INFN-LNS e Centro di AdroTerapiae Applicazioni Nucleari ... · INFN-LNS e Centro di AdroTerapiae...

INFN-LNS e Centro di AdroTerapia e

Applicazioni Nucleari Avanzate

G. Cuttone

Laboratori Nazionali del Sud - Catania

2. INFN & HADRONTHERAPY:

THE CATANA PROTON THERAPY CENTER

• Beam line elements

• The DOSIMETRIC COMMISIONING: Absolute and relative dosimetry

• Treatment procedure

• Patient’s follow up

3. ACTUAL STATUS OF HADRONTHERAPY: THE CATANA SPIN-OFF

OUTLINEOUTLINEOUTLINE

1. Why proton beams in tumour radiation treatment

Why clinical proton beam?WhyWhy clinicalclinical protonproton beambeam??

• penetration depth is well-defined and adjustable

• most energy at end-of -range

• protons travel in straight lines

• dose to normal tissue minimised

• no dose beyond target

PROTONS PERMIT TO DELIVER AN HIGH DOSE TOTHE TUMOUR SPARING THE SOURRONDING TISSUES

Why clinical proton beam?WhyWhy clinicalclinical protonproton beambeam??

Between the eyesBetween the eyes

IMRT vs PROTONSIMRT IMRT vsvs PROTONSPROTONS

AbdomenAbdomen

BrainBrain

• In 90’ years INFN supported TERA in R&D project.

• INFN, in collaboration with University of Catania, realized in

its laboratory (Lab. Naz. Del Sud) the first Italian

protontherapy facility.

• INFN has UNIQUE capability in Italy in accelerators

development.

• Considering its particular features, INFN was involved in

CNAO to guarantee the necessary expertise.

• In 2005 INFN was encharged by Health Minister to produce

a document about protontherapy in our country.

INFN & HadrotherapyINFN & INFN & HadrotherapyHadrotherapy

In Catania we developed a

facility

(named CATANA)

for the treatment of ocular

tumours with 62 AMeV proton

beams

CATANA collaborationCATANA collaborationCCentro entro didi AAdrodroTTerapiaerapia e e AApplicazionipplicazioni NNucleariucleari

AAvanzatevanzate

G. Cuttone D. Rifuggiato

G.A.P. Cirrone A. Amato

L. Calabretta M.G. Sabini

Physics Department, University of CataniaCSFNSM

S. Lo Nigro F. Di Rosa

P.A. Lojacono V. Mongelli

I.V. Patti L.M. Valastro

A. Reibaldi J. Ott

G.Profeta M.L. Rallo

G. Privitera V. Salamone

L. Raffaele C. Spatola

Radiologic Institute

University of Catania

Ophthalmologic Institute

University of Catania

INFN-Laboratori Nazionali del Sud

LNS SuperconductingCyclotron is the

unique machine in in Italy and SouthEurope used forprotontherapy

Treatment of the choroidal and iris

melanoma

In Italy about 300 new cases for year

CyclotronLocation

Treatment Room Location

Laboratori Nazionali del Sud –INFN Catania, Italy

ProtonBeam

CATANA

LNS Accelerator Layout

Ocular Protontherapy

Unique Italian Facility

CATANA proton therapy beam line (until June 2004)CATANA CATANA protonproton therapytherapy beambeam line (line (untiluntil JuneJune 20042004))

CATANA proton therapy beam line (new location)CATANA CATANA protonproton therapytherapy beambeam line (line (new locationnew location))

Scattering

system

Modulator & Range shifter

Monitor

chambers

Ligth

field

Laser

CATANA proton therapy beam lineCATANA CATANA protonproton therapytherapy beambeam lineline

DOUBLE SCATTERER FOIL WITH CENTRAL STOPPER

15 µµµµm + 25 µµµµm + 7 mm thickcopper beam stopper

Lateral dose distributionLateralLateral dose dose distributiondistribution

0

20

40

60

80

100

120

-20 -15 -10 -5 0 5 10 15 20

Distance from central axis (mm)

