Jul 3 – 7, 2023
Online
Europe/Zurich timezone

Speakers list

Piero Fossati, MedAustron

CV: Piero Fossati graduated in Medicine and Surgery at the University of Rome in 2002, completed his specialization in Radiotherapy in 2006 at the University of Milan and completed his training in particle therapy at NIRS in Chiba Japan in 2007 and 2009. He has participated in establishing clinical operations with protons and carbon ions at CNAO (Pavia, Italy). He is now head of the carbon ion program and scientific director of MedAustron (Wiener Neustadt, Austria).His main interest is the clinical use of carbon ion radiotherapy focusing on producing high-level evidence for established indications and exploring new potential applications and synergies. He is co-author of the ICRU report on carbon ions radiotherapy.

Ester Orlandi, CNAO

CV: Ester Orlandi has more than 20 years’ experience in radiation oncology in Head & Neck cancer. She worked until March 2020 at the National Cancer Institute of She fully dedicated to head and neck Cancer radiotherapy, oncological multidisciplinary approach and translational research. Since March 2020, she is the Chief of Radiation Oncology department of Italian National Cancer for Hadrontherapy CNAO.She is involved in Italian and international groups/trials on many topics mainly concerning multidisciplinary oncology management, QOL for Head and neck Cancer patients. Since March 2020 up to today, she is a representative of the EORTC Head & Neck group for the Radiation Oncology Scientific Council (ROSC). Since January 2021 she is ESMO faculty member for the Head and Neck Cancer group and since December 2022 is Scientific Committee member for ESMO 2024. Since April 2019 up to today she is Consilour of the Italian Association of Head and Neck Oncology (AIOCC). She is the author and co-author of 6 book chapters and 200 scientific journal articles in impacted peer review journals.

Abstract 1: Salivary gland cancers and paranasal sinuses carcinoma Salivary gland cancers (SGCs) and sinonasal carcinoma (SNCs) are very rare disease and are morphologically heterogeneous. Several hystotypes are known to be radioresistant to conventional photon based-radiotherapy (RT). Among these, adenoid cystic carcinoma (ACC) remains a major challenge for radiation oncologists Due to Its ability to evade immune surveillance and anatomicalcomplexity, embracing or intersecting radiosensitive structures following neural pathways ACC can make advantages from proton therapy (PT) and carbon ion RT (CIRT). Proton therapy can be used to achieve a good dose distribution in complex ACC volumes and may be potentially advantageous over advanced photon techniques in selected cases. High local control were reported in Japanese and American series. The interest in CIRT arose in Germany and Japan rapidly spread around the world, with many particle facilities that are built even in Europe and China. Evidence that ACC may benefit from CIRT, alone or in combination with photon based intensity modulated RT in terms of LC, OS and toxicity, including R2 and inoperable cases has been reported in the latest years. In the field of high-precision therapy for SNCs, particle therapy, including PT and CIRT, marks a new era. A recent meta-analysis has been recently conducted to compare the effectiveness of CIRT, PT and intensity modulated RT (IMRT) and estimate OS and LC in a real-world setting including 2282 patients from 49 cohorts (8 CIRT cohorts, 20 PT cohorts, 21 IMRT cohorts. The 3-year OS and LC were significantly higher after CIRT than PT or IMRT. However, this meta-analysis suffers from major pitfalls, as the number of patients, the tumor sites, and the RT settings were quite different among groups. Moreover, the lack of toxicity data prevents clear conclusions on the advantage provided by CIRT.So far, no guidelines are available to help clinicians in the choice between IMRT and particle therapy, particularly as regards PT. For non-radioresistant or relatively radioresistant tumors, such as SCC, SNUC, and neuroendocrine sinonasal carcinomas, for which the first goal is to reduce the risk of neurological radiation-induced adverse effects while achieving similar tumor control as compared to IMRT, a normal tissue complication probability (NTCP) model-based approach could be pursued For radioresistant tumors, in particular in the case of gross residual disease after surgery, the use of PT and CIRT is strongly recommended in view of the capability of escalating the dose toward the target while minimizing radiation to neurological structures.

Abstract 2: CNAO trials The Italian National Center for Oncological Hadrontherapy (CNAO) has been always devoted to clinical research in order to build evidence for particle therapy in the oncology landscape. In the last year several clinical prospective studies have been designed and conducted within a multidisciplinary and multiprofessional framework. CNAO is promotor or collaborator of several single center or multicenter observational and/or interventional clinical trials. Here we reported some of them. A clinical registry, REGAL (NCT05203250) has been set up to collect retrospective and prospective standardized data of patients treated with particle therapy. Recently, two phase II non randomized controlled trials of induction chemotherapy followed by surgery or (chemo)radiation with IMRT or particle therapy for resectable (SINTART1, NCT02099175) and unresectable (SINTART 2, NCT02099188) sinonasal cancers with poor prognosis have been published. For naïve locally advanced adenoid cystic carcinoma patients CNAO is starting a prospective phase II study to investigate the potential dosimetric and radiobiological advantages in terms of the reduction of acute and mid-term toxicities by using a novel fractionation schedule consisting in a simultaneous integrated boost (SIBACIRT, NCT05733910) Results from a phase 2 feasibility study on patients with high-risk prostate cancer treated with CIRT boost to the whole prostate of 16.·6 GyRBE in 4 fractions, followed by a pelvic photon based IMRT phase of up to 50 Gy to the pelvic lymph nodes and whole prostate have recently demonstrated a safe toxicity profile. A monocentric prospective phase 2 study is currently ongoing aimed to reproduce the results obtained at NIRS with radical CIRT (with or without immunotherapy) for mucosal melanoma of lower genital tract in terms of progression-free survival (PFS) and local control (LC) (CYCLE, NCT05478876).

Semi Harrabi, HIT

CV: Semi Harrabi is a radiation oncologist (Oberarzt) at University Hospital Heidelberg and primary responsible for the Heidelberg Ion Beam Therapy Centre (HIT). His field of interest and expertise lie in pediatric cancers, neuro-oncology, sarcoma and the application of high-precision radiotherapy with charged particles. His research aims to develop innovative treatment options with protons, helium and carbon ions to improve outcome and decrease the burden of treatment related sequelae. He is an active member of both national and international working groups related to particle therapy or pediatric oncology and serves on the steering committees for low grade glioma (LOGGIC), osteosarcoma (COSS), rhabdomyosarcoma (CWS), the SIOPE radiation oncology working group and the Green Journal’s editorial board. Further, he is co-founder of the consortium reference radiotherapy for the German pediatric oncology society and head of the national radiotherapy reference institution for pediatric malignancies.

Shigeru Yamada, QST Hospital

CV: Shigeru Yamada  graduated in University School of Medicine in Japan and continued his studies at Chiba University in Japan where he finished his Ph.D.  He worked at the Medical Staff and Surgery Dedpartment at the Chiba university and later as Chief at the  Chiba Cancer Center Hospital .He also finished his Postodoctoral Fellowship at the  Radiation Biophysics, NASA Johnson Space Center, Houston, USA and continued his career as a Chief Medical Doctor at  NIRS, Japan where he also became Chief Medical Doctor.Then, he proceed his professional path as a Director, Dept. of Charged Particle Therapy Research at NIRS , QTS where he became Deputy Director of QST Hospital  and Director since 2022.He also participated in Carbon Ion Radiotherapy for Locally Recurrent Rectal Cancer of Patients with Prior Pelvic Irradiation  and Carbon-ion Radiotherapy for Colorectal Cancer researches and published the second at the Journal of The Anus,Rectum and Colon 5.He also worked for the Project : Efficacy and feasibility of re-irradiation using carbon ions for pancreatic cancer that recurs after carbon-ion radiotherapy and did  Clinical and Translational Radiation Oncology and also for Multi-institutional Study of Carbon-ion Radiotherapy for Locally Advanced Pancreatic Cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1403 Pancreas that was published in Int J Radiat Oncol Journal ,in  Biol, Phys domaines.Lastly , he participated at the Carbon-ion radiotherapy for locally recurrent rectal cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) and at the Carbon-Ion Radiation Therapy for Pelvic Recurrence of Rectal Cancer ,also publised in the Int J Radiat Oncol Journal.
 

Abstract: Carbon-ion Radiotherapy for patients with locally recurrent rectal cancer Shigeru Yamada, Hirotoshi Takiyama, Tetsuro Isozaki and Makoto Shinoto, affiliations. QST Hospital, National Institutes for Quantum Science and Technology, Chiba, Japan.

