Proton therapy. Changing the way. www.iba-protontherapy.com



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Proton therapy Changing the way you treat cancer www.iba-protontherapy.com

Making a difference today, leading the way to the future In the world of medical technology, state-of-the-art is a continually moving target. To be on the leading edge, you need to offer the most advanced treatment. The clinical advantages of proton therapy compared to conventional radiation therapy are well known: it is a viable and successful option, with more than 80,000 patients treated worldwide. And as more people in medical and patient communities learn about the benefits of this advanced treatment, demand will increase, leading to the need for more proton therapy facilities. IBA has designed, developed and equipped more proton therapy centers around the world than anyone else, providing equipment as well as scientific and engineering expertise. We use a pragmatic, modular approach that is scalable to meet your specific business goals. Whether you want a single- or multi-room facility, freestanding or as addition to your radiation therapy department, we can help your vision become a reality and help you bring the real advantages of proton therapy to more patients and communities. iba Proton therapy // 1

Proton therapy Offer a compassionate treatment solution The most advanced cancer treatment Proton therapy is used today to treat many cancers and is particularly appropriate in situations where treatment options are limited and conventional radiation therapy presents unacceptable risks to patients. These situations include eye and brain cancers, tumors close to the brain stem and spinal cord, prostate, liver, lung and breast cancers, and pediatric cancers. 1 5 6 1. Central nervous system Adult Low and High Grade Gliomas Pediatric Gliomas Acoustic Neuromas recurrent or Unresectable Meningiomas recurrent or Unresectable Craniopharyngiomas Chordomas and Low Grade Chondrosarcomas Arteriovenous Malformations Medulloblastomas Pituitary Adenomas Posterior Fossa Tumors. Eye & orbit Uveal Melanomas Macular Degeneration Choroidal Melanomas Retinoblastomas Choroidal Metastases Orbital Rhabdomyosarcomas Choroidal Hemangiomas Optic Gliomas. Head & Neck Paranasal Sinus Salivary Glands Carcinomas Nasopharynx Primary and Recurrent Esophogeal Carcinomas Recurrent Carcinomas. Thorax Non Small Cell Lung Carcinomas Breast Cancer Early Stage-Medically Inoperable Paraspinal Tumors Soft Tissue Sarcomas Lymphomas How proton therapy works Proton therapy is an advanced form of radiation therapy that uses a high-energy proton beam for cancer treatment. In contrast to conventional radiation therapy, proton beams deliver their maximum energy within a precisely controlled range, known as the Bragg peak, thereby reducing adverse effects to adjacent healthy tissues. In IBA-equipped proton therapy centers, cyclotrons accelerate protons to an extremely high speed, generating a controlled beam, which is delivered very precisely in the treatment rooms, through a nozzle, to the targeted tumor. With proton therapy, there is significant potential to reduce side effects, improve overall outcomes in cancer treatment and offer a better quality of life to patients. Key advantages of the proton beam in cancer treatment: Little to no radiation outside the tumor; Lower risk of induced disorders (e.g. secondary cancers or child growth abnormality); Better quality of life during and after treatment. 5. Gastrointestinal malignancies Oesophageal Carcinomas Reccurent Rectal Cancer Pancreatic Cancer Hepatocellular Carcinomas 6. Pelvis Early Stage Prostate Carcinomas Locally Advanced Prostate Carcinomas Locally Advanced Cervix Carcinomas Pelvic Sarcomas Pediatric Malignancies Ewing s Sarcomas Retroperitoneal Sarcomas Gynecologic Carcinomas Bragg peak: proton beams release the majority of their destructive energy within a small range inside the tumor, depositing less entrance dose and no exit dose. This peculiarity of proton beams enables physicians to treat tumors with unequaled precision, safety and efficiency. As a major cancer center, you cannot really move into the future without adding proton therapy to be part of what you can offer patients. Dr. Zelig Tochner Professor of Radiation Oncology, University of Pennsylvania Health System. // iba proton therapy iba Proton therapy //