Relative dose

%3%100%:

%3%200)(

:)(

2025:

90.025%50

%90:

50.1:

Tolleranze

minmax

minmax

%95

%20%80

≤×+

−=

≤+

×−=

>⇒=

≥⇒==

≤→

PP

PPRFlatness

ba

baABSSratioAreaSimmetry

mmmmw

mmsizefield

sizefieldHratioField

mmdpenumbraLateral

T

r

ϕ

ϕ

Lateral dose distribution in a clinical proton beamLateralLateral dose dose distributiondistribution in a in a clinicalclinical protonproton beambeam

95 %

50 %

20 %

Depth dose distribution – Energy modulationDepthDepth dose dose distributiondistribution –– EnergyEnergy modulationmodulation

Generation of the Spread Out Bragg Peak (SOBP)Generation of the Spread Out Bragg Peak (SOBP)

]%100)/[( minmax ×= DDRl

�� ENTRANCE DOSE = D(z=0)

�� DISTAL PENUMBRA = d80%→→→→20%

�� LONGITUDINAL UNIFORMITY

Modulated clinical proton beamModulatedModulated clinicalclinical protonproton beambeam

0

10

20

30

40

50

60

70

80

90

100

110

0 5 10 15 20 25 30 35

Depth in water (mm)

Dose (%)

ZREF

Rres

Rp(10%)

SOBP

�� MODULATION REGION (SOBP) = W95%

0

10

20

30

40

50

60

70

80

90

100

0 5 10 15 20 25 30 35

Depth in water (mm)

Relative Ionizzation (%)

Markus Ionization Chamber

31.150.503.194.6830.14MARKUS

Practical Range

(d10%, ICRU 59)

Distal -dose falloff

d80%-20%

F.W.H.M.Peak-PlateuRatio

Peak Depth

DETECTOR

28.390.570.84103.921.31MARKUS

Beam Range

(90% Distal)


d80%-20%


d90%-10%

Maximum Dose (%)

Modulation (SOBP)

DETECTOR

0

20

40

60

80

100

120

0 10 20 30 40Depth in water (mm)

Relative Dose (%)

95%

R90%

80%

20%

Modulated Region

Experimental SOBP curvesExperimentalExperimental SOBP SOBP curvescurves

FULL ENERGY BEAM

0

20

40

60

80

100

-20 -15 -10 -5 0 5 10 15 20

Distance from axis [ mm ]Signal [ % ]

Radiochromic Film

222.400.850.92GAF HS

(ISP)

Width of 95% level (mm)

Simmetry(%)

P80% - 20%

(mm)

FieldRatio

90% / 50%

DETECTOR

Experimental lateral dose distributionExperimentalExperimental laterallateral dose dose distributiondistribution

Absolute Dosimetry: Energy Released in Water (Gray)

Relative Dosimetry: Three dimensional dose distribution

measurements

⇓Considering the high gradient dose, conformation and

small fields often used the detectors have to be kindly

characterized in terms of spatial resolution, energy or

fluence dependence to be used in protontherapy.

Dosimetric commissioning: absolute & relative dosimetryDosimetricDosimetric commissioningcommissioning: : absoluteabsolute & relative & relative dosimetrydosimetry

Relative and Relative and AbsoluteAbsolute DosimetryDosimetry are are

fundamentalfundamental forfor::

CustomizingCustomizing of TPS of TPS

Monitor Monitor UnitUnit CalculationCalculation

QualityQuality ControlControl

ICRU 59 AND TRS 398 IAEA ICRU 59 AND TRS 398 IAEA

RECOMMENDATIONRECOMMENDATION

⇓⇓⇓⇓⇓⇓⇓⇓

““ FOR MEASUREMENTS OF DEPTHFOR MEASUREMENTS OF DEPTH--DOSE DOSE

DISTRIBUTION IN PROTON BEAMSDISTRIBUTION IN PROTON BEAMS

THE USE OF PLANETHE USE OF PLANE--PARALLEL CHAMBERS IS PARALLEL CHAMBERS IS

RECOMMENDEDRECOMMENDED””

