Protons: Challenges and Opportunities

The University of TexasThe University of Texas

M.D. Anderson Cancer Center

Proton Therapy Center

• Michael Gillin, PhD• Professor and Deputy Chair• Department of Radiation Physics• U.T. MDACC

140 MeV Protons and 50 MeV Electrons (U of Michigan)

140 MeV proton PDD vs 50 Mev Electron PDD

100.00

120.00

80.00

100.00

Proton 140 MeV 8 cm SOBPProton 140 MeV 10 cm SOBP Electron 50 MeV

40.00

60.00

20.00

40.00

0.000 50 100 150 200 250 300

Protons: Flat peak, sharp drop off. Range controlled to within 1 mm in water. What clinical sites benefit from these characteristics?

8 89

56

7

5

6

7

3

4

5

3

4

5

2

3

2

3 Proton therapy:2/26/-4/6/07

1 1

Spine: 2/26-3/14

• 20 yr old male• Medulloblastoma

MRI: 5/9/07

• Medulloblastoma• 23.4 Gy to whole brain and spine• 30.6 Gy boost to tumor bed → 54 Gy

Place of Protons in the PantheonPlace of Protons in the Pantheon

• For the additional cost of protons ( which is certainly > a factor of 20) , what benefits do protons provide? (Maintenance costs for ~ 25 linacs: ~ $3M; for 1 proton unit ~ $6M/year)

• What treatment sites does the absence of an exit dose benefit the patient?

• Pediatrics – without question for certain sites• Unusual tumors – base of skull and cervical• Unusual tumors – base of skull and cervical

spineLung ? MDACC is investigating this• Lung ? MDACC is investigating this.

120 MeV, Medium snoutRange: 4.4 to 6.4 cm

16 month old

RetinoblastomaNote: Retinoblastoma

45 CGE (40.9 Gy)Limited Penetration of beamof beam

Protons Stop in Water: 32 cm in water for 250 MeV protons for a 10 cm x 10 cm field

Passive Modulation and Discrete Spot Scanning

A Spot – Short Burst of Single Energy Protons

100%

p g gy

100%

80%

60 %

40%

20%

0%

Basic Proton PhysicsBasic Proton Physics

• Protons lose their energy in a medium primarily through numerous electromagnetic interactions with atomic electrons. Protons lose only a small fraction of their energy in each interaction (at most 4m/M = 0.0022) and are deflected by only small angles in each interaction.

• The proton mass electronic stopping power in a material, S(E)/ρ, is defined as S(E)/ ρ = (1/ ρ) (dE/dx)

Proton Mass Electronic Stopping pp gPower (MeV cm-2 g-1) ICRU 59

E(MeV) Water Air Bone PolystyreneE(MeV) Water Air Bone Polystyrene

250 3.911 3.462 3.646 3.827

200 4 492 3 976 4 186 4 397200 4.492 3.976 4.186 4.397

150 5.445 4.816 5.070 5.331

100 7 289 6 443 6 778 7 140100 7.289 6.443 6.778 7.140

75 9.063 8.006 8.420 8.882

50 12 45 10 99 11 55 12 2150 12.45 10.99 11.55 12.21

25 21.75 19.15 20.10 21.36

20 26.02 22.94 24.06 25.62

10 45.67 40.06 41.96 45.00

5 79.11 69.09 72.28 78.20

1 260.8 222.9 233.9 257.7

0.1 816.1 730.1 791.2 916.4

Charged Particles Interaction in Matter

• A 1 MeV charged particle would typically undergo approximately 105 interactions before losing all of its kinetic energy.

• Charged particles can be roughly characterized g g yby pathlength, which is traced out by most such particles of a given type in a specific medium.g y

• Range is the expectation value of pathlength, namely the mean value for a very largenamely the mean value for a very large population of identical particles.

• 250 MeV protons 10 cm x 10 cm field: Range• 250 MeV protons, 10 cm x 10 cm field: Range 32.6 cm in water.

Energy loss per unit distanceEnergy loss per unit distance, dE/dxdE/dx

Energy loss results in a reduction of speed

Proton Energy VelocityProton Energy VelocityMeV M/s 200 2 x 106

2 2 x 1032 2 x 10

Basic Proton PhysicsBasic Proton PhysicsAt i i l i t ti• At increasing energy, nuclear interactions become more important. In the therapeutic energy range the probability of nuclear events isenergy range, the probability of nuclear events is small compared with the probability of electron interactions although each nuclear event caninteractions, although each nuclear event can transfer a significant portion of the proton energy to the medium.

