AAPM 49th Annual Meeting

CE - Therapy

PROTON THERAPY
Alfred Smith, Ph.D.
M. D. Anderson Cancer Center Houston, TX

Harald Paganetti, Ph.D.

Massachusetts General Hospital, Boston, MA

Topics Covered
History of Proton Therapy
Worldwide Facilities Rationale for Proton Therapy Physics of Proton Beams Treatment Delivery Techniques Proton Treatment Technology Clinical Commissioning Treatment Planning

History and Current Status of Proton Therapy

Abbreviated History of Protons

1919 1930 1946 1955 1961 1972 Rutherford proposed existence of protons E. O. Lawrence built first cyclotron Robert Wilson proposed proton therapy Tobias et al treated patients at LBL Kjellberg et al treated patients at HCL MGH received first NCI grant for proton studies at HCL First hospital-based proton facility at LLUMC 28 facilities worldwide treating patients; over 55,000 patients treated with protons.

1991 2006

Charged Particle Therapy Facilities

25 facilities worldwide are treating patients.
6 in Japan (4 hospital-based) Chiba, NCC East-Kashiwa, HIBMC-Hyogo, PMRCTsukuba, WERC-Wakasa, Shizuoka Cancer Center 6 in the United States ( 4 hospital-based) LLUMC, MGH, MDACC, Univ. of Florida, Univ. of Indiana, UC Davis 9 in Europe/Russia 4 Additional facilities (UK, China, Korea, South Africa) 15 additional institutions worldwide are either building a new facility or are seriously planning to have a particle therapy facility.

Particle Therapy Facilities Worldwide

In operation

In preparation

Considering

Treating: Protons 25, Carbon ions 3

Courtesy of Takashi Ogino, MD, PhD, NCC Kashiwa, Japan

Rationale for Proton Therapy

Need for Improved Local Control in Cancer Treatment (selected sites)

(all numbers are estimates)
Tumor Site Deaths/ year Deaths due to Local Failure

Head/Neck Gastrointestinal Gynecologic Genitourinary Lung Breast Lymphoma Skin, Bone, Soft Tissue Brain Total

22,000 135,000 28,000 55,000 160,000 41,000 20,000 15,000 12,000 488,000

13,200 (60%) 54,000 (40%) 14,000 (50%) 27,500 (50%) 40,000 (25%) 4,920 (12%) 2,400 (12%) 5,000 (33%) 10,800 (90%) 171,820 (35%)

Over 1,350,000 new cancer patients per year in the US

Photons

Protons

Fundamental Things to Remember about Protons

Photons

Protons Stop! Photons dont stop. Proton dose at depth (target) is greater than dose at surface. Photon dose at depth (target) is less than dose at dmax.

Ideal dose distribution

Protons

Rhabdomyosarcoma of Paranasal Sinus (7 y old boy)

6 MV Photons (3 field)

160 MeV Protons (2 field)

Photon IMXT (9 field)

Proton IMRT (9 field)

Proton Physics
The physics of proton beams Passive scattering systems Pencil beam scanning systems

Electromagnetic energy loss of protons

p e

120%

100%

80%

Relative Dose [%]

60%

Mass Electronic Stopping Power is the mean energy lost by protons in electronic collisions in traversing the distance dx in a material of density .

40%

S/ = 1/[dE/dx] 1/v2
Where v = proton velocity
0 5 10 15 20 25 30

20%

0%

Depth in Water[cm]

Normalized (at peak) Bragg Curves for Various Proton Incident Energies Range Straggling will cause the Bragg peak to widen with depth of penetration
1.2

Relative Dose

0.8

0.6

0.4

100 MeV 130 MeV 160 MeV 180 MeV 200 MeV 225 MeV 250 MeV

0.2

0 0 5 10 15 20 25 30 35 40

Depth in Water (cm)

Normalized (at entrance) Bragg Curves for Various Proton Incident Energies

50 40 Relative Dose 30 20 10 0 -10 0 10 20 30 Depth in Water (cm) 40 50 100 MeV 130 MeV 160 MeV 180 MeV 200 MeV 225 MeV 250 MeV

Dose depositions in water from 160 MeV protons. Beam slit delimiters with width W cm. Depth for 160 MeV Protons for Uniform particle distributions.

various field sizes

30

200 MeV Beam - PDD vs Aperture size F2 data - snout at 45 cm

120 100 80
2 cm x 2 cm

25

D o se (M eV /cm )

20

PDD

W = 0.1 cm W = 0.16 cm W = 0.24 cm W = 0.5 cm W = 1 cm W = 2 cm

60 40

5 cm x 5 cm 10 cm x 10 cm 18 cm x 18 cm

15

10

20
5

0
0 0 5 10 15

50

100
Depth (mm)

150

200

250

Depth (cm)

Loss of in-scattering (charged particle equilibrium) results in deterioration of Bragg peak and non uniformity of SOBP.