⇓⇓⇓⇓⇓⇓⇓⇓

ParallelParallel plateplate MARKUS PTWMARKUS PTW isis the golden the golden

standard standard forfor depthdepth dose dose measurementsmeasurements


ADVANCED MARKUS CHAMBERADVANCED MARKUS CHAMBER

�� Response: 670 pC/Gy

�� Directional dependence: smaller than 0.1% for tilting of the chamber by up to 10º

�� Electrode Acrylic (PMMA), graphite coated 5 mm Ø

�� Leakage current ± 4 fA

�� VP = 400 V �� V××××cm-1 = 4000 �� kS = 1.00 (1÷÷÷÷100 Gy/min.).

�� Pressure equilibrium ≤≤≤≤ 10 sec

�� Temperature equilibrium = 2-3 min./K


1 2 3

4 5 6

1) Film Kodak: XV and EDR2 2) TLD 3) Radiochromic Film

4) Scanditronix Diode 5) PTW Natural Diamond 6) Mosfet

• In collaboration with ISS (S. Onori..) and DFC Florence (M. Bucciolini…)


THE MOPI ONLINE MONITORTHE MOPI ONLINE MONITORTHE MOPI ONLINE MONITOR

Sensitive area 12.8X12.8 cm2

Total thickness ~ 200 µmH2O equiv.Number of strips/chamber 256Strip width 400 µmPitch 500 µmReadout rate up to 4 kHz (1 Hz)

2 ionization chambers with anode segmented in strips (x,y)

cathode

electronics card

spacer

anode

strips

anode

horizontal stripscathode

aluminized mylar

15µm Al

35µm kapton

beam

p beam

x-y ion. strip chambersMOPI

ionization chambers

THE MOPI ONLINE MONITOR:TEST SET-UPTHE MOPI ONLINE MONITOR:TEST SETTHE MOPI ONLINE MONITOR:TEST SET--UPUP

GEANT4 simulation

OptimizationOptimization of of itsits

elementselements

GEANT4 Complete simulation of the CATANA beam line:GEANT4 Complete GEANT4 Complete simulationsimulation of the CATANA of the CATANA beambeam line:line:

TPS TPS checkcheck respectrespect the the veryvery

precise Monte Carlo precise Monte Carlo methodmethod

Design Design possibilitypossibility of a of a

generalgeneral hadronhadron therapytherapy

beambeam lineline

Monte Carlo Simulation of the entire beam line using GEANT4:

Improvement of our beam line and dosimetry

Give a general purpose tool for the design of new hadron-

therapy beam line

Validation of the treatment system software

GEANT4 simulation

GEANT4 SimulationGEANT4 GEANT4 SimulationSimulation

Physics modelsPhysics modelsPhysics models

Standard Processes

Standard + hadronic

Low Energy Low Energy+ hadronic

OK0.699Low En. + Had

OK0.51Low Energy

TestP-valueprocess

OK0.40Standard + Had.

OK0.069Standard.

Kolmogorov test

CLIPS: CLIPS: characterizecharacterize

position and position and sizesize of of

tumourtumour volumevolume

Surgical Phase (Tantalum clips insertions)Surgical Phase (Tantalum clips insertions)Surgical Phase (Tantalum clips insertions)

The Surgical Phase

The Treatment Planning Phase

The Verification Phase

The Treatment Phase

A typical treatmentA typical treatmentA typical treatment

Two orthogonal X-Rays tubes for the visualization of the clips

EYEPLANEYEPLAN

Originally developed by Michael Goitein and Tom

Miller (Massachussetts General Hospital), is now

maintained by Martin Sheen (Clatterbridge Center

for Oncology) and Charle Perrett (PSI)

Treatment Planning System PhaseTreatment Planning System PhaseTreatment Planning System Phase

This point is chosen in order to spare the organs at risk, and to maintain the best polar angle.