• Nuclear interactions essentially remove primary protons from the beam and result in the pproduction of secondary particles, which have a higher RBE.

Energy Loss by Nuclear Interactions

• The probability for inelastic nuclear reactions increases rapidly with increasing proton energy – it dominates the energy loss of protons for E exceeding a few hundred MeV.

• The relative probability for an inelastic nuclear interaction in solid organic materials is about 1% gfor a 25 MeV proton, 25% for a 200 MeV proton, and dominates the energy loss for E > 500 MeV.

Basic Proton PhysicsBasic Proton Physics18

• Neutron production has a non-negligible impact due to the production of heavy 8

10

12

14

16

mS

v/G

y) Large SnoutMedium SnoutSmall Snout

a in-field, Neutrak®

to the production of heavy charged particles generated by subsequent 0

2

4

6

8

H/D

(m

g y qnuclear interactions.

• High energy neutron in

00 5 10 15 20 25 30 35

Proton Range (cm)

4.0

c t f fi ld N t k®

the field, past range.• Low energy out of the

2.0

2.5

3.0

3.5

mS

v/G

y)

c out-of-field, Neutrak®

field.0.5

1.0

1.5

H/D

(m

0.00 5 10 15 20 25 30 35

Proton Range (cm)

Proton Commissioning: A Phased Project both in terms of timeProject, both in terms of time available and beams/snouts

• There is one proton accelerator and four clinical treatment rooms (3 rooms with gantries one of which is discrete spot scanning) and one experimental roomgantries one of which is discrete spot scanning) and one experimental room.

• The beam is available in only one room at a time. Thus, time can spent waiting for the beam. Treatment times can last from 20 minutes to 90 minutes.

• Clinical commissioning was a phased project, both in terms of energies available and beamlines ready to treat patientsbeamlines ready to treat patients.

• Clinical commissioning began in March 2006. The first patient on G1 was treated in May, 2006. Last commissioning measurements for scattering were made in March, 2008. Discrete spot scanning started in May, 2008. Eye line and experimental room have yet to be commissionedhave yet to be commissioned.

S h ti h i th l ti f tSchematic showing the location of magnets

The magnetic fields increase in synchronously with the proton energy.

Scattering: 8 different energies 3 different snouts – largest 25 cm x 25 cm

Scanning: 94 different energies

Gantry190 tons SAD ≥ 2 6 mSAD ≥ 2.6 mDiameter: 5.5 m Rotating speed: 1 RPM maxRotation: ±190ºRotation: 190Positioning accuracy: 0.5º

Counter balance serves as beam block

Isocenter Accuracy: Isocenter must be contained within h f 1 dia sphere of ≤ 1 mm diameter over

360º rotation

20 nC per pulse or 1011 protons per pulse

Comparison of F2 and G2 SOBP_ Medium Snout SOBP 10 cm (F2 snout position 13 cm G2 Snout position 5 cm Normalized to dmax)(F2 snout position 13 cm, G2 Snout position 5 cm, Normalized to dmax)

120.0

100.0

80.0

D F2_250 MeV, Range 28.5 cm

40 0

60.0

PDD _ g

G2_250 MeV, Range 28.5 cmF2_225 MeV, Range=23.6 cmG2_225 MeV, Range=23.6 cmF2_200 MeV, Range=19.0 cmG2 200 MeV Range=19 0 cm

20 0

40.0 G2_200 MeV, Range=19.0 cm

0.0

20.0

0.00 50 100 150 200 250 300 350

Depth (cm)

G2_250MeV_RMW91_range28.5cm_mediumsnout@5cm

100

120 G2_250MeV_RMW88_range25.0 cm_largeSnout@5cm120

60

80

PDD SOBP 4 cm, Measured 4.2 cm

SOBP 10 cm, Measure 10.2 cm 60

80

100

PDD

SOBP 4 cm, Measured 3.9 cm

0

20

40 SOBP 16 cm, Measured 16.1cmSOBP 12 cm, Measured 12.0 cmSOBP 8 cm, Measured 8.1 cmSOBP 6 cm, Measured 6.1 cmSOBP 14 cm Measured 14 3 cm

20

40

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

0 50 100 150 200 250 300 350

Depth (mm)

SOBP 14 cm, Measured 14.3 cm 0

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

,

In a water phantom with passive modulation, the depth of the distal 90% d b ll d i hi 1 f 2 30

G2_160MeV_RMW76_range13.0cm_mediumsnout@5cm

120

G2_160MeV_RMW4_range 11.0 cm_large Snout at 5 cm

120

dose can be controlled to within 1 mm from 2 cm to > 30 cm.

