Gli Aspetti Tecnologici dell'Adroterapia - C.R. ENEA Frascati

Gli Aspetti Tecnologici dell’Adroterapia
Parte 1
Sandro Rossi
Fondazione CNAO
Corso teorico-pratico sull’adroterapia: l’alta tecnologia applicata alla clinica
CNAO, Pavia, 17-18 Maggio 2013

Introduzione: il razionale dell’adroterapia
Stato dell’arte: il Centro Nazionale di Adroterapia Oncologica
Panoramica: la tecnologia e attività di R&S

Adroterapia consente di trattare casi “difficili”
PRECISIONE
EFFICACIA
Tumori vicini ad organi critici
Tumori radioresistenti,
che non rispondono
alla radioterapia convenzionale

Direzione del fascio di radiazioni nella materia
Precisione dell’adroterapia
Posizione del
tumore

Adroni: irraggiamento conforme
Larghezza del tumore
5

Adroni: irraggiamento conforme
Raggi-X (IMRT) – 9 campi Protoni – 1 campo

(M. Belli et al.)
Ioni Carbonio: efficacia biologica
4
3
2
1
RBE
1 10 100 LET
10 – 20 keV/µm = 100 – 200 MeV/cm =
20 – 40 eV/(2 nm)
Ridotta dipendenza da presenza di ossigeno
7

Patologie trattate con ioni carbonio al NIRS di Chiba

Terapia con Raggi-X (fotoni di 5 – 20 MeV)
Protonterapia
In Italia: 120'000 pz/anno
Categoria A: pazienti elettivi = 1'000 pz/anno
Numero di potenziali pazienti
Categoria B: probabili vantaggi = 12'000 pz/anno
Terapia con ioni carbonio
% tumori radioresistenti 1'500 pz/anno
(Commissione Ministero della Salute – Anno 2009)
Si giustifica il CNAO (ca. 2000 paz/anno)
e in prospettiva altri centri per protoni

Prevista dal Ministero della Salute
Art. 92 della Legge 23 dicembre 2000, n. 388
Insediata il 21 Novembre 2001

•L’età media
•45% femmine
•55% maschi
Oggi al CNAO lavorano 90 persone
48%
• Ingressi di
personale
nel triennio
2010 -2012

NAZIONALI
Fondazione TERA: progetto definitivo, specifiche alta tecnologia, ricerca
INFN: co-direzione AT, > 15 task tecnici, ricerca e formazione
Università di Milano: coordinamento medico e formazione
Università di Pavia: task tecnici, radiobiologia e formazione
Università di Catania: fisica medica
IL CNAO ESEMPIO DI SISTEMA
LA RETE DI COLLABORAZIONI
Università del Piemonte Orientale: attività mediche
Politecnico di Milano: posizionamento paziente, radioprotezione
Istituto Europeo di Oncologia: attività mediche, autorizzazioni
Fondazione Ospedale San Matteo di Pavia: attività mediche, logistica
Comune di Pavia: terreno e autorizzazioni
Provincia di Pavia: viabilità e autorizzazioni

INTERNAZIONALI
CERN (Geneva): task tecnici, progetto PIMMS
GSI (Darmstadt): linac e componenti speciali
LPSC (Grenoble): ottica, betatrone, low-level RF, sistema di controllo
Med-Austron (Vienna): collaborazione tecnica per il centro MA
Roffo Institute (Buenos Aires): attività mediche
NIRS (Chiba): attività mediche, radiobiologia, formazione
HIT (Heidelberg): attività di ricerca
IL CNAO ESEMPIO DI SISTEMA
LA RETE DI COLLABORAZIONI

Le fasi del CNAO
Fase 0: organizzazione Anni: 2002 - 2004
Fase 1: costruzione Anni : 2005 - 2009

Giugno 2005

19 Novembre 2009
7 Novembre 2005
La costruzione del CNAO è terminata a fine 2009
16

Le aree del CNAO
Espansione per gantry:
spazio sufficiente per
contenere due gantry simil-HIT
meeting
rooms
conference
room
direction offices
Centrale elettrica
(132 kV --> 15 kV)
(2 x 20 MVA)
library
Circa 3500 mq
Futuro Bld.
della ricerca:
circa 2000 mq

