1. Dept of Radiation Oncology MGH
HST.187: Physics of Radiation Oncology #5. Intensity-modulated radiation therapy: IMRT and IMPT Part 2: IMPT
Joao Seco, PhD
Alexei Trofimov, PhD
Dept of Radiation Oncology MGH
March 6, 2007

2. Flexible field definition, sharper dose gradients
IMRT is a treatment technique with multiple fields, where each field is designed to deliver a non-uniform dose distribution.The desired (uniform) dose distribution in the target volume is obtained after delivery of all treatment fields.
Flexible field definition, sharper dose gradients
Higher dose conformity
Improved sparing of healthy tissue
IMRT Coll. Work Group
IJROBP 51:880 (2001)

3. Protons vs. Photons
Ideal

4. Intensity Modulated Proton Therapy
IMPT = IMRT with protons

5. Intensity Modulated Proton Therapy
Planning approaches
Delivery options (inc. MGH plan)
Overview of IMPT treatments / development
Special considerations for IMPT
IMPT vs. 3D-conformal proton vs. photon IMRT in the clinic

6. Proton depth-dose distribution: Bragg peak Depth = additional degree of freedom with protons
H.Kooy
BPTC

7. A. Lomax: “Intensity modulation methods for proton RT”
Phys. Med. Biol. 44: (1999)
Field incidence
Distal Edge
Tracking
Field incidence
2D modulation
Field incidence
2.5 D modulation
Field incidence
3D modulation

8. IMPT – Example 1 (distal edge tracking)

9. IMPT – Example 2 (3D modulation)

10. Treatment planning for IMPT: KonRad TPS (DKFZ)
- Bragg peaks of pencil beams are distributed throughout the planning volume
- Pencil beam weights are optimized for several beam directions simultaneously, using inverse planning techniques
- Output of optimization: beam weight maps for diff energies

11. Intensity Modulated Proton Therapy
Planning approaches
Delivery options (MGH plan, other sites)
Overview of IMPT treatments / development
Special considerations for IMPT
IMPT vs. 3D-conformal proton vs. photon IMRT in the clinic

12. IMRT delivery with multi-leaf collimators

13. Proton IMPT with Scanning
Protons have charge 
can be focused, deflected (scanned) magnetically!
A proton pencil beam
E.Pedroni (PSI)

14. Proton IMPT with Scanning
A “layer” is irradiated by scanning a pencil beams across the volume
E.Pedroni (PSI)

15. Proton IMPT with Scanning
Several layers are irradiated with beams of different energies
E.Pedroni (PSI)

16. Proton IMPT with Scanning
Complete treatment:
a homogenous dose
conformed distally and
proximally
E.Pedroni (PSI)

17. : pencil beam scanning nozzle for MGH
Vacuum
Chamber Y
Intensity
Fast
Slow
Modulated
Beam Z
Pair of X
Beam
Quads
monitor
Scanning
Magnets
Continuous scanning. Modulation in current and speed.
Pencil beam spot width (s) at the isocenter: ~4-10 mm
Several identical paintings (frames) of the same target slice (layer)
Max patient field (40x30) cm2

18. Beam delivery: continuous magnetic scanning in 2D
Beam fluence variation along the scan path is achieved by simultaneously varying the beam current and scanning speed:
Actual scan is ~50 times faster (0.4 sec)

19. Scan functions: degeneracy of the solution

20. Intensity Modulated Proton Therapy
Planning approaches
Delivery options (MGH plan, other sites)
Special considerations for IMPT
Overview of IMPT treatments / development
IMPT vs. 3D-conformal proton vs. photon IMRT in the clinic

21. plan
delivery
The effect of delivery uncertainties in IMPT: fluctuations in the beam position during the scan
planned dose distr
dose difference due to fluct’s