In the past 29 years, more than 15,024 patients were treated with Carbon Ion Radiotherapy (CIRT) at the National Institutes for Quantum Science and Technology (QST). Carbon ion beams are characterized by favorable dose distribution and enhanced biological effects. Most of the radiation therapy for gastrointestinal cancer is palliative treatment, because they are surrounded by normal tissues with high radiosensitivity such as the gastrointestinal tract, and most of them are radiation-resistant cancers such as adenocarcinoma. We will introduce the results of CIRT for patients with locally recurrent colorectal cancer (LRRC) among gastrointestinal cancers.

With recent advances in surgical techniques and procedures, the pelvic recurrence rate of rectal cancer has been decreasing. However, the rate of LRRC is still 5 to 20 % today. Surgical resection is the first choice, but in many cases, LRRCare not completely resectable, and so generally, surgical resection is not pursued . CIRT is used to treat LRRC so as to improve longterm local control and survival rates.

Between April 2001 and August 2012, 180 patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and phase 2:143 patients, respectively). An analysis of 151 patients (155 lesions) treated with 16 fractions of 73.6 Gy (RBE) (gray relative biologic effectiveness) showed a 5-year local control rate of 88% and overall survival of 59%. In the literature, the reported 5-year survival rates for LRRC treated with conventional radiation and with resection ranged from 0 to 40 % and 20 to 40 % , respectively. The results of this study indicate that carbon-ion beam therapy is a safe and effective treatment for locally recurrent rectal cancer and a potential alternative to surgery(1). On the other hand, 224 patients treated in 16 fractions of 70.4 or 73.6 Gy (RBE) from 2003 to 2014 at three Japanese heavy ion radiotherapy centers were retrospectively analyzed. The LC rates were 88% at 5 years and the OS rates were 51% at 5 years. These results indicate that good treatment efficacy can be achieved regardless of institution(2).

Furthermore, Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation after X-ray irradiation(3). The total CIRT dose of 70.4 Gy (RBE) was administered in 16 fixed fractions during 4 weeks. No grade 4 or higher toxicity was noted and the local control rate was 90% and the survival rate was 61% at 3 years. Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity.

To expand the indications for CIRT , use of a bioabsorbant polyglycolic acid spacer was approved in July 2020, allowing a sufficient margin for CIRT, even in cases with a short distance between the tumor and the gastrointestinal tract or bladder. We introduce these spacer techniques to reduce the toxicity of these normal tissues.

The case study will present the indications for spacers and the indications for reirradiation of CIRT.

1. Yamada S, Kamada T, Ebner DK, et al. Carbon-ion radiation therapy for pelvic recurrence of rectal cancer. Int J Radiat Oncol Biol Phys. 2016;96:93–101.

2. Shinoto M, Yamada S, Okamoto M, et al. Carbon-ion radiotherapy for locally recurrent rectal cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1404 Rectum. Radiother Oncol. 2019;132:236–40.

3. Yamada S, Takiyama H , Isozaki Y et al. Carbon Ion Radiotherapy for Locally Recurrent Rectal Cancer of Patients with Prior Pelvic Irradiation. Ann Surg Oncol 2022; 29:99–106.

Yiota Foka, GSI/SEEIIST

CV: Foka is a senior researcher currently involved in medical applications and the development of a next-generation ion facility for tumour cancer research and therapy with ions within the framework of the collaboration of the NIMMS/CERN group and her home institute GSI, where she holds a permanent position. Her career was mostly developed within the ALICE experiment at the CERN LHC, where she also served in management positions such as deputy physics coordinator, outreach coordinator, and system coordinator for data quality monitoring and event display. Active in the dissemination of information on scientific advances via the organization of conferences, seminars, and educational outreach activities she introduced and coordinates the new particle therapy masterclass since 2019.

Manuela Cirilli, CERN

CV: Manuela Cirilli is Medical Applications Adviser in CERN’s Knowledge Transfer (KT) group, and she also leads KT’s Communication, Marketing and Training section.
Prior to joining CERN’s KT group in 2010, Manuela was an experimental researcher in particle physics. She first came to CERN in 1997 as PhD student, to take part in the NA48 experiment to measure CP violation in the kaon system. In 2001 she joined the ATLAS collaboration, and worked on the construction and commissioning of the precision muon chambers. She has extensive experience in detector construction and commissioning, data analysis, and databases, and has held several coordination roles in both the NA48 and ATLAS Collaborations. Manuela holds a PhD in Particle Physics from the “Scuola Normale Superiore” in Pisa, Italy, as well as a Master in Science Communication and Journalism from the University of Ferrara, Italy. In parallel to her scientific career, Manuela has been engaging in science communication and popularisation since the early 2000s, for a variety of audiences and stakeholders of all ages. She is also a teacher and coach in science communication, science writing, and public speaking. Manuela is also actively involved in promoting STEM careers among young women and girls.

Abstract: From physics to particle therapy technology. Since the discovery of X-rays at the end of the 19th century, physics has been having a tremendous impact on modern medicine. Physics phenomena underpin many advanced techniques and technologies that are routinely used in hospitals for both diagnosis and treatment of diseases. In addition, many of the state-of-the-art technologies behind these healthcare innovations were initially developed for nuclear/particle physics research. We’ll take a closer look at particle physics in particular.

Nicholas Sammut, Umalta

CV: Nicholas Sammut is an associate professor at the University of Malta specialising in accelerator technology and instrumentation and is currently coordinating work package 5 (Education and Training) of the HITRIplus project. He is affiliated with the Department of Microelectronics and Nanoelectronics as well as the Centre of Entrepreneurship and Business Incubation at the university.

Arnold Pompos, UTSW

CV: 1994 ΜS ( High Energy Theretical Physics ) from Charles University in Prague, Czech Republic, 2002 PhD ( High Energy Experimental Physics ) from Purdue University, West Lafayette, Indiana, USA, 2006 Postdoc stationed at Fermi National Laboratory, Chicago, IL, USA, 2008 Finished Residency in Universty of Nebraska Medical Center in the field of Therapeutic Radiation Oncology Medical Physics, 2010 Certified by American Board of Radiology in Therapeutic Radiation Oncology Medical Physics, 2009 Assistant Professor of Physics, UT Southwestern Medical Center, Dallas, TX, 2015 Associate Director of Medical Physics Residency Program, UTSW, 2015 Lead Physicists for UTSW effort to Plan the First Heavy Ion Therapy and Research Center in US, 2017 Director of Clinical Medical Physics, Associate Professor of Physics, UT Southwestern Medical Center, Dallas, TX, 2019 Director of Strategic Expansion Planning, Radiation Oncology, UTSW, Dallas, TX, 2021 - Present: Associate Vice Chair for Strategic Expansions and Capital Investments, Radiation Oncology, UTSW, Dallas, Texas, USA.

Amelia Barcellini, CNAO 

CV: Amelia Barcellini is a Medical Doctor. She graduated in Medicine and Surgery at the University of Pisa in 2013 and completed her specialization in Radiotherapy in 2017 at the University of Milano Bicocca. She is part of the Radiation Oncology Unit of the National Center for Oncological Hadrontherapy (CNAO) since 2018 where she is engaged in clinical and research activity. Her main interests lie in clinical and preclinical research on gynecological, gastrointestinal, and rare tumors.

Abstract: Primary melanomas originating from the gynecological tract are rare and aggressive cancers with locally aggressive growth patterns, frequent metastatic spread, and poor outcomes. Clinical studies reported favorable local control rates with carbon ion radiotherapy compared to conventional radiotherapy with mild toxicity, also in the case of combination with immunotherapy.

Ovarian cancers, on the other hand, are not uncommon and it is one of the major causes of cancer-related deaths among women. Despite the improvement in cytoreductive surgery as well as the integration of bevacizumab and PARP-I, recurrence is a frequent event and in this context, radiotherapy is shifting from a palliative to a curative aim. Half of high-grade serous ovarian cancer exhibits a high degree of genomic instability due to deficiencies in homologous recombination (HR). Preclinical data showed an increased use of HR after carbon ions and that wild-type and HR-deficient ovarian cell lines were more strongly sensitized to carbon ions.

This presentation will focus on the rationale, indications, and therapeutic potential of carbon ions in these different and challenging settings and their future perspectives.

Alexander Helm, GSI

CV: Dr. Helm graduated in Biotechnology at the University of Applied Sciences in Darmstadt, Germany. He is a researcher at the Biophysics Department of GSI Helmholtz Center for Heavy Ion Research GmbH. He has been working in the field of heavy ion radiobiology since 2009, with research activities on e.g. cytogenetic damage or cardiovascular effects. His current research interest is the immunomodulation of radiation, particularly of heavy ion radiotherapy.