Il sincrotrone per protoni e ioni carbonio

Hospital based: safety, efficiency, reliability, maintainability
High Energy
Transfer
Lines
Linac
Ion Sources
Synchrotron
Treatment
Rooms

Starting point… THE PATIENT
Hospital based: safety, efficiency, reliability, maintainability
1 Beam particle species p, He 2+ , Li 3+ , Be 4+ , B 5+ , C 6+ , O 8+
2 Beam particle switching time ≤ 10 min
3 Beam range
1.0 g/cm 2 to 27 g/cm 2 in one treatment room
3.1 g/cm 2 to 27 g/cm 2 in two treatment rooms
Up to 20 g/cm 2 for O 8+ ions
4 Bragg peak modulation steps 0.1 g/cm 2
5 Range adjustment 0.1 g/cm 2
6 Adjustment/modulation accuracy ≤± 0.025 g/cm 2
7 Average dose rate 2 Gy/min (for treatment volumes of 1000 cm 3 )
8 Delivery dose precision ≤± 2.5%
9 Beam axis height (above floor)
150 cm (head and neck beam line)
120 cm (elsewhere)
10 Beam size 1
4 to 10 mm FWHM for each direction
independently
11 Beam size step 1 1 mm
12 Beam size accuracy 1 ≤± 0.25 mm
13 Beam position step 1 0.8 mm
14 Beam position accuracy 1 ≤± 0.2 mm
15 Field size 1
16 Field position accuracy 1 ≤± 0.5 mm
17 Field dimensions step 1 1 mm
18 Field size accuracy 1 ≤± 0.5 mm
(Basic specifications of CNAO facility)
5 mm to 34 mm (diameter for ocular treatments)
2×2 cm 2 to 20×20 cm 2 (for H and V fixed beams)

4 (Cortesia Aprile 2008 di Siemens Medical)
(Cortesia di GSI)
Tecnica di
irraggiamento
sistema attivo

Le fasi del CNAO
Fase 0: organizzazione Anni: 2002 - 2004
Fase 1: costruzione Anni : 2005 - 2009
Fase 2: sperimentazione Anni: 2010 - 2013
Fase 3: funzionamento Anni : 2014 …

Certificazione di qualità: ISO 9001 e ISO 13485

Dosimetry and Radiobiology
Preventive intercomparison CNAO vs INT-MI
with X-rays (linac 6 MV, 2 Gy): difference < 0.1%
(in collaborazione con gruppi radiobio INFN)
Field10x10 cm 2 ,
33x33 spots,
scanning step 3 mm
(16 energie)

Results Survival curves of cells crypts
in 3 SOBP positions
Facility Beam D10 (Gy) Variance RBE10 Variance
position
D10
(%)
Cobalt-60
γ rays
--- 14.86±0.08(*)
NIRS Proximal 10.38 (+) 1.44 (*)
Middle 9.46(+) 1.57(*)
Distal 8.29(+) 1.80(*)
GSI Proximal 10.21(+) 1.47(*)
Middle 9.40(+) 1.63(*)
Distal 8.37(+) 1.80(*)
CNAO Proximal 9.85 5.1 % NIRS 1.51 4.7% NIRS
3.5% GSI
2.7 % GSI
Middle 9.75 3.1% NIRS 1.52 3.18% NIRS
3.7% GSI
6.7% GSI
Distal 8.5 2.5% NIRS 1.75 2.78% NIRS
1.5% GSI
2.78% GSI
Carbon beam at CNAO is biologically
identical to the ones in NIRS and GSI
(difference in RBE < 7%)

PROTONI
22 Settembre 2011: il trattamento del primo paziente

13 Novembre 2012: 1°paziente con ioni Carbonio al CNAO
Recidiva locale di carcinoma adenoideo cistico
12 frazioni da 4.1 GyE , 4 frazioni a settimana, 49.2 GyE totali.
Boost di ulteriori 4 frazioni da valutare in base a tolleranza.
3 campi in IMPT