Precise dose delivery, fewer side effects Technological advances in conventional external beam radiation therapy have led to a new approach: Intensity Modulated Radiation Therapy (IMRT). To reach the right amount of dose in the target, IMRT multiplies the number of beam incidences needed and spreads unnecessary dose in the surrounding healthy tissue. For the patient, this means receiving a much higher integral dose during IMRT treatment compared to a similar treatment in proton therapy. With proton therapy, you avoid depositing unnecessary dose in surrounding healthy tissues because the physics of protons enables the physician to deliver highly conformal treatments. Proton therapy delivers high-energy radiation doses directly to the tumor. Today, cancer affects us all: However, data is strongly suggestive that, thanks to its precise dose delivery, proton therapy reduces by 50 to 80%,, the risk of radiation-induced secondary cancers. In the case of secondary cancers or cancer resurgence, retreatment is made possible by the lower Integral Dose delivered during a proton therapy treatment. For a deeper understanding of proton therapy, reference may be made to the following works: Thomas F. Delaney, Hanne M. Kooy, Proton and charged particle radiotherapy, 007, Lippincott Williams & Wilkins James M. Metz and Charles R. Thomas, Jr., Proton Therapy, 010, Radiation Medicine Rounds, Volume 1, Issue Patient s testimony* When he learned he had prostate cancer, Ben Smith, a 55 year old aerospace engineer from Florida, analyzed his options and looked for the best treatment. Smith refused to risk the possible side effects (impotence and incontinence) and sought for a more palatable solution: proton therapy. The proton beams are so precise; if that s where you want the radiation to go, that s where it goes, he says. After doing all the research, I thought, This is it. This is what I have to have. During his treatment at UFPTI, Smith, married with two children, enjoyed visits from his family and friends, read, attended some college football games and kept in shape at the local YMCA. Three weeks after his last therapy session, he returned to work. One year later, Smith has regular blood analyses done and returns to UFPTI for follow-up visits. Ben is doing great, says his doctor. His prostate has shrunk considerably and he has no side effects from his treatments. * IBA Proton Therapy Today, October 007. it is estimated that 1 person in every will suffer from cancer during his lifetime; analyses 1 indicate that 1% of us will contract more than one cancer, a proportion that has dramatically increased over the last years; Harald Paganetti, Proton Therapy Physics, 01, Series in Medical Physics and Biomedical Engineering, Massachusetts General Hospital and Harvard Medical School, Boston, USA the majority of the cancer patients will receive radiation therapy at some point during treatment. 1 Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 00. MacDonald SM, et al. Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons, International Journal of Radiation Oncology, Biology, Physics, 008,71():979-86. Merchant TE., et al. Proton versus photon radiotherapy for common pediatric brain tumors: comparison of models of dose characteristics and their relationship to cognitive function, Pediatric Blood and Cancer, 008, 51(1):110-7. Chung CS, et al. Comparative analysis of second malignancy risk in patients treated with Proton Therapy versus conventional Photon Therapy, International Journal of Radiation Oncology, Biology, Physics, 008. More precise dose delivery, fewer side effects, excellent results proton therapy is changing how cancer is treated. IBA is helping to make this compassionate treatment modality available to more patients worldwide. // iba proton therapy iba Proton therapy // 5

