Personalized volume de-escalated elective nodal irradiation in oropharyngeal squamous cell carcinoma (DeEscO): a study protocol.

Background
Definitive (chemo)radiotherapy of oropharyngeal squamous cell carcinoma (SCC) consists of treatment of the macroscopic tumor and prophylactic irradiation of the lymphatic drainage system: the elective clinical target volume (CTV). In this study, we reduce the elective CTV based on the personalized factors T-stage, clinical lymphatic involvement, and lateralization of the primary tumor.Methods
The primary objective is to evaluate efficacy and safety of an individualized de-escalation of elective node irradiation volumes. We collected a multi-institutional dataset of 598 oropharyngeal SCC patients in whom detailed lymph node involvement was reported. Based on the data, we developed a model of lymphatic tumor progression to estimate the probability of occult metastases in the clinically negative lymph node levels (LNLs). The dataset can be visualized on https://lyprox.org/. Based on this model and clinical judgement, we created tables that define the personalized elective CTV for different combinations of T-stage, midline extension and clinical LNL involvement. The primary endpoint of this multicentric, prospective, single-arm trial is the rate of out-of-field nodal recurrences after 2 years. The study will be conducted in 6 centers across Switzerland and 120 patients will be enrolled.Discussion
This study sets out to personalize the elective CTV in oropharyngeal SCC patients, with the goal to de-escalate radiotherapy for patients and herewith improve therapy-associated toxicity and quality of life. The results of this study may be used to personalize treatment in oropharyngeal SCC patients.Trial Registration
The trial was registered on ClinicalTrials.gov NCT06563362, on 20/08/2024. Ethical approval was obtained on 21/01/2025, BASEC-Nr 2024-01936. Protocol Version 2.1, 12/05/2025.