Outcomes of Phase I Trial of Patients With Recurrent Head and Neck Squamous Cell Carcinoma Treated With Re-Irradiation With Stereotactic Body Radiation Therapy and Concurrent Cisplatin

Abstract

Stereotactic body radiation therapy (SBRT) offers a treatment option for patients with unresectable, previously radiated, locoregionally recurrent head and neck cancer. Given the resistant and advanced nature of many of these cancers, the addition of chemotherapy to radiotherapy is typically recommended as a radiosensitizer. We therefore performed a phase I clinical trial in order to establish a maximum tolerated dose of SBRT with concurrent chemotherapy in locoregionally recurrent head and neck cancer. We previously reported our safety data, and now present our secondary outcome endpoints.Major inclusion criteria were recurrence of previous squamous cell carcinoma of the head and neck in patients who had previously undergone radiotherapy to doses ≥ 45 Gy to the area of recurrence, ≥ 6 months prior to enrollment, and who were medically unfit for surgery, deemed unresectable, or refused surgery. Patients were treated with radiation therapy every other day for five fractions at three dose levels: 30 Gy, 35 Gy, and 40 Gy. Cisplatin was given prior to every SBRT fraction at a dose of 15 mg/m2. Secondary end points reported herein are locoregional control (LRC), freedom from distant metastasis (FFDM), and overall survival (OS).Twenty patients were enrolled and of those 18 patients were evaluable for secondary endpoints. Nine patients had a primary tumor in the oropharynx, four patients in the oral cavity, three in the neck, one in the larynx, and one simultaneously in the larynx and neck. Five patients received a radiation dose of 30 Gy, three patients received a dose of 35 Gy, and 9 patients received a dose of 40 Gy. With a median follow up of 9 months the 1-year OS was 38.9%. LRC at 1 year was 45.7% and FFDM at 1 year was 87.8%. Median time to locoregional progression was eight months. There was a trend to improved OS with increasing SBRT dose, 40 Gy vs < 40 Gy, (P = 0.08). Locoregional control at 1 year was also significantly improved with increased SBRT dose, 12.5% for patients that received < 40 Gy vs 85.7% for patients that received 40 Gy (P = 0.005). Median gross tumor volume (GTV) was 11.725 cm3. There was an improved 1-year locoregional control with a GTV ≤11.725 cm3 of 64.8% vs 0% for tumors > 11.725 cm3 (P = 0.01).Patients with recurrent head and neck cancer typically present with advanced, unresectable disease, and therefore have limited definitive treatment options. This phase I study demonstrates that SBRT with concurrent Cisplatin provides reasonable locoregional control and overall survival with radiation doses of 40 Gy.