy. Clin Cancer Res 2005; Vol. 11 (13): pp
4761–4769. (absence of separated results for PET and PET-CT)
269. Schoder H, Larson SM, Yeung HW. PET-CT in oncology: integration into clinical management of
lymphoma, melanoma, and gastrointestinal malignancies. J Nucl Med 2004 Jan; 45 (Suppl 1): pp
72S–81S. (secondary trial)
270. Schoder H, Yeung HW, Gonen M, Kraus D, Larson SM. Head and neck cancer: clinical usefulness
and accuracy of PET-CT image fusion. Radiology 2004 Apr; 231 (1): pp 65–72. Epub 2004 Feb 27.
(absence of the classical comparative method)
271. Schrevens L, Lorent N, Dooms C, Vansteenkiste J. The role of PET scan in diagnosis, staging, and
management of non-small cell lung cancer. Oncologist 2004; 9 (6): pp 633–643. (secondary trial)
272. Schreyer AG, Kikinis R. Combined PET-CT colonography: Is this the way forward?. Gut 2006; Vol. 55
(1): pp 10–12. (secondary trial)
273. Schuetze SM. Imaging and response in soft tissue sarcomas. Hematol Oncol Clin N Am 2005; Vol. 19
(3): pp 471–487. (secondary trial)
274. Schwaiger M, Wieder H. Role of PET in lymphoma. Chang Gung Med J 2005 May; 28 (5): pp 315–325.
(secondary trial)
275. Schwartz DL, Ford EC, Rajendran J, Yueh B, Coltrera MD, Virgin J, Anzai Y, Haynor D, Lewellyn B,
Mattes D, Meyer J, Phillips M, Leblanc M, Kinahan P. Krohn K. Eary J. Laramore GE. FDG-PET-CT
imaging for preradiotherapy staging of head-and-neck squamous cell carcinoma. Int J Radiat
Oncol Biol Phys 2005; Vol. 61 (1): pp 129–136. (absence of assessed intervention)
276. Schwartz DL, Ford EC, Rajendran J, Yueh B, Coltrera MD, Virgin J, Anzai Y, Haynor D, Lewellen B,
Mattes D, Kinahan P, Meyer J, Phillips M, Leblanc M, Krohn K, Eary J, Laramore GE. FDG-PET-CT-
315

316
guided intensity modulated head and neck radiotherapy: a pilot investigation. Head & Neck 2005;
Vol. 27 (6): pp 478–487. (absence of assessed intervention)
277. Selzner M, Hany TF, Wildbrett P, McCormack L, Kadry Z, Clavien P-A. Does the novel PET-CT imaging
modality impact on the treatment of patients with metastatic colorectal cancer of the liver?. Ann
Surg 2004; Vol. 240 (6): pp 1027–1036. (absence of the classical comparative diagnostic test)
278. Shim SS, Lee KS, Kim BT, Choi JY, Shim YM, Chung MJ, Kwon OJ, Lee EJ. Integrated PET-CT and the
dry pleural dissemination of peripheral adenocarcinoma of the lung: diagnostic implications.
J Comput Assist Tomogr 2006 Jan-Feb; 30 (1): pp 70–76. (absence of independent assessment of CT
from the perspective of diagnostics without knowledge about clinical results)
279. Singh AK, Grigsby PW, Dehdashti F, Herzog TJ, Siegel BA. FDG-PET lymph node staging and survival of
patients with FIGO Stage IIIb cervical carcinoma. Int J Radiat Oncol Biol Phys 2003; Vol. 56 (2): pp
489–493. Date of Publication: 01 JUN 2003. (absence of assessed intervention)
280. Sironi S, Buda A, Picchio M, Perego P, Moreni R, Pellegrino A, Colombo M, Mangioni C, Messa C,
Fazio F. Lymph node metastasis in patients with clinical early-stage cervical cancer: Detection with
integrated FDG PET-CT. Radiology 2006; Vol. 238 (1): pp 272–279. (absence of the classical
comparative method)
281. Sironi S, Messa C, Mangili G, Zangheri B, Aletti G, Garavagalia E, Vigano R, Picchio M, Taccagni G,
Maschio AD, Fazio F. Integrated FDG PET-CT in patients with persistant ovarian cancer: corelation
with histologic findings. Radiology 2004 Nov; 233 (2): pp 433–440. (absence of comparative
diagnostic method)
282. Solberg TD, Agazaryan N, Goss BW, Dahlbom M, Lee SP. A feasibility study of 18 F-fluorodeoxyglucose
positron emission tomography targeting and simultaneous integrated boost for intensity-modulated
radiosurgery and radiotherapy. J Neurosurg 2004; Vol. 101 (Suppl. 3): pp 381–389. (absence of
comparative diagnostic method)
283. Som P, Urken M, Biller H, Lidov M. Imaging the postoperative neck. Radiology 1993; Vol. 187: pp 593–
603. (absence of assessed intervention)
284. Spraul CW, Lang GE, Lang GK. Value of positron emission tomography in the diagnosis of malignant
ocular tumors. Ophthalmologica 2001; Vol. 215 (3): pp 163–168. (absence of assessed intervention)
285. Stahl A, Stollfuss J, Ott K, Wieder H, Fink U, Schwaiger M, Weber WA. FDG PET and CT in locally
advanced adenocarcinomas of the distal oesophagus: Clinical relevance of a discordant PET
finding. World J Gastroenterol 2005; Vol. 11 (46): pp 7284–7289. Date of Publication: 14 DEC 2005.