22. Beam size in IMPT
S Safai

23. Proton dose in the presence of range uncertainty

24. Proton dose in the presence of range uncertainty (a dense target)
Lower protondose

25. IMPT – DET (Distal Edge Tracking)
Tumor
T. Bortfeld

26. Distal Edge Tracking: Problem with range uncertainty
Tumor
Brainstem
T. Bortfeld

27. In-vivo dosimetry / range verification with PET
K. Parodi (MGH)
MGH Radiology

28. IMPT in the presence of range uncertainties: DET vs. 2.5D
DET (+1 mm)
DET (+3 mm)
DET (+5 mm)
2.5D
2.5D (+1 mm)
2.5D (+3 mm)
2.5D (+5 mm)

29. Robust IMPT optimization
J Unkelbach (MGH)
“Standard” optimization
Phantom test case
Robust optimization

30. Degeneracy of IMRT solution: different modulation patterns may produce clinically “equivalent” dose distributions

31. Proton Treatment Field
Brass Collimator
Proton Treatment Field
M Bussiere, J Adams

32. Scanning with a range compensator

33. Scanning and IMPT
Is scanning = intensity-modulation ?

34. IMPT delivery: Spot scanning at PSI (Switzerland)
A Lomax Med Phys (2004)

35. PSI gantry radmed.web.psi.ch/asm/gantry/intro/n_intro.html
Gantry radius 2m
Rotation (a): 185 deg
“Step-and-shoot” scanning:
200 MeV proton beam is stopped at regular intervals, no irradiation between “beam spots”
magnets
range shifter
beam
monitor
sweeper
quad
200 MeV

36. PSI ProSCAN

37. Scanning and IMPT Is scanning = intensity-modulation ?
Is beam scanning = IMPT?

38. Dose conformation with IMPT
1 field
3 fields
3D IMPT
3D-CPT
1 field
3 fields
1 field
SFUD – single field uniform dose
?? 2.5-D IMPT ??
A Lomax (PSI)

39. Scanning and IMPT Is beam scanning = IMPT ?
Is scanning = intensity-modulation ?
Is intensity-modulation = IMPT ?

40. Spread-Out Bragg Peak (SOBP)
Wheel rotates
@ 10 / sec RM

41. Spread-Out Bragg Peak (SOBP)
Wheel rotates
@ 10 / sec RM

42. Spread-Out Bragg Peak (SOBP)
Wheel rotates
@ 10 / sec RM

43. Beam-current modulation: flat-top SOBP

44. Beam-current modulation: sharper fall-off

45. IMPT fields for a prostate treatment
Double scattering
“IMPT”

46. Intensity Modulated Proton Therapy
Planning approaches
Delivery options (MGH plan, other sites)
Special considerations for IMPT
Overview of IMPT treatments / development
IMPT vs. 3D-conformal proton vs. photon IMRT in the clinic

47. Delivery of IMPT: Spot scanning at PSI (Switzerland)
Since 1996:
Combination of magnetic, mechanical scan
Energy selection at the synchrotron + range shifter plates
A Lomax Med Phys (2003)

48. GSI Darmstadt: scanned carbon beam
© Physics World
D Shardt (GSI)

49. GSI patient case: Head+Neck Carbon Proton (IMPT)
Plan: O. Jaeckel (GSI) Plan: A.Trofimov (MGH)

52. Depth scanning at GSI (270 MeV C-ions) U. Weber et al. Phys. Med. Biol
Weaknesses of lateral scanning:
complicated scanning pattern
need to interrupt the beam
Depth scanning:
Target volume is divided into cylinders spaced at ~0.7 FWHM (or 4-5 mm)
Cylinders are filled with SOBP (or arbitrarily shaped distribution)
Synchrotron , 270 MeV C-12

53. Scanning directions Fast scanning in depth (2 sec/cylinder)
Slower lateral scanning (sweeper magnet)
Yet slower azimuthal scanning (gantry rotation)

54. GSI: IMPT with depth scanning
Same dose conformity as with lateral scanning
A simpler, uninterrupted scanning pattern
Treatment time a factor of 4 longer than with 2D raster scanning
GSI: IMPT with depth scanning

55. Proton Therapy Center – MD Anderson CC, Houston
PTC-H
3 Rotating Gantries
1 Fixed Port
1 Eye Port
1 Experimental Port
Pencil Beam Scanning Port
Passive Scattering Ports
Experimental Port
Accelerator System
Hitachi, Ltd.
M. Bues (MDACC)
Large Field Fixed
Eye Port