Fixation Point ChoiceFixationFixation PointPoint ChoiceChoice

θ

FixationLight

φ

θ Polar Angle

φ Azimuthal Angle

Isocenter

Fixation PointFixation PointFixation Point

Introduction of data in the simulation phaseIntroductionIntroduction of data in the of data in the simulationsimulation phasephase

IsodosesIsodoses curvescurves forfor differentdifferent planesplanes

Treatment Planning System OutputTreatment Planning System OutputTreatment Planning System Output

Patiens look the fixation light during the treatment

PROTON BEAM

Fixation PointFixation PointFixation Point

At the end of patient positioning phase the radiotherapistdraws the eye’s contour on a dedicated monitor in order tomonitoring in any moment the eye’s position during the treatment.

Dose: 15.0 CGE per day

Fractions: 4

Treatment Time: 45-60 sec.

Total Dose: 60 CGE

Treatment PhaseTreatment PhaseTreatment Phase

TREATMENT MODALITIES






• Clinical results




Patient Distribution by PathologiesPatient Distribution by PathologiesPatient Distribution by Pathologies

1 patient (1.01 %)Conjunctival MALT-NHL

92 patients (89.89 %)Uveal Melanoma

2 patient (2.02 %)Conjunctival Papilloma

2 patient (2.02 %)Eyelid Carcinoma

and metastases

1 patient (1.01 %)Conjunctival

rhabdomyosarcoma

4 patients (4.04 %)Conjunctival Melanoma

60

16

9

14

15

6

3

8

2

1

1

Total

number of patients :

150

Patient Distribution by Origin Region

1

1

51%

49%

Women

Men

Patient Distribution by SexPatient Distribution by SexPatient Distribution by Sex

The patients’age ranges between 14yrs and 81yrs

(the mean age is 48 yrs)

2 %Not evaluable

5 %Not evaluable2 %Increased

18 %Stable24 %Stable

77 %Increased

ECOGRAPHIC

REFLECTIVITY

70 %Reduced

TUMORAL THICKNESS

128Patients with Follow up

150PatientsTotal Number

(June 2007)

PATIENTS FOLLOW-UP

(March 2002 – November 2007)PATIENTS FOLLOWPATIENTS FOLLOW--UP UP

(March 2002 (March 2002 –– November 2007)November 2007)

98 %TOTAL SURVIVAL

95 %Eye retention rate

1Other

3Metastatis

95 %LOCAL CONTROL

4Dead patients

128PatientsTotal Number

(November 2007)

SURVAIVAL RESULTS

The realization of a ProtonTherapy center in Catania has been stated in the Health

Framework Agreement Document signed on 23 dec. 2003 by:

Ministero della SaluteMinistero della SaluteMinistero della SaluteMinistero della Salute

Regione SicilianaRegione SicilianaRegione SicilianaRegione Siciliana

Ministero dellMinistero dellMinistero dellMinistero dell’’’’Economia e delle FinanzeEconomia e delle FinanzeEconomia e delle FinanzeEconomia e delle Finanze

Omissis

Articolo 6

Centro di protonterapia nell’area di Catania

Le parti si impegnano ad effettuare le verifiche di ordine programmatico e tecnico-sanitario ai fini della realizzazione di un centro di protonterapianell’area di Catania, in conformità alle indicazioni contenute in un recente

studio dell’AIRO (Associazione Italiana di Radioterapia Oncologica) nell’ambito della nascente rete italiana dei centri di adroterapia e ad individuare le fonti finanziarie cui attingere per la relativa copertura.

Omissis

CATANA Spin-off: SICILIAN PROTONTHERAPY ProjectCATANA CATANA SpinSpin--offoff: SICILIAN PROTONTHERAPY Project: SICILIAN PROTONTHERAPY Project

CATANA Spin-off: Some Important MilestonesCATANA SpinCATANA Spin--off: Some Important Milestonesoff: Some Important Milestones

In 2002, the First Italian Protontherapy Facility Funded by INFN

and Catania University started in Catania at INFN-Laboratori

Nazionali del Sud

On March 7th 2003 Sicilian Region has approved to realize an

HadronTherapy Center in Catania, based on a Cyclotron for

protons and heavy charge particles. It has to be realized as

“Scientific collaboration between Region, INFN and University of

Catania also open to private contributions”

