Proceedings of the 2024 National Association for Proton Therapy, Proton Collaborative Group, and Particle Therapy Co-operative Group—North America Proton Therapy Research Forum: Refining Particle Therapy Trial Design and Identifying High-need Areas for Continued Investigation

The article reports on a research forum convened by major proton/particle-therapy associations in North America, aimed at advancing clinical trial design for particle therapy and pinpointing underserved research areas. The forum organizers gathered stakeholders — clinicians, physicists, trialists — to assess current trial methodologies, barriers to trial execution, and strategic priorities. Key discussion points included: the need for robust randomized controlled trials comparing proton/particle therapy with photon therapy, the importance of standardized endpoints (e.g., normal-tissue toxicity, quality of life, cost-effectiveness), and the challenge of enrolment and funding in a growing but still limited particle-therapy infrastructure. The proceedings highlight that although particle therapy centers are proliferating, the evidence base remains incomplete; specific tumour sites and vulnerable populations (such as paediatric, re-irradiation, and rare cancers) were flagged as high-need areas.
The forum concludes that to fully realise the potential of particle therapy, future trials must be better designed: enriched for meaningful endpoints, sufficiently powered, and targeted to the populations most likely to benefit. Additionally, collaboration across centres, alignment of trial infrastructure, and strategic prioritisation of high-need indications will be crucial. Without these efforts, the promise of particle therapy risks being under-delivered due to weak evidence and poor trial uptake. The authors thus call for coordinated action by clinical networks, funders, and technology developers to refine trial design and expedite investigation into the areas with greatest unmet need.

Actionable Recommendations:
1 – Standardize Trial Endpoints and Data Collection
Establish uniform outcome metrics — including toxicity grading, quality-of-life assessments, and cost-effectiveness data — to enable meaningful comparison across proton and photon trials.
2 – Prioritize High-need Populations
Focus clinical trials on tumour types and patient groups with the greatest potential benefit from particle therapy, such as paediatric cancers, re-irradiation cases, skull-base tumours, and rare malignancies.
3 – Promote Multi-institutional Collaboration
Create coordinated trial networks across proton centers to overcome low patient volumes at individual sites, enhance statistical power, and accelerate evidence generation.
4 – Refine Trial Design and Methodology
Implement adaptive and pragmatic trial designs that better reflect real-world clinical practice, while integrating biological and dosimetric correlates to strengthen clinical relevance.
5 – Secure Sustainable Funding and Policy Support
Advocate for governmental and industry funding streams dedicated to particle-therapy research, ensuring stable resources for long-term multicentre trials and translational studies.

International Journal of Radiation Oncology, Biology, Physics – Volume 123, Issue 4p1146-1158 – November 15, 2025 – https://doi.org/10.1016/j.ijrobp.2025.06.3880