Ioni
Carbonio Protoni
Abruzzo 1
Basilicata 1
Calabria 1 1
Campania 2
Emilia Romagna 3 4
Lazio 6
Liguria 2 4
Lombardia 7 12
Marche 2
Piemonte 1 7
Puglia 1 6
Sardegna 1
Sicilia 1 2
Toscana 3 6
Veneto 3 3
Totale complessivo 22 58
Provenienza geografica pazienti arruolati
12
11
10
9
8
7
6
5
4
3
2
1
0
Ioni Carbonio Protoni

La fase di funzionamento
I trattamenti saranno effettuati nell’ambito del Sistema
Sanitario Nazionale e una rete consentirà il reclutamento
efficiente dei pazienti
A regime il CNAO arriverà a trattare circa 2000 pazienti
per anno
Una sala sperimentale sarà realizzata al CNAO e tempo
fascio sarà dedicato ad attività di ricerca clinica,
radiobiologica e traslazionale

European Network for LIGht ion Hadron Therapy

Expansion and Research spaces integrated in facility layout
Extra space to host 2 C-gantries
(Partial underground level of CNAO)
Laboratories and
research spaces
Experimental Room
Project of research beamline
ready fall 2013
Beam line devoted to clinical,
radiobiology and physics research
(collaboration with INFN)

Tecnologia e attività di R&S:
Accelerators Technology
Dose Delivery Systems
Gantry for carbon ions
Patient positioning and dose verification
Imaging and software
ACKNOWLEDGMENTS: U. AMALDI
Panoramica
(Useful ref.: U. Linz Ed., Ion Beam Therapy, Springer 2011 and refs therein)

Loma Linda University Medical Center: first patient 1992
First hospital based
protontherapy centre
(1992)
2009:160 sessions/d
7m
synchrotron
Optivus Ltd. commercialises this centre

45,000
40,000
35,000
30,000
25,000
20,000
15,000
10,000
5,000
0
Research centres
Protontherapy is booming
40,000 patients
> 84 000 patients
22 PT centers
Hospitals
1950 1960 1970 1980 1990 2000 2010
Carbon Ions: > 9000 patients; 6 centres (+2 planned)
45
40
35
33 centres
(+16 planned)
30
25
20
15
10
5
0

EPAC - 30 June 2006
IBA
Protontherapy: a market exists …
Mitsubishi
Varian
Hitachi
37

Coming up: Single room facility
250 MeV synchrocyclotron rotating around the patient
MEVION S250
Superconducting SC
Diameter 1.8 m

Expansion in 2010
HIMAC
Heavy Ion Medical Accelerator in Chiba
(First patient in 1995)
Superconducting
gantry
Carbon Ion facilities
2 synchrotrons 800 MeV/u,
therapy and nuclear physics
Japan: Hyogo + Gunma – (China Lanzhou 2013+Shangai 2014)

Ion-
Sources
Synchrotron
LINAC
Treatment halls by
Siemens Medical
HIT - Heidelberg
First patient: end 2009
So far about 1.000 patients
High Energy Beam Transport Line
Quality
Assurance
Gantry

Med-Austron (based on CNAO/INFN design + DDS)
• 3 ion sources for phase 1 (one additional source possible)
• Pre-accelerator – RFQ & IH Linac
• Main accelerator – synchrotron (77 m circ.) CNAO/CERN/PIMMS design
• Extraction line
• Irradiation rooms: research: horizontal,
medical: horizontal & vertical, horizontal, proton-gantry

New medical accelerators (?): IBA Superconducting cyclotron
700 tons

+ Simplicity of fixed field
+ Potential for fast (ms) variable energy
+ Rapid cycling (200 Hz, repainting)
- High intensities
- Multistage accelerators
- Complicated magnets
- Complicated RF cavity
- Dense lattice (ext. diff.)
New medical accelerators (?): FFAG
(original idea dates back to 1950’s)
Only existing reasearch facility: KURRY 150 MeV proton scaling FFAG

