Proton therapy, yesterday, today and tomorrow

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1 Proton therapy, yesterday, today and tomorrow Opening of the BNEN 14th Academic Year Mol, September Yves Jongen (Founder, CRO) IBA Group Protect, Enhance and Save Lives - 1-1

2 Cancer, we are all concerned 1/3 of population will get cancer 33M cancers in M cancers in /2 of people survive cancer 21/10/2015 Protect, Enhance, and Save Lives - 2

3 Proton therapy Precise dose delivery, fewer side effects

4 Precise dose delivery, fewer side effects Why protons? Deliver maximum energy within a precisely controlled range Deposit a high and conformal dose Deposit very low entry dose and no exit dose sparing healthy tissue The benefits Reduce risk of secondary cancers Reduce unnecessary dose to the critical structures like heart while treating a lung cancer reduced by 5X Risk of growth abnormality for children: dramatically reduced Expanding list of key Indications Head & neck, Spinal cord, Eyes, Orbits, Pelvis, Prostate, Lung, Pediatric cancers, Protect, Enhance, and Save Lives - Protect, Enhance and Save Lives 4

5 RHABDOMYOSARCOMA TREATMENT WITH DOUBLE SCATTERING X-Rays Proton Therapy Fractionated proton radiotherapy is superior to 3D conformal photon radiation in the treatment of orbital RMS ( ) Proton radiation therapy minimizes long-term side effects (*) Images Courtesy Torunn I Yock, MD Burr Proton Therapy Center Boston USA (*) Yock, T. et al; «Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons.», Int J Radiat Oncol Biol Phys Nov 15;63(4):1161- Protect, 8. Epub Enhance 2005 and Jun Save 13 Lives - 5 -

6 Lecture outline How did we get here? Proton therapy today Rapidly developing medical evidence Two accelerator technologies Limited importance of accelerator World market of PT equipment Future trends Protect, Enhance and Save Lives - 6 -

7 How it started Protect, Enhance and Save Lives - 7 -

8 First idea by Robert Wilson in 1946 Protect, Enhance and Save Lives - 8 -

9 The early days 1946; Bob Wilson suggested the possible use of the Bragg peak of high energy ions in the radiotherapy of cancer ("Radiological Use of Fast Protons", Radiology 1946:47:487-91) 2 decades later: clinical use of particle beam therapy in cancer treatment 1950s/60s; 1 st patient treatments at LBNL, Uppsala University, HCL Berkeley; heavy ions. Harvard; protons Protect, Enhance and Save Lives - 9 -

10 The Harvard Synchrocyclotron Protect, Enhance and Save Lives

11 HCL contributions to present day PT Dr. Herman Suit s team at MGH and the HCL constitute the base of today s proton therapy physics and technology; Michael Goitein, Bernie Gottschalk, Andy Koehler, Janet Sisterson, Miles Wagner, Skip Rosenthal and Ken Gall This team played an important consulting role in the design of the IBA system at MGH Protect, Enhance and Save Lives

12 Andy Koehler and Jason Burns in the MCR (1989) Protect, Enhance and Save Lives

13 The next step: Hospital based facilities Success at HCL suggested that the technology belonged in hospitals vs. labs In 1983, Proton Therapy Cooperative Group (PTCoG) was formed to develop hospital based PT facilities (35 members) PTCoG has evolved to >700 people meeting annually The 54th PTCoG meeting will organized in San Diego (USA) on May ( Protect, Enhance and Save Lives

14 Loma Linda Pr. James (Jim) Slater at Loma Linda University Medical Center (LLUMC) was the first to raise the funds needed to build a hospital based PT facility Accelerator development was subcontracted by LLUMC to Fermilab; Synchrotron technology was selected Gantry development was subcontracted to SAIC Protect, Enhance and Save Lives