George Ciangaru

Narayan Sahoo

Multiple Coulomb Scattering

p

Protons are deflected frequently in the electric field of the nuclei

Beam broadening can be approximated by a Gaussian distribution

Lateral dose fall-off: Protons vs. Photons

80/20 Penumbra Comparison
1.00 80 - 20 % D istan ce (cm ) 0.75 0.50 0.25 0.00 15 cm 20 cm Norm alization Depth 25 cm

Protons

15 MV Photons
17 cm

Paganetti

Urie

Nuclear interactions of protons

p p p p , n

A certain fraction of protons undergo nuclear interactions, mainly on 16O Nuclear interactions lead to secondary particles and thus to local and non-local dose deposition (neutrons!) In passive scattering systems neutrons are produced in the first and second scatterers, modulation wheel, aperture, range compensator in addition to those produced in the patient.

Pedroni et al PMB, 50, 541-561, 2005 Effect on the lateral dose distribution
Primary fluence

Secondaries from nuclear interactions Effect on Depth Dose

110 100 90 80 70 60 50 40 30 20 10 0

230 MeV protons Total Absorbed Dose

Relative Dose [%]

'Primary' Dose
0 5 10 15 20

'Secondary' Dose
25 30 35

Depth in Water [cm]

Proton Therapy Beam Delivery Technology

Physics of the Passive Scattering Mode of Proton Beam Delivery

Goitein, Lomax, Pedroni - Med. Phys.

Passive Scattering Nozzle with Range Modulation Wheel

How a Spread Out Bragg Peak (SOBP) is formed.

Modulation wheel rotates in the beam. Pull-back (energy shift) determined by height of step. Weight determined by width of step. Multiple SOBPs can be obtained by gating beam.

Deficiencies of Proton Passive Scattering Techniques

Uniform SOBP - excess normal tissue dose.

Requires custom aperture and compensator Inefficient - high proton loss produces activation and neutron production.
Chu, Ludewigt, Renner - Rev. Sci. Instrum.

The Pencil Beam Scanning Mode of Proton Beam Delivery

Goitein, Lomax, Pedroni - Med. Phys.

Pencil Beam Scanning Nozzle

Beam 3.2m Profile Monitor Scanning Magnets

Performance
Range Adjustability Max. field size Beam size in air SAD Dose compliance 4 36 g/cm2 0.1 g/cm2 30 x 30 cm 6 10mm > 2.5 m +/- 3% (2 )

Ceramic Ceramic Vacuum Chamber Chamber

Spot Position Monitor Dose Monitor 1, 2

Iso Center

Irradiation time < 2 min to deliver 2 Gy to 1 liter

Energy Filter Energy Absorber

Proton Accelerators Isocentric Gantries Typical Facility

Hitachi 250 MeV synchrotron ring 7 MeV Linac injector

Typical Accelerators used in proton therapy facilities

ACCEL Superconducting Cyclotron

IBA 230 MeV Cyclotron

250 MeV

M. D. Anderson Gantry

Proton and Carbon Ion Gantries

190 tons Hitachi 600 tons

Siemens 120 tons Heidelberg

Proton Therapy Center - Houston

PTC-H 3 Rotating Gantries 1 Fixed Port 1 Eye Port 1 Experimental Port Experimental Port

Pencil Beam Scanning Port

Passive Scattering Port

Accelerator System (slow cycle synchrotron)

Large Fixed Port Eye Port

Clinical Commissioning
Tests for system functionality and safety Treatment Planning System commissioning Collection of data for input to planning system Validation of planning system output Beam calibration Calibration of transmission ionization chambers Measurement of dependence of dose on range modulation, field size, etc. Patient treatment and machine QA

Pristine Bragg Peaks

120.0

250 MeV
G2_250MeV_RMW88_range25.0 cm_largeSnout@5cm
140MeV_Range 10 cm 120MeV_Range 6.4 cm

PTCH-G2, Pristine Bragg Peaks

120 100 80

100.0

100MeV_Range 4.3 cm 250MeV_Range 28.5 cm 225MeV_Range 23.6 cm

80.0

200MeV_Range 19.0 cm 180MeV_Range 16.1 cm

PDD

160MeV_Range 13 cm

PDD

60.0

60 40 20

40.0

20.0

SOBP 4 cm , Measured 3.9 cm SOBP 6 cm , Measured 5.9 cm SOBP 8 cm , Measured 7.9 cm SOBP 10 cm , Measured 10.0 cm SOBP 12 cm , Measured 12.2 cm SOBP 14 cm , Measured 14.3 cm SOBP 16 cm , Measured 16.6 cm