(absence of assessed intervention)
286. Stahl A, Wieder H, Piert M, Wester HJ, Lordick F, Ott K, Rummeny E, Schwaiger M, Weber WA. PET-CT
molecular imaging in abdominal oncology. Abdom Imaging 2004 Vol. 29: pp 388–397. (secondary
trial)
287. Stahl A, Wieder H, Piert M, Wester HJ, Senekowitsch-Schmidtke R, Schwaiger M. Positron emission
tomography as a tool for translational research in oncology. Mol Imaging Biol 2004; Vol. 6 (4): pp
214–224. (secondary trial)
288. Steinert HC, Santos Dellea MM, Burger C, Stahel R. Therapy response evaluation in malignant pleural
mesothelioma with integrated PET-CT imaging. Lung Cancer 2005; Vol. 49S1: pp S33–S35. (absence
of reference method)
289. Steinert HC, von Schulthess GK. Initial clinical experience using a new integrated in-line PET-CT
system. Br J Radiol 2002 Nov; 75 Spec No: pp S36–38. (review)
290. Steinert HC. PET in lung cancer. Chang Gung Med J 2005 May; 28 (5): pp 296–305. (secondary trial)
291. Strasberg SM, Siegal BA. Annals for Surgery: Letters to the editor [1] (multiple letters). Ann Surg 2002;
Vol. 235 (2): pp 308–310. (letter)
292. Sung J, Espiritu JI, Segall GM, Terris MK. Fluorodeoxyglucose positron emission tomography studies in
the diagnosis and staging of clinically advanced prostate cancer. BJU International 2003; Vol. 92
(1): pp 24–27. (absence of assessed intervention)
293. Suzuki A, Kawano T, Takahashi N, Lee J, Nakagami Y, Miyagi E, Hirahara F, Togo S, Shimada H, Inoue
T. Value of 18 F-FDG PET in the detection of peritoneal carcinomatosis. European Journal of Nuclear
Medicine & Molecular Imaging 2004; Vol. 31 (10): pp 1413–1420. (absence of assessed intervention)

294. Swetter SM, Carroll LA, Johnson DL, Segall GM. Positron emission tomography is superior to
computed tomography for metastatic detection in melanoma patients. Ann Surg Oncol 2002 Aug;
9 (7): pp 646–653. (absence of assessed intervention)
295. Syed R, Bomanji JB, Nagabhushan N, Hughes S, Kayani I, Groves A, Gacinovic S, Hydes N, Visvikis D,
Copland C, Ell PJ. Impact of combined (18)F-FDG PET-CT in head and neck tumours. Br J Cancer
2005 Mar 28; 92 (6): pp 1046–1050. (absence of the classical comparative method)
296. Tanaka T, Kawai Y, Kanai M, Taki Y, Nakamoto Y, Takabayashi A. Usefulness of FDG-positron emission
tomography in diagnosing peritoneal recurrence of colorectal cancer. Am J Surg 2002 Nov; 184 (5):
pp 433–436. (absence of assessed intervention)
297. Tatsumi M, Cohade C, Nakamoto Y, Fishman EK, Wahl RL. Direct comparison of FDG PET and CT
findings in patients with lymphoma: initial experience. Radiology 2005 Dec; 237 (3): pp 1038–1045.
(separated assessment of hybrid images for PET and CT, absence of the results for combined image)
298. Tatsumi M, Kitayama H, Sugahara H, Tokita N, Nakamura H, Kanakura Y, Nishimura T. Whole-body
hybrid PET with 18F-FDG in the staging of non-Hodgkin's lymphoma. J Nucl Med 2001 Apr; 42 (4): pp
601–608. (absence of assessed intervention)
299. Teknos TN, Rosenthal EL, Lee D, Taylor R, Marn CS. Positron emission tomography in the evaluation of
stage III and IV head and neck cancer. Head & Neck 2001; Vol. 23 (12): pp 1056–1060. (absence of
assessed intervention)
300. Terhaard CH, Bongers V, Van Rijk PP, Hordijk G-J. F-18-fluoro-deoxy-glucose positron-emission
tomography scanning in detection of local recurrence after radiotherapy for laryngeal/pharyngeal
cancer. Head & Neck 2001; Vol. 23 (11): pp 933–941. (absence of assessed intervention)
301. Tierney PA, Farag I, Saunders CA. The use of positron emission tomography and computed
tomography in the assessment of trismus associated with head and neck malignancy. J Laryngol
Otol 1998; Vol. 112 (3): pp 303–306. (casuistic description)
302. Tisch M, Hengstermann F, Kraft K, Von Hinuber G, Maier H. Follicular dendritic cell sarcoma of the
tonsil: Report of a rare case. Ear, Nose, & Throat Journal 2003; Vol. 82 (7): pp 507–509. (absence of
assessed intervention)
303. Torizuka T, Kanno T, Futatsubashi M, Okada H, Yoshikawa E, Nakamura F, Takekuma M, Maeda M,
Ouchi Y. Imaging of gynecologic tumors: Comparison of 11 C-choline PET with 18 F-FDG PET. J Nucl
Med 2003; Vol. 44 (7): pp 1051–1056. (absence of assessed intervention)
304. Townsend DW, Beyer T. A combined PET-CT scanner: the path to true image fusion. Br J Radiol 2002
Nov; 75 Spec No: pp S24–30. (secondary trial)
305. Truong MT, Erasmus JJ, Macapinlac HA, Marom EM, Mawlawi O, Gladish GW, Sabloff BS, Bruzzi JF,
Munden RF. Integrated positron emission tomography/computed tomography in patients with nonsmall
cell lung cancer: normal variants and pitfalls. J Comput Assist Tomogr 2005 Mar-Apr; 29 (2): pp
205–209. (absence of end-points)
306. Truong MT, Erasmus JJ, Macapinlac HA, Podoloff DA. Teflon injection for vocal cord paralysis: Falsepositive
finding on FDG PET-CT in a patient with non-small cell lung cancer. AJR Am J Roentgenol
2004; Vol. 182 (6): pp 1587–1589. (casuistic description)
307. Truong MT, Erasmus JJ, Munden RF, Marom EM, Sabloff BS, Gladish GW, Podoloff DA, Macapinlac
HA. Focal FDG uptake in mediastinal brown fat mimicking malignancy: a potential pitfall resolved
on PET-CT. AJR Am J Roentgenol 2004; Vol. 183 (4): pp 1127–1132. (absence of assessed cancers)
308. Turlakow A, Yeung HW, Salmon AS, Macapinlac HA, Larson SM. Peritoneal carcinomatosis: Role of
18 F-FDG PET. J Nucl Med 2003; Vol. 44 (9): pp 1407–1412. (absence of assessed intervention)
309. Unger JB, Ivy JJ, Ramaswamy MR, Charrier A, Connor P. Whole-body [ 18 F]fluoro-2-deoxyglucose
positron emission tomography scan staging prior to planned radical hysterectomy and pelvic
lymphadenectomy. International Journal of Gynecological Cancer 2005; Vol. 15 (6): pp 1060–1064.
