COMPORT: Compartmentalization in Postoperative Radiotherapy for Head and Neck Squamous Cell Carcinoma – a single-arm phase II clinical trial

Vollständiger Abstract

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Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. Postoperative radiotherapy (PORT) ± chemotherapy improves outcomes in patients with high- and intermediate-risk pathologic features but is associated with substantial morbidity. While de-escalation strategies have been explored mainly in HPV-positive oropharyngeal cancer, prospective evidence across broader HNSCC populations is lacking. Retrospective evidence suggests that a pathology-driven, tailored PORT strategy may safely reduce treatment volumes while maintaining acceptable oncologic control. This trial prospectively evaluates the safety and efficacy of compartmentalized PORT (COMPORT) of the four most common HNSCC localizations. Methods COMPORT is a multicenter, single-arm phase II trial with Bayesian design that will enroll 50 patients with resected oral cavity, oropharynx, larynx, and hypopharynx HNSCC and an indication for adjuvant PORT, as recommended by a multidisciplinary tumor board. Eligible patients will be treated according to a COMPORT-specific algorithm, omitting low-risk anatomical compartments. In some cases, this results in complete omission of PORT. Primary endpoint is the rate of recurrence in omitted (non-irradiated) compartments within 30 months. Secondary endpoints include loco-regional control, progression-free survival, overall survival, physician-rated toxicity (TAME score), and quality of life (MDADI, EORTC QLQ-C30 and HN43). In this trial, COMPORT will be considered successful if the probability that recurrence rates remain below 18% (historical rate + 10% safety margin) exceeds 90%. An interim safety analysis will be performed after 20 enrolled patients with ≥ 6 months follow-up. The trial will be stopped if recurrences in omitted compartments exceed 5 cases. Discussion COMPORT will provide prospective evidence on de-escalated and tailored PORT in HNSCC as a strategy to reduce treatment toxicity and improve quality of life, while preserving adequate oncologic outcomes. By validating this approach across diverse HNSCC subsites, the study may lay the foundation for a more individualized, less morbid standard of care, which should be validated with a subsequent randomized non-inferiority trial. Trial registration ClinicalTrials.gov NCT07058805, registered on 22.06.2025. Cantonal Ethics Committee KEK-BE 2025–01420.