Six versus five fractions per week (chemo)-radiotherapy for locally advanced head and neck squamous cell carcinoma - A nationwide cohort study from the Swedish head and neck cancer register.

Abstract

Radiotherapy (RT) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) can be intensified by delivering 6 (6fx/w) instead of 5 (5fx/w) fractions per week. Randomized trials have demonstrated superiority for 6fx/w in patients treated without concurrent chemotherapy (CRT). This real-world analysis compares 6 vs 5 fx/w in LA-HNSCC all-comers, treated predominantly with CRT, where fractionation schedules were determined by region-specific guidelines, resembling a natural experiment. All RT-treated patients from 2017 onwards across the six Swedish health care regions with T3-4 (all sites), T1-2 N3 (p16/HPV-positive oropharynx (HPV+ OPSCC)), T1-2N2c-N3 (all other sites) ≤ 70 years were included. Treatment schedules followed regional guidelines: three regions used 5fx/w, three used 6fx/w. Overall survival (OS) was the primary endpoint; loco-regional control (LRC) secondary. Multivariable Cox-Regressions and adjusted Kaplan-Meier estimates compared outcomes for patients treated at centers utilizing 5fx/w or 6fx/w. Data was acquired from the prospective Swedish Head and Neck Cancer Register. 405 (320 with CRT) treated at 6fx/w centers and 535 (352 with CRT) patients at 5fx/w centers were included. Median overall treatment time was 40 days (IQR 38-43) for 6fx/w and 46 days (IQR 46-49) for 5fx/w centers. Baseline characteristics were similar. Five-year OS was 67% for 6fx/w and 66% for 5fx/w (HR 0.93, 95%CI 0.73-1.19). Five-year LRC was significantly improved with 6fx/w (84%) vs 5fx/w (78%), HR 0.69 (95%CI 0.49-0.97). Findings remained in subgroup analyses, although the absolute benefit was larger for p16-negative HNSCC. Moderately accelerated RT with 6fx/w improved loco-regional control in LA-HNSCC patients treated mainly with CRT, without OS benefit.