(absence of assessed intervention)
310. Van Eijkeren ME, De Schryver A, Goethals P, Poupeye E, Schelstraete K, Lemahieu I, De Potter CR.
Measurement of short-term 11 C-thymidine activity in human head and neck tumours using positron
emission tomography (PET). Acta Oncologica 1992; Vol. 31 (5): pp 539–543. (absence of assessed
diagnostic method)
317

311. Van Kouwen MCA, Oyen WJG, Nagengast FM, Jansen JBMJ, Drenth JPH. FDG-PET scanning in the
diagnosis of gastrointestinal cancers. Scand J Gastroenterol – Supplement 2004; Vol. 39 (241): pp
85–92. (secondary trial)
312. Vansteenkiste JF, Stroobants SG, Dupont PJ, De Leyn PR, De Wever WF, Verbeken EK, Nuyts JN,
Maes FP, Bogaert JG. FDG-PET scan in potentially operable non-small cell lung cancer: do
anatometabolic PET-CT fusion images improve the localisation of regional lymph node metastses?.
Eur J Nucl Med 1998 Nov; 25 (11): pp 1495–1501. (absence of assessed intervention)
313. Veit P, Kuhle C, Beyer T, Kuehl H, Herborn CU, Borsch G, Stergar H, Barkhausen J, Bockisch A, Antoch
G. Whole body positron emission tomography/computed tomography (PET-CT) tumour staging with
integrated PET-CT colonography: Technical feasibility and first experiences in patients with
colorectal cancer. Gut 2006; Vol. 55 (1): pp 68–73. (absence of the classical comparative method)
314. Visvikis D, Cheze-Le Rest C, Jarritt P. PET technology: Current trends and future developments. Br J
Radiol 2004; Vol. 77 (923): pp 906–910. (review)
315. Visvikis D, Costa DC, Lonn AHR, Bomanji J, Gacinovic S, Ell PJ. CT-based attenuation correction in
the calculation of semi-quantitative indices of [18F]FDG uptake in PET. Eur J Nucl Med Mol Imaging
2003 Mar; 30 (3): pp 344–353. Epub 2002 Dec 20. (absence of end-points)
316. von Schulthess GK, Steinert HC, Hany TF. Integrated PET-CT: current applications and future
directions. Radiology 2006 Feb; 238 (2): pp 405–422. (secondary trial)
317. von Schulthess GK. Positron emission tomography versus positron emission tomography
/computed tomography: from “unclear” to “new-clear” medicine. Mol Imaging Biol 2004 Jul-Aug;
6 (4): pp 183–187. (review)
318. Wakabayashi H, Akamoto S, Yachida S, Okano K, Izuishi K, Nishiyama Y, Maeta H. Significance of
fluorodeoxyglucose PET imaging in the diagnosis of malignancies in patients with biliary stricture. Eur
J Surg Oncol 2005; Vol. 31 (10): pp 1175–1179. (absence of assessed intervention)
319. Wasyliw CW, Caride VJ. Incidental detection of bilateral elastofibroma dorsi with F-18 FDG PET-CT.
J Nucl Med 2005; Vol. 30 (10): pp 700–701. (casuistic description)
320. Wechalekar K, Sharma B, Cook G. PET-CT in oncology – A major advance. Clinical Radiology 2005;
Vol. 60 (11): pp 1143–1155. (review)
321. Weckesser M, Konemann S, Brinkmann M, Willich N, Schober O. PET-CT in radiotherapy. Radiologe
2004 Nov; 44 (11): pp 1096–104. (article in German)
322. Wegner EA, Barrington SF, Kingston JE, Robinson RO, Ferner RE, Taj M, Smith MA, O'Doherty MJ. The
impact of PET scanning on management of paediatric oncology patients. Eur J Nucl Med Mol
Imaging 2005 Jan; 32 (1): pp 23–30. Epub 2004 Jul 31. (absence of assessed intervention)
323. Weng L-J, Schoder H. Melanoma metastasis to the testis demonstrated with FDG PET-CT. Clin Nucl
Med 2004; Vol. 29 (12): pp 811–812. (casuistic description)
324. Wieder HA, Beer AJ, Lordick F, Ott K, Fischer M, Rummeny EJ, Ziegler S, Siewer JR, Schwaiger M,
Weber WA. Comparison of changes in tumor metabolic activity and tumor size
during chemotherapy of adenocarcinomas of the esophagogastric junction. J Nucl Med 2005 Dec;
46 (12): pp 2029–2034. (absence of assessed intervention)
325. Wiering B, Krabbe PF, Jager GJ, Oyen WJ, Ruers TJ. The impact of fluor-18-deoxyglucose-positron
emission tomography in the management of colorectal liver metastases. Cancer 2005 Dec 15; 104
(12): pp 2658–2660. (secondary trial)
326. Wiering B, Ruers TJM, Oyen WJG. Role of FDG-PET in the diagnosis and treatment of colorectal liver
metastases. Expert Review of Anticancer Therapy 2004; Vol. 4 (4): pp 607–613. (secondary trial)
327. Windorbska W, Lewandowska A. Positron emission tomography – The new diagnostic tool in
oncology. Nowotwory 2004; Vol. 54 (1): pp 50–53. (secondary trial)
328. Wolthaus JWH, van Herk M, Muller SH, Belderbos JSA, Lebesque JV, de Bois JA, Rossi MMG, Damen
EMF. Fusion of respiration-correlated PET and CT scans: Correlated lung tumour motion in
anatomical and functional scans. Phys Med Biol 2005; Vol. 50 (7): pp 1569–1583. (absence of
assessed intervention)
329. Wong W-L, Hussain K, Chevretton E, Hawkes DJ, Baddeley H, Maisey M, McGurk M. Validation and
clinical application of computer-combined computed tomography and positron emission
318

