Reduction of Radiotherapy Dose to the Elective Neck in Head and Neck Squamous Cell Carcinoma; Update of the Long-Term Tumor Control of a Randomized Clinical Trial

A multicenter prospective randomized controlled trial was performed to investigate whether dose reduction to the elective nodal volume (PTVelect) in head and neck squamous cell carcinoma (HNSCC) reduces radiation-induced dysphagia, primary endpoint, without compromising tumor control, secondary endpoint. In this abstract, we report on the long-term follow-up of the secondary endpoint. Patients with non-metastatic HNSCC were treated with primary (chemo)radiotherapy (RT) including irradiation of the bilateral elective neck. Patients were randomized (1:1) between the standard arm, irradiation to PTVelect up to an equivalent dose of 50 Gy and the experimental arm, irradiation to PTVelect up to an equivalent dose of 40 Gy. The primary tumor and involved nodes were treated according to the standard of care up to an equivalent dose of 70 Gy (PTV high dose). (NCT01812486) Secondary endpoints were overall survival (OS), local recurrence (LR), regional recurrence (RR) and distant metastasis (DM). OS was estimated using Kaplan-Meier method and compared with log-rank test. LR, RR and DM were assessed using competing risk method and compared with Pepe and Mori’s test. RR were projected on the initial RT planning computed tomography studies to identify the localization of recurrence. Between 2008 and 2011, 200 patients were enrolled. Median follow up was 7.6 years (IQR 6.6-8.7). The 5 year (5Y) OS was 56.5% (CI95% 45.7;65.9) in the 40 Gy arm versus 49.6% (CI95% 39.0;59.2) in the 50 Gy arm (p=0.56). In the reduced 40 Gy arm, 5Y-LR was 17.2% (CI95% 10.4;25.4) versus 13.8% (CI95% 7.7;21.5) in the standard 50 Gy arm (p=0.39); 5Y-RR was 14.0% (CI95% 7.9;21.8) versus 7.5% (CI95% 3.3;14.0) (p=0.10) and 5Y-DM rate was 12.9% (CI95% 7.1;20.6) versus 24.4% (CI95% 16.3;33.5), respectively (p=0.07). Majority of RR in the 40 Gy arm (9 of 13) were projected in the PTV high dose and 2 RR were seen outside the treated RT volume (Table 1). Only 2 RR occurred in PTVelect irradiated up to 40 Gy which was the same number as RR occurring in the 50 Gy PTVelect. At 5 years of follow-up, no statistically significant differences regarding OS, LR, RR nor DM were observed between both treatment arms. This study is underpowered to undoubtedly demonstrate non-inferiority and to change the standard of care to 40 Gy. However, since only two RR in the PTVelect in both treatment arms were observed, reducing the dose to PTVelect appears safe and these results support further research in de-escalating the dose to the elective neck.Abstract 31; Table 1Regional recurrences classified according to the treatment arm (LRR: Locoregional recurrence; IRR: Isolated regional recurrence)40 Gy50 GyRecurrence n=13Recurrence n=7PTV high dose9IRR5PTV high dose5IRR1LRR2LRR1RR + DM2LRR + DM1RR + DM2PTV elect2IRR1PTV elect2IRR1RR + DM1LRR + DM1Outside planning volume2LRR2 Open table in a new tab