PURPOSE: Patients with oligometastasis may have prolonged survival with multisite stereotactic ablative radiation therapy (SABR). Evidence to support this paradigm is scarce in squamous cell carcinoma of the head and neck (HNSCC). The multicenter open-label randomized GORTEC 2014-04 (NCT03070366) phase 2 study assesses survival without definitive quality of life (QoL) deterioration of omitting upfront chemotherapy in oligometastatic patients with HNSCC using SABR alone, in the French Head and Neck Intergroup. METHODS AND MATERIALS: Eligible participants (≥18 years old with 1-3 oligometastases, the Eastern Cooperative Oncology Group score 0-2) were randomly assigned (1:1) to receive chemo-SABR or SABR alone. Salvage treatments were left to the physician's appreciation. The standard therapy was considered to be systemic therapy and SABR (chemo-SABR
EXTREME regimen [5 fluorouracil/platinum/cetuximab]). The primary endpoint was 1-year (±3 months) overall survival rate without definitive deterioration (ie, without subsequent better QoL score) of the global European Organisation for Research and Treatment of Cancer QoL Questionnaire-Core30 score. RESULTS: Between September 2015 and October 2022, 69 participants were assigned to receive chemo-SABR (N = 35) or SABR alone (N = 34)
57 had lung-only metastases (82.6%), and 40 had isolated metastasis (58.0%). The median baseline QoL score was 66.7 (IQR, [50.0-83.3]). The median follow-up was 55.3 months (95% CI, 45.0-69.7). Of participants (N = 59) evaluable for the primary endpoint, 16 of 29 (55.2%, 90% CI, 0.38-0.71) and 16 of 30 (53.3%, 90% CI, 0.37-0.69) were alive and free of QoL deterioration at 1 year in the SABR-alone and chemo-SABR arms. However, QoL deterioration was deeper with chemo-SABR (50.0
IQR, [41.7-66.7]) than with SABR alone (16.7
IQR, [16.7-41.7]). In intent-to-treat analysis (N = 69), median survival was 42.3 months (95% CI, 26.5-not reached) with chemo-SABR and 41.1 months (95% CI, 32.1-66.9) with SABR alone
median progression-free survival was 12.9 (95% CI, 7.5-17.3) and 7.4 months (95% CI, 4.2-15.6) in the chemo-SABR and SABR alone arms, respectively. Rates of severe treatment-related toxicities were 21 of 35 (60.0%) with chemo-SABR and 3 of 34 (8.8%, no grade 5) with SABR alone. CONCLUSIONS: Using SABR alone, the omission of upfront EXTREME-based chemotherapy and maintenance cetuximab in oligometastatic patients with HNSCC resulted in similar survival but much less severe QoL deterioration and fewer toxicity rates. SABR alone could be a reasonable alternative in oligometastatic patients with HNSCC.