Clinically efficient cancer treatment examples 1 Prostate Carcinoma. Pediatric Ependymoma. Proton therapy spares the hormone and intellectual centers of the brain, as well as the middle ear, more than the most sophisticated conventional radiation therapy techniques. Current literature indicates that avoiding even low doses to these important areas of the brain can significantly reduce adverse effects and the risk of secondary cancer. Current X-ray therapy methods can result in excessive radiation doses in the rectum and bladder. With proton therapy, the prostate carcinoma can be treated with only lateral beams delivered with the Pencil Beam Scanning method that reduces the dose delivered to the rectum and bladder. With this technique, the Integral Dose given to the patient is much lower; hence the patient has a lower risk of induced complications in surrounding healthy organs. Pencil Beam Scanning can be used similarly for Intensity Modulated Proton Therapy and Single Field Uniform Dose treatments. Left: proton therapy with scattering delivery technique. Right: X-ray radiation. Left: proton therapy with Pencil Beam Scanning delivery technique. Right: X-ray radiation. Non Small Cell Lung Cancer (NSCLC). 1 Images with the courtesy of Stefan Both PhD, Assistant Professor of Radiation Oncology, University of Pennsylvania Health System. Cotter SE, et al. Proton radiotherapy for solid tumors of childhood, Technology in Cancer Research and Treatment 01, 11():67-78. Mendenhall NP, et al. Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer International Journal of Radiation Oncology, Biology, Physics, 01, 8(1):1-1. Sejpal, S. Early findings on toxicity of proton beam therapy with concurrent chemotherapy for non small cell lung cancer, Cancer. 011, 117(1):00-1. The therapeutic dose delivered during X-ray treatment of lung cancer is often limited by the risk to healthy tissue surrounding the tumor. With proton therapy, the radiation dose delivered to the collateral lung and other healthy tissues surrounding the tumor can be reduced, creating a potential opportunity for dose escalation and consequent improved patient survival. Left: proton therapy with scattering delivery technique. Right: X-ray radiation. 6 // iba proton therapy iba Proton therapy // 7

Making proton therapy accessible to patients worldwide The key indications for proton therapy represent up to 0% of all cancers treated in conventional radiation therapy. Despite this high potential, very few patients today are treated with proton therapy because access is so limited. IBA is committed to changing this; we are dedicated to making proton therapy more available to patients, as well as more affordable to healthcare systems. 8 // iba proton therapy iba Proton therapy // 9

IBA, a safe path to superior treatment Benefit from unrivaled experience gained through 0+ projects With more than 5 years of experience, IBA, the market leader, has designed and equipped the majority of clinically operating proton therapy centers around the world, with over 0 projects that are already operational or at various stages of development. As access to proton therapy increases around the world, IBA continues to innovate and provide compassionate solutions with more patient-friendly treatment rooms and more precise therapies. Partnering and collaborating with renowned clinical institutions, IBA is committed to making proton therapy, the most precise cancer treatment, available worldwide. Facts: In 011, more than 0% of patients who received proton therapy in an hospital environment were treated on an IBA system. IBA has installed over 50% of the clinical PT treatment rooms in the market. Over the first 10 projects, IBA reduced installation and commissioning times almost fivefold (from 57 to 1 months). Record time to first patient of 1 months from Building Occupancy Date at CDH (Chicago). ROOMS The Proton Therapy Center LLC (TPTC) Provision Healthcare Knoxville, TN, USA Opening in 01 ROOMS ProCure Proton Therapy Center in Oklahoma City Oklahoma City, OK, USA Treating since 009 ROOMS ProCure Proton Therapy Center Seattle, WA, USA Opening in 01 1 ROOM Willis-Knighton Cancer Center Shreveport, LA, USA Opening in 01 5 ROOMS Hampton University Proton Therapy Institute Hampton, VA, USA Treating since 010 ROOMS CDH Proton Therapy Center, A ProCure Center Chicago, IL, USA Treating since 011 ROOMS Indiana University Health Proton Therapy Center Bloomington, IN, USA Treating since 00 ROOMS Centre de Protonthérapie de I Institut Curie Paris (Orsay), France Treating since 009 ROOMS Skandionkliniken Uppsala, Sweden Opening in 01 ROOMS Westdeutsches Protonentherapiezentrum Essen (WPE) Essen, Germany ROOMS Bronowice Cyclotron Center Kraków, Poland Opening in 01 ROOMS Federal High-Tech Medical Center Dimitrovgrad, Russia, Europe Opening in 01 ROOMS National Cancer Center Kashiwa, Japan Treating since 1998 ROOMS National Cancer Center Ilsan, Korea Treating since 007 Be part of a community of experts ROOMS University of Florida Proton Therapy Institute Jacksonville, FL, USA Treating since 006 ROOMS Wanjie Proton Therapy Center Zibo, China Treating since 00 Today IBA is the sole player in the proton therapy market that can enable its new customers to leverage the experience of its users community. IBA organizes on an annual basis the Proteus User Meeting which brings together practitioners from all sites installed by IBA, joined by IBA experts, in order to exchange best practices. Customers benefit from a learning curve that allows us to significantly reduce the time required to reach first patient treatments. Even before reaching an agreement, IBA shares its know-how in building design, project management and project financing with its future partners. Transparency and collaboration are key in advancing proton therapy. This is the reason why IBA and its customers work together to lay the foundation for advancing proton therapy as a universally accepted clinical treatment. Leading institutions have already chosen IBA. Join them to develop the future of cancer care together. ROOMS ProCure Proton Therapy Center Princeton, NJ, USA Treating since 01 5 ROOMS University of Pennsylvania Health System Roberts Proton Therapy Center Philadelphia, PA, USA Treating since 009 This map has been last updated in September 01. Proteus PLUS Proteus ONE ROOMS Massachusetts General Hospital Burr Proton Therapy Center Boston, MA, USA Treating since 001 ROOMS Agenzia Provinciale Per la Protonterapia (ATreP) Trento, Italy Opening in 01 5 years of experience and innovation, reference centers IBA leads the world in regulatory clearance for Proton Therapy systems with FDA clearance in the United States, CE marking in Europe and KFDA clearance in South Korea. This together with experience 1 ROOM Universitatklinikum Carl Gustav Carus Dresden, Germany Opening in 01 gained on more than 0 projects worldwide ensures a safe and fast path to treatment while lowering substantially the technical and financial risk of the project. ROOMS Proton Therapy Center Czech s.r.o. Prague, Czech Republic Opening in 01 10 // iba proton therapy iba Proton therapy // 11