New medical accelerators (?): BNL fast cycling synchrotron
30 Hz repetition rate (repainting?)
Fast energy change
(first publication 1999’s, S. Peggs et al.)
Injection linac at 8 MeV/u
Racetrack, FODO in the arcs, D=0 ss
Fast inj+extr, C = 60 m
(from D. Trbojevic et al. IPAC2011)

150 MeV/u
Source EBIS - SC
Cyclotron K 600 - SC
200 tons
Linac CCL @ 5.7 GHz
16 modules
RF power
system
New medical accelerators (?): TERA cyclinac for C-ions
16 Klystrons
(P peak = 12 MW)
Linac for Image Guided Hadron
THerapy LIGHT 150-400 MeV/u
CABOTO =
CArbon BOoster for
Therapy in
Oncology
400 MeV/u
Energy is adjusted in 2 ms in the full range by changing the power pulses sent to the
accelerating modules
Charge in the spot is adjusted every 2 ms with the computer controlled source
300 Hz

Technology status and R&D:
Accelerators Technology
Dose Delivery Systems
Gantry for carbon ions
Patient positioning and dose verification
Imaging and software
Panoramica

Methods for imparting the dose with carbon ions:
layer stacking (NIRS+Japan)
Wobbling and multileaf collimator adapted
to transverse shape of each slice
(energy changed with synchrotron and range shifter)
Conformation, components activation, secondary neutrons

Methods for imparting the dose with carbon ions:
active scanning: “raster scanning” à la GSI (HIT+CNAO)
The synchrotron beam is moved
continuously
Energy changed with the synchrotron
NIRS decided recently to adopt the active scanning

Slow extraction
Bucket channeling
Ripples
Beam
0 V
Improvements:
beam extraction optimization
High-density,
slow -moving
Extracted beam
Low-density,
fast moving
Transverse
beam size
Resonance
lines
x, ∆p/p, Qh
Intensity dinamic range: ≈1000
FWHM = 4-10 mm
Intensity ripple (∆I/I) ≤ ± 20% at 2 kHz
(extraction with a betatron core - PIMMS)
50 ms

“Minimal” choice: breathing synchronisation
(already applied in Chiba and HIT)
Interesting also for IMRT:
lots of efforts and devices
(Review in Riboldi et al, Lancet Oncology 2012)
Improvements: On-line imaging
External surrogates with
correlation models
X-rays
(Courtesy of Medical Intelligence)
Ultrasound, MRI
Particle radiography

GSI approach
p +1 or C +6
Improvements: tumour tracking with active scanning
Tranverse
variation
4D
Energy
variation

Monitoring system (CNAO)
Double system of ICs:
(integral, stripX,Y) – (integral, pixel)
Two measures: Intensity, Position, Profile
Redout frequency: 1 MHz (integral),
10 kHz (strip, pixel)
Resolution: 0.1 mm strip, 0.2 mm pixel
Area: 20 x 20 cm2
Non uniformity < 1%
Short term stability < 0.3%
(NIMA 698 (2013) 202-207) Issue: monitoring spots of C-ions at low intensity

Technology status and R&D:
Accelerators Technology
Dose Delivery Systems
Gantry for carbon ions
Patient positioning and dose verification
Imaging and software
Panoramica

PSI proton gantry
(Courtesy M. Pullia)
Comparison of dimensions
GSI carbon ion gantry

(Courtesy T. Haberer)
Main Parameters
Diameter [m] 13
Length [m] 25
Overall weight [t] 600
Maximum power [kW] 600
Rotational weight [t] 420
Maximum allowed deformation [mm] 0,5
Heidelberg ion gantry: unique in the World!
First patient October 19 th , 2012

Bmax = 2.88 T
Gmax = 9.0 T/m
HIMAC superconducting gantry is in construction
Combined function magnets:
bending and focusing (BM1 ~ BM6)
(Courtesy T. Murakami)
B and G changing vs cycle
Scanning magnets at
the middle point
Combined function magnets (BM9 ~ BM10)
-> square irradiation field
-> parallel beams