56. Basic Design Parameters for PBS at PTC-Houston
Step and shoot delivery
Minimum range: 4 cm
Maximum range: 30 cm
Field size: 30 x 30 cm
Source-axis-distance: 250 cm
Spots size in air, at isocenter:
4.5 mm for range of 30 cm
5 mm R=20 cm
6.5 mm R=10 cm
11 mm R=4 cm
Varian Eclipse TPS
Beam
3.2m
Scanning
Magnets
Beam Profile
Monitor
Helium
Chamber
Position Monitor
Dose Monitor 1, 2
Isocenter
Hitachi, Ltd.
M. Bues (MDACC)

57. Intensity Modulated Proton Therapy
Planning approaches
Delivery options (MGH plan, other sites)
Overview of IMPT treatments / development
Special considerations for IMPT
IMPT vs. 3D-conformal proton vs. photon IMRT in the clinic

58. Clinical relevance of intensity-modulated therapy (protons vs photons)
high
Complex anatomies/geometries (e.g., head & neck) with multiple critical structures
Cases where Tx can be simplified, made faster
Cases where integral dose is limiting (e.g., pediatric tumors)
Cases where it may be possible to reduce side-effects (improve patient’s quality of life)
IMPT
Conformality
3D PT
IMXT
3D CRT
low
Integral dose
high
J Loeffler, T Bortfeld

59. Comparative treatment planning
Purpose: to identify sites, tumor geometries that would benefit the most from a certain treatment modality or technique
3D-CPT IMPT IMXT
J Adams
A Chan (MGH)
Dose [Gy/GyE]

60. Nasopharyngeal carcinoma Clinical plan: composite proton+X-ray
BPTC: 12 proton fields
CTV to 59.4 GyE (33 x 1.8 Gy)
GTV to 70.2 GyE (+ 6 x 1.8 Gy)
MGH Linac: 4 fields (lower neck, nodes)
to 60 Gy
J Adams
A Chan (MGH) G N
Case 1

61. IMXT plan For delivery on linac with 5-mm MLC 6 MV photons
7 coplanar beams
Case 2

62. IMPT plan Bragg peak placement in 3D Proton beam energies: 80-170 MeV
4 coplanar fields
Case 3

63. Dose-volume histograms (DVH)

64. Nasopharyngeal carcinoma: dose to tumor
Case 2
3D-CPT IMPT IMXT
Comparable target coverage

65. (Some) common complications in Head+Neck Tx
Compromised vision
Optic nerves, chiasm (“tolerance”: 54 Gy), eye lens (<10 Gy)
Compromised hearing
Cochlea (<60 Gy)
Dysphagia / aspiration during swallowing
Salivary glands: e.g. parotid (mean <26 Gy)
Larynx, constrictors, supraglottic, base of tongue
Suprahyoid muscles: genio-, mylohyoid, digastric
Xerostomia (dry mouth)
Salivary glands
Difficulty chewing, trismus
Mastication muscles: temporalis, masseters, digastric
Compromised speech ability
Vocal cords, arytenoids, salivary glands

66. Dose-response models: e.g. parotid gland
Eisbruch et al
(IJROBP 1999)
Dose-response models: e.g. parotid gland
Saarilahti et al
(Radiother Onc 2005)
Roesink et al
(IJROBP 2001)

67. Complications may arise from irradiation to doses well below the organ “tolerance”
Roesink et al. (IJROBP 2001)
Chao et al
(IJROBP 2001)

68. Treatment planning for nasopharyngeal carcinoma
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 submandibular glands
mastication and suprahyoid muscles

69. Nasopharyngeal carcinoma: sparing of normal structures
Superior sparing with protons
Brainstem
Suprahyoid muscles
Sublingual, minor salivary glands

70. Nasopharyngeal carcinoma: sparing of normal structures (2)
IMXT/IMPT better than 3D-CPT
Salivary glands
Supraglottic structures

