Stereotactic Body Radiation Therapy (SBRT) With or Without Daily Systemic Therapy for Re-Irradiation of Unresectable, Recurrent, Head and Neck Squamous Cell Carcinoma

Abstract

Patients with unresectable, previously irradiated recurrent/second primary head and neck squamous cell cancers (SCC) have limited therapeutic options. Stereotactic body radiotherapy (SBRT) may overcome this inherent radioresistance, and radiosensitizing systemic therapy may further enhance RT effect. In this analysis we compared the outcomes of patients who received concurrent systemic therapy to a historical cohort to evaluate oncologic outcomes.Eligible patients had recurrent or second primary squamous cell carcinoma of the head and neck who were previously irradiated, ≥6-month interval prior to SBRT, and deemed unfit/unresectable or refused surgery. Patients were treated with SBRT to 30-40 Gy for five fractions every other day. Kaplan-Meier log-rank and Cox-proportional regression hazards analysis was performed to evaluate patient/disease factors predictive of locoregional control (LRC), and overall survival (OS), measured from the end of SBRT.A total of 63 patients met the inclusion criteria; seventeen patients enrolled on the phase 1 trial received cisplatin 15 mg/m2 prior to each fraction, and 3 patients received concurrent weekly cetuximab. The remainder of patients did not receive concurrent chemotherapy. The majority of cases were recurrences (n = 45, 71.4%). SBRT dose was 30-40 Gy (median 40 Gy). Median follow-up of the entire cohort was 6.6 months (range). One year LRC was 43.4% for patients receiving systemic therapy and 68.7% for the historical cohort (P = 0.14), and 1 year OS was 32.9% and 44.1%, respectively (P = 0.39). The addition of systemic therapy was not associated with a significant LRC or OS benefit on univariate or multivariate analysis (HR 0.80, 95% CI 0.29-2.2, P = 0.67). Gross tumor volume (GTV) ≤10 cc was significantly associated with improved LRC on univariate analysis (HR 0.31, 95% CI 0.12-0.81, P = 0.02) and trended toward significance on multivariate analysis (HR 0.3695% CI 0.13-1.02 P = 0.06). GTV≤10 cc was significantly associated with improved OS on both UVA (HR 0.27 95% CI 0.13-0.57, P < 0.01) and MVA (HR 0.20 95% CI 0.09-0.49, P < 0.01).Systemic therapy with SBRT did not appear to improve LRC or OS over SBRT alone for in the re-irradiation setting of patients with recurrent or second primary squamous cell carcinomas. We found that small tumors (GTV ≤10 cc) may be better suited for SBRT compared to larger ones (GTV > 10 cc).