Protons: Challenges and Opportunities The 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 120.00

100.00 Proton 140 MeV 8 cm SOBP Proton 140 MeV 10 cm SOBP Electron 50 MeV 80.00

60.00

40.00

20.00

0.00 0

50

100

150

200

250

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

300

9 8

8

7

7

6

6

5

5

4 3 2 1

4 3 2

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

1

Spine: 2/26-3/14 MRI: 5/9/07 • 20 yr old male • Medulloblastoma • 23.4 Gy to whole brain and spine • 30.6 Gy boost to tumor bed → 54 Gy

Place 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 spine • Lung ? MDACC is investigating this this.

120 MeV, Medium snout Range: 4.4 to 6.4 cm 16 month old Note:

Retinoblastoma

Limited Penetration of beam

45 CGE (40.9 Gy)

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 p – Short Burst of Single g Energy gy Protons

100% 80% 60 % 40% 20% 0%

Basic 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 g Power (MeV cm-2 g-1) ICRU 59 E(MeV)

Water

Air

Bone

Polystyrene

250

3.911

3.462

3.646

3.827

200

4 492 4.492

3 976 3.976

4 186 4.186

4 397 4.397

150

5.445

4.816

5.070

5.331

100

7 289 7.289

6 443 6.443

6 778 6.778

7 140 7.140

75

9.063

8.006

8.420

8.882

50

12 45 12.45

10 99 10.99

11 55 11.55

12 21 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 g particles can be roughly g y characterized by pathlength, which is traced out by most such given type y in a specific medium. particles of a g • Range is the expectation value of pathlength, namely the mean value for a very large population of identical particles. • 250 MeV protons, protons 10 cm x 10 cm field: Range 32.6 cm in water.

Energy loss per unit distance distance, dE/dx Energy loss results in a reduction of speed Proton Energy Velocity MeV M/s 200 2 x 106 2 2 x 103

Basic Proton Physics • At increasing i i energy, nuclear l iinteractions t ti become more important. In the therapeutic energy range, range the probability of nuclear events is small compared with the probability of electron interactions although each nuclear event can interactions, transfer a significant portion of the proton energy to the medium. • Nuclear interactions essentially remove primary protons from the beam and result in the p production 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 g materials is about 1% interaction in solid organic for a 25 MeV proton, 25% for a 200 MeV proton, and dominates the energy loss for E > 500 MeV.

Basic Proton Physics 18

a

16

in-field, Neutrak®

H/D (m mSv/Gy)

14 Large Snout Medium Snout Sm all Snout

12 10 8 6 4 2 0 0

5

10

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20

25

30

35

Proton Range (cm) 4.0

c

3.5

out-of-field, t f fi ld Neutrak® N t k®

3.0

H/D (m mSv/Gy)

• Neutron production has a non-negligible impact due to the production of heavy charged particles generated by g y subsequent q nuclear interactions. • High energy neutron in the field, past range. • Low energy out of the field.

2.5 2.0 1.5 1.0 0.5 0.0 0

5

10

15

20

25

Proton Range (cm)

30

35

Proton Commissioning: A Phased Project both in terms of time Project, 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 room 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 patients 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 commissioned commissioned.

S h Schematic ti showing h i th the llocation ti off magnets t

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

Gantry 190 tons SAD ≥ 2.6 26m Diameter: 5.5 m Rotating speed: 1 RPM max Rotation: ±190º 190 Positioning accuracy: 0.5º Counter balance serves as beam block Isocenter Accuracy: Isocenter must be contained within a sphere h off ≤ 1 mm diameter di 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 cm, G2 Snout position 5 cm, cm Normalized to dmax) 120.0

100.0

PDD

80.0

F2_250 _ MeV, Range g 28.5 cm G2_250 MeV, Range 28.5 cm

60.0

F2_225 MeV, Range=23.6 cm G2_225 MeV, Range=23.6 cm F2_200 MeV, Range=19.0 cm G2 200 MeV G2_200 MeV, Range=19 Range=19.00 cm

40 0 40.0

20 0 20.0

0.0 0

50

100

150

200 Depth (cm)

250

300

350

G2_250MeV_RMW91_range28.5cm_mediumsnout@5cm

120

G2_250MeV_RMW88_range25.0 cm_largeSnout@5cm 120

100 100

60 40 20 0 0

50

SOBP 4 cm, Measured 4.2 cm SOBP 10 cm, Measure 10.2 cm SOBP 16 cm, Measured 16.1cm SOBP 12 cm, Measured 12.0 cm SOBP 8 cm, Measured 8.1 cm SOBP 6 cm, Measured 6.1 cm SOBP 14 cm cm, Measured 14 14.33 cm 100 150 200

80

PD D

PDD

80

60

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

40 20

250

300

0

350

0

Depth (mm)

50

100

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250

300

350

Depth (mm)

In a water phantom with passive modulation, the depth of the distal 90% d dose can b be controlled ll d to within i hi 1 mm ffrom 2 cm to > 30 cm. G2_160MeV_RMW4_range 11.0 cm_large Snout at 5 cm

G2_160MeV_RMW76_range13.0cm_mediumsnout@5cm 120

120

100

100

80

80

40 20 0 0

20

40

60

80

100

Depth (mm)

PD DD

PDD

SOBP 10 cm,, Measured 10.6 cm SOBP 8 cm, Measured 8.2 cm SOBP 6 cm, Measured 6.1 cm SOBP 4 cm cm, Measured 44.00 cm

60

SOBP 4 cm, cm Measured 3 3.8 8 cm SOBP 6 cm, Measured 5.8 cm SOBP 8 cm, Measured 7.8 cm SOBP 10 cm

60

40

20

120

140

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180

0 0

20

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80 Depth (mm)

100

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160

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

•

•

PTC H is a synchrotron facility which 3 large field passively scattered beamlines. passively y scattered Each p beamline 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 0.5 5 seconds with 1.5 seconds between pulses. The dose rate is approximately 100 cGy/minutes. SOBP widths idth range ffrom 1 cm to t 16 cm, in 1 cm increments. Range shifters can control the range in water to within 1 mm.