Abstract: Radiation not only works through mere cell inactivation. It is acknowledged to feature immunomodulatory effects, which can elicit systemic immune responses. This has been exploited in cancer therapy, i.e. combining radiotherapy with immunotherapy, in order to treat metastatic cancer disease with partly highly encouraging results. However, still only a fraction of patients responds to such treatments. Heavy ion radiotherapy, due to its peculiar physical and biological effects, is believed to increase the immunomodulatory effects and the fraction of responding patients. It is therefore pivotal to understand by which mechanisms and dose regiments radiation triggers immune responses and how high LET heavy ion radiotherapy differs from conventional radiotherapy. This lecture will provide an overview of immunomodulatory effects of radiation and highlight the potential for an increased efficiency of heavy ion radiotherapy in that context.

Barbara Vischioni, CNAO

CV: Dr. Barbara Vischioni is a Medical Doctor and holder of a PhD in Molecular Oncology. She graduated from the “Università degli Studi” of Milan in 2000, and from 2001 to 2006, she conducted her doctoral research at the Pharmacology Laboratory at the Free University (VU) in Amsterdam, where she defended her thesis in molecular oncology in 2006.

After completing her PhD, Dr. Vischioni pursued a residency in the Radiation Oncology Department at the European Institute of Oncology in Milan from 2006 to 2009. From 2009 up to 2013 she was appointed at the National Center for Oncological Hadrontherapy (CNAO) as co-coordinator of the biological qualification of treatment ion beams and research radiobiological activities. In the same time frame, Dr. Vischioni also visited as a clinical research fellow the Gray Institute for Radiation Oncology and Biology in Oxford, UK, and the National Institute for Radiological Sciences (NIRS) in Chiba, Japan.

Since the beginning of the CNAO clinical proton and carbon ion treatments, Dr. Vischioni is a radiation oncology consultant. Now as senior consultant her main interests lie in translational research, head and neck, rare, and prostate tumors.

Abstract: Reirradiation is a challenging treatment option for patients with recurrent or persistent head and neck tumors, as traditional radiation therapy is associated with high rates of toxicity. Particle reirradiation, including proton and carbon ion therapy, has emerged as a promising alternative due to its ability to deliver a high radiation dose to the tumor while minimizing damage to surrounding healthy tissue. In this presentation, I will review the existing literature on particle reirradiation for head and neck tumors, with a focus on the clinical outcomes of proton and carbon ion reirradiation, including tumor control, patient survival, and treatment-related toxicity, in comparison with the data recently published from CNAO (National Center for Oncological Hadrontherapy). In 2017, the Italian Ministry of Health has included hadrontherapy in the Essential Levels of Care, recognizing its effectiveness for selected tumor indications, such as for tumors located in the head and neck region both in primary and recurrent setting: sarcomas (including chordomas and chondrosarcomas), paranasal and orbital tumors, and salivary gland tumors. At CNAO we use carbon ions especially for their radiobiological properties of higher effectiveness in radioresistant tumors compared to both proton and photon radiotherapy, and proton for the physical properties of sparing normal tissues and increasing the dose to the target. Further research is needed to optimize treatment protocols and identify the patients who are most likely to benefit from differential photons and ions treatments.

Bradford S. Hoppe, Mayo Clinic

 

CV: Bradford S. Hoppe MD, MPH is a Professor of Radiation Oncology and Medical Director of Particle Therapy at Mayo Clinic Florida.  He received his MD from Cornell Medical College, MPH from Harvard School of Public Health, and completed his residency at Memorial Sloan Kettering Cancer Center.  Dr. Hoppe spent 12 years at University of Florida, where he held the James E. Lockwood endowed professorship. He is chair of the NRG lymphoma working group and secretary of PTCOG-NA. His research focuses on the introduction of novel radiotherapy (RT) modalities into the clinic, including IMRT, proton therapy, and carbon ion radiotherapy.  He conducted pioneering work in proton therapy in the management of lymphoma, thymoma, lung cancer, and pancreatic cancer.  He has authored/co-authored over 180 articles published in many journals, including New England Journal of Medicine, Journal of Clinical Oncology, JAMA Oncology, Blood, Cancer, and Annals of Oncology.

Abstract: Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several treatment sequelae and reduced functional quality of life. Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating carbon ion radiotherapy, proton therapy, and the surgical treatment of pelvic sarcoma involving the bone. We describe the rationale and design of this clinical trial currently open to enrollment.

Carola Lütgendorf-Caucig, MedAustron

CV: Dr. Carola Lütgendorf-Caucig first graduated from the University of Vienna, Austria, and Humboldt University of Berlin as a Doctor of Medical Science. In 2005, she finished her Master of Public Health (MPH) at Universität Wien, and in 2016, her Master of Business Administration (MBA) at the WU Executive Academy, Austria. She has worked as the Lead of the Lung Cancer Program and the Lymphoma Program at the Department of Radiation Oncology at the Medical University of Vienna. Since 2016 she has been the Lead of the Pediatric Program and the CNS Program of MedAustron Ion Therapy Center and since 2018 she has been Clinical Co-Director and the director of the Institute. 

Abstract: Ewing and Rhabdomyosarcoma. Pediatric soft tissue sarcomas are a group of malignant neoplasms but challenging due to the fragile population. This lecture will give an overview of Ewing Sarcoma and Rhabdomyosarcoma in childhood. Ewing sarcoma is a tumor that arises primarily in the bone and soft tissue. While rare, Ewing sarcoma is the second most common malignant bone tumor in children and adolescents. Rhabdomyosarcoma is the most common soft tissue sarcoma in children, arising within embryonic mesenchymal tissues during the process of differentiation into muscle, fascia, and fat. Accurate diagnosis and staging, and prompt, carefully orchestrated therapy are particularly critical when treating Pediatric Ewing sarcoma and Rhabdomyosarcoma.

 Giulia Riva, CNAO

CV: Radiation oncologist working at CNAO since 2019. Fields of interest: skull base pathologies (such as chordomas, condrosarcomas, meningiomas), neuroncology, brain re-irradiation. Currently engaged in the research of encephalic toxicity after particle treatment.

Abstract: Chordoma is a rare primary bone tumor arising from notochord remnants with an incidence of 0.8–1 per million, with approximately one-third arising from the midline clivus and skull base.

Skull base chondrosarcoma is another rare malignant bone tumor arising from the chondrocytes or their precursor cells involved in the endochondral ossification, commonly at the petroclival junction, representing 6% of all skull base tumors and approximately 0.15% of all intracranial neoplasms. Because of their deep location, with proximity to cranial nerves and major vascular structures, gross-total surgical resection is achieved only rarely. Consequently, a combination of surgery, understood as maximum safe resection, and irradiation has become the mainstay of treatment. Both pathologies are considered radioresistant. Particle therapy, using protons and carbon ions, has the physical advantage of a finite range of dose deposition in brain tissue in depth with a steep dose fall-off after the Bragg peak, facilitating better normal tissue sparing, with a lower risk of radiation associated toxicities.

Jacques Balosso, ARCHADE

CV: Jacques BALOSSO, French, born in 1960, is Professor of Radiation Oncology and Radiobiology at Grenoble-Alpes University (UGA ex UJF) since 2003. From 2009 to 2017, he chaired the Cancerology and Radiotherapy Department of the Grenoble university hospital. His fields of study focus on gastro-intestinal cancers, radiobiology applied to radiotherapy, application of synchrotron radiation to radiotherapy at ESRF, medical physics and radiation protection. Finally, he has been involved since 1999 in the scientific development of hadrontherapy in France, notably as director of ETOILE and coordinator of France HADRON and he joined in September 2017 the ARCHADE project of hadrontherapy research in Caen in Normandy. Presently he’s the scientific coordinator of ARCHADE and chairperson of the radiotherapy and protontherapy department of François Baclesse Center in Caen, France, and member of the steering committee of ENLIGHT.

Abstract: THE FRENCH TRIAL

As part of the development of hadrontherapy projects in France, in 2010 the Ministry of Health and the National Health Insurance Fund requested that the promoters of this new form of radiotherapy organize the scientific monitoring of French patients treated with carbon therapy in Europe, first in Heidelberg (HIT) then also in Pavia (CNAO). This request led to the setting up of a transnational randomized study financed for the scientific part by the clinical research hospital program (which is a competitive grant by the Ministry of Health to French investigators in all fields of medicine) and for the treatment part by the health insurance itself, which fully funds the treatments in the two arms of the study.

