Summary Talk of the Workshop

Transcription

1 Medical experience

2 History of IBT Pituitary 1st He pt Treatment 1st C, Ne pt Eye treatment Phase-1 He Phase I-II Ne Phase I-II Ne & He 1st Comp Tx Plan 3D planning LBNL CT LBNL MRI Image Correlation 1957 Uppsala 1961 MGH/HCL 1967 Dubna

3 LBL: evolution of treatment planning

4 the first clinical proton therapy center: LLUMC

5 IBT facilities in the USA Courtesy of Mark Buntaine (Still-Rivers Rivers-Systems)

6 is prostate cancer a good indication? 1. The dose distribution difference between IMRT & protons is very small, so there is no reason to believe there should be a difference. 2. Neutron contamination issues? 3. Not cost effective? 4. Early stage pts require long fu & many pts & PSA inadequate! High risk pts Tx systemic Dz? 5. The NCI will not fund a study that does not use Overall Survival as an endpoint (e.g. RTOG 0815) 6. There are very few Centers & it is not in their $$$ best interest to turn away pts. MRIII

7 is prostate cancer a good indication? Conclusions: In the range higher than 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, whereas rectal sparing was similar IJROBP 69, 444, 2007

8 prostate cancer: H-scattering vs. X-IMRT 7F-IMRT 2F-proton Ratio V70(Bla) V30(Rec) V

9 example: prostate cancer LLUMC tumor stages ca patients T1c-T2c 23% each T1a/b & T3 3% each 2-F proton 10Y survival (bned) 73% (brachytherapy: 70%) complications grade 2 9% grade 3 <1% grade 4 none 6-F photon equivalent survival rates no surgery, no hormone therapy necessary

10 prostate cancer: pro and con protons 1. Proton Beam Radiotherapy touted as best choice but not supported by the evidence! 2. Same doses will yield same results! 3. Risk of second cancers higher with passive scanning? 4. Cost of facilities is prohibitive and not Green!: a. Single prototype vaults ~ 20 M b. Multi-vault units: 70 to 140 M 5. Brachy yields equal or better results & is: a. Less expensive b. More available c. Has broader applications d. Potential for further improvements? MRIII 10

11 neutrons: scanning vs scattering 10 x 10 cm 2 field Doses are highly facility dependent Full benefit of protons (6-MV) achieved with scanning technique but none use it! MRIII These data are considered incorrect! Hall, IJROBP 65:1-7;2006) 11

12 pro and con of heavy ions relative dose 1,2 1 0,8 0,6 narrower Bragg peak 60-Co 14.5 MeV Neu 20 MeV e 160 MeV H 270 MeV/u C 70 MeV Pi carbon proton increased biol. effectiveness nuclear fragmentation 0,4 0, less lateral scattering more expensive lateral scattering (mm) proton helium carbon depth in water (cm)

13 prostate treatment with carbon ions Comparison of CRT vs. XRT (with or without hormones) for prostate cancer shows 10-15% higher OS for CRT Tsujii et al., 2008

14 contributions of PSI to proton therapy The Spot Scanning Gantry at PSI Spot scanning and a compact gantry for proton therapy of deep seated tumors PSIs (and Eros Pedronis) pioneering contribution to cancer treatment GG-Erce 09

15 PSI: the eye tumor program OPTIS The eye is the perfect model for proton therapy: NO bones, NO strong inhomogeneities, a mobile and controllable organ, a well circumscribed functional compartment GG03/09 but nevertheless not an easy case! GG-Erce 09

16 2993 Patients analyzed (2006), who received proton radiation therapy between III/1984 and VIII/2005 Follow up 15 months 21 years; median 5ys 3ms Confirmed diagnosis of melanoma (HOJG Lausanne) Unilateral disease No reduced (<2mm) safety margin Negative familial history Visible fundus No adjuvant chemotherapy Proton dose of 4x15= 60 Gy RBE (former CGE, Cobalt Gray Equivalent) GG 03/09 GG-Erce 09