Novel gantry for carbon ions
The ULICE WP6 collaboration realized a conceptual design of a mobile isocenter gantry,
• Innovative layout
• Cheaper and simplified mechanical structure
• Less magnets in the gantry line
Rationale for the choice
• Total weight reduced as well as deformations
• Well known magnet technology
• Layout scalable to SC magnets

Project in progress by CEA (France) in collaboration with IBA
12.2 tons
B = 5 tesla
Two layer helical wires
on a straight cylinder
give a dipole field
(S. Caspi et al.)
ISSUES: field quality for scanning beams;
changing fields (energy) for active scanning
90° magnet following a design
by INFN-Genoa and TERA
Project in progress at LBL - Berkeley

Technology status and R&D:
Accelerators Technology
Dose Delivery Systems
Gantry for carbon ions
Patient positioning and dose verification
Imaging and software
Panoramica

High precision devices for patient positioning
(Treatment room #1 at CNAO)

3D Real-time IR Optical Tracking (OTS)
• Real time reconstruction of spherical markers
and surfaces
• Sub-millimeter accuracy : peak 3D errors

Projectile
Pre-collision Post-collision
12 C
Atomic nucleus
of tissue
16 O
15 O
11 C
Dose visualisation: “in beam PET”
Projectile fragment
Neutron
Target fragment
Courtesy of GSI
[kGy]
D ose
]
Counts [10
3
6
4
2
0
5
0
Dose
Activity
β +
0 50 100 150 200
Depth [mm]
ISSUES: low statistics;
blood flow dilution;
off-line PET logistics

Proton Range Radiography (PRR)
Secondaries emission and reconstruction
Electronic telescope for the measure of position and residual range of
protons; it gives the density map of the traversed volumes; it permits
to check in real time the treatment planning assumptions on position
and dimensions of the traversed tissues and organs.
Nuclear Scattering
Tomography (NST)
(U. Amaldi et al.)
Three-dimensional map of the
tissues densities obtained by
vertex reconstruction of high
energy protons interactions (>
600 MeV).
Interaction Vertex
Imaging (IVI)
Density of interaction
vertex reconstruction
gives information on the
Bragg peak position.
PROMPT radiation (Gamma) - Enlight

Technology status and R&D:
Accelerators Technology
Dose Delivery Systems
Gantry for carbon ions
Patient positioning and dose verification
Imaging and software
Panoramica

1(+1) CT Medical Imaging rooms
CNAO – Surface Level
NIRS - 30th November 2007
Advanced Medical Imaging Modalities (fusion sw)
1 MR (3T) room
1(+1) CT-PET rooms
Advanced 3D molecular imaging modalities
tumour molecular profiling
dose painting with different LET ions
( sources and accelerators choices)
(O. Jäkel, in IBT, Springer2011)

Treatment Planning System
TPS is directly related to scanning modality and RBE evaluation model
Need to include management of moving organs and integration of in-room imaging
(TPS used at CNAO)

Siemens
TPS
Imaging Modalities
(CT, MR, CT-PET))
DICOM
DICOM
RT Ion
PT Archive
(Short-term)
Oncological Information System
DICOM RT Ion
DICOM
RT Ion
DICOM
PACS
PPS-PVS
Elekta MOSAIQ V 2.0
DOP
OIS
Long Term Storage R&V
DICOM RT Ion
Management of patients data in multiple rooms: patient throughput
Networking with hospitals and clinics: patient recruitment
DTMI
CNAO
Synchrotron
Control
System
and
Dose Delivery
System

Conclusioni
I centri di protonterapia sono “centri commerciali” (e
“single room solutions” sono in arrivo). Non si può dire
altrettanto dei centri con ioni carbonio.
Gli sviluppi della tecnologia in adroterapia non si limitano al
settore degli acceleratori, ma investono uno spettro molto
ampio di sistemi: alcuni più urgenti di altri.
Collaborazioni, confronti, rete sono parole chiave per il
successo dell’adroterapia e sono utili per stabilirne
l’evidenza clinica (l’aumento del numero di pazienti trattati
è un fattore importante) .

GRAZIE PER L’ATTENZIONE