tomography with 2-[18F]fluoro-2-deoxy-D- glucose head and neck images. Am J Surg 1996; Vol. 172
(6): pp 628–632. (absence of assessed intervention)
330. Wright J, Dehdashti F, Herzog T, Mutch D, Huettner P, Rader J, Gibb R, Powell M, Gao F, Siegel B,
Grigsby P. Preoperative lymph node staging of early-stage cervical carcinoma by [ 18 F]-fluoro-2deoxy-D-glucose-positron
emission tomography. Cancer 2005; Vol. 104 (11): pp 2484–2491. Date of
Publication: 01 DEC 2005. (absence of assessed intervention)
331. Yau YY, Chan WS, Tam YM, Vernon P, Wong S, Coel M, Chu SK. Application of intravenous contrast
in PET-CT: does it really introduce significant attenuation correction error?. J Nucl Med 2005; Vol. 46
(2): pp 283–291. (absence of end-points)
332. Yau YY, Samman N, Yeung RWK. Positron emission tomography/computed tomography true fusion
imaging in clinical head and neck oncology: Early experience. Journal of Oral & Maxillofacial
Surgery 2005; Vol. 63 (4): pp 479–486. (absence of the classical comparative method, casuistic
description)
333. Yen TC, Lai CH. Positron emission tomography in gynecologic cancer. Semin Nucl Med 2006 Jan; 36
(1): pp 93–104. (secondary trial)
334. Yeung HWD, Schoder H, Smith A, Gonen M, Larson SM. Clinical value of combined positron emission
tomography/computed tomography imaging in the interpretation of 2-deoxy-2-[F-18]fluoro-Dglucose-positron
emission tomography studies in cancer patients. Mol Imaging Biol 2005; Vol. 7 (3):
pp 229–235. (absence of the classical comparative method)
335. Yi JG, Marom EM, Munden RF, Truong MT, Macapinlac HA, Gladish FW, Sabloff BS, Podoloff DA.
Focal uptake of fluorodeoxyglucose by the thyroid in patients undergoing initial disease staging with
combined PET-CT for non-small cell lung cancer. Radiology 2005; Vol. 236 (1): pp 271–275. (absence
of verification of the study results in application of reference test)
336. Yoshida Y, Kurokawa T, Kawahara K, Tsuchida T, Okazawa H, Fujibayashi Y, Yonekura Y, Kotsuji F.
Incremental benefits of FDG positron emission tomography over CT alone for thepreperative staging
of ovarian ccancer. AJR Am J Roentgenol 2004 Jan; 182 (1): pp 227–233. (absence of assessed
intervention)
337. Yun M, Lim JS, Noh SH, Hyung WJ, Cheong JH, Bong JK, Cho A, Lee JD. Lymph node staging of
gastric cancer using 18 F-FDG PET: a comparison study with CT. J Nucl Med 2005 Oct; 46 (10): pp
1582–1588. (absence of assessed intervention)
338. Zacharias T, Barrier A, Montravers F, Houry S, Lacaine F, Huguier M. Cardio-esophageal cancer. Is
18Fluorodeoxyglucose positron emission tomography worthwhile?. Hepatogastroenterology 2004
May-Jun; 51 (57): pp 741–743. (absence of assessed intervention)
339. Zanation AM, Sutton DK, Couch ME, Weissler MC, Shockley WW, Shores CG. Use, accuracy, and
implications for patient management of [18F]-2-fluorodeoxyglucose-positron emission /
computerized tomography for head and neck tumors. Laryngoscope 2005; Vol. 115 (7): pp 1186–
1190. (absence of the classical comparative method)
340. Zangheri B, Messa C, Picchio M, Gianolli L, Landoni C, Fazio F. PET-CT and breast cancer. Eur J Nucl
Med Mol Imaging 2004 Jun; 31 (Suppl 1): pp S135–142. Epub 2004 May 5. (secondary trial)
341. Zimmer LA, Branstetter BF, Nayak JV, Johnson JT. Current use of 18F-fluorodeoxyglucose positron
emission tomography and combined positron emission tomography and computed tomography in
squamous cell carcinoma of the head and neck. Laryngoscope 2005; Vol. 115 (11): pp 2029–2034.
(secondary trial)
342. Zimny M, Hochstenbag M, Lamers R, Reinartz P, Cremerius U, ten Velde G, Buell U. Mediastinal
staging of lung cancer with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography
and a dual-head coincidence gamma camera. Eur Radiol 2003; Vol. 13 (4): pp 740–747. (absence
of assessed intervention)
343. Zimny M, Wildberger JE, Cremerius U, DiMartino E, Jaenicke S, Nowak B, Bull U. Combined image
interpretation of computed tomography and hybrid PET in head and neck cancer. Nuklearmedizin
2002; Vol. 41 (1): pp 14–21. (absence of assessed intervention)
344. Zinzani PL, Chierichetti F, Zompatori M, Tani M, Stefoni V, Garraffa G, Albertini P, Alinari L, Ferlin G,
Baccarani M, Tura S. Advantages of positron emission tomography (PET) with respect to
computed tomography in the follow-up of lymphoma patients with abdominal presentation. Leuk
Lymphoma 2002 Jun; 43 (6): pp 1239–1243. (absence of assessed intervention)
319

345. Zinzani PL, Fanti S, Battista G, Tani M, Castellucci P, Stefoni V, Alinari L, Farsad M, Musuraca G,
Gabriele A, Marchi E, Nanni C, Canini R, Monetti N, Baccarani M. Predictive role of positron emission
tomography (PET) in the outcome of lymphoma patients. Br J Cancer 2004 Aug 31; 91 (5): pp 850–
854. (absence of assessed intervention)
