Head and neck proton therapy in France: A missed opportunity or a challenge in front of us?

Following major advances of the best of photon-techniques such as intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT) and, to arrive soon, magnetic resonance (MR)-linac radiotherapy, there are still substantial opportunities in the treatment of head and neck cancers to further reduce the toxicity burden. Proton therapy represents another attractive option in this high-quality and highly competitive precision radiotherapy landscape. Proton therapy holds promises to reduce toxicities and to escalate the dose in radioresistant cases or cases where dose distribution is not satisfactory with photons. However, the selection of patients for proton therapy needs to be done using evidence-based medicine to build arguments in favor of personalized precision radiation therapy. Referral to proton therapy versus IMRT or SBRT should be registered (ProtonShare® platform) and envisioned in a formalized clinical research perspective through randomized trials. The use of an enrichment process using a model-based approach should be done to only randomize patients doomed to benefit from proton. To tackle such great opportunities, the French proton therapy challenge is to collaborate at the national and international levels, and to demonstrate that the extra-costs of treatment are worth clinically and economically in the short, mid, and long-term. In parallel to the clinical developments, there are still preclinical issues to be tackled (e.g., proton FLASH, mini-beams, combination with immunotherapy), for which the French Radiotransnet network offers a unique platform. The current article provides a personal view of the challenges and opportunities with a focus on clinical research and randomized trial requirements as well as the needs for strong collaborations at the national and international levels for PT in squamous cell carcinomas of the head and neck to date.

[Proton therapy in France in 2019]. / État des lieux de la protonthérapie en France en 2019.

Among over 100 proton therapy centres worldwide in operation or under construction, French proton therapy is coming to full maturity with the recent opening of the Nice (1991, upgrade in 2016) and Caen (2018) facilities next to the Orsay (1991, upgrade in 2010) centre. Proton therapy is a national priority for children and young adults in all three centres. The patient-related activity of the three French centres is coordinated via the Protonshare portal to optimise referral by type of indication and available expertise in coordination with the French society of radiation oncology SFRO and French radiotherapy centres. The centres are recognised by the French Health Care excellence initiative, promoted by the ministry of Foreign Affairs. The three centres collaborate structurally in terms of clinical research and are engaged at the international level in the participation to European databases and research initiatives. Concerted actions are now also promoted in preclinical research via the Radiotransnet network. Ongoing French developments in proton therapy are well presented in international hadron therapy meetings, including European Proton Therapy Network and Particle Therapy Cooperative Oncology Group. Proton therapy teaching in France is offered at several levels and is open to colleagues from all radiation oncology centres, so that they are fully informed, involved and trained to facility recognition of possible indications and thereby to contribute to appropriate patient referral. This close collaboration between all actors in French radiation oncology facilitates the work to demonstrate the required level of medical and scientific evidence for current and emerging indications for particle therapy. Based on that, the future might entail a possible creation of more proton therapy facilities in France.

[Is proton beam therapy the future of radiotherapy? Part I: clinical aspects]. / La protonthérapie: avenir de la radiothérapie? Première partie: aspects cliniques.

Proton beam therapy uses positively charged particles, protons, whose physical properties improve dose-distribution (Bragg peak characterized by a sharp distal and lateral penumbra) compared with conventional photon-based radiation therapy (X-ray). These ballistic advantages apply to the treatment of deep-sited tumours located close to critical structures and requiring high-dose levels. [60-250 MeV] proton-beam therapy is now widely accepted as the "gold standard" in specific indications in adults--ocular melanoma, chordoma and chondrosarcoma of the base of skull --and is regarded as a highly promising treatment modality in the treatment of paediatric malignancies (brain tumours, sarcomas…). This includes the relative sparing of surrounding normal organs from low and mid-doses that can cause deleterious side-effects such as radiation-induced secondary malignancies. Other clinical studies are currently testing proton beam in dose-escalation evaluations, in prostate, lung, hepatocellular cancers, etc. Clinical validation of these new indications appears necessary. To date, over 60,000 patients worldwide have received part or all of their radiation therapy program by proton beams, in approximately 30 treatment facilities.