Optimum radiation dose for palliation in head and neck squamous cell carcinoma (OpRAH) - A phase 3 randomized controlled trial.

Purpose: Radiotherapy is frequently employed for palliative treatment in locally advanced head and neck squamous cell carcinoma (HNSCC) but radiation dose fractionation regimens are not well-defined. We designed this phase 3 randomized controlled trial to compare two weekly hypo fractionated regimes and study the effect on progression-free survival (PFS) in this subset of patients.

Materials and methods: Non-metastatic locally advanced HNSCC patients (n = 305) who were not suitable for curative treatment were randomized to Arm A (20 Gy/5#/5 days) and Arm B (30 Gy/5#/5 days). PFS and OS were recorded along with acute toxicity using patient-reported quality of life HN QLQ 43.

Results: From April 2020 to August 2023, 390 patients were randomized, of which 305 were eligible for final analysis. At a median follow-up of 13.9 months, PFS and median overall survival (OS) for the entire cohort was 7.4 and 10.03 months, respectively. PFS (p-0.553) and OS (p-0.203) did not differ significantly between the two groups. Toxicity rates were similar between the two arms and dose escalation was well tolerated. Patients with a better PS were found to have significantly better OS. No significant benefit in OS or PFS was observed in patients who received neoadjuvant chemotherapy (NACT), underwent definitive conversion, or received palliative chemotherapy at progression.

Conclusion: This is the largest phase 3 RCT to analyze the safety and efficacy of weekly palliative radiotherapy regimens and has not demonstrated further improvement with dose escalation.