world cancer report - iarc

Fig. 5.10 Five-year relative survival rates of lung
cancer patients after diagnosis.
rant transcripts of the Fragile Histidine Triad
(FHIT) gene, located at chromosome
3p14.2, occur in pre-neoplastic and neoplastic
lesions and such changes have
been linked to smoking and asbestos
exposure. Homozygous deletions and
transcriptional silencing due to methylation
in the locus of the cyclin-dependent
kinase inhibitor p16 INK4A on chromosome
9p have been found in about 40% of lung
cancer cases. Other oncogenes have also
been implicated in lung carcinogenesis: in
particular, ERBB1 and ERBB2; C-MYC, N-
MYC and L-MYC, and BCL2 [16]. No clear
correlations have been established as yet
between particular genetic changes and
histological type of tumour.
Management
Staging of lung cancer is based on an
assessment of the presence of distant
metastases and the condition of the chest
and mediastinum (the tissues and organs
separating the lungs), in accordance with
the universally used TNM system (Box:
TNM, p124). Although treatment protocols
are subject to refinement and improvement,
the outlook for patients diagnosed
with lung cancer is poor by comparison
with many other cancers. The main prognostic
factors are stage of the tumour and
performance status; other important factors
include amount of weight loss, gender
(men having a poorer prognosis than
186 Human cancers by organ site
women), serum concentration of lactate
dehydrogenase and the detection of bone
and liver metastases.
Non-small cell carcinomas are grouped
together because of similarity in the
response of the different subtypes to
treatment. Early stage tumours are treated
by surgical resection, if possible, with
patients who refuse or who are deemed
medically unfit for surgery being treated
with radiotherapy. More advanced stage
disease may be treated with a combination
of surgery and radiotherapy. Radiotherapy
can be effective for palliation of
superior vena cava obstruction, haemoptysis
(expectoration of blood), pain, dyspnoea
(shortness of breath), brain metastases
and atelectasis (partial or complete
lung collapse) [17]. The introduction of
cisplatin-containing drug combinations
improves the rate of response to therapy,
with accompanying moderate to severe
toxicity. Combination chemotherapy
(using cisplatin and etoposide, or mitomycin,
vinblastine and cisplatin) with
radiotherapy also seems to convey a survival
advantage in patients with stage III
disease. More recently, paclitaxel has
shown significant activity when used as a
single agent. Other drugs credited with
response rates of at least 15% include
gemcitabine, docetaxel and vinorelbine.
The mainstay of treatment for small cell
Table 5.1 Genetic alterations in lung tumours.
Fig. 5.11 A smoking-induced lung cancer. Autopsy
specimen of a large-cell carcinoma of the left lung
(T) with nearby metastases (arrow).
lung cancer is chemotherapy, with concomitant
radiotherapy being used at an
early point for patients with limited disease.
Surgery may be considered in the
case of a patient with a small isolated
lesion [17]. Combinations of drugs, as a
general rule, yield better results than the
respective agents used alone and those
commonly used include cisplatin and
etoposide, cyclophosphamide, doxorubicin
and vincristine, and cyclophosphamide,
doxorubicin and etoposide.
More recently, the taxanes paclitaxel and
docetaxel and the camptothecins irinotecan
and topotecan have shown promise as
single agents and in combination. Despite
good initial responses to therapy, relapse
Gene Locus Alteration Frequency (% of tumours)
Small cell Adeno- Squamous cell
carcinoma carcinoma carcinoma
p53 17p13 Deletion, 70-90 30 50
mutation (G:C>T:A),
(overexpression)
KRAS 12p21 Mutation (GGT>TGT)