During the Hadrontherapy for Life symposium held in March 2025 in Caen, France, leading international experts reviewed global carbon-ion and proton therapy programs, highlighting strategies, emerging outcomes, and ongoing efforts to treat complex and radio-resistant tumors.
Global advances in carbon-ion and particle therapy are reflected in diverse clinical strategies and promising outcomes from leading centers worldwide.
Current research efforts now focus on personalization - immunotherapy combinations, multi-ion approaches (helium, oxygen), and MR-guided, biomarker-driven adaptation - while underscoring the need for stronger international collaboration to overcome funding barriers and accelerate Phase III trials.
AUSTRIA | Piero Fossati, MedAustron
MedAustron, Austria’s only particle therapy center, has treated >2,600 patients since initiating proton therapy in 2016 and carbon-ion therapy in 2019.
The center focuses on pediatric oncology, CNS tumors, head-and-neck cancers, sarcomas, and complex re-irradiation cases.
Its multi-ion capabilities, including helium and soon oxygen, combined with registry-based research, support personalized approaches aimed at improving local control and minimizing toxicity.
ITALY | Ester Orlandi, CNAO
Since 2011, CNAO has treated >5,500 patients with protons and carbon ions.
Clinical efforts focus on head-and-neck tumors, sarcomas, chordomas, chondrosarcomas, and ocular melanoma, with ongoing projects exploring simultaneous integrated boosts, biomarker-driven trials, AI-based predictive models, and combinations with immunotherapy.
Multi-institutional collaborations ensure robust evidence generation and integration of advanced particle therapy into routine practice.
GERMANY | Semi Harrabi, HIT
The HIT facility has treated ~10,000 patients since its opening in 2009, with an equal split between protons and carbon ions.
The center features three treatment rooms, including a rotating heavy-ion gantry, and employs advanced imaging for adaptive radiotherapy.
HIT’s clinical focus encompasses adenoid cystic carcinoma, recurrent disease, pediatric tumors, and other complex indications, while ongoing research explores MR-guided adaptive therapy, variable RBE, multi-ion approaches, LET optimization, and AI-driven planning.
JAPAN | Shigeru Yamada, QST Tatsuya Ohno, Gunma University
Japanese particle therapy centers account for a substantial share of global experience, treating ~11,000 patients in 2023 across seven CIRT centers.
QST has treated >16,000 patients since 1994 and currently manages >900 annually, offering ultra-short regimens for a range of tumors and advancing multi-ion therapy to enhance LET in radioresistant cases.
Gunma University treats ~800 patients per year, focusing on pediatric sarcomas, head-and-neck, and locally advanced cervical cancers, often integrating CIRT with image-guided brachytherapy and concurrent immunotherapy.
FRANCE | Jacques Balosso, Grenoble-Alpes University
The ETOILE project identified high-priority indications for carbon-ion therapy through a structured process involving epidemiologic studies and expert tumor boards.
Tumors with high local failure, radioresistance, and precise imaging definition, such as adenocarcinomas, sarcomas, chordomas, and hepatocellular carcinomas, were selected. This informed the design of the three-room ÉTOILE center, which can treat ~1,000 patients annually, and guided the PHRC-ÉTOILE transnational randomized trial with CNAO.
UNITED-KINGDOM | Ellie Light, University of Liverpool
In the United Kingdom, efforts focus on assessing the clinical integration of CIRT for radioresistant tumors such as NSCLC, pancreatic cancer, prostate cancer, skull-base chordomas, chondrosarcomas, and selected soft tissue sarcomas.
Evidence suggests improved local control, survival, and reduced toxicity compared with photons and protons.
The upcoming Normandy cyclotron in France may serve as a hub for comparative studies and collaborative trials, supporting the future establishment of a UK CIRT center and participation in international research initiatives.
Particle therapy is increasingly recognized as a precision modality for highly radio-resistant tumors and lesions near critical structures.
High LET beams, including carbon and helium ions, enable precise dose escalation and hypofractionation. Current advances focus on multi-ion therapy, hypoxia-guided adaptive planning, and MR-guided delivery.
Broader adoption will require international collaboration, biomarker-driven trials, and strategies to overcome logistical and funding challenges.