17 Conclusion - OPTIS Summary Talk of the Workshop Center for Proton Therapy OPTIS Proton radiotherapy for ocular melanoma results in very satisfying local control (overall 97%@5ys, 96%@10ys, 94%@15ys) and tumor specific survival (overall 91%@5ys, 83%@10ys, 79%@15 ys) Differentiated outcome analysis shows that age tumor size (diameter and thickness) localization and relation to other structures (optic disc, ciliary body, iris) have the strongest influence on local failure, enucleation rate and survival GG 03/09 GG-Erce 09

18 tumor Summary Talk of the Workshop example: uveal melanoma MGH, PSI, LLUMC: ca patients 15Y local control 95% eye retained 80% 20/200 vision saved: 40% 5Y survival > 70% local control similar to enucleation number of metastases not increased more flexible than plaque therapy HMI, Berlin

19 PSI: pediatric tumors XRT PT Choroid-Plexus Carcinoma 2 year old girl Slide courtesy of B. Timmermann GG-Erce 09

20 dose distribution: an example protons dose (%) 100 photons Relapsing desmoid tumor in a 12 y/o boy field spot scanning 9-field IMRT Lomax, 2003

21 dose distribution: an example protons photons dose (%) x higher integral dose for photons field spot scanning 9-field IMRT Lomax, 2003

22 example: comparative dose distribution for child with medulloblastoma conventional X-rays intensity-modulated X-rays spot-scanned scanned protons target volume (spinal cord) Miralbell et al, 2002

23 Summary Talk of the Workshop Pediatric Proton Therapy Conclusion Patients are treated within or in adaptation to existing protocols overall 86% Outcomes are very satisfying with good local control rates Acute toxicities where extension and protocol-defined safety margins require irradiation of normal tissues up to dose levels with known risk of acute (and late) toxicities. Protons can reduce CTX-related toxicities through sparing of normal tissues (e.g. oral mucosa). Local recurrences occured in-field; no geographic misses, but local relapses due to aggressiveness of the disease (? higher local doses beneficial?) Late toxicities Grade 3 & 4 were related to the tumor geometry site, size, shape and necessary dose levels; 1 grade 5 fatalty occured in a high risk patient who was treated for recurrent disease. 1/51 GG-Erce 09

24 25 Years of Proton Radiation Therapy at PSI - Conclusion Philosophy and performance in all medical and related projects at SIN/PSI were positive Indications for proton therapy at a physics research institute were wisely chosen according to medical needs and technical/logistic possibilities A new technology was introduced into the spectrum of Radiation Oncology with caution and great care, ongoing improvement and learning All developments were focussed on patient safety & comfort and were optimized according to medical needs Clinical outcomes for various tumors and sites were good to excellent Outcome analyses and comparison with other centers showed appropriate and in part outstanding treatment results Adverse effects or events were understood and actions were taken Technology and medical results have made PSI a reference place for PT GG-Erce 09

25 PSI: outlook From bony tumors, tumors attached to bones or in immobile anatomic positions to Soft Tissue tumors in a soft tissue environment to Mobile soft tissue tumors moving with respiration Step I. upper GI (Liver / Bile / Pancreas) Step II. Lung Ca, Mesothelioma, Mediastinal tumors Slide courtesy of E. Hug GG-Erce 09

26 CNAO: treatment indications Who shall we treat at CNAO? RO, CNAO

27 CNAO: identifying new indications RO, CNAO

28 Category A Summary Talk of the Workshop All the tumors in which the use of hadrontherapy IBT is clearly demonstrated to be advantageous, being the only way to give a curative dose to the target volume minimizing the incidence of severe side effects Category B ranking of indications A great variety of tumors characterized mainly by a local evolution, with a limited probability of distant spread, and therefore potentially cured if the locoregional control can be obtained RO, CNAO

29 Category A. Protons New patients per year Patients treatable with protons Uveal Melanoma % Chordomas of the skull base and of the spinal column % Chondrosarcomas of the cephalic extremity and of the trunk % Meningiomas of the skull base % Paraspinal tumours % Schwannomas of the cranial nerves % Pituitary adenomas % Paediatric solid tumours % TOTAL

