Dose-painting after multi-block endoscopic endonasal surgery in sinonasal tumours: protocol for the SinocaRT randomised phase II trial.

introductionSinonasal carcinomas are rare malignancies with an overall poor prognosis. These tumours arise in close proximity to vital structures, critical organs and cranial nerves involved in essential sensory and endocrine functions. Although multimodal treatment strategies combining surgery and radiotherapy (RT) are required to maximise the chances of cure while sparing surrounding tissues and reducing the risk of recurrence, they are associated with substantial cumulative morbidity. Building on high conformality and steep gradients of modern dose-painting RT, multidisciplinarity can be exploited on technical inter-disciplinary aspects. In particular, minimally morbid endoscopic endonasal multi-block surgery (EES), together with accurate histosurgical mapping, can be leveraged to individualise target tumour subvolumes delineation by risk level to avoid unnecessarily large irradiation and reduce the morbidity of RT while maintaining or improving local tumour control. METHODS AND ANALYSIS: We designed a randomised multicentre phase II study to assess whether EES-based histosurgical mapping delineation and optimisation using a dose-painting approach can reduce treatment-related toxicity compared with standard intensity-modulated RT using conventional delineation in sinonasal carcinomas. The primary endpoint is the proportion of patients free from severe clinically significant radiation-induced toxicity involving the nasal mucosa, eyes, auditory system, endocrine system and/or brain within 3 months following RT completion. Secondary objectives include assessing the proportion of patients free from severe toxicities at 12 months, tumour control, quality of life, tolerance profile, RT plan quality and the association of histoclinical characteristics and radiomic features with toxicities. To ensure tumour control and avoid quality biases on toxicity outcomes, multidisciplinary volume delineation with the surgeon, as well as prospective individual case review (ICR) of the first 2 cases for each centre and both technique arms, and retrospective ICR for all cases, will be conducted.Eligible patients will be 1:1 randomised between dose-painting based on histosurgical mapping (experimental arm) or standard delineation/optimisation (control arm), with stratification according to RT modality (photons or protons). We plan to enrol 52 patients. RT will start no earlier than 4 weeks and no later than 8 weeks after surgery, and will be delivered over a 7-week period. Patients will be followed-up for 18 months after completion of RT. We hypothesise that dose-painting RT, which relies on extensive interdisciplinary optimisation, will enable a selective de-escalation of irradiated volumes, which should translate into lower treatment-related toxicities. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Comité de Protection des Personnes Nord-Ouest IV (N°ID-RCB: 2022-A02011-42; cppnordouestiv@univ-lille.fr) on 12 April 2023, and authorisation from the National Agency for Medical and Health Products Safety on 15 May 2023. The most recent amendment (V2) was approved on 25 January 2024. Written informed consent will be obtained from all participants. Final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines. TRIAL REGISTRATION NUMBER: NCT05943119.