Proton therapy, at the heart of our company Patient care is what really counts Over the years and through countless efforts in R&D and partnership with its customers, IBA has played an active role in developing proton therapy around the globe. We deeply believe that proton therapy will help control cancer worldwide in the most compassionate way possible. Having pioneered the field of proton therapy to become the worldwide leader today, IBA remains committed to following this path and offering its customers ever more flexible and accessible state-of-theart proton therapy solutions to make this extraordinary treatment modality available to more and more patients worldwide. Proton therapy is and will remain our focus and the key driver of our company growth. Years of continuous improvement lead IBA to meet the highest standard of quality at all levels of the organization. To ensure that the quality is well managed, IBA is certified ISO 185 while meeting all quality requirements of regional regulatory bodies (FDA, CE marking, KFDA). Facts: R&D represents 1% of IBA turnover and 1% of its workforce. On December 1, 011, the IBA patent portfolio contained 6 patents or patent applications covering 117 different inventions. In 011, proton therapy revenue growth was close to 50%. Leveraging its experience and years of collaboration with its customers and partners, IBA has developed a deep understanding of what it takes to build, operate and maintain a proton therapy center. This experience has laid the basis for the services we have developed to ensure that we bring our customers projects to completion in the most efficient and cost-effective way, and make sure you have the time to continue focusing on the single most important element patient care. IBA s experience and knowledge cover all aspects of the process, from site selection to design, construction, system integration and facility management. Our commitment is to ensure your clinical success by providing reliable tools with the highest availability possible. To date, the IBA service organization experience has helped centers around the world to successfully deliver more than 00,000 fractions to cancer patients. Your team will be able to focus on the clinical aspects of cancer care while the IBA team ensures that your proton therapy system runs at top performance and meets the highest safety and reliability standards. IBA s service offering includes: Consulting Services Upgrades and Migration Financing Support Education and Training Maintenance and Operation Information and Communication Our experience with IBA has been excellent. The quality of the equipment has been wonderful. The people that they ve had on board have been experts in their field, and they ve done a wonderful job of maintaining our system and providing for a smooth operation. Stuart Klein, MHA Executive Director. University of Florida Proton Therapy Institute. 1 // iba proton therapy iba Proton therapy // 1