15 Massachusetts General Hospital (MGH) (1) 1992, MGH obtained the budget needed to build an in hospital PT facility from NCI and private donors. An international tender was launched After a first selection, 3 groups remained in the race: Varian, allied with Maxwell-Brobeck proposed a synchrotron based system Siemens proposed 2 solutions; a synchrotron and a superconducting isochronous cyclotron (designed by Pierre Mandrillon from CERN & Nice) IBA, allied with General Atomics, proposed a solution based on a resistive isochronous cyclotron of 230 MeV IBA was selected by MGH with contract signature in 1994 and with the goal to treat the first patient in 1998 Protect, Enhance and Save Lives

16 Massachusetts General Hospital (MGH) (2) At the end of the MGH tender, one observer noted: «This tender may well cause the end of 3 good accelerator companies: perhaps for the companies which did not get the contract, but certainly for the company that got it» The Brobeck division of Maxwell was closed The special projects division of Siemens was closed. It was purchased by the managers and restarted business under the name of ACCEL. ACCEL sold a proton therapy cyclotron to PSI, and a protontherapy system in Munich. ACCEL was eventually acquired by Varian IBA encountered problems too. The cyclotron, beam lines and gantries came on spec, on time and on budget. We significantly underestimated badly effort and methodology needed for the software development. The first patient was treated in 2001, 7 years after the contract! Protect, Enhance and Save Lives

17 : Japan active 1995 to 2000, the public authorities of Japan, financed the construction of 4 PT facilities and one carbon/proton facility by 3 Japanese companies; Hitachi, MELCO and SHI 1991, IBA and SHI signed an agreement to jointly develop a proton therapy system; NCC in Kashiwa 1 st patient treatment in 1998 After 2000, orders for PT facilities around the world began to grow Protect, Enhance and Save Lives

18 Proton therapy today Protect, Enhance and Save Lives

19 Unprecedented Growth of Operational PT Rooms Observed number of PT rooms in operation, patients treated with PT and medical publications Total number of rooms worldwide, patient evolution index based on number of rooms Patients Treated # rooms sold # rooms in operation Protect, Enhance and Save Lives 19

20 Treatment Room Potential Region Current number of treatment rooms Treatment Room Potential North America South America Europe incl. Russia Asia World Protect, Enhance, and Save Lives - Protect, Enhance and Save Lives Source : IBA internal modeling based on Netherlands Model Based Approach 20

21 Unique product offering with Multi-room & Compact Proteus PLUS Proteus ONE* 360 m² 1800 m² At comparable scope, it represents a saving of > 30% for the hospital *Proteus ONE & Proteus Plus features PBS and Cone Beam CT * Subject to review by Competent Authorities (FDA, European Notified Bodies, et al.) before being put on the market.

22 IBA Leading the Installed Base Proton Centers Sold Share ProNova 1% Varian 16% Mevion 3% MELCO 6% SHI 8% IBA 52% AVO 1% Hitachi 13% IBA Total Room Sold Market Share Pronova 1% SHI 5% Varian 18% MELCO 11% Mevion 5% AVO 0% Hitachi 15% IBA 43% Protect, Enhance and Save Lives 22

23 IBA s Three Key Areas of Focus in PT Clinical Relevance Affordability Technology Increasing potential to grow the niche from 1% to 20% of RT Protect, Enhance and Save Lives 23

24 Publications per year Clinical Relevance Exponential Growth in PT Publications Protect, Enhance and Save Lives Year Number of publications up to July

25 Clinical Relevance Growth in Prospective Clinical Studies Ongoing clinical trial Total 122 ocular spine pancreas prostate bone soft tissues breast pediatric planning study Randomized studies Non-randomized comparison studies Total number of prospective studies head and neck liver esophagus, gastric, anal uterus, cervix lung brain, skullbase lymphoma, hodgkins others Worldwide prestigious cancer institutes as Principle Investigators leading the clinical studies PI Institutes Source: Protect, Enhance and Save Lives 25