30 Category A. Carbon ions New patients per year Patients treatable with Carbons Salivary gland tumours % Maxillary sinus adenocarcinomas % Mucosal melanoma of the head and neck area and other districts % Bone sarcomas % Soft tissue sarcomas % Liver/Biliary tract/pancreatic tumours % Recurrent tumours % TOTAL

31 possible indications tumor type applicability (%) pat./year in Germany chordoma and chondrosarcoma eye melanoma basal meningioma pediatric tumors soft tissue sarcomas nasopharyngeal tumors gliomas grade I & II glioblastoma hepatocellular carcinoma prostate carcinoma NSC lung carcinoma solitary metastases local recurrencies Sum 21000

32 estimate of patient numbers First Author (Country) Year Bengt (Sweden) 2005 Orrecchia (Italy) 1998 Baron (France) 2004 Type of study Rad Onc, Physicist, tumor registry stats for Sweden, literature, #pts getting RT Estimation based # RT pts Estimation based # RT pts Conclusions per yr or ~ 14-15% of all RT pts 16% 14.5% Mayer (Austria) 2004 Estimation based # RT pts 13.5% approx. 15% of RT patients are presently considered candidates for IBT

33 criteria for usage tumors neighboring critical structures pediatric tumors deep-lying irregularly shaped extensive tumors profit from precision steep dose gradient favorable dose distribution well demarcated non-invasive tumors improved local tumor control lower risk for healthy tissue simplified treatment plan

34 Eye & Orbit uveal melanoma retinoblastoma choroidal hemangioma Summary Talk of the Workshop FDA-approved indications CNS chordoma/chondrosarcoma gliomas, meningeoma pediatric brain tumors, metastases Head & Neck oropharynx CA nasopharynx CA recurrent tumors Chest NSC lung cancer Abdomen paraspinal tumors soft tissue sarcomas Pelvis prostate CA cervix CA Wilms tumor

35 example: cervical cancer Cervical cancer is the second most common cancer among women worldwide Estimated new cases and deaths in the year 2000 Survival rates vary between regions 69% in the North American Surveillance Epidemiology and End Results registry (SEER) 49% in developing countries RM, MedAustron

36 cervical cancer: treatment results Radiotherapy of locally extended disease: Conventional RT Proton Therapy Mean 5-year survival Mean 10-year survival 65-70% (Stage IIB) 89% (Stage IIB) 34-52% (Stage III B) 40% (Stage IIIB/IV) 0-19% (Stage IV) Gerbaulet A et al. GEC ESTRO handbook of brachytherapy Arimoto T, et al. Cancer 1991; 68:79. 2 Kagei K, et al. Int J Radiat Oncol Biol Phys 2003; 55:1265.

37 major schools of thought 1. Unethical to do Trial - Protons are obviously better so no trial needed 2. Ethical to do Trial - Protons not obviously better so a trial is needed 3. Not ready to do Trial quite yet -Protons are better but need to Tweak before trial started 4. Waste of time & money to do Trial - obviously not better, conceptual framework does not justify trial. a. They (don t) have them and (don t) believe it b. They are financially motivated c. They are a. & b.

38 5th school of thought 5. Ethical to do Trial - Protons are in principle better but treatment methodology might not always be optimum. So a trial is needed a. They don t have them but believe in them b. They are financially motivated c. They are a. & b.

39 necessary initiatives Correct methodology Clear guidelines Controlled clinical trials Reproducibility of results Small series Technical heterogeneity Clinical heterogeneity

40 IBT publications YEARS STUDIES CLINICAL PHYSIC BIOLOGICAL TOTAL IJ ROBP, Lancet, Radiother Oncol, JCO, Semin Oncol, Rad Prot Dosimetry, Phys Med Biol, Head and Neck, Int J Clin Oncol, J Radiat Res, J Thorac Oncol, Lung Cancer RO, CNAO

41 hadron therapy vs. ion beam therapy Hadrons: subatomic particles built from quarks baryons Ions:charged atoms or molecules with a lack or excess of electrons Nucleus: ion with maximum positive charge mesons therapy with protons or other ions = IBT