In 2003, the 5th Scientific Commission of INFN funded SCENT, an

R&D project studying a Superconducting Cyclotron for Medical

Applications

SCENT

“A New Cyclotron for Hadron Therapy”

February 2003: the 5th CSN-INFN approve SCENT experiment

March 2003: the Sicily region, inside its developing plane for the

health, decided to include the realization of a centre for

hadrotherapy in Catania area

April 2006: contact between IBA and INFN to find out a

collaboration agreement

July 2006: agreement of cooperation between IBA and INFN for

marketing and construction of a SCENT Cyclotron

Superconducting Cyclotron for Exotic Nuclei and Therapy

Why proposing a cyclotron?WhyWhy proposingproposing a cyclotron?a cyclotron?

• A vast majority of the tumors treated in MGH, Chiba or GSI do

not require the very highest energy of a synchrotron

• The minority of tumours located too deep to be treated in

Carbon (Prostate, Uterus) could also be treated with lighter

ions such as Helium or Protons

• A cyclotron offers the best beam current control for ultra-fast

pencil beam scanning

• The cyclotron is a much simpler machine, with most of the

parameters constants. It does not require a large team of Ph.

D. physicists to operate

• A cyclotron is significantly smaller (6 m vs. 20 m in diameter)

and significantly less costly than the synchrotron.

Range in water:

Protons 250 MeV 374 mm

Carbon 300 A MeV 174 mm

Ions qac

→→→→qe

Emax

A MeV

BρρρρT××××m

RF*

MHz

Isource

nA

Iextr.

nA

Pex

W

H2 12 250 4.883 91 2500 500 125

12C 6 300 4.890 91 2000 100 + 50

* armonich h=4, +without buncher & extraction efficiency 50%

SC able to accelerate H2+ and light ions up to 300 A MeV

The magnetic field is produced by twin coils

The isochronous fields for H2+ and for light ions fully stripped are very similar

(±0.4%)

SCENT: A SC for Medical ApplicationsSCENT: A SC SCENT: A SC forfor MedicalMedical ApplicationsApplications

AIRO Report on Hadrontherapy states that in Italy more than

3600 patients are elegible for carbon ions treatment.

In the framework of SCENT we defined some pathologies taking

clinical advantages from the availability of 300 AMeV Carbon

Ions:

Base of skull and Brain tumors

NSCLT

Spinal Cord tumors

Soft Tissue Sarcoma

Why is it useful to get 300 AMev Carbon Ions?Why is it useful to get 300 AMev Carbon Ions?

SC(EN)T

a Superconducting Cyclotron

for Therapy

Max. Energy for Proton, 6Li, C

Sectors

Rpole

Bo

<Bmax>

Spiral angle

Hill gap

Valley gap

RF frequency

Outer Diameter

Weight

(250) 300 AMeV

4

132 cm

3.07 T

4.22 T

(73°) 80°

(50) 30 mm

(105) 90 cm

(93)97 MHz

5100 mm

≈≈≈≈ 420 tons

6Li @ 300 AMeV 339 mm, 100% of patients

Distribution of maximum depths in HIMAC treatments

patients 1750, N° targets 6323

12C @ 300 AMeV,Max. depth

174mm, 74% of targets

SC(EN)T

Proton Beam

Extracted by

stripper

@ 250 Mev

Carbon beam extracted be E.D. @ 300A MeV

E. D. inside RF DEE, width= 34°,

Electric Field 92 kV/cm

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Catania Project at Cannizzaro Hospital

INFN: LNS & Turin sect.

Funded in the specific line

“COMBATING CANCER”

WP4 Medical Applications and

QA Definition

ThankThank YouYou forfor YourYour AttentionAttention !!!!!!

LNS

ThatThat’’s s allall, , folksfolks

INFN-LNS e Centro di AdroTerapiae Applicazioni Nucleari ... · INFN-LNS e Centro di AdroTerapiae...

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