26 Protect, Enhance and Save Lives

27 GROWING INTERNATIONAL RECOGNITION OF PT BENEFITS UK Government - Oct, 2012 Dutch Government - Dec, 2009 The Government recognises that ensuring patients have access to high quality modern radiotherapy techniques such as Proton Beam Therapy (PBT) will support improved outcomes, increase cure rates and improve patient experience by minimising long-term side effects of treatment. A substantial number of Dutch cancer patients could potentially benefit from future treatment with proton radiotherapy, resulting in less clinically relevant side effects, improvement of local tumour control, and prevention of secondary cancers. Protect, Enhance, and Save Lives

28 Two accelerator technologies Cyclotrons; beam is accelerated in a spiral path in a fixed magnetic field. The beam is generally accelerated up to the maximum energy, corresponding to the deepest range in patient, and is decelerated outside of the cyclotron to the required energy by an energy degrader. Cyclotrons come in two varieties: isochronous cyclotrons (continuous) and synchrocyclotrons (pulsed) Synchrotrons; the beam is accelerated on a fixed path, the magnetic field increases during the beam acceleration. beam can be extracted at the energy needed for the treatment. After acceleration, the magnetic field needs to be lowered to accept the next bunch of particles. The beam of the synchrotron is therefore not continuous. Synchrotrons require an injector accelerator, generally a proton linac. Protect, Enhance and Save Lives

29 IBA superconducting synchrocyclotron 29 Protect, Enhance and Save Lives

30 IBA 230 MeV resistive isochronous cyclotron Protect, Enhance and Save Lives

31 Hitachi Proton Therapy Synchrotron Protect, Enhance and Save Lives

32 The limited importance of accelerators in PT Accelerator, while important is < 20% of the budget and footprint of a large PT system. Key technologies which define the quality of a proton therapy system are: Beam delivery technology: what method is available: Scanning? Scattering? Both? What are the technical specifications in each mode? The speed of treatment? HW and SW tools to position accurately and reproducibly the target in the proton beam (positioning the target is not the same as positioning the body) All the tools for Image Guided Proton Therapy (Digital X-Ray, CBCT, Fluoro, Optical patient anatomy monitoring etc.) Seamless integration of the proton therapy workflow into the radiation oncology department Protect, Enhance and Save Lives

33 Emerging trends for the future Protect, Enhance and Save Lives

34 Emerging trends Shift from big multiroom systems toward one and two rooms systems New, superconducting designs IMPT using spot scanning Reduction of the neutron dose to the patient Image Guided Proton Therapy (IGPT) Range verification in vivo and in real time Protect, Enhance and Save Lives

35 Emerging trends 1: one and two room systems Most PT systems today have 3-5 treatment rooms; lowest cost/room Patient recruitment for larger system can be challenging Smaller hospitals with more limited patient base, want PT Most active manufacturers are considering today the development of smaller, less expensive one or two room systems Compact, reasonably priced one (or two) room systems will probably dominate sales in the future Protect, Enhance and Save Lives

36 Protect, Enhance and Save Lives

37 IBA Proteus ONE 7 0 % v o l u m e r e d u c t i o n F o o t p r i n t o f a t e n n i s c o u r t Protect, Enhance and Save Lives * CBCT and 220 Compact Gantry are ongoing developments. The marketing approval will be subject to review by competent authorities (FDA, Notified bodies, et al )

38 IBA ProteusONE treatment room Protect, Enhance, and Save Lives

39 Emerging trends 2: superconducting systems Magnetic rigidity of 230 MeV protons is 2.33 T m If you want smaller systems, you need smaller radii, and this means higher magnetic fields. Resistive magnets are limited to 2T for cyclotrons, 1.6 T for beam line magnets. If you want to go to higher magnetic fields, you need superconducting magnets. SC magnets technology is mature for fixed field magnets (like cyclotrons). For variable field magnets, like beam lines or synchrotrons, there is more to do. Superconducting cyclotrons (S2C2 or isochronous) will probably be the accelerator of choice tomorrow. SHI is now following IBA, Varian and Mevion Superconducting gantries are being designed and prototypes are being tested. Pronova and IBA are investigating Protect, Enhance and Save Lives

