Very accelerated radiotherapy or concurrent chemoradiotherapy for N3 head and neck squamous cell carcinoma: Pooled analysis of two GORTEC randomized trials

Objective To analyze the outcome of N3 patients treated with very accelerated radiotherapy (VART) or different schedules of concurrent chemoradiotherapy (CRT) within two phase III trials. Patients and methods Data of 179 patients with N3 HNSCC from two GORTEC randomized trials (96-01 and 99-02) were pooled. Patients received either VART: 64.8 Gy/3.5 weeks or one of the 3 following CRT regimens: Conventional CRT: 70 Gy/7 weeks + 3 cycles carboplatin-5FU; Moderately accelerated CRT: 70 Gy/6 weeks + 2 cycles carboplatin-5FU; Strongly intensified CRT: 64 Gy/5 weeks + cisplatin (days 2, 16, 30) and 5 FU (days 1–5, 29–33) followed by 2 cycles adjuvant cisplatin-5FU. Results Median follow-up was 13.3 and 5.2 years for GORTEC 96-01 and GORTEC 99-02, respectively. Five-year overall survival (OS) was 13.8%. No significant difference was observed between CRT versus VART in terms of OS (hazard ratio [HR]: 0.93, p = 0.68), loco-regional progression (HR: 0.70, p = 0.13), or distant progression (HR: 0.86, p = 0.53). OS was worse for patients with T3-4 tumors versus early T stage (11.0% versus 25.7%, p = 0.015). In multivariate analysis, the oropharyngeal subsite presented a higher risk of distant metastasis (as first event 46.5% vs 19.2%, p < 0.001),). A significant interaction between treatment modalities and subsites has been observed concerning loco-regional and distant failures. Conclusion The outcome of N3 HNSCC was extremely poor despite treatment intensification and no difference between CRT and VART. Both distant metastases and loco-regional failures remain important treatment challenge.