0
0.0 0 50 100 150 200 250 300 350 Depth (mm)

50

100

150

200

250

300

350

G 2 _ 1 6 0 M e V _ R M W 7 6 _ ra n g e 1 3 .0 c m _ m e d iu m s n o u t@ 5 c m

160 MeV

G2- NZL AT2.2 Modula t ion Te st( A- 3) UF10E120 R a nge 6.9[ c mH2O]

120 MeV

Depth (m m )

1 2 0 1 0 0 8 0 PDD 6 0 4 0 2 0 0 0

110%

100%

90%

80%

S O B P 1 0c m ,M e a s u re d1 0 .6c m S O B P 8c m ,M e a s u re d8 .2c m S O B P 6c m ,M e a s u re d6 .1c m S O B P 4c m ,M e a s u re d4 .0c m

2 0 4 0 6 0 8 0 1 0 0 1 2 0 1 4 0 1 6 0 0 1 8 D e p th(m m )

70%

60%

50%

40%

SOBP4cm ? 3.8cm T0521R SOBP3cm ? 2.9cm T0522L+M+P 20% SOBP2cm ? 1.9cm T0521T
30%

SOBP1cm ? 1cm T0521U

10% 0% 0 10 20 30 40 50 60 70 80 90 100

PTCOG 46

Educational Workshop

De pt h in Wa t e r [ mm H2O]

The CT scanner used to acquire treatment planning images should be calibrated.

Relative Stopping Power & Calibration Curve
1.8 1.6

Comparison of measurements with treatment planning calculations

250 MeV, Range 28.5 cm, SOBP Width 16 cm

120.0 100.0

Relative Stopping Power

1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0

80.0

PDD

M eas. 16.1 cm Calc7551 16.1 cm

60.0 40.0

ICRP tissues
0 500 1000 1500

20.0 0.0

-1000

-500

HU
PTCOG 46 Educational Workshop Al Smith

0
PTCOG 46

50

100

150

200

250

300

350

Distance (mm) Educational Workshop

Bone-Water Interface Profile, 250 MeV, Depth = 17.9 cm G1, 250 MeV, d=17.9 cm

Comparison of measurements with treatment planning calculations

Comparison of Measurements and Treatment Planning Calculations Bone-Water Interface Profiles

G2, RMW 250 MeV, d= 23.3 cm, Cross 250 91, Mev, depth = 23.3 cm, Cross Plane ScanPlane
120

120 100

100

Relative Dose

Relative Dose

80 60 40 20

SOBP04 Calc SOBP04 Meas. SOBP10 Calc SOBP10 Meas. SOBP16 Calc SOBP16 Meas.

80 Measured Eclipse 60 40 20

0 -15 -10 -5 0 5 10 15

0 -10
PTCOG 46

Off-Axis Distance (cm)

PTCOG 46 Educational Workshop

-5

10

Off-axis Distance (cm) Educational Workshop

Prostate Patient Treatment Plan

QA of Prostate Treatment using patient treatment parameters/appliances and EBT film in water phantom.
Treatment plan on CT anatomy converted to dose distribution in water phantom.

CTV Rectum Bladder Femoral heads

PTCOG 46

Educational Workshop

Al Smith

PTCOG 46

Educational Workshop

Measurements in water phantom using EBT film, patient aperture, and range compensator
Cross Field Profile A to P through Isocenter
EBT film m easurement
1

Patient Treatment QA Measurements compared with treatment planning calculations converted to water phantom. Data measured in water phantom using Pin-Point ion chamber. Treatment aperture and range compensator were both inserted.
Eclipse vs. Measured - Crossplane

Eclipse

0.8

Dose (arb units)

0.6

100
0.4

0.2

80
15 35 55

0 -65 -45 -25 -5

Lateral Distance (mm)

60
Cross Field Profile F to H through isocenter

40
1 0.8

Dose (arb units)

20
0.6

EBT film measurement Eclipse

0.4

0
0.2

0
10 30 50 70

4 Eclips e

6 Measured

10

12

0 -70 -50 -30 -10

Lateral Distance (mm)