The study took a long time to be set up due to its transnational characteristics. Finally, it opened for inclusion in December 2017 with a project to randomize 250 patients equally between the experimental arm where patients are referred to the CNAO for their carbon therapy and in a standard arm where patients are treated in France by photontherapy or protontherapy . The main criteria was the relapse free survival and a difference of 20% at 5 years was the hypothesis used to calculate the patient number.

The first inclusions took place at the end of 2017. In 2023 with five years of hindsight, we see that only 58 patients were included in the study and only half could be randomized (n = 29) because one in two patients, despite meeting the inclusion criteria, were considered inappropriate for carbon therapy at CNAO and therefore only half of the patients were randomized.

This represents a very great difficulty despite the opening of more than twenty centers in France, calling into question this process which by its very slowness represents a disproportionate financial and human resource investment.

Many attempts have been made to increase inclusion capacities, namely it has been proposed that the study be duplicated in countries with hadrontherapy and engaged in prospective clinical studies, Germany, Italy, Austria. Each time this possibility was ruled out by the investigators requested for various reasons.

The objective clinical approach by randomization is the only way to demonstrate the usefulness of carbon therapy which, previously, thanks to phase one and two studies, has been able to demonstrate its effectiveness. However, these two notions cannot be superimposed and the French health authorities and the health insurance which finances the treatments require that the usefulness be demonstrated, that is to say a significant cost/effectiveness advantage compared to the reference treatments.

The extremely slow recruitment in the PHRC-ETOILE led the promoter at the beginning of 2023 to discuss stopping this study, at least in its randomized form, and to study a modality which would make it possible to continue to address the patients selected with very specific eligibility criteria in European carbon therapy centers, while attempting to set up a comparative cohort in order to continue to carry out comparative work. This is an important condition for the French health authorities. Furthermore, comparisons based on bio-mathematical models do not satisfy our health authorities.

In total, the PHRC-ETOILE in its first form, which we could call the ETOILE-1 study, will now ended, the patients will of course be monitored for several years and we will study the implementation of an ETOILE-2 study.

Co-authors : Jacques Balosso , Olivia Febvey‑Combes, Annie Iung, Hélène Lozano, Abdoulkader Soumai Alloh, Catherine Cornu, Magali Hervé, Zohra Akkal, Michel Lièvre, Valérie Plattner, Francesca Valvo, Cristina Bono, Maria Rosaria Fiore, Viviana Vitolo, Barbara Vischioni, Stéphanie Patin, Hubert Allemand, François Gueyffier, Jennifer Margier, Pascale Guerre, Sylvie Chabaud, Roberto Orecchia and Pascal Pommier

Ref : Balosso J, Febvey-Combes O, Iung A, Lozano H, Alloh AS, Cornu C, Hervé M, Akkal Z, Lièvre M, Plattner V, Valvo F, Bono C, Fiore MR, Vitolo V, Vischioni B, Patin S, Allemand H, Gueyffier F, Margier J, Guerre P, Chabaud S, Orecchia R, Pommier P. A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy - including photon and proton

therapy - for the treatment of radioresistant tumors: the ETOILE trial. BMC Cancer. 2022 May 23;22(1):575. doi: 10.1186/s12885-022-09564-7.

Joao Seco, DKFZ

CV: Prof Seco graduated with a PhD from the University of London, at the Institute of Cancer Research (ICR) and Royal Marsden Hospital in London, UK. He then went on to become an Assistant Professor of Radiation Oncology at Harvard Medical School in Boston, working at the Massachusetts General Hospital (MGH). He then returned to Europe to work at the German Cancer Research Center, DKFZ in Heidelberg, heading up a new group dedicated to ion beam research and with the focus on 1) novel imaging technologies to reduce Bragg peak positioning errors in patients and 2) on investigating the mechanism of radiation triggered DNA damage via reactive oxygen species. He is also presently the Chair of Medical Physics at the Department of Physics and Astronomy, Heidelberg University and is a member of the EFOMP Scientific Committee, representing the DGMP, German Society for Medical Physics.

Abstract: The lesson will focus on providing an overview of treatment for radiation therapy, with direct application to particle therapy. An overview is provided of 3D conformal and of intensity modulated treatment planning. The concept of beamlet is introduced and explained within the context of for intensity modulated treatment planing. A short review of passive versus active is also presented and discussed within the context of particle treatment planning.

Katharina Seidensaal, HIT

Abstract: Osteosarcoma is the most prevalent malignant bone tumor in children and adolescents and is rarely seen in adults. Most osteosarcomas arise at the distal femur and the proximal tibia and are treated with a regimen of chemotherapy and surgery. There is a substantial number of patients with axial primary tumors (5–10%), which are non-resectable without unacceptable mutilation and thus have significantly reduced long-term survival chances. Particle therapy has demonstrated significant promise in the treatment of inoperable osteosarcoma. Particularly, in the challenging context of craniofacial osteosarcoma the long-term local control is promising and superior to the local control that can be achieved in case of inoperable pelvic tumors. The ability to achieve dose escalation while sparing critical structures makes particle therapy an attractive alternative to conventional radiotherapy. Further research and advancements are needed to optimize its role in the comprehensive management of inoperable osteosarcoma.

Kazutoshi Murata, QST

CV: Current Position: Chief Physician, Radiation Oncology Section, Department of Diagnostic Radiology and Radiation Oncology, QST Hospital,, National Institute for Quantum Science and Technology. Education: College/University:2006 M.D., Gunma University School of Medicine, 2014 Ph.D. in Radiation Oncology, Gunma University Graduate School of Medicine. Professional Experience / Appointment: 2012 – 2015 Assistant Professor Department of Radiation Oncology, Gunma University Hospital, 2015 – 2020 Assistant Professor of Gunma University Heavy Ion Medical Center, 2019 – 2020 Clinical fellow of Department of Radiation Oncology in Medical University of Vienna, 2020 – present Chief Physician, QST Hospital. Specialty and research field of interest: Gynecological radiation oncology, Breast Cancer, Particle therapy, Brachytherapy

Abstract: Breast cancer is increasingly being detected at earlier stages, and partial breast irradiation for patients with low-risk-group tumor has come to be applied in the US and Europe as an alternative to whole-breast irradiation. Based on those experiences, some institutes have tried using particle beams for partial breast irradiation for postoperative or radical intent for early breast cancer, but technical difficulties have hindered its progress. The National Institute of Radiological Sciences has been preparing for carbon-ion radiotherapy (C-ion RT) with radical intent for stage I breast cancer since 2011, and we carried out the first treatment in April 2013. In this lecture, we explain our first experience of C-ion RT as a treatment procedure for breast tumor.

Maciej Pelak, MedAustron

CV: Dr. Maciej Pelak is a radiation oncology specialist from Poland. He completed his medical studies in his hometown of Lublin in 2010. Between 2011 and 2017 he received his training in radiation oncology in Maria Sklodowska-Curie memorial National Institute of Oncology in Poland (including PhD degree in 2015) and Medical University of Katowice, Poland. Since 2017 he is a specialist in radiation oncology and since then has only worked in particle therapy centres: First PSI Villigen, Switzerland until 2018 and from 2018 until present in MedAustron Ion Therapy Center in Austria. His areas of interest include neuro-oncology, head & neck oncology (group lead for H&N tumours in MedAustron) and sarcomas. He also works as an expert for the Polish National Agency for Medical Technology Assessment (AOTMiT) as well as a tutor at Medical University of Krems and University of Applied Sciences Wiener Neustadt.

Abstract: Malignant melanoma is a rare, aggressive disease originating from melanocytes. It can occur anywhere on the skin or within mucosal membranes in the body. It combines a range of features which make it a therapeutic challenge: the ease with which it can disseminate locally, regionally and distantly, resistance to conventional radiation and chemotherapy. The standards of management for cutaneous melanoma are well established and involve wide surgical excision with radiation and immune therapy used both as adjuvant treatment in high-risk patients and in palliative/oligometastatic setting. Mucosal melanoma in its most frequent location – head and neck – remains a challenge for primary treatment as well. Its radiation resistance has drawn attention of particle therapy, but how successful has it been so far? The lecture will summarize the epidemiology of mucosal melanoma, differences against the cutaneous form, the application of particle therapy and research perspectives for this unique disease.

Makoto Shinoto, QST

CV: Dr. Shinoto graduated from Kyushu University School of Medicine in 2003. After completing his residency in radiation oncology, he got trained in carbon ion radiotherapy at the National Institute of Radiological Sciences (NIRS) from 2009 to 2012. Between 2012 and 2020, he worked as a radiation oncologist at Kyushu University Hospital and Ion Beam Therapy Center, SAGA HIMAT Foundation, specializing in gastrointestinal cancers and sarcomas. In 2020 he returned to QST Hospital (NIRS), where he now works as a section chief of pancreatic cancer.His main interest is the dose escalation and LET optimization with carbon ion radiotherapy for pancreatic cancer. 