346. Zissin R, Metser U, Hain D, Even-Sapir E. Mesenteric panniculitis in oncologic patients: PET-CT findings.
Br J Radiol 2006; Vol. 79 (937): pp 37–43. (absence of clear results)
320

21. TABLE OF ILLUSTRATIONS
Table 1. Morbidity and mortality rates for selected malignant cancer types in Poland in 2002 [4] .........................................31
Table 2. histological malignancy grades of lung cancer............................................................................................................40
Table 3. TNM staging system of the clinical advancement of the lung cancer.........................................................................40
Table 4. Killonian classification of non-Hodgkin’s lymphomas ...................................................................................................48
Table 5. Hodgkin’s disease and non-Hodgkin’s lymphomas staging according to Ann Arbor staging system .....................49
Table 6. REAL classification of lymphoid tumors...........................................................................................................................49
Table 7. TNM and AJCC staging system of esophageal cancer.................................................................................................55
Table 8. FIGO staging for endometrial cancer .............................................................................................................................59
Table 9. FIGO staging for cervical cancer...................................................................................................................................62
Table 10. AJCC and FIGO staging for ovarian cancer ...............................................................................................................65
Table 11. TNM staging system by AJCC........................................................................................................................................68
Table 12. AJCC staging system for exocrine pancreatic cancer ..............................................................................................75
Table 13. 5-year survivals in pancreatic cancer by disease stage ...........................................................................................78
Table 14. TNM staging system and tumor classification for colon cancer .................................................................................82
Table 15. Astler-Coller classification of colorectal cancers .......................................................................................................83
Table 16. Search strategy...............................................................................................................................................................93
Table 17. Measurement results of assessing diagnostic tests ......................................................................................................96
Table 18. Characteristics of parameters of diagnostic efficacy .................................................................................................97
Table 19. List of the results of a search targeted at selected patient populations.....................................................................99
Table 20. Initial characteristics of patients by trial .....................................................................................................................101
Table 21. Description of intervention ...........................................................................................................................................103
Table 22. Description of diagnostic tests compared..................................................................................................................104
Table 23. Consistency between T-staging and reference test, by PET-CT vs. CT trial. .............................................................106
Table 24. Number of TP, FP, FN and TN patients in N-staging using PET-CT and CT..................................................................110
Table 25. Evaluation of the diagnostic accuracy of PET-CT and CT in N-staging. ...................................................................111
Table 26. Lung cancer staging results for PET-CT and CT by trial .............................................................................................116
Table 27. Initial characteristics of lymphoma patients ..............................................................................................................122
Table 28. Description of PET-CT imaging for both studies...........................................................................................................123
Table 29. List of diagnosis reference tests ...................................................................................................................................124
Table 30. Test diagnostic efficacy in detecting cancer in node locations...............................................................................125
Table 31. Test diagnostic efficacy in detecting cancer locations outside of nodes ...............................................................126
Table 32. Diagnostic efficacy in lymphomas detection in locations in and outside of nodes. ..............................................127
Table 33. Diagnostic accuracy in detecting lymphomas .........................................................................................................138
Table 34. Results of lymphoma staging by PET-CT as compared to CT. ...................................................................................138
Table 35. Odds ratio for correct lymphoma staging: PET-CT vs. CT...........................................................................................139
Table 36. Patient characteristics in Cerfolio 2005.......................................................................................................................142
Table 37. PET-CT imaging Cerfolio 2005 ......................................................................................................................................142
Table 38. T-staging results for each of the diagnostic methods as compared to the reference test (Cerfolio 2005) ...........144
Table 39. PET-CT, EUS-FNA and CT diagnostic efficacy in tumor restaging ..............................................................................144
Table 40. Proportion of cases correctly staged, understaged and overstaged by the diagnostic methods analysed. ......145
321

Table 41. Odds ratio for correct T-staging NNT for diagnostic methods analyzed: PET-CT vs. EUS and PET-CT vs. CT...........146
Table 42. Diagnostic efficacy of PET-CT, EUS-FNA and CT in assessing lymph node involvement.........................................146
Table 43. Diagnostic efficacy of PET-CT, EUS-FNA and CT in M-staging: stage M1a ...............................................................148
Table 44. Diagnostic efficacy of PET-CT and CT in M-staging: stage M1b................................................................................148
Table 45. Diagnostic efficacy of PET-CT, EUS-FNA and CT in assessing complete response...................................................150
Table 46. Initial patient characteristics in Kula 2005 ..................................................................................................................152
Table 47. PET-CT test characteristics............................................................................................................................................153
Table 48. Characteristics of patients diagnosed with malignant female genital tumor in Grisaru 2004. ...............................155
Table 49. Information on PET-CT scanner type and scanning method.....................................................................................156
Table 50. Number of patients with TP, FP, FN and TN results in the group with the disease staged: PET-CT vs.
conventional methods (CT, MRI and USG) .................................................................................................................157
Table 51. EBM parameters of the diagnostic efficacy in disease staging: PET-CT vs. conventional methods (CT, MRI
and USG) .......................................................................................................................................................................157
Table 52. Patients with TP, FP, FN and TN results in the group with disease recurrence assessed, PET-CT vs. conventional
methods (CT, MRI and USG).........................................................................................................................................159
Table 53. EBM parameters of the diagnostic efficacy in assessing disease recurrence: PET-CT vs. conventional
methods (CT, MRI and USG).........................................................................................................................................159
Table 54. Number of patients with TP, FP, FN and TN results, PET-CT vs. conventional methods (CT, MRI and USG) .............161
Table 55. EBM parameters of diagnostic efficacy in disease staging and disease recurrence assessment; PET-CT vs.