Developing robust clinical evidence for hadrontherapy remains a major challenge in France, where limited funding mechanisms, low accrual rates, and restrictive reimbursement frameworks slow the adoption of advanced modalities such as proton and carbon ion therapy.
Current national efforts focus on reducing morbidity, adaptive radiotherapy, and innovations like multi-ion therapy, FLASH, and spatially fractionated irradiation.
A promising strategy involves combining prospective registries, interventional comparative studies, and basket trial designs that group tumors by shared biological characteristics rather than histology. Coupling this framework with systematic in-room imaging, hypoxia tracking, liquid biopsies, and multi-omics analyses would enable biologically informed escalation to carbon ions or combined proton-carbon treatments, supporting national adoption, reimbursement, and clinical impact of advanced particle therapies.
CARBON-ION RADIOTHERAPY IN PANCREATIC CANCER
PDAC remains a severe public health crisis, characterized by a growing global incidence and its projection to become the second leading cause of cancer death by 2040. The inherent radio-resistance of PDAC, coupled with its aggressive, early metastatic spread and challenging anatomical proximity to critical GI structures, severely limits definitive local control with conventional modalities.
CIRT represents a highly promising future opportunity by leveraging high LET beams to maximize biological efficacy while significantly reducing dose to sensitive adjacent tissues.
Innovative clinical strategies utilizing PBS and moderate hypofractionation for locally advanced PDAC have demonstrated mild toxicity and promising clinical results, including a 73% two-year local control rate and median overall survival >24 months.
Future research aims for further dose escalation via Simultaneous Integrated Boost (SIB) techniques to strategically increase the high LET dose within the hypoxic tumor core, thereby overcoming intrinsic radio-resistance outcomes.
CARBON-ION RADIOTHERAPY IN PEDIATRIC ONCOLOGY
The remarkable improvement in pediatric cancer survival, now approaching 85–90%, shifts focus from disease eradication to mitigating long-term morbidity. Particle therapy is essential in this shift, offering superior conformality to protect developing organs and preserve neurocognitive and sensory function.
Helium ions provide a refined alternative to protons, with sharper distal fall-off and reduced lateral scattering - critical for skull-base and posterior fossa tumors.
For highly radio-resistant diseases such as inoperable pediatric osteosarcoma, CIRT delivers meaningful biological advantages, achieving local control rates near 80% with acceptable toxicity. Active scanning also minimizes neutron dose, alleviating concerns about secondary malignancies.
Emerging data support expanding CIRT for pediatric osteosarcoma, chordoma, and select skull-base entities. Coordinated international efforts remain essential to consolidate evidence and refine treatment paradigms.
Experts discussed current challenges and future strategies for carbon-ion research, focusing on case-mix, patient selection, and the integration of biological. They highlighted the lack of validated hypoxia-imaging methods, the need for stepwise trial designs, and the logistical and financial barriers to international studies.
Discussions also addressed reoxygenation dynamics, immune interactions, and opportunities to expand carbon-ion therapy to common tumors.
The session provides valuable insights for shaping upcoming trials.
Watch the full video for detailed expert perspectives and ongoing initiatives.
The Symposium Hadrontherapy for Life was recorded in Caen, Normandy – in collaboration with the University of Caen-Normandy, CYCLHAD, François Baclesse Cancer Center, Normandy Hadrontherapy (NHa), Région Normandie and IBA.
The statements of the healthcare professionals included in these videos reflect only their opinion and personal experience. They do not necessarily reflect the opinion of any institution with whom they are affiliated or CYCLHAD.
MR: Magnetic Resonance, CNS: Central Nervous System, CNAO: National Center for Oncological Hadrontherapy, AI: Artificial Intelligence, HIT: Heidelberg Ion-Beam Therapy Center, CT: Computed Tomography, RBE: Relative Biological Effectiveness, LET: Linear Energy Transfer, CIRT: Carbon-Ion Radiotherapy, NSCLC: Non-Small Cell Lung Cancer, PDAC: Pancreatic Ductal Adenocarcinoma, GI: Gastrointestinal, PBS: Pencil Beam Scanning.