Abstract: In Japan, pancreatic cancer is as the fourth most common cancer-related cause of death. The survival rates for this lethal cancer remain in the single digits, making effective therapy a constant challenge. Although the only opportunity for a cure is through radical resection, over half of the patients already have metastases at the time of diagnosis. In close to one-third of cases, vascular invasion causes unresectable locally advanced pancreatic cancer (LAPC) diagnosis. Advanced pancreatic cancer patients have had better results when treated with multi-agent chemotherapy regimens such as leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOFLFIRINOX) and gemcitabine with nab-paclitaxel (GnP). The use of radiation is controversial on the other hand. Recent reports indicate that the conventional dose of radiotherapy may not be effective with no overall survival improvement of chemoradiotherapy compared with chemotherapy alone.Carbon-ion radiotherapy was the first in the world to safely succeed in dose escalation and has achieved favorable results in treating LAPC. The local control rate improved with higher doses, which may have contributed to further enhance the survival outcome. Current dose intensities, meanwhile, are still insufficient to manage LAPC and achieve long-term survival. Therefore, to overcome this dreadful pancreatic cancer, we are carrying out further dose-escalation clinical trial.

Maria Bonora, CNAO

CV: Dr. Maria Bonora is a Medical Doctor. She graduated from “Università degli Studi di Pavia" in 2008, and later pursued a residency in the Radiation Oncology Department at the European Institute of Oncology in Milan, from 2009 to 2014, and at the National Center for Oncological Hadrontherapy (CNAO) in Pavia from 2014 to 2015. From June 2011 to June 2012 Dr. Bonora also visited as a observership The Royal Marsden NHS Foundation Trust in Sutton, United Kingdom. Since late 2015 Dr. Bonora works as a radiation oncology consultant at CNAO. She is engaged in clinical activity and resarch. Her main interests lie in clinical proton and carbon ion treatments and head and neck tumors.

Maria Rosaria Fiore, CNAO

CV: Maria Rosaria Fiore has almost 20 years of experience as radiation oncology. She is part of the Radiation Oncology Unit of the Italian National Cancer for Hadrontherapy CNAO since 2007. She landed at CNAO’s foundation after some years of experience in other health institutions both in Italy and abroad. Currently she is the referent of the Sarcoma’s pathology group and Ocular Melanoma at Cnao. She has been fully dedicated on the treatment especially of rare malignancies of spine and sacrum in particulary Chordoma’s istology subtype. She is involved in Italian and international groups/trials on many topics mainly concerning multidisciplinary oncology management such as Sacro trial. She is part of scientific associations among others to the Italian Sarcoma Group society (ISG) and European Musculo-Skeletal Oncology Society (EMSOS). Dr Fiore is the author and co-author of several scientific journal articles published in impacted peer review journals.

Abstract: Chordoma and Chondrosarcoma – Sacrum and Spine. Chordomas and chondrosarcoma are the most frequent primary spine malignancies. The common characteristics are locally aggressive growth pattern, high local recurrence rates and the proximity to structures deputed to relevant functions, as spinal cord, bowel, kidney, nerve roots and vascular structures. The therapeutic strategy is still a challenging multidisciplinary approach. Surgery is the main therapy for these tumors. En-bloc tumor resection with wide margins is recommended for most primary spine tumors. However, complete resection is not always possible due to the difficulty of removing the tumor without damaging the surrounding structures. When less invasive surgery is preferred to limit the morbidity, adjuvant radiotherapy is often recommended for mobile spine chordomas and chondrosarcomas. The limited radiation tolerance of nearby structures like the spinal cord, cauda equine, bowel, and nerve roots has been a challenge to delivering effective curative high dose to the tumor. Historically, doses below 60Gy have been associated with low local control, while improved results in terms of local control and disease-free time are obtained with doses above 66-70Gy. Recent advances in radiation therapy have focused on proton and heavy-ion therapies, which have favorable physical properties for avoiding nearby non-target structures. Furthermore, carbon ion has a superior radiobiological efficacy, which is theoretically more effective on radio-resistant tumors. Carbon ions radiotherapy (CIRT) are considered one of the best options for cancer treatment using particles because they can achieve both better dose distribution and higher biological effectiveness. CIRT has been also studied as an alternative to surgery for the treatment of large sacral chordoma when surgical resection with adequate oncological margins cannot be achieved by surgery alone or when surgery with wide margin is expected to be highly disabling. CIRT has shown promising results in treating sacral chordomas. The evidence for charged-particle therapies, such as CIRT, in the treatment of sacral chordomas is growing. Prospective and retrospective studies have supported the use of particle therapy in treating sacral chordoma. Although studies have reported favorable results using particle radiation therapy for both chordoma and chondrosarcoma, the current evidence for charged-particle therapies in the management of these tumors is still limited, and further research directly comparing charged-particle and photon-based therapies is necessary. After the 2000s, prospective and retrospective studies have been supporting the better results using particle therapy, and there is a continued effort to find high-quality evidence levels.

Mack Roach, UCSF

CV: Dr. Roach is a Professor of Radiation Oncology and Urology in the Department of Radiation Oncology at the University of California, San Francisco. He is a major authority on the treatment of localized prostate cancer. His research interests involve the application the optimal imaging and delivery modalities and criteria for selecting specific targets for radiation. Dr. Roach was a leader in establishing the American College of Radiology (ACR) Appropriateness Criteria Guidelines for defining how men with prostate cancer should be treated with radiotherapy and currently serves on the NCCN Guidelines Committee for Prostate Cancer. Dr. Roach has co-authored more than 200 peer-reviewed journal articles, book chapters and/or editorials. He has lead two large Phase III Trials evaluating the role of whole-pelvic radiation in men with prostate cancer with nearly 4000 men will have been enrolled on these two studies. He is currently also very active in the efforts to develop the capacity to harness heavy charged particles for the treatment of radiation resistant cancers.

Abstract: SHIPP (Stereotactic Heavy ions vs Protons vs Photons) for Unfavorable Intermediate Risk (UIR) prostate cancer: A Phase II Randomized trial – Roach et al.

In 2013, we formed the North American Particle Therapy Alliance (NAPTA), a multi-institutional consortium of experts in clinical radiation oncology, radiobiology, and the physics of accelerator design and delivery. The long-term goal of NAPTA is to perform clinically relevant research involving protons and carbon ion beams, including developing the infrastructure to conduct future clinical trials. In close collaboration with carbon ion partners, we propose a randomized Phase II trial, “SHIPP”, Stereotactic Heavy Ions (carbon) vs. Protons vs. Photons (x-rays), to provide high-level evidence for the safety and efficacy of ultra-hypofractionated carbon ion, proton, and photon RT for UIR prostate cancer. We will investigate and mitigate existing physical and biological uncertainties in particle therapy as they pertain to the proposed trial. This will establish the feasibility of a future Phase III clinical trial to test the hypothesis that SBRT (stereotactic body radiotherapy) using high-LET carbon ion RT will lead to better outcomes than photon or proton RT for UIR prostate cancer, via the following Specific Aims: Specific Aim 1: Minimize uncertainties across photon, proton, and carbon ion SBRT for UIR prostate Ca.

1.1 Establish optimal consensus planning margins to account for anatomical variations by comparing SBRT prostate treatment plans across modalities and institutions.

1.2 Minimize uncertainties by developing and implementing a carbon prostate SBRT credentialing program, including a carbon prostate phantom, and credential all institutions participating in this trial to ensure consistency across all delivery modalities within the study.

At the completion of this aim, we will develop recommendations for best practices of patient imaging and positioning as well as treatment planning to enable a rigorous, unbiased Phase II trial.

Specific Aim 2: Evaluate the safety and efficacy of carbon, proton, and photon based SBRT.

Tentatively PSMA PET-negative men with localized UIR prostate cancer will be randomized to SBRT, delivering 4 or 5 fractions of carbon ions, protons, or x-rays followed by adjuvant short-term androgen deprivation therapy (ADT). The SHIPP trial will have the following outcome measures:

1. Co-Primary endpoints:

1.1. Quality of life (QoL) patient-reported outcomes will be assessed using the (1) percentage of patients with >5 point reduction in the EPIC bowel domain at 1 year compared with baseline and (2) the percentage of patients with >2 point reduction in EPIC urinary domain at 1 year compared with baseline.