40 Varian superconducting cyclotron Protect, Enhance and Save Lives

41 Mevion superconducting synchrocyclotron Protect, Enhance and Save Lives

42 IBA superconducting synchrocyclotron Protect, Enhance and Save Lives

43 ProNova two rooms layout with SC gantry magnets Protect, Enhance and Save Lives

44 Emerging trends 3: IMPT using spot scanning While scattering is still favored by some institutions for moving tumors scattering only allows uniform fields Intensity Modulated Proton Therapy (IMPT) is made possible by spot scanning, or pencil beam scanning There are always treatment cases exceeding the limits of the treatment field (Medulloblastoma): IMPT allows also much more robust field patching. Most facilities sold today feature only scanning treatments. My opinion- the use of scattered beams will progressively disappear At UPenn, the introduction of PBS has doubled the number of patients for whom PT was the preferred mode of treatment Protect, Enhance and Save Lives

45 Most Advanced Arc Therapy Passive Proton Therapy : 4 Fields Pencil Beam Scanning : 1 Field Protect, Enhance, and Save Lives Images courtesy of Elekta

46 Emerging trends 4: IGPT To stay ahead of classical X-ray therapy, PT needs to develop the imaging tools, in and out of the treatment room Although not generalized today, true 3D daily imaging will become extensively used tomorrow, not only for tumor localization, but also for daily plan correction Cone Beam CT (CBCT) and CT on rail are competing technologies in this field. Both have merits and disadvantages. The future will tell us which technology becomes preferred Besides imaging hardware, the treatment image manipulation software will become increasingly powerful and necessary Protect, Enhance and Save Lives

47 In room CT or CBCT? CBCT, Penn Medicine, USA CT-on-Rails, Trento, Italy Protect, Enhance, and Save Lives - Protect, Enhance and Save Lives

48 Optimum quality CBCT images requires the X-Ray tube to be far from isocenter limit of ring-type CBCT s Protect, Enhance and Save Lives

49 Combining X-Ray modalities in the Proteus One Fixed Stereoscopic X-ray CBCT Flat panels X-ray tube X-ray tube Flat panel Flatpanel X-ray tubes Protect, Enhance and Save Lives

50 Emerging trends 5: Reducing the neutron dose Proton stopping in the patient body undergo nuclear reactions, causing therefore the emission of neutrons. There is a minimum neutron dose outside the treatment field which is unavoidable in proton treatments We start to see more clinical data validating the relation between the neutron dose given in proton therapy and the induction of secondary cancers Therefore, reducing the neutron dose associated by the proton treatment will be increasingly important, especially for pediatric patients In an ideal case, the neutron irradiation is limited to the neutrons generated by the protons stopping in the patient body. This is the case for PBS proton treatment In contrast, treatments by scattering subject the patient to a much larger neutron flux coming from other elements such as patient specific apertures, scatterers, range shifters etc. Protect, Enhance and Save Lives

51 H*(10) (msv/gy) PBS Proteus ONE vs. gantry mounted cyclotron with scattering only: Neutron Dose (Pediatric Medulloblastoma) Scattering Gantry Mounted Cyclotron ProteusONE Ideal PBS Esophagus Thymus Heart Thyroid Adrenals Liver Pancreas Bladder Kidneys Brain Protect, Enhance and Save Lives

52 Emerging trends 6: precisely measuring the range of the proton beam in the patient The range of a proton beam in an actual patient has very large uncertainties, due to day to day variations in the patient anatomy Large safety margins on the range are therefore used in the current practice of PT, cancelling part of the advantage of protons over x-ray The advantages of protons over photons would be significantly increased if we could watch in real time the range of the proton pencil beam in the patient This can be done if we image the prompt gammas coming from nuclear reactions caused by the proton beam in the patient Protect, Enhance and Save Lives

53 Concept of prompt gamma camera Scintillator + photodetector Slit collimator Proton pencil beam (scan the tumor, spot by spot, in X, Y, Z) Protect, Enhance and Save Lives

54 Thank you Protect, Enhance and Save Lives

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