Passive Scattering Nozzle with Range Modulation Wheel The aperture and compensator production shop – 4 talented mechanists.

Commissioning Equipment • PTW scanner – 4 seconds per point • TG 51 tanks with PTW TN30013 and Markus chambers. • Other water tanks • Solid water • EBT and EDR 2 film • Special Jigs

Farmer Type Local Standards PTW TN30013 • Typical calibration factor: 5.441 x 107 Gy/C • Vented sensitive volume of 0.6 cm3 • Suitable as therapy chamber for use in water • Flat energy response • Protocol – TRS 398

Parallel Plate Chambers • PTW TN34045 (0.02 cc polyethylene-graphite window) Typical factor: 1.349 x 109 Gy/C • PTW Bragg Peak Chamber (8 cm diameter, 10.5 cc, 0.411 g/cm2 front window. Typical factor: 3.225 x 108 Gy/C This chamber h b iis used d ffor th the discrete spot scanning beam 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, g which should limit toxicity Patient with T2, N0, MX 3 fields, Lateral and 2 Posterior Oblique Fields

COPD 87.5 CGE Limited dose to the noninvolved lung

Note: Penetration through lung

87.5 CGE DVH DVH Idolatry

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

The discrete spot scanning nozzle – the only moving object bj t iis th the proton. t

Sub-dose monitor Main dose monitor

The maximum field size is 30 cm x 30 cm at isocenter, with 94 different proton energies of ranges from 4.0 cm to 30.6 30 6 cm cm. Multi-field Multi field IMPT

Proton Scanning Beams for IMPT 94 energies to modulate the depth • Monte Carlo simulated data (Uwe Titt Titt, Ph Ph.D.) D) are used as input data for the planning system – Validated with limited number of energies – Integrated depth doses are in MeV/cm3 and need to 2 be converted to Gy/MUmm y

Th llower th The the proton t energy th the smaller ll the th width idth off th the Bragg B Peak. P k

10 1.0

72.5 MeV 148.8 MeV 221.8 MeV

D (rel. units)

0.8 0.6 0.4 0.2 0.0 0

1

2

3

4

5

6

x (cm) Spot size in air: FWHM ranges from approximately 12 mm to approximately 36 mm mm.

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

1.0

08 0.8

D (re el. units)

08 0.8

D (re el. units)

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

1.0

0.6 04 0.4

0.6 04 0.4 0.2

0.2 72.5 MeV

148.8 MeV

0.0

0.0 0

1

2

3

4

5

6

x (cm)

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

D (rrel. units)

0.6 0.4 0.2 221.8 MeV 00 0.0 2

3

x (cm)

2

3

4

5

Spot size in water at various depths for various energy beams.

0.8

1

1

x (cm)

1.0

0

0

4

5

6

6

QA test for spot location.

Scanning Beam One Non-Prostate Non Prostate Patient 10 YO Recurrent Rhabdomyosarcoma JL • Ranges 12 cm to 19 cm • 20 llayers 652 spots t R and d 17 llayers 642 spots L • TPS dose 88.8 cGy – 20.1 MU • 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 JL • • • • • • • • • • • • • • • •

CP 0 1 2 3 4 5 6 7 8 9 10 11 12 … 17

Spot 30 37 69 82 53 53 61 48 50 40 37 31 22

Energy (MeV) (M V) 178.6 176.2 173 7 173.7 171.3 168.8 166 2 166.2 163.9 161.6 159.5 59 5 157.4 155.3 153.2 151.0

3

143.2

Weight 0.057048 0.068263 0 129447 0.129447 0.148287 0.084155 0 086347 0.086347 0.098074 0.065658 0.068745 0 068 5 0.050372 0.045654 0.038943 0.024910 0.003271

Calibration of Dose Monitor for Discrete Spot Scanning • A MU is defined at the center of a 1 liter volume which is receiving g a uniform dose,, – – – – – – –

Max range: 30.6 cm; Max Energy: 221.8 MeV Min range: 21.0 cm; Min Energy: 178.6 MeV Total 18 energies (18 layers) Spot spacing: 8mm Total spots: 6760 Total MU: 217.13 217 13 Dose at the isocenter: 217.13 cGy at the center of the volume

PTC H Current Staffing A Large Cast 24 Hours/Day 7 Days/Week • R Radiation di ti O Oncologists l i t – Wild estimate: ti t ~ 8 FTE FTEs • Anesthesia Staff - > 2 • Clinical Physicists ~ 8 FTEs (Ron, (Ron Narayan, Narayan Richard Richard, Richard, Jim, Kazumichi, and many others) • Dosimetrists: 9 • RTTs – 2 to 4 per beam line g –3 • Anderson engineers • Hitachi engineers – 7 • Machinists – 5 • RNs, Data Managers, etc. – not enough • Administrators – too many

Place 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 cervical spine • Lung ? MDACC is investigating this 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 120.00

100.00 Proton 140 MeV 8 cm SOBP Proton 140 MeV 10 cm SOBP Electron 50 MeV 80.00

60.00

40.00

20.00

0.00 0

50

100

150

200

250

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

300

Cranial spinal patient supine

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