conventional methods (CT, MRI and USG) .................................................................................................................161
Table 56. Characteristics of population included in the analysis of PET-CT efficacy in the assessment of ovarian
cancer recurrences......................................................................................................................................................165
Table 57. Number of patients with TP, FP, FN and TN results in Hauth 2005 ...............................................................................166
Table 58. PET-CT and CT diagnostic efficacy in assessing ovarian cancer recurrences. .......................................................167
Table 59. Location of lesions detected by PET-CT and CT scanning, Hauth 2005....................................................................168
Table 60. Number of patients with TP, FP, FN and TN results in Makhija 2001 ...........................................................................168
Table 61. Sensitivity of PET-CT and CT in Makhija 2001...............................................................................................................169
Table 62. Meta-analysis of PET-CT and CT sensitivity in detecting ovarian cancer recurrence .............................................170
Table 63. Initial characteristics of subjects of each study .........................................................................................................173
Table 64. Description of scanner and method used for PET-CT examination...........................................................................174
Table 65. Number of patients with TP, FP, FN and TN results in Zimmer 2003, PET-CT vs. CT/MRI .............................................175
Table 66. EBM parameters of diagnostic efficacy in detecting thyroid cancer recurrence, PET-CT vs. CT/MRI ...................176
Table 67. Number of patients with TP, FP, FN and TN results in both studies, PET-CT vs. I 131 whole-body scintigraphy..........177
Table 68. Sensitivity calculated for each study, PET-CT vs I 131 whole-body scintigraphy........................................................178
Table 69. Comparison of sensitivity in evaluating recurrence, PET-CT vs I 131 whole-body scintigraphy ................................179
Table 70. Comparison of specificity, PET-CT vs. I 131 whole-body scintigraphy .........................................................................179
Table 71. comparison of diagnostic accuracy, PET-CT vs. I 131 whole-body scintigraphy.......................................................180
Table 72. Diagnostic accuracy in evaluating disease recurrence, PET-CT vs. I 131 whole-body scintigraphy .......................181
Table 73. EBM parameters of diagnostic efficacy of imaging methods compared, PET-CT vs I 131 whole-body
scintigraphy ..................................................................................................................................................................182
Table 74. Initial characteristics of patients examined................................................................................................................184
Table 75. Characteristics of PET-CT scanner and method. ........................................................................................................185
Table 76. Number of lesions detected with the imaging methods compared vs. the reference test for each feature of
the TNM staging system. ..............................................................................................................................................187
Table 77 Diagnostic sensitivity in lesion staging for each feature of the TNM system: I 124 PET-CT vs. traditional methods
(CT, I 131 WBS, USG) .........................................................................................................................................................187
Table 78. Characteristics of subject population in Branstetter 2005 .........................................................................................190
Table 79. Test results for each of the of methods compared vs. reference test: Branstetter 2005; per number of lesions....192
322

Table 80. Diagnostic efficacy parameters of the methods compared in Branstetter 2005 per number of lesions ...............192
Table 81. Population characteristics in Goerres 2005 ................................................................................................................194
Table 82. Test results for each of the methods compared vs. the reference test in Goerres 2005; calculated per patient .195
Table 83. Diagnostic efficacy parameters for the technologies compared in Goerres 2005, calculated per patient.........196
Table 84. Population characteristics............................................................................................................................................199
Table 85. Impact of PET-CT on revisions to head and neck cancer therapy ...........................................................................201
Table 86. Revisions in treatment of head an neck cancer based on PET-CT findings .............................................................202
Table 87. Initial characteristics of patients in Heinrich 2005. .....................................................................................................204
Table 88. Characteristics of PET-CT scanner and the procedures used in testing. ..................................................................205
Table 89. Number of patients with TP, FP, FN and TN results in Heinrich 2005: PET-CT vs. contrast CT.....................................207
Table 90. Diagnostic efficacy parameters of the imaging methods compared: PET-CT vs. contrast CT ...............................207
Table 91. Number of patients with TP, FP, FN and TN results in M-staging, PET-CT vs. conventional methods .......................208
Table 92. EBM parameters of diagnostic efficacy for the diagnostic methods compared; PET-CT vs. conventional
methods ........................................................................................................................................................................209
Table 93. Probability of revision of oncological procedure in patients diagnosed using the methods compared: PET-CT
vs. conventional methods............................................................................................................................................210
Table 94. PET-CT details ................................................................................................................................................................214
Table 95. CT details.......................................................................................................................................................................214
Table 96. Scanning findings vs. reference test............................................................................................................................216
Table 97. Correct response to treatment ....................................................................................................................................216
Table 98. Scanner and PET-CT procedure...................................................................................................................................219
Table 99. Sensitivity and accuracy of the diagnostic methods compared in detecting residual lesions after ablation of
colorectal liver metastasis, PET-CT vs. CT ...................................................................................................................220
Table 100. Initial characteristics of patients included in trials ...................................................................................................222
Table 101. Description of intervention .........................................................................................................................................224
Table 102. Description of diagnostic tests compared................................................................................................................225
Table 103. Number of patients with TP, FP, FN and TN results in detecting cancer in patients with varied location of the
disease using PET-CT and MRI. ....................................................................................................................................226
Table 104. Accuracy in detecting cancer in patients with the disease in varied location using PET-CT vs MRI . .................226
Table 105. Consistency of the T feature with the reference test for patients with neoplasm in varied locations, PET-CT vs
MRI.................................................................................................................................................................................228
Table 106. Average values of PET-CT and MRI accuracy in T-staging in patients with neoplasm in varied locations. ........230
Table 107. Consistency of N-staging results with the reference test in patients with neoplasm in varied locations, PET-
CT vs. MRI ......................................................................................................................................................................232
Table 108. Average values of PET-CT and MRI accuracy in N-staging in patients with neoplasm in varied locations. .......233
Table 109. The diagnostic accuracy of N-staging in patients with neoplasm in varied locations. PET-CT vs. MRI................234
Table 110. Diagnostic accuracy evaluation parameters for N-staging using PET-CT vs MRI, as calculated in Schmidt