2. Secondary endpoints:

2.1. EPIC-26 (sexual)

2.2. Acute (≤30 days after RT completion) and late (>30 days after RT completion) genitourinary and gastrointestinal toxicity as measured by the National Cancer Institute’s Common Terminology Criteria for Adverse Events (v 4.0);

2.3. Post-treatment PSA endpoints: Nadir (lowest PSA attained after recovery of testosterone), biochemical control (Phoenix Definition)

Specific Aim 3: Refine RBE estimates and understanding for CIRT based on outcomes from Aim 2.

3.1 Identify which clinical RBE model (LEM vs. MKM vs. RMF) best describes clinical outcomes in Aim 2 by re-calculating individual institutional patient treatment plans using these different RBE models and correlating the RBE-weighted dose from each RBE model with toxicity outcomes.

3.2 Validate and intercompare the clinical RBE model in use at each institution by conducting cell survival RBE measurements in vitro and in an anthropomorphic pelvic phantom.

Based on the results of the randomized Phase II trial, we will determine whether a definitive Phase III trial is justified. For example, if carbon ion RT results in less toxicity and/or in a trend for lower PSAs, these findings would strongly support moving forward with a Phase III trial.

Masaru Wakatsuki, QST Hospital

CV: Current Position: Director of Department of Radiation Medicine, QST Hospital, National Institute for Quantum Science and Technology. Education: 1996-2002: Gunma University, School of Medicine with Medical Doctor Degree,2004-2007: Gunma University, Graduate School of Medical Science with Doctor of Philosophy degree. Professional Experience / Appointment: 2008–2009 Assistant professor, Gunma University,2009–2011 Research fellow, Harvard Medical School / MGH, 2011–2016 Medical Doctor, National Institute of Radiological Sciences, 2016–2020 Professor, Jichi medical University, 2020–present Director of Department of Radiation Medicine, QST Hospital, National Institute for Quantum Science and Technology. Specialty and research field of interest: Gynecological radiation oncology, Liver Cancer, Particle therapy, Brachytherapy

Abstract: This lecture will introduce the effectiveness of carbon ion radio therapy for liver tumors. Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastatic liver tumors are the most common indications for carbon-ion radiotherapy. All of them are indicated for patients who have either refused or are refractory to standard treatments such as surgical resection or ablation.Hypo fractionated irradiation of less than four times has been achieved for treatment of any of these diseases, and safety efficacy has been established. In particular, intrahepatic cholangiocarcinoma and hepatocellular carcinoma larger than 4 cm have been covered by Japanese health insurance since April 2022, and their effectiveness has been recognized, resulting in an increase in the number of patients treated.The first half of today's presentation will focus on treatment results, while the second half will present actual cases.

Niklas Wahl, DKFZ

CV: Niklas Wahl is a postdoctoral researcher and leader of the group Radiotherapy Optimization, embedded into the Department of Medical Physics in Radiation Oncology led by Prof. Jäkel, at the German Cancer Research Center – DKFZ. His career at DKFZ started in 2015, studying probabilistic proton dose calculation and optimization to obtain his PhD with honors in 2018. Afterwards, he continued as postdoctoral researcher and project coordinator, expanding his research to other numerical and computational challenges in radiotherapy treatment planning focusing on proton and ion beams. His research touches the topics of FLASH particle therapy, AI integration, nano-dosimetric planning and range-guided as well as multi-modality therapy. Niklas Wahl currently leads the development of the open-source treatment planning toolkit matRad. Besides his research activities, Niklas Wahl is part of multiple scientific and educational outreach activities like the Particle Therapy Masterclass since 2019.

Razvan Galalae, Klinikum Bremerhaven

Reiko Imai, QST

CV: Dr. Imai graduated from Gunma University School of Medicine. After completing her residency in radiation oncology, she got trained in carbon ion radiotherapy (CIRT) at the National Institute of Radiological Sciences (NIRS) in 2000. Between 2007 and 2009, she worked for the International Atomic Energy Agency (IAEA) as a radiation oncologist. In 2009 she returned to NIRS and joined the Sarcoma group. Since October 2015, Dr. Imai has been the Section Chief of Sarcoma at QST Hospital. She is also the chief of Sarcoma Section of Japanese Carbon-ion Radiation Oncology Study (JCROS) Group. She received the 2nd prize for best paper award at the 19th International Society of Limb Salvage General Meeting in 2017 and Alfred Miller Award of Sacro-Pelvic Tumor Study Group Meeting in 2018. She is a Radiation Oncology Specialist accredited by Japan Radiological Society and Japanese Society for Therapeutic Radiation and Oncology.

Abstract: Soft tissue sarcomas have a broader range of indications for resection than bone sarcomas, resulting in fewer cases treated with carbon ion radiotherapy (CIRT). Generally, CIRT is not indicated for soft tissue sarcomas in the extremities; however, proximal femoral sarcoma in elderly patients may be considered because amputation is offered as an alternative. In the case of retroperitoneal sarcomas, cases with vertebral body or iliac bone involvement within the treatable size range are often considered eligible. The current results of retroperitoneal sarcoma will be presented, and case presentations will also be conducted during the lecture.

Roberto Orecchia, IEO

CV: He graduated from the University of Turin and during his post-doctoral period, he obtained degrees in Radiotherapy, Medical Oncology and Diagnostic Imaging. From 1994 to 2018, he was Full Professor of Radiotherapy at the University of Milan and currently holds the role of Emeritus Professor in the same university. Since 1994, he is Head of the Department of Medical Imaging and Radiation Sciences of the European Institute of Oncology (IEO) in Milan and from January 2015, he is also the IEO’s Scientific Director. From 2010 to the end of 2018, he was also Scientific Director at the National Center of Oncological Hadrontherapy (CNAO) the only Centre in Italy that uses hadrontherapy with both protons and carbon ions to treat tumours. Currently, he is member of the CNAO’s Scientific Board.His clinical and research activities focus on various fields of radiotherapy and oncology, from the beginning characterized by a strong interest in innovation. To date he has published over three hundred and seventy scientific articles in journals listed in the Pub-Med.

Rossana Ingargiola, CNAO

CV: Dr. Rossana Ingargiola, Medical Doctor, graduated from the University of Palermo in 2013, and pursued a residency in Radiation Oncology at University of Milan at the European Institute of Oncology in Milan (IEO). After completing residency she worked at Department of Radiotherapy, Foundation of the IRCCS National Cancer Institute of Milan, particularly dedicated to Head and Neck cancers.  Since 2020 she is working at the National Center for Oncological Hadrontherapy (CNAO) as Radiation Oncologist dedicated to Particle therapy with protons and carbon ions in Head and Neck cancers and Reirradiation. She is focused both on clinical activity and research and she is the Principal Investigator of some clinical studies. She is part of coordinator members of reirradiation group on behalf of Italian Association of Radiation Oncologist (AIRO).

Abstract: In this lecture 2 clinical cases of re-irradiation treated at CNAO will be presented.

Shinichiro Mori, QST Hospital

Biography: (Education) March,2000 Allied Health Sciences (B.S.) Osaka University, Faculty of Medicine, Japan.March, 2002 Medicine (M.S.) Osaka University, School of Medicine, Japan.March, 2006 Medicine (PhD) Osaka University, School of Medicine, Japan

(Licensure and Certification) April,2000: Radiation technologist (Japan). April,2004: Certification of Medical Physicist (Japan)

(Hospital or Affiliated Institution Appointments) April,2002-March,2006 Technical Staff National Institute of Radiological Sciences.May,2006-May,2007 Research Fellow Massachusetts General Hospital, MA, Department of Radiation Oncology.June,2007-November,2007 Research Associate Japan Society for the Promotion of Science.December,2007-March,2016 Researcher, Medical Physicist National Institute of Radiological Sciences, Department of Medical Physics.April,2016 - Group leader National Institutes for Quantum and Radiological Science and Technology (QST)

(Major Committee Assignments) 1.ICRU Prescribing, Recording, and Reporting Ion-Beam Therapy (ICRU93) 2007-2016, 2.AAPM Task Group 290 Respiratory Motion Management for Particle Therapy, 2014-2021, 3.PTCOG H&N subcommittee, co-chair (physics), 2023.