60

80

100

DD SOBP 10 cm, Measured 10.6 cm

60

80

100

DD SOBP 4 cm Measured 3 8 cm

0

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40

60

PD ,

SOBP 8 cm, Measured 8.2 cmSOBP 6 cm, Measured 6.1 cmSOBP 4 cm Measured 4 0 cm

20

40

60

PD

SOBP 4 cm, Measured 3.8 cmSOBP 6 cm, Measured 5.8 cmSOBP 8 cm, Measured 7.8 cmSOBP 10 cm

00 20 40 60 80 100 120 140 160 180

Depth (mm)

SOBP 4 cm, Measured 4.0 cm0

0 20 40 60 80 100 120 140 160Depth (mm)

Basic Passive Scattering Characteristics:8 energies, 3 snouts, Range Shifters

• PTC H is a synchrotron facility• PTC H is a synchrotron facility which 3 large field passively scattered beamlines.

• Each passively scattered p ybeamline has 3 nozzles, 25cm x 25cm, 18cm x 18cm, and 10cm x 10cm, and 8 proton energies, 250, 225, 200, 180, 160, 140, 120, and , , , , , ,100 MeV. Thus there are 24 options per beamline.

• For passive scattering, the beam pulse is approximately 0 5pulse is approximately 0.5 seconds with 1.5 seconds between pulses. The dose rate is approximately 100 cGy/minutes.SOBP idth f 1 t• SOBP widths range from 1 cm to 16 cm, in 1 cm increments. Range shifters can control the range in water to within 1 mm.

Passive Scattering Nozzle with Range Modulation WheelModulation Wheel

The aperture and compensatorcompensator production shop – 4 talented mechanists.

Commissioning EquipmentCommissioning Equipment

• PTW scanner – 4 seconds per point

• TG 51 tanks with PTW TN30013 and Markus chambers.

• Other water tanksOther water tanks• Solid water

EBT and EDR 2 film• EBT and EDR 2 film• Special Jigs

Farmer Type Local StandardsPTW TN30013

• Typical calibration factor: 5.441 x 107

Gy/C• Vented sensitive

volume of 0.6 cm3 • Suitable as therapySuitable as therapy

chamber for use in waterwater

• Flat energy responseProtocol TRS 398• Protocol – TRS 398

Parallel Plate ChambersParallel Plate Chambers• PTW TN34045 (0.02 cc

polyethylene-graphite window) Typical factor:window) Typical factor: 1.349 x 109 Gy/C

• PTW Bragg PeakPTW Bragg Peak Chamber (8 cm diameter, 10.5 cc, 0.411 g/cm2 front window. Typical factor: 3.225 x 108 Gy/C This h b i d f thchamber is used for the

discrete spot scanning beam and is not largebeam and is not large enough.

RPC TLD Results at PTC H

Remote monitoring with TLD is possible and indicates a stable system

Protons have a limited range,gwhich should limit toxicity

Patient with T2, N0, MX

COPDNote:

3 fields,

87.5 CGE

Limited dose to the non-involved lung

Note:Penetration through lung

Lateral and 2

Posterior involved lung

Oblique

Fields

87.5 CGE DVHDVH Idolatry

Mean Dose Lt Lung 34 Gy, Rt Lung < 1 cGy, ICTV 91 Gy

The discrete spot scanning nozzle –the only moving

bj t i th tobject is the proton.

The maximum fieldThe maximum field size is 30 cm x 30 cm at isocenter, with 94 different

Sub-dose monitor

Main dose monitor

with 94 different proton energies of ranges from 4.0 cm to 30 6 cmto 30.6 cm.

Multi-field IMPTMulti field IMPT

Proton Scanning Beams for IMPT94 energies to modulate the depth

• Monte Carlo simulated data (Uwe Titt Ph D )• Monte Carlo simulated data (Uwe Titt, Ph.D.) are used as input data for the planning system

Validated with limited number of energies– Validated with limited number of energies– Integrated depth doses are in MeV/cm3 and need to

be converted to Gy/MUmm2y

Th l th t th ll th idth f th B P kThe lower the proton energy the smaller the width of the Bragg Peak.

1 0

0.8

1.0 72.5 MeV 148.8 MeV 221.8 MeV

0.6nits

)

0.4

(rel

. u

0.2

D

0 1 2 3 4 5 60.0

x (cm)x (cm)

Spot size in air: FWHM ranges from approximately 12 mm to approximately 36 mmmm to approximately 36 mm.