2005 in relation to the number of lymph nodes assessed. ........................................................................................235
Table 111. Consistency of distant metastasis staging (M feature) with reference test in patients with neoplasm in
varied locations, PET-CT vs MRI ...................................................................................................................................236
Table 112. Average values of PET-CT and MRI accuracy in M-staging in patients with neoplasm in varied locations........237
Table 113. Evaluation of the efficacy of PET-CT and MRI in detecting distant metastasis in patients with
neoplasm in varied locations...................................................................................................................................238
Table 114. Parameters of diagnostic efficacy in M-staging with the use of PET-CT and MRI, calculated in Schmidt 2005
based on the number of pathological changes........................................................................................................239
Table 115. Consistency between the reference test and cancer staging results (TNM feature) in patients with
neoplasm in varied locations, PET-CT vs. MRI.............................................................................................................240
Table 116. Average values of PET-CT and MRI accuracy in TNM-staging in patients with neoplasm in varied locations....242
323

Table 117. Influence of PET-CT vs MRI scanning results on therapy changes in patients with neoplasm in varied
locations........................................................................................................................................................................243
Table 118. Initial characteristics of patients with neoplasm in varied locations included in Antoch 2004............................246
Table 119. Description of the intervention in Antoch 2004.........................................................................................................247
Table 120. Description of the diagnostic CT tests performed in Antoch 2004 ..........................................................................248
Table 121. Consistency of T-staging with the reference test in patients with neoplasm in varied locations in Antoch
2004, PET-CT vs CT.........................................................................................................................................................249
Table 122. Consistency between the reference test and N-staging results in patients with carcinomas in varied
locations, PET-CT vs CT .................................................................................................................................................250
Table 123. Consistency between the reference test and M-staging in patients with neoplasm in varied locations, PET-
CT vs. CT ........................................................................................................................................................................251
Table 124. Evaluation of the efficacy of PET-CT and CT in detecting metastasis in patients with neoplasm in varied
locations........................................................................................................................................................................251
Table 125. Parameters of the diagnostic efficacy of M-staging using PET-CT and CT in patients with typical indications
for PET in Antoch 2004. .................................................................................................................................................252
Table 126. Consistency between the reference test and cancer staging in patients with neoplasm in varied locations,
PET-CT vs. CT..................................................................................................................................................................253
Table 127. Influence of the diagnostic methods compared on therapy in patients with neoplasm in varied locations,
PET-CT vs. CT..................................................................................................................................................................253
Table 128. Initial characteristics of patients included in trials. ..................................................................................................256
Table 129. Description of intervention .........................................................................................................................................257
Table 130. Description of the diagnostic tests compared .........................................................................................................257
Table 131. Number of metastasis patients with TP, FP, FN and TN results in the diagnostics of primary tumor using PET-CT
and CT ...........................................................................................................................................................................259
Table 132. PET-CT sensitivity vs. CT sensitivity in detecting primary carcinomas of unknown locations................................259
Table 133. Average values of PET-CT and CT sensitivity in primary carcinoma detection in patients with metastasis to
the neck area. ..............................................................................................................................................................261
Table 134. Antoch 2003 quality assessment: QUADAS checklist...............................................................................................264
Table 135. Lardinois 2003 quality assessment: QUADAS checklist ............................................................................................265
Table 136. Cerfolio 2005 quality assessment: QUADAS checklist.............................................................................................266
Table 137. Shim 2005 quality assessment: QUADAS checklist..................................................................................................267
Table 138. Antoch 2004 quality assessment: QUADAS checklist (mixed) ................................................................................268
Table 139. Antoch 2003 quality assessment: QUADAS checklist (mixed) ...............................................................................269
Table 140. Schmidt 2005 quality assessment: QUADAS checklist ............................................................................................270
Table 141. Freudenberg 2005 quality assessment: QUADAS checklist ....................................................................................271
Table 142. Gutzeit 2005 quality assessment: QUADAS checklist...............................................................................................272
Table 143. Freudenberg 2003 quality assessment: QUADAS checklist .....................................................................................273
Table 144. Schaefer 2004 quality assessment: QUADAS checklist............................................................................................274
Table 145. Cerfolio 2005 quality assessment: QUADAS checklist (esopaegal and gastric cancer) .....................................275
Table 146. Kula 2005 quality assessment: QUADAS checklist ...................................................................................................276
Table 147. Grisaru 2004 quality assessment: QUADAS checklist...............................................................................................277
Table 148. Hauth 2005 quality assessment: QUADAS checklist................................................................................................278
Table 149. Makhija 2001 quality assessment: QUADAS checklist ............................................................................................279
Table 150. Nahas 2005 quality assessment: QUADAS checklist................................................................................................280
Table 151. Freudenberg 2004 quality assessment: QUADAS checklist .....................................................................................281
Table 152. Zimmer 2003 quality assessment: QUADAS checklist .............................................................................................282
Table 153. Wild 2006 quality assessment: QUADAS checklist....................................................................................................283
Table 154. Branstetter 2005 quality assessment: QUADAS checklist .........................................................................................284
324

Table 155. Goerres 2005 quality assessment: QUADAS checklist ............................................................................................285
Table 156. Koshy 2005 quality assessment: QUADAS checklist................................................................................................286
Table 157. Heinrich 2005 quality assessment: QUADAS checklist.............................................................................................287
Table 158. Antoch 2004 quality assessment: QUADAS checklist...............................................................................................288
Table 159. Veit 2006 quality assessment: QUADAS checklist ....................................................................................................289
Table 160. Result of the serach in Cochrane database.............................................................................................................290