(Awards and Honors) 2004 Young Investigator Award. The 4th S.Takahashi Memorial International Workshop on 3 Dimensional Conformal Radiotherapy.2007 Japan Society of Medical Physics (JSMP) 94th annual meeting, Award in therapeutic field.2010 American Society for Radiation Oncology (ASTRO), poster award, 3rd prize,2011 Japanese Society of Radiological Technology (JSRT) Dr Doi prize in 2011 (therapeutic field),2012 Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology,2013 Japan Society of Medical Physics (JSMP) 106th annual meeting, Award in therapeutic field,2016 The British Institute of Radiology, Best of BJR

Abstract: The treatment of patient positional accuracy including moving targets presents a special challenge in particle beam treatment.Relevant to particle beam treatments are motions that exceed approximately 0.5 cm and that happen within approximately 4 min (intra-fractional) or that change the patient geometry on a day-to-day basis (inter-fractional). Imaging plays a central role for intra- and inter-fractional changes. Prior to treatment, it is required to estimate the extent of positional variation and to build patient-specific motion models. During treatment delivery, it is important to monitor the positional changes and to correctly apply its mitigation approaches. To establish a relation between images of the same patient taken at different time instances, image registration needs to be employed. Different implementations and resulting ambiguities are introduced. Patient-specific positional variation effects and those mitigation strategies should be considered during treatment planning.In this presentation, I would like to emphasize the importance of “imaging” and “image guidance” in advanced particle beam therapy from a clinical point of view.

Silvia Molinelli, CNAO

CV: After graduation in physics in 2003 at the University of Pavia, I joined the medical physics unit of the San Raffaele Hospital in Milan for a 4 years training period and I received the specialization in medical physics at the University of Milan in July 2007. In 2006 I obtained a MSc in Radiation Biology at the University College of London, with a thesis project at the Erasmus medical center in Rotterdam. Since September 2007 I have been working as a medical physicist at the CNAO foundation in Pavia, including the beam commissioning and protocol definition phase. My activity is now focused on treatment planning and carbon ion modelling.

Abstract: Carbon ion radiotherapy (CIRT) is an advanced technique characterized by an excellent conformal dose distribution and unique radiobiological features, demanding high accuracy in all treatment phases, from imaging to delivery, to make the most of its well-known advantages. Organ motion is one of the sources of geometric and dosimetric uncertainty, which could lead to potential degradation of the therapeutic ratio. Particularly, in the abdominal region, both intra- and inter-fraction anatomy variations (i.e.: variable breathing pattern, organ position and filling status) may significantly limit its spatial accuracy. Special protocols for motion monitoring and motion mitigation during treatment imaging, planning and delivery are therefore necessary to guarantee target dose coverage and compliance of dose constraints for close-by gastro-intestinal organs at risk ( GI-OARs).

At the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy), the current approach for intra-fraction motion mitigation consists of the acquisition of a 4DCT for patient simulation, 4D-robust optimization of treatment plans and gated dose delivery combined with rescanning and abdominal compression. The use of 4DMRI acquisitions, showed the efficacy of our respiratory motion mitigation approach in minimizing dose degradation. To increase plan robustness against inter-fraction anatomical changes before and during the RT course, we adopted an ffline adaptive protocol for abnominal patients based on plan optimization on multiple anatomical scenarios, acquired at different days from RT-start. Plan quality assessment during delivery relies on weekly re-evaluative 4DCTs based on which a decision is taken on re-planning or treatment prosecution. This approach resulted overall safe and beneficial in terms of GI-OARs sparing and target coverage, for treatments located in the liver and neoadjuvant pancreatic protocols. Nevertheless, when the tolerance dose of adjacent radiosensitive GI-OARs is well below the prescription dose, i.e. in radical panceatic adenocarcinoma treatments, the need for an effective online adaptive protocol becomes evident.

Slavisa Tubin, MedAustron

CV: Dr. Tubin is a 44-years-old board-certified radiation oncologist and scientific investigator, currently working as a director of clinical radiobiology and scientific co-director at the MedAustron Center for Ion Therapy and Research (AUT). His research interests focus on immunomodulation. He is a principle investigator of ongoing national and international prospective trials on intentional induction of the non-targeted effects using partial tumor irradiation approach. He graduated at the University of Rome “La Sapienza” in 2008, and finished his residency in Rome in 2012. During 2010-2011, he joined the University of Miami performing the preclinical in vitro and in vivo research on radiation-induced bystander effects. The finding of those studies led to the development of a novel and unique technique for partial tumor irradiation. Dr. Tubin is leading the ESTRO focus group for innovative and unconventional radiotherapy techniques. He is ass. professor by Albert Einstein College of Medicine in New York.

Abstract: Unresectable recurrent bulky tumors represent a large spectrum of highly complex clinical scenarios that are very challenging to treat. Conventional radiotherapy is ineffective in most of these cases leaving the patients desperate and hopeless. This is due to the large tumor volume and the proximity of the tumor to critical organs and tissues, whose limiting dose constraints make it impossible to apply an ablative dose of radiation, especially if those regions have already been irradiated previously. Additionally, conventional radiotherapy applied to larger treating volumes is associated with lymphopenia, which negatively affects survival. Usually, the only therapeutic option that can be offered to those patients is palliative or best supportive care. That is why improved treatment outcomes for this patient population is needed. Recently, a small group of scientists inspired by the immunomodulatory potential of ionizing radiation moved beyond conventional treatment by giving the radiotherapy quite a different, unconventional form that might overcome the obstacles that make conventional radiotherapy impotent, resulting in an improved therapeutic ratio. This innovative, partial tumor irradiation, adopts different radiobiological mechanisms of action that are based on modulation of anti-tumor immune response. Often, a very dramatic bulky tumor regression, including even complete tumor response, can be observed. The principle behind this innovative approach is to improve the radiotherapy therapeutic ratio by adding an immune-mediated tumor cell killing component to the radiation-mediated tumor cell killing in order to boost the anti-tumor effect. The available literature suggests the safety and effectiveness of this unconventional approach characterized by the high neoadjuvant and immunogenic potential. This lecture will focus on rational, indications and therapeutic potential of novel partial tumor irradiation using carbon-ions, combined particle therapy and immunotherapy, and their future perspectives.

Tatsuya Ohno, GHMC

CV: Dr. Ohno is a radiation oncologist, Professor and Chair of Department of Radiation Oncology of Gunma University, and Director of Gunma University Heavy Ion Medical Center, Japan. He is a core member of the Japan Carbon-ion Radiation Oncology Study Group (J-CROS) since 2014. He has served as a Course Director on International Training Course on Carbon-ion Radiotherapy hosted by NIRS/QST and Gunma University since 2012. He has published many papers on clinical and basic research and has advised many overseas heavy ion radiotherapy projects.

Abstract: Carbon-ion radiotherapy for gynecological malignancy. The standard of care for locally advanced cervical cancer is concurrent chemoradiotherapy consisting of external beam radiotherapy, brachytherapy, and cisplatin-based chemotherapy. For brachytherapy, the implementation of 3D treatment planning and dose-volume histogram parameter evaluation represents a major advancement in the last decade. Recent clinical studies with 3D image-guided brachytherapy have shown increased local control and decreased late morbidities in patients with locally advanced cervical cancer, as compared with historical controls. On the other hand, large gross tumor volume at the time of brachytherapy, large high-risk clinical target volume, prolonged overall treatment period, and adenocarcinoma histology were associated with risk of local failure. Thus, there is a need for improving clinical outcomes by implementing novel dose escalation strategies, improving target dose coverage, shortening the overall treatment period, and incorporating new treatment modalities.

Carbon ion radiotherapy (C-ion RT) offers excellent dose distribution, enabling a concentrated administration of a sufficient dose within a target volume while minimizing the dose in the surrounding normal tissues. Additionally, C-ion RT provides biological advantages not seen in proton or photon therapy, owing to high linear energy transfer (LET); C-ion RT induces increased double-stranded DNA structures, causing irreversible cell damage independently of cell cycle phase or oxygenation, more so than lower LET irradiation such as proton and photon therapy. Several phase I/II clinical studies have been performed to establish an appropriate dose fractionation regimen for C-ion RT for locally advanced cervical cancer and gynecological malignant melanoma. In this lecture, recent our challenge of C-ion RT in combination with 3D image-guided brachytherapy for uterine cervical adenocarcinoma will be presented. Japan Carbon-Ion Radiation Oncology Study Group (J-CROS): Since 1994, National Institute of Radiological Sciences (NIRS, now QST hospital) in Chiba has conducted more than 50 phase I/II dose escalation studies using carbon ion beams for various types of cancer. Especially, short-course hypofractionated regimen has been developed. Standard dose and fractionation schedules have been established according to the cancer site and disease progression.