PTCOG 46

Educational Workshop

Al Smith

PTCOG 46

Educational Workshop

Al Smith

Treatment Planning

Acquisition of imaging data (CT, MRI) Conversion of CT values into stopping power (not electron density) Delineation of regions of interest Selection of proton beam directions Optimization of the plan

Treatment Planning

Passive scattered proton beams Scanned Proton Beams Intensity modulated proton beams Comparative Treatment Plans

Dose shaping: Range compensator

High-Density Structure

Target Volume

Beam

Critical Structure

Double scattering system

Aperture

Body Surface

Hanne Kooy, MGH

SOBP Modulation
High-Density Structure

Target Volume

Beam

Critical Structure

Body Surface Aperture

Hanne Kooy, MGH

Aperture and Range Compensator

To be designed by the planning system !

Hanne Kooy, MGH

Compensator smearing to account for uncertainties

BEAM

Hanne Kooy, MGH

Dosimetry and QA for SOBP proton fields

120

Dose [%]

100 80 60 40 20 0 0 50 100 150 200

Beam range: 17.19 cm Modulation width: 6.78 cm

Depth [mm]
120

Dose [%]

100 80 60 40 20 0 0 20 40 60 80 100 120 140 160

Beam range: 13.47 cm Modulation width: 8.65 cm

Depth [mm]
120

Dose [%]

100 80 60 40 20 0 0

Beam range: 12.0 cm Modulation width: 4.0 cm

20 40 60 80 100 120 140

Depth [mm]

Field dependent (!) absolute dosimetry

Volume for absolute dosimetry

Output Factor

D cal iic

cGy MU

EXAMPLE 1: Para-spinal case using 3 fields

10 Gy 15 Gy 20 Gy 25 Gy 30 Gy 35 Gy 40 Gy 45 Gy 46 Gy

CTV

brainstem

EXAMPLE 2: Para-spinal case using 6 fields (involves metal CT artifacts)

15 Gy 20 Gy 25 Gy 30 Gy 35 Gy 40 Gy 45 Gy 50 Gy 51 Gy

CTV

spinal cord

Field Patching
Abutting the distal dose edge of one field to the dose boundary of other field(s). Useful if target is close to critical structures Not necessarily homogeneous dose to the target for each beam (IM!) Range an penumbra uncertainties need to be considered

Urie M. M. et al (1986), Med Phys. 13, 734.

Field Patching
THROUGH Field A followed by PATCH field B, followed by PATCH field C
B

PTV 50 50 Critical Structure

Match at 50% isodose, lateral + distal, levels

Hanne Kooy, MGH

 Marc Bussiere, MGH

EXAMPLE 3: Nasopharynx case using 14 fields (plus additional photon fields to the lower neck)

CTV-2
25 Gy 30 Gy 35 Gy 40 Gy 45 Gy 50 Gy 55 Gy 60 Gy 67 Gy

CTV-2 Parotid Brainstem

CTV-1

Spinal Cord

GTV 76 Gy CTV1 60-66 Gy CTV2 60 Gy Nodes 54 Gy

Treating moving targets with protons

Effect of respiration on dose

Range fluctuations due to respiration in the lung

Shinishiro Mori, MGH

Effect of respiration on dose

Range Fluctuation on Cardiac MRI

Shinishiro Mori, MGH

Burr Proton Therapy Center (2001-) Patient Population

Brain Spine Prostate Skull Base Head & Neck Trunk/Extremity Sarcomas Gastrointestinal Lung 32% 23% 12% 12% 7% 6% 6% 1%

In general, 1-3 fields / day

Thomas DeLaney, MGH

Treatment Planning

Passive scattered proton beams Scanned Proton Beams Intensity modulated proton beams Comparative Treatment Plans

Depth Dose

Typical Spot Beam in Water

Beam Profile

G. Ciangaru, MDACC

Beam Scanning

No compensator, no aperture, no scattering system required Eros Pedroni, PSI

A major problem with spot scanning:

The target can move !

Remedies:
Rescanning Beam Gating Real time tumor tracking with markers

Alfred Smith, MDACC

1. Evenly spaced/weighted spots

to achieve uniform field 2. 1mm spot error due to delivery error or patient motion. 3. Optimum spacing/weighting to achieve sharper penumbra

Pedroni

Eros Pedroni, PSI

Dosimetry and QA of pencil beams

Energy/Range large number of energies required. energy spacing must provide dose uniformity over all depths Spot size and shape spot size/shape dependence on energy spot orientation as a function of gantry angle Spot position accuracy Validation of treatment planning calculations Validation of treatment delivery Measurements require methods for rapid collection large amounts of data Real-time beam information
Alfred Smith, MDACC

Ionization Chamber Array

Water column with 26 small ionization chambers of 0.1 cm3 Dose box

PTCOG 46

Educational Workshop

Pedroni, PSI, Switzerland

Pedroni, PSI, Switzerland Orthogonal IC array measurements performed at different water depths using a computer controlled water column and compared with calculations.

