Status of H 1 and C 12
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1 Status of H 1 and C 12 Herman Suit No Conflict of Interest 1
2 Goal of a New Treatment Modality Tumor Control Probability or No in Complication Rate 2
3 Truism No Advantage to: any Patient for any Radiation Dose to any Normal Tissue 3
4 H 1 and C 12 Radiation Therapy Widely Accepted Expanding Number of Facilities 4
5 Number of Particle Treated Patients Through 2012 H 1 93,886 C 12 10,756 H 1 and C PTCOG Data M Jarmann through
6 Number of Particle Therapy Centers Active Planned Proton Carbon 6 5 PTCOG Data M Jarmann
7 Gantries in Planned Centers Number ? H C 12 None PTCOG Data M Jarmann
8 Rationale
9 Sole Rationale: H 1 Therapy Dose Distribution: Superior to Highest XRT Technology for Most Anatomic Sites No Dose Deep to Target for Each Beam 9
10 Sole Rationale: H 1 Therapy RBE is Accepted to be 1.10 and is Used as a Generic Value Paganetti etal 10
11 Superior Dose Distribution Dose to Target No or Dose to non Target TCP and or No in NTCP 11
12 12 A Trofimov 2010
13 RBE Corrected Depth Dose Curves 13
14 Spread Out Bragg Peak Design the Distributions of Proton Beam Energies [Range in the Patient] that Yield a Uniform Distribution of Biologically Effective Dose Throughout the Defined Target 14
15 1 H Bragg Peak vs Energy [Depth] H Kooy etal 2009 Fig.5 15
16 Rationale: C 12 Therapy Principle Rationale: Dose Distribution is Superior to H 1 High LET 16
17 Rationale: C 12 Therapy Dose Distribution is Superior to H 1 More Narrow Penumbra Ease of Correction for Heterodensities 17
18 Target Abuts OAR Trofimov, 2011
19 19
20 Isocentric Gantry at the NPTC 20
21 Dose [BED] Determines Response Probability Independent of Beam, ie Gamma, Electron, Protons, Carbon Ion... 21
22 1 H vs 12 C ion Therapy Central Question Re High LET: Does 12 C ion RT Yield a TCP For Defined NTCP Relative to 1 H RT? 22
23 vs H 1 vs C 12 ion Therapy Comparison Requires Uniform: Dose in BED/Fraction GTV, CTV, PTV Positioning - Monitoring Scoring of End Point 23
24 C 12 : LET and RBE Disadvantage: RBE Quite Variable with dose/fraction 24
25
26 Questions and Time 26
27 12 C ion RBE vs LET Ando and Team Determined RBE vs LET for 13 Brain Tumor and 4 Normal Fibroblast Cell Lines No Evidence for RBE of Tumor Cell Lines 27
28 Rationale: C 12 Therapy Clinical Beams High LET an Advantage in Clinical Beams? High and Variable LET and RBE: RBE
29 12 C ion Therapy If High LET is an Advantage, Tumor RBE> Normal Tissue RBE 29
30 IGR 30
31 High LET: Fast Neutrons Principal Rationale: High RBE 3 Low OER, viz ~1.7 vs ~3 for X rays 31
32 Edinburgh H/N Phase III Trial of Fast Neutrons Single Variable: LET Same Number of Dose fractions MacDougal etal 1990 MacDougall etal
33 Edinburgh H/N Phase III Trial 165 Patients 20 Fx 4 wks 15 MeV FN vs 4 MV x-ray 125 cm vs 100 cm TSD MacDougal etal 1990 MacDougall etal
34 Edinburgh H/N Phase III Trial RBE Set at Gy vs 55 Gy 2.75 GyE/Fraction 55 GyE vs 55 Gy in 4 wks MacDougal etal 1990 MacDougall etal
35 Edinburgh H/N Phase III Trial All Patients Completed Planned RT No Patient Lost to Follow-up MacDougal etal
36 Edinburgh H/N Phase III Trial 5 yr Local Control: FN vs X 44% VS 45% 5 yr Survival: 19% vs 30% Fatal Complications 7 vs 0 MacDougall etal
37 Edinburgh H/N Phase III Trial Late NTCP RBE Higher than Planned RBE Lower for TCP than for Late NTCP MacDougall etal
38 12 C to Normal Tissues No Known Advantage of High LET Irradiation of Normal Tissues 38
39 12 C to Normal Tissues Not Indicated Post- Operatively Except for Residual Tumor Pediatric Patients 39