71. Nasopharyngeal carcinoma: sparing of normal structures (3)
IMPT may further improve sparing
Mastication muscles
Oral cavity, palate, base of tongue
Cochleae
Optic structures, temporal lobes

72. Nasopharyngeal carcinoma: sparing of normal structures (4)
IMPT may further improve sparing
Mastication muscles
Oral cavity, palate, base of tongue
Cochleae
Optic structures, temporal lobes

73. Retroperitoneal sarcoma C. Chung, T.Delaney
Radiation dose:
50.4 Gy (E) in 1.8 Gy/fx
to 100% of CTV and
›95% of PTV
Pre-op Boost of 9 Gy (total 59.4 Gy (E))
Post-op Boost of 16.2 Gy (total 66.6 Gy (E))
Organ at Risk (OAR) constraints
Liver: 50% < 30 GyE
Small Bowel: 90% < 45 GyE
Stomach, Colon, Duodenum: max 50 GyE
Kidney: 50% < 20 GyE
3D CPT : added 2% to range and 5mm smear compensation. No PTV in plan
IMPT: 5 mm margin to CTV
IMRT: 5 mm margin to CTV

74. 36 yo M with myxoid liposarcoma:Transverse
IMXT
(photon
IMRT)
3D CPT
IMPT

75. 36 yo M with myxoid liposarcoma: Sagittal
IMXT
3D CPT
IMPT

76. Boost
IMXT
IMPT

77. PTV Conformity Index (CI)= V95% / PTV Range (N=10) Mean IMXT
1.19 – 1.50
1.35
3D CPT
1.37 – 2.34
1.78 (p=0.032)
IMPT
1.05 – 1.30
1.15 (p=0.005)
Lower is better

78. Dmean to OAR Dmean to liver (n=8) Preop boost (n=3) IMXT
0.94 – 24.6 Gy, mean 11.8 Gy
12.0 – 24.6 Gy,
mean 16.7 Gy
3D CPT
0.01 – 20.9 Gy, mean 6.61 Gy (p=0.01)
_____
IMPT
0.99 – 18.6 Gy, mean 5.73 Gy
(p=0.03)
2.8 – 18.6 Gy,
mean 9.2 Gy

79. Dmean to OAR (2) Dmean to stomach (n=8) Preop boost (n=3) IMXT
4.03 – 44.2 Gy, mean 15.4 Gy
13.3 – 43.6 Gy,
mean 28.4 Gy
3D CPT
0 – 50.0 Gy,
mean 11.8 Gy (p=NS)
_____
IMPT
0 – 36.5 Gy,
mean 7.85 Gy
(p=0.02)
3.5 – 35.2 Gy,
mean 16.8 Gy

80. Prostate carcinoma:
(GTV + 5mm) to 79.2 Gy
(CTV + 5mm) to 50.4 Gy
IMRT
3D CPT
IMPT

81. Prostate: IMRT vs 3D-CPT vs IMPT

82. Burr Proton Therapy Center (2001-) Patient Population
Brain 32%
Spine 23%
Prostate 12%
Skull Base 12%
Head & Neck 7%
Trunk/Extremity
Sarcomas 6%
Gastrointestinal 6%
Lung %
T. DeLaney, MD

83. IMPT vs. photon IMRT
More tumor-conformal dose: reduction in dose to healthy organs (including skin)  (?) increased tumor control, reduced complications (acute and late).
Proton integral dose smaller (factor 1.5-3)
Proton dose conformality much better at low and medium doses, but usually equivalent to IMRT in high-dose range
Treatment delivered with fewer fields (2-3 vs. 5-7);
Patient-specific devices/QA are not strictly required  more treatments at lower cost
Precision of delivery can be increased with robust planning methods, in-vivo range/dose verification

84. Acknowledgements JA Adams M Bussiere S McDonald, MD H Paganetti, PhD
K Parodi, PhD
S Safai, PhD
H Shih, MD
J Unkelbach, PhD
Ion Beam Applications
T Bortfeld, PhD
GTY Chen, PhD
T DeLaney, MD
J Flanz, PhD
H Kooy, PhD
J Loeffler, MD
M Bues, PhD