Beams-eye-view of dose in water U axis profile

T axis profile

Eros Pedroni, PSI

Mirror M D Anderson Cancer Center CCD Scintillating Plate, Mirror and Camera

CCD Camera used for pencil beam scanning QA.

Martin Bues, MDACC

Scintillating Plate

Beam

Spot Pattern Test

Uniform Field Scanning Test

Scintillating screen viewed with a CCD through a 45 mirror

WER 6.65 CM

ideal for non homogeneous dose distributions

W= 6.65 cm

WE R 7.82 CM

W= 7.82 cm

Measurement vs.
PTCOG 46

Calculation
Educational Workshop Pedroni, PSI, Switzerland

Eros Pedroni, PSI

Treatment Planning

Passive scattered proton beams Scanned Proton Beams Intensity modulated proton beams Comparative Treatment Plans

Intensity-Modulated Proton TherapyIMPT

Alex Trofimov, MGH

IMPT Treatment Planning

Bragg peaks of pencil beams are distributed throughout the planning volume Pencil beam weights are optimized for several beam directions simultaneously (inverse planning)

Alex Trofimov, MGH

IMPT Delivery
Spot scanning at PSI (Switzerland)

IMPT Delivery

Built-in magnets for IMPT Two (red) dipole magnets to deflect the beam in X and Y respectively Two (yellow) quadrupole magnets to focus the beam in X and Y respectively

Hanne Kooy, MGH

IMPT in clinical practice

+ + + + great flexibility and variability no need for apertures/compensators easy delivery of large fields beamlet optimization routines requires very high degree of precision

Treatment Planning

Passive scattered proton beams Scanned Proton Beams Intensity modulated proton beams Comparative Treatment Plans

Example (IM protons vs. IM photons)

Photon IMRT

Proton IMPT

Jan Wilkens, DKFZ

Example (protons vs. IM photons)

Nasopharynx (case shown earlier)

A Composite plan (14 proton fields, 4 photon fields)

proton fields CTV to 59.4 GyE (33 x 1.8 Gy) GTV to 70.2 GyE (+ 6 x 1.8 Gy) Photon fields lower neck, nodes to 60 Gy
G

N N

Alex Trofimov, MGH

B IMXT plan (7 coplanar photon beams)

Alex Trofimov, MGH

C IMPT plan (4 coplanar photon beams)

Alex Trofimov, MGH

DVH for target structures

Comparable target coverage

Alex Trofimov, MGH

 Critical normal structures (always outlined): brain stem, spinal cord, optic structures parotid glands, cochlea Extra structures were outlined on 3 data sets esophagus, base of tongue, larynx minor salivary, sublingual and submand. glands mastication and suprahyoid muscles

Alex Trofimov, MGH

DVH for some critical structures

Alex Trofimov, MGH

DVH for some critical structures

Alex Trofimov, MGH

Example (standard protons vs. photons)

Medulloblastoma

Medulloblastoma
Irradiation of the whole cranium and spinal axis Low Risk 23.4 CGE High Risk 36.0 CGE Spine Include Vertebral Body Cranium Constrain Auditory System < 40 CGE Pituitary / Hypothalamus ~ 45 CGE Posterior Cranial Fossa Boost Total 54 CGE

Hanne Kooy, MGH

Protons

Photons

Copyright MGH/NPTC 2003

Example (protons vs. IM photons)

Prostate

(a)

IMRT

Prostate carcinoma: (GTV + 5mm) to 79.2 Gy (CTV + 5mm) to 50.4 Gy

Dose [Gy]

(b)

3D CPT

(c)

IMPT

Dose [CGE]

Dose [CGE]

Alex Trofimov, MGH

 Alex Trofimov, MGH

Summary
Proton planning offers more options in terms of beam directions and field shaping than photon planning For specific sites IMRT and protons can be comparable in terms of dose conformality Protons are able to reduce the dose to most critical structures compared to photons Proton therapy is able to reduce the integral dose compared to photons by up to a factor of 3 IMPT is the method of choice

Thanks to Hanne Kooy (MGH, Boston) Alex Trofimov (MGH, Boston) George Chen (MGH, Boston) Martin Bues (MDACC, Houston) George Ciangaru (MDACC, Houston) for providing slides and figures