0 8

1.0 d = 2.0 cm d = 3.0 cm d = 4.0 cm

0 8

1.0 d = 5.0 cm d = 10.0 cm d = 14.9 cm

0 4

0.6

0.8

el. u

nits

)

0 4

0.6

0.8

el. u

nits

)

0.2

0.4

D (r

e

72.5 MeV0.2

0.4

D (r

e

148.8 MeV

0 1 2 3 4 5 60.0

x (cm)0 1 2 3 4 5 6

0.0

x (cm)

0.8

1.0 d = 5.0 cm d = 20.0 cm d = 30.6 cm

Spot size in water at various depths for various energy

0.4

0.6

rel.

units

) beams.

0 0

0.2

0.4

D (r

221.8 MeV

0 1 2 3 4 5 60.0

x (cm)

QA test for spot location.

Scanning BeamOne Non Prostate PatientOne Non-Prostate Patient

10 YO Recurrent Rhabdomyosarcoma JL

• Ranges 12 cm to 19 cm20 l 652 t R d 17 l• 20 layers 652 spots R and 17 layers 642 spots L

• TPS dose 88.8 cGy – 20.1 MUTreatment delivery time: < 1 minute• Treatment delivery time: < 1 minute

Recurrent Rhabdomyosarcoma 10 YO Male Scanning Beam

21 energy changes with ranges from 12.0 cm to 18.9 cm – 655 spots

BLLPB Field 17 CP JLBLLPB Field 17 CP JL• CP Spot Energy (M V) Weight• CP Spot Energy (MeV) Weight• 0 30 178.6 0.057048• 1 37 176.2 0.068263• 2 69 173 7 0 129447• 2 69 173.7 0.129447• 3 82 171.3 0.148287• 4 53 168.8 0.084155• 5 53 166 2 0 0863475 53 166.2 0.086347• 6 61 163.9 0.098074• 7 48 161.6 0.065658• 8 50 159.5 0.0687458 50 59 5 0 068 5• 9 40 157.4 0.050372• 10 37 155.3 0.045654• 11 31 153.2 0.038943• 12 22 151.0 0.024910• …• 17 3 143.2 0.003271

Calibration of Dose Monitorfor Discrete Spot Scanning

• A MU is defined at the center of a 1 liter volume which is receiving a uniform dose, g ,– Max range: 30.6 cm; Max Energy: 221.8 MeV– Min range: 21.0 cm; Min Energy: 178.6 MeVMin range: 21.0 cm; Min Energy: 178.6 MeV– Total 18 energies (18 layers)– Spot spacing: 8mmSpot spacing: 8mm– Total spots: 6760– Total MU: 217 13Total MU: 217.13– Dose at the isocenter: 217.13 cGy at the center of the

volume

PTC H Current StaffingA Large CastA Large Cast

24 Hours/Day 7 Days/WeekR di ti O l i t Wild ti t 8 FTE• Radiation Oncologists – Wild estimate: ~ 8 FTEs

• Anesthesia Staff - > 2• Clinical Physicists 8 FTEs (Ron Narayan Richard• Clinical Physicists ~ 8 FTEs (Ron, Narayan, Richard,

Richard, Jim, Kazumichi, and many others)• Dosimetrists: 9Dosimetrists: 9 • RTTs – 2 to 4 per beam line• Anderson engineers – 3g• Hitachi engineers – 7• Machinists – 5• RNs, Data Managers, etc. – not enough• Administrators – too many

Place of Protons in the PantheonPlace of Protons in the Pantheon

• What treatment sites does the absence of an exit dose benefit the patient?

• Pediatrics – without question for certain sites• Unusual tumors – base of skull and cervicalUnusual tumors base of skull and cervical

spine• Lung ? MDACC is investigating this• Lung ? MDACC is investigating this.• IMPT – The Holy Grail – Miraculous Powers?

• Very costly adventure both in terms of manpower and funds.

140 MeV Protons and 50 MeV Electrons (U of Michigan)

140 MeV proton PDD vs 50 Mev Electron PDD

100.00

120.00

80.00

100.00

Proton 140 MeV 8 cm SOBPProton 140 MeV 10 cm SOBP Electron 50 MeV

40.00

60.00

20.00

40.00

0.000 50 100 150 200 250 300

Protons: Flat peak, sharp drop off. Range controlled to within 1 mm in water. What clinical sites benefit from these characteristics?

Cranial spinalpatient supine

> 50 cranial spinal patients treated in 3 years. Each new field requires new compensators. Spinal fields change each week.