Subsequently, Hyogo Ion Beam Medical Center (2001), Gunma University (2010), SAGA Heavy Ion Medical Accelerator in Tosu (2013), and Ion-beam Radiation Oncology Center in Kanagawa (2015) have started their treatment. The best available treatment regimens developed at NIRS/QST were used and sometimes up-dated. With the increasing facilities, there was a growing interest in multi-institutional collaboration to produce evidence in Japan. The Japan Carbon-Ion Radiation Oncology Study Group (J-CROS) was organized in 2014. The J-CROS includes a Steering committee, Subcommittee for 12 cancer diseases, Cost-effectiveness committee, QA/QC committee, and Data center. Regular meeting was held in twice per year. E-mail communications and online meetings are also activated. Since 2016, Structure of Advanced Medical Care in particle therapy was updated in Japan. Multi-center prospective study and National registry with identical policy were started. Data from J-CROS was summarized as a particle therapy committee report of JASTRO and then submitted to the Ministry of Health, Labour and Welfare of Japanese government. Recently, Osaka Heavy Ion Therapy Center and Yamagata University have launched their treatment in the framework of J-CROS. Annual patient number treated with carbon ion radiotherapy almost reached 4,000 in 2021.

Thomas Held, HIT

CV: Thomas Held’s research field includes the implementation of interdisciplinary prospective clinical trials in radiation oncology with a focus on head and neck tumors. He is investigating the potential, side effects and patients’ perspective of high-precision treatment approaches such as ion beam therapy as principal investigator in several grant-funded clinical and preclinical investigations. Major ongoing projects include technical innovations, tumor imaging, molecular diagnostics and machine learning in translational radiation oncology. As consultant, clinical expert and group leader, he is responsible for personalized head and neck radiation oncology.

Abstract: Adenoid cystic carcinoma represents a rare and heterogenous tumor entity with locally aggressive growth pattern and frequent metastatic spread to the lungs. Due to intrinsic radioresistance, photon irradiation is rather ineffective. Several clinical studies reported favorable local control rates with carbon ion radiotherapy. Moreover, acute and late side effects can be significantly reduced. This presentation will share the Heidelberg approach of treating patients with adenoid cystic carcinoma in the primary and recurrent situation with a focus on clinical trials, technical innovations, molecular diagnostics and tumor imaging.

Walter Tinganelli, GSI

CV: Walter Tinganelli is a radiobiologist with international research experience. Since January 2019, Walter has been the Clinical Radiobiology Group Leader at the GSI, Germany. Master of Science in Biotechnology at the University of Naples Federico II, Walter did his Ph.D. in Radiobiology at the Technical University of Darmstadt in Germany. Graduated “Magna Cum Laude,” Walter worked for two years as the International Open Laboratory Group Director at the National Institute of Radiological Sciences (NIRS) in Japan. Back in Europe, he worked as the Principal Investigator of the Clinical Radiobiology Group at the Helmholtz Research Center for Heavy Ion (GSI) in Darmstadt, Germany. From November 2015 to December 2018, Walter worked as a Project Manager and Principal Investigator at the National Institute of Nuclear Physics, part of the National Institute of Nuclear Physics (INFN) in Trento, Italy. Walter is also part of the Life Science Working Group of the European Space Agency (ESA). Major research fields: Cancer research, Cell Biology, Particle Therapy, Radiobiology, Radioimmunotherapy, Space Radiation, in vitro and in vivo models.

Abstract: Radiobiology is a field that studies the effects of ionizing radiation on living organisms. It is a multidisciplinary science that investigates how radiation interacts with cells, tissues, and organisms. Radiobiologists aim to understand the mechanisms underlying both these beneficial and harmful interactions. Radiobiology plays a significant role in advancing cancer treatment techniques, like particle therapy. Particle therapy selectively targets cancer cells while preserving healthy tissues. But understanding radiobiology also contributes to establishing radiation safety standards and assessing risks in various domains such as nuclear energy, space exploration, and medical diagnostics. In this talk, we will explore the molecular and cellular processes behind radiobiology to identify potential risks associated with radiation exposure. We will discuss fundamental concepts like RBE and OER before moving on to more advanced topics like radioimmunotherapy and FLASH Radiation.

Hitoshi Ishikawa, QST

CV: Position: Deputy Hospital Director, QST Hospital, National Institutes for Quantum and Radiological Science.

EDUCATION: 1995 M.D., Gunma University, School of Medicine, Gunma, Japan,2002 Ph.D., Gunma University, Graduate School of Medicine, Gunma, Japan.

FACULTY APPOINTMENT: 2002-2004 Research Associate, Department of Radiation Oncology, Gunma University, School of Medicine.2004-2006 Head Physician, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences (NIRS).2006-2011 Assistant Professor for Department of Radiation Oncology, Gunma University, School of Medicine.2011-2017 Associate Professor of Department of Radiation Oncology, University of Tsukuba, Faculty of Medicine 2017-2020 Professor, Department of Radiation Oncology, University of Tsukuba, Faculty of Medicine 2020-Present Current position.

AWARD: 2007 Research Encouragement Award, International Association for the Sensitization of Cancer Treatment,2009 Umegaki Award, Japanese Society for Radiation Oncology (JASTRO),2009 Research Encouragement Award, Kitakanto Medical Society,2013 Excellent Presentation Award from Japan Society of Clinical Oncology,2016 Award for Best Educational Lecturer, Japanese Society for Radiation Oncology,2020 Abe Award, Japanese Society for Radiation Oncology (JASTRO).Activity:#Councilors of JASTRO (2010-present), Japanese Lung Cancer Society (2013-present), Japanese Esophageal Society (2015), Japanese Society of Thermal Medicine (2017).#Directors of Japanese Society of Thermal Medicine (2019-), JASTRO (2022-), Japanese Lung Cancer Society (2022-), Radiation Biology Group of JASTRO (2017-), International Association for Sensitization of Cancer Treatment (2019-).#Member of Guideline Committee (JASTRO, Japanese Lung Cancer Society, Japanese Esophageal Society, Japanese Urological Association, Japanese Society of Thermal Medicine).

SKILL: IMRT, Brachytherapy, Proton Therapy, Carbon-ion Therapy, Hyperthermia, BNCT.

Abstract: Carbon-ion therapy for prostate cancer Hitoshi Ishikawa, Noriyuki Okonogi, Shuri Aoki, Mio Nakajima, Masaru Wakatsuki, Hiroshi Tsuji, Shigeru Yamada National Institutes for Quantum Science and Technology Carbon-ions make a better dose distribution with greater biological effects on the tumors than photons and protons. Since carbon-ion radiotherapy (CIRT) provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, it has been tested for prostate cancer as well as renal cell carcinoma and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma, which are known to be radioresistant urological tumors, at our institute since 1994. So far, CIRT for prostate cancer has been provided to more than 4500 prostate cancer patients. In the initial study (protocol 9402), 35 T2b-T3 prostate cancer patients, and the dose was escalated from 54 Gy (RBE) to 72 Gy (RBE) in 20 fractions, and the tolerable dose to the rectum and the basic methodology for CIRT for prostate cancer were established. The second study (protocol 9703) was initiated in 1998, and early-stage prostate cancer was treated with CIRT alone, while high-risk prostate cancer was treated with CIRT combined with ADT. A total of 97 patients were enrolled in these studies and a recommended dose of 66.0 Gy (RBE) was determined. In 2015, the Japan Carbon-ion Radiation Oncology Study Group was established to start a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. At our institute, a new study has been started to test a ultra-hypofractioned CIRT for prostate cancer.

Carbon-ion therapy for renal cell cancer Hitoshi Ishikawa, Noriyuki Okonogi, Shuri Aoki, Mio Nakajima, Masaru Wakatsuki, Hiroshi Tsuji, Shigeru Yamada National Institutes for Quantum Science and Technology.

The gold standard treatment for patients with renal cell carcinoma (RCC), which is known to be a radioresistant tumor, is surgical removal of the primary tumor, and ablative therapies such as cryotherapy, radiofrequency ablation, and stereotactic body radiotherapy (SBRT) are also offered for elderly patients or patients with comorbidities with small-sized (<4cm) RCCs. On the other hand, no reatment options are established for RCC patients with large localized tumors (>4 cm) or for patients unmet for surgery due to advanced disease stage, comorbidities, advanced age, or refusal of surgery. At our institute, carbon-ion radiotherapy (CIRT) was started to treat primary RCC patients in 1997, since it offers not only higher dose concentrations but also increased biological efficacy due to an inherently high-linear energy transfer, compared to photon-based radiotherapy. Through two prospective studies of CIRT for primary RCC, 12-fraction CIRT is now our standard treatment. Furthermore, we are now testing a new prospective phase I/II study for 4-fraction CIRT. In 2026, CIRT for primary RCC will be determined whether it is covered by the national health insurance system or not, and the working group of the Japan Carbon-ion Radiation Oncology Study Group is now systematically reviewing accumulated evidence and investigating registry data obtained from all Japanese institutions.