40 RBE and 12 C Tumor Gains Were High RBE an Advantage The Largest Gain would be at Small D/F Actual Practice is Large D/F 40
41 Protons Therapy Proposed Robert Wilson Proposed in Radiology 1946 a Full Description of Dose Distributions Achievable by Proton Beams 41
42 Proton Therapy Initiated Cornelius Tobias and John Lawrence UC Berkeley 1954 RBE Determinations Single Dose to Intracranial Lesions 42
43 Proton Therapy Initiated Soon Joined by Upsalla MGH [Neurosurgeons Boston], Moscow 43
44 Low Dose/Fraction Proton RT May 1972 began Modification of Harvard Cyclotron [HCL] for RT of Cancer Patients by Low Dose/Fraction RT Commenced Dec
45 Low Dose/Fraction Proton RT Partners MGH/HCL with MEEI Absolutely Critical Support by NCI 45
46 MGH Strategy Single Variable: Dose Distribution 46
47 MGH Strategy 3] Standard Fractionation 4] Target Positioning Error 5] Confirm Target Position by Diagnostic Quality Imaging [x 1, 2 or more] before Each Field, ie PTV 47
48 MGH Strategy 6] Treat Curable Patients 7] Long Term Follow-Up Data 8] Escalate Dose with Caution 9] Physician-Physicist Team 48
49 1 st Patient: Low Dose/Fx 12/73 4 y/o with Posterior Pelvic Sarcoma Radiation Fraction/wk 4 H 1 Fractions/wk and 1 Fraction/wk + Chemotherapy 49
50 1 st Patient: Local Control No Bowel, Nerve or Skin Morbidity Developed DM No Clinical Evidence of Pelvic Tumor 50
51 1 st Patient: Low Dose/Fraction 51
52 Position Confirmation Films Review 52
53 Positioning Film Review From Left to Right Michael Goitein Physicist A Creative Genius Herman Suit Physician Joel Tepper Resident A Star Career 53
54 Uveal Melanoma 4505 Patients MGH/MEEI PSI Local Control 95% at 10 yrs Retained Eye 84% DM 5-65% Size Dependent 54
55 Ocular Melanoma RT Method # Pts LC > 5 yrs H % I % Chang
56 Uveal Melanoma PRT Plan 56
57 1 st Uveal Melanoma Proton Pt 57
58 Now Three Impressive L C Results by C 12 Ion RT Mucosal Melanoma Primary Renal Cell Carcinoma Chordoma of Base of Skull 58
59 C 12 Therapy: Mucosal Melanoma Chiba: 72 Pts GyE 5 Yr LC 84% Yanagi GyE 3 Yr 81% Jingu
60 12 C RT: 1 0 Renal Cell Ca 10 Pts 4.3 cm Diameter 6 Inoperable 4 Refused Surgery 72 Gy(RBE) 16 Fx 4 wks CTV mm > GTV + 5 mm Caudal Nomiya etal
61 12 C Ion RT: 1 0 Renal Cell Ca Fiducial Markers Respiration Gated 5 yr Local Control 100% Nomiya etal
62 Proton Therapy Results Skull Base Chordoma [42 ] 81% 5 Yrs PSI Chondrosarcoma [200] 95% 15 yrs MGH 62
63 Chordoma of Skull Base 100% Local Control at 5 years 90% 80% 70% 60% 50% 40% C BED ( =2). 1. H X. 63
64 Sacral Chordoma Center Pts LC H 1 MGH 8 86% 3 yrs C 12 NIRS 95 88% 5 yrs
65 Head/Neck SCC Beam Pts Dose-D/F Referenc e 1 H % 5 Loma Linda 12 C % 5 NIRS 65
66 Head/Neck Adenocystic Beam Pts Dose-D/F Ref 1 H % 3 MGH 12 C % 5 NIRS 66
67 Hepatocellular Carcinoma # Dose D/F TCP Late Ref Pts GyE GyE G III NTCP 1 H % 5 with GII Tsukuba 12 C % 25% NIRS % 13% NIRS 67
68 Non Small Cell Lung Carcinoma 100% Local Control at 2 years 90% 80% 70% 60% 50% 40% C 1. H BED ( =10) 68
69 Prostate Carcinoma 100% 90% bned at 5 years 80% 70% 60% 50% 40% C. BED ( =2) 1 H + X 69
70 Prostate : H 1 vs C12 Low Risk Patients bned H % 10 yr C % 5 yr Zietman 2009 Ishikawa
71 Prostate: H 1 vs C12 Intermed Risk Pts bned H 1 10 yr 69 70% C 12 5 yr 278[ADT] 97%» Zietman 2009 Ishikawa
72 Prostate T3-4: +H 1 93 Patients 76 GyE 5 yr LC 92% Shipley etal
73 Technology Goals for 2033 Error to Near Zero Deliver Dose to Defined Target
74 Highest Feasible Technology Real Time Imaging Minimum Target Motion Beam On Time for each Field 0.5 sec Fiducial Markers Anesthesia
75 Thank You 75
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