Avoiding Adjuvant Prophylactic Neck Irradiation in Lateralized Oral Cavity Cancer (APRON)

Oral cavity squamous cell carcinoma (OCSCC) is the second most common cancer in India with an age standardised ratio of 10.3 per 100,000 (both sexes combined) (1). Most patients (60%-80%) present in advanced stages with a high risk of nodal involvement. The current standard of care involves surgery followed by adjuvant radiotherapy (RT), often including elective nodal irradiation (ENI) even in pathologically node-negative patients. However, recent evidence suggests that well-selected patients with adequate surgical clearance may be adequately treated with limited volumes of ENI, potentially sparing them unnecessary toxicity. The APRON study is a single-arm, phase II trial evaluating whether limiting ENI is non-inferior to standard adjuvant RT in carefully selected patients with lateralized oral cavity cancers. Eligible patients are adults with biopsy-proven squamous cell carcinoma of the bucco-alveolar region or oral tongue who have undergone margin-negative resection and adequate elective nodal dissection (≥18 nodes). Only well-lateralized tumours (≥1 cm from midline for tongue cancers) are included. The primary endpoint is regional control at 2 years, defined as any nodal recurrence (ipsilateral or contralateral). Secondary endpoints include swallowing function (MD Anderson Dysphagia Inventory; modified barium swallow), local and regional recurrence-free survival, disease-free and overall survival, acute/chronic toxicity, quality of life, salvage rates for recurrence, and dosimetry comparisons. The study also assesses the safety and efficacy of moderate hypofractionation (50 Gy/20 fractions) in the adjuvant setting. A sample size of 106 patients is planned, with early stopping rules for safety. Statistical analysis will use the Clopper-Pearson method for nodal failure rates and propensity score matching with historical controls for non-inferiority testing. By limiting ENI in well-selected patients, APRON aims to reduce treatment-related morbidity while maintaining oncologic efficacy, potentially improving functional outcomes and preserving regional immune function. The study is expected to provide valuable evidence for de-escalated adjuvant strategies in OCSCC management. CTRI NUMBER: CTRI/2025/03/082341.