Proteus Series: Meeting your every need in proton therapy IBA offers a modular approach to proton therapy that is scalable and adaptable to the specific goals of a particular medical group. A number of customers choose to start with a larger center of or treatment rooms, while others opt to expand their existing radiation therapy practice with a single proton therapy treatment room. Based on this approach, IBA Proton Therapy has developed proton therapy solutions with specific configurations to meet your every need in proton therapy:. Proteus TK: The turnkey tworoom proton therapy center This proton care center combines the latest technologies from the best partners and every device required to optimize cancer treatment. IBA has established long-term partnerships and collaboration programs with suppliers to achieve seamless interoperability with the ProteusTK. Everything has been designed to ensure a fast, smooth and risk-free set up. Proteus ONE in combination with Philips Ambient Experience, improving the overall patient and staff experience. 1. Proteus PLUS: The universal proton therapy solution It offers the possibility to configure the center in accordance with customer needs, providing a choice of different beam delivery modes and types of treatment rooms ensuring perfect patient positioning. This proven proton therapy solution combines the latest technologies with the experience gained over 0 years of partnership with top clinical institutions. 1 ProteusTK is a turnkey solution that offers a fully integrated proton therapy center.. Proteus ONE 1 : The compact and affordable proton therapy solution ProteusONE benefits from the latest technologies and offers extended treatment solutions, while having a footprint lower than the size of a tennis court. Its design enhances the patient experience by fostering a soothing environment while making the medical staff daily practice safer and easier. Smaller, more affordable, easier to install and easier to operate, ProteusONE helps make proton therapy available to more patients worldwide. protons are possible For many institutions, a barrier to proton therapy is the complexity of the project (high costs, large equipment, long project). To counter these barriers, IBA experts have developed the ProteusONE: a compact singleroom system that substantially minimizes the space, reduces the cost and shortens the installation time required to build a proton therapy center. With ProteusONE, protons are possible for more patients worldwide. ProteusPLUS is the most reliable and proven proton therapy system today. ProteusONE is a compact single-room proton therapy solution. 1 ProteusONE is the brand name of a new configuration of the Proteus 5 including some new developments subject to review by competent authorities (FDA, Notified bodies, et al...) before marketing. 1 // iba proton therapy iba Proton therapy // 15

Contact us Americas Toll-free: 1 877 IBA PBT T +1 90 6100 Europe, Middle East and Africa T + 10 0 F + 10 75 9 Russia & CIS T/F +7 95 68 69 00 E-mail: info@iba-russia.ru Asia Pacific T +86 10 8080 9186 E-mail: info-pt@iba-group.com Visit us online at: www.iba-protontherapy.com While all care has been taken to ensure that the information contained in this publication is correct, we accept no responsibility for any inaccuracy and reserve the right to modify this information. Technical specifications are based on standard operating conditions and may be subject to variations. Pictures and illustrations are not contractual. ProteusPLUS is the brand name of the Proteus 5 FDA cleared and CE marked product. ProteusTK is a solution including a configuration of the Proteus 5. ProteusONE is the brand name of a new configuration of the Proteus 5 including some new developments subject to review by competent authorities (FDA, Notified bodies, et al...) before marketing. Empath is a registered trademark of IBA Particle Therapy. IBA, a Belgian company, is listed on the pan-european stock exchange EURONEXT and its annual reports can be downloaded on the website: www.iba-worldwide.com. Published by IBA S.A., Chemin du Cyclotron, 18 Louvain-la-Neuve, Belgium. This brochure is printed on ECF woodfree coated paper. It was produced with plants that comply with ISO 1001, the environmental management standard. 16 // iba proton therapy

IBA Group IBAL01/0 Proton therapy 01 IBA Proton Therapy Having pioneered in the field of proton therapy to become the worldwide leader today, IBA remains committed to following this path and offering its customers ever more compact, flexible and accessible state-of-the-art proton therapy solutions. Every day, our experts work relentlessly to make this extraordinary treatment modality available to more patients worldwide. Years of collaboration between IBA and its customers and partners helped treat over 0 000 patients worldwide. Leveraging this experience, IBA has developed a deep understanding of what it takes to build a proton therapy center. Our customers benefit from a learning curve of over 0 years that allowed IBA to significantly reduce the time required to reach first patient treatment. Leading institutions have chosen IBA to set-up their proton therapy center. Join them to develop the future of cancer care together. Visit us online at: www.iba-protontherapy.com www.iba-protontherapy.com