Table 161. Results of the serach in Pubmed data basis .............................................................................................................291
Table 162. Results of serach in Embase database .....................................................................................................................292
Table 163. MeSH terms used for the search strategy .................................................................................................................292
325

22. TABLE OF GRAPHS
Graph 1. Meta-analysis of the diagnostic accuracy of PET-CT in T-staging ............................................................................108
Graph 2. Meta-analysis of the diagnostic accuracy of CT results in T-staging........................................................................108
Graph 3. Odds ratio for the consistency between the reference test and T-staging results, PET-CT vs. CT. ..........................109
Graph 4. Meta-analysis of PET-CT diagnostic accuracy in N-staging......................................................................................112
Graph 5. Meta-analysis of the diagnostic accuracy of CT in N-staging ..................................................................................113
Graph 6. Odds ratio for the consistency of N-staging with the reference test, PET-CT vs. CT. ................................................114
Graph 7. Diagnostic accuracy of PET-CT in cancer staging (TNM) .........................................................................................118
Graph 8. Meta-analysis of the diagnostic accuracy of CT in cancer staging (TNM)..............................................................119
Graph 9. Odds ratio for the consistency between the reference test and total cancer staging results, PET-CT vs. CT ........119
Graph 10. PET-CT sensitivity..........................................................................................................................................................127
Graph 11. CT sensitivity ................................................................................................................................................................128
Graph 12. PET-CT specificity.........................................................................................................................................................129
Graph 13. CT specificity ...............................................................................................................................................................130
Graph 14. Positive likelihood ratio for PET-CT scanning .............................................................................................................131
Graph 15. Positive likelihood ratio for..........................................................................................................................................132
Graph 16. Negative likelihood ratio for PET-CT study.................................................................................................................133
Graph 17. Negative likelihood ratio for CT study........................................................................................................................134
Graph 18. Diagnostic odds ratio for PET-CT.................................................................................................................................135
Graph 19. Diagnostic odds ratio for CT .......................................................................................................................................136
Graph 20. PET-CT accuracy .........................................................................................................................................................137
Graph 21. CT accuracy................................................................................................................................................................137
Graph 22. Meta-analysis of PET-CT sensitivity in detecting ovarian cancer recurrence. .......................................................169
Graph 23. Meta-analysis of CT sensitivity in detecting ovarian cancer recurrence ...............................................................170
Graph 24. Meta-analysis of PET-CT sensitivity in detecting thyroid cancer recurrence..........................................................178
Graph 25. Meta-analysis of diagnostic accuracy of PET-CT .....................................................................................................180
Graph 26. Meta-analysis of diagnostic accuracy of I 131 whole-body scintigraphy ................................................................181
Graph 27. Meta-analysis (fixed effects model) of the proportion of patients for head and neck cancer therapy was
revised following PET-CT examination ........................................................................................................................202
Graph 28. Meta-analysis of the diagnostic accuracy of PET-CT in T-staging in patients with neoplasm in varied
locations........................................................................................................................................................................229
Graph 29. Meta-analysis of the diagnostic accuracy of MRI in T-staging in patients with neoplasm in varied locations...230
Graph 30. Odds ratio for the consistency between the reference test and T- staging results for patients with neoplasm
in varied locations, PET-CT vs. MRI ..............................................................................................................................231
Graph 31. Meta-analysis of the diagnostic accuracy of PET-CT in N-staging in patients with neoplasm in varied
locations........................................................................................................................................................................232
Graph 32. Meta-analysis of the diagnostic accuracy of MRI in N-staging in patients with neoplasm in varied locations..233
Graph 33. Odds ratio for the consistency between the reference test and N-staging result in patients with neoplasm in
varied locations, PET-CT vs. MRI ..................................................................................................................................234
Graph 34. Meta-analysis of the diagnostic accuracy of PET-CT in M-staging in patients with neoplasm in varied
locations........................................................................................................................................................................236
Graph 35. Meta-analysis of the diagnostic accuracy of MRI in M-staging in patients with neoplasm in varied locations .237
Graph 36. Odds ratio for the consistency of M-staging results with the reference test in patients with neoplasm in
varied locations, PET-CT vs MRI ...................................................................................................................................238
326

Graph 37. Meta-analysis of the diagnostic accuracy of PET-CT in cancer staging in patients with neoplasm in varied
locations........................................................................................................................................................................241
Graph 38. Meta-analysis of the diagnostic accuracy of MRI in cancer staging in patients with neoplasm in varied
locations........................................................................................................................................................................242
Graph 39. Odds ratio for the consistency of TNM-staging results with the reference test in patients with neoplasm in
varied locations, PET-CT vs MRI ...................................................................................................................................243
Graph 40. Meta-analysis of PET-CT diagnostic sensitivity in patients with metastasis to neck area ......................................260
Graph 41. Meta-analysis of CT diagnostic sensitivity in patients with metastasis to the neck area.......................................261
Graph 42. Odds ratio for primary carcinoma detection in patients with metastasis to the neck area .................................262
327

23. TABLE OF FIGURES
Figure 1. Global incidence and mortality rates for the most common tumors types in developing and developed
countries [1] ....................................................................................................................................................................30
Figure 2. European average relative 5-year survival rates (%) for 42 selected tumor types; adults aged 15–99,
diagnosed in 1990–1994, with the follow-up period till 1999 [5]..................................................................................34
Figure 3. Incidence and mortality rates for ovarian cancer in selected geographic regions [7] ............................................64
Figure 4. Algorithm of therapeutic procedure for pancreatic cancer; source: The Polish Oncology Union, Zalecenia
postępowania diagnostyczno-terapeutycznego w nowotworach złośliwych u dorosłych, edited by M.
Krzakowski [6] .................................................................................................................................................................77
Figure 5. Annihilation and detection of gamma rays .................................................................................................................87
Figure 6. Dissemination of tumor: metastatic lymph nodes in the left groin a) CT mage; b) PET/CT image; c) PET image ....88
328