Palliative Radiotherapy in Locally Advanced Head and Neck Cancer after Failure of Induction Chemotherapy: Comparison of Two Fractionation Schemes

CONTEXT: Among patients with locally advanced head and neck squamous cell cancers (LAHNSCC), the prognosis after nonresponse or progression despite induction chemotherapy (IC) is dismal, and further treatment is often palliative in intent. Given that nonresponse to chemotherapy could indicate subsequent radioresistance, we intended to assess the outcomes with two different fractionation schemes. AIMS: To compare the outcomes of two fractionation schemes- ’standard’ (consisting 3GyX5 daily fractions for 2 consecutive weeks) versus ‘hybrid’ (6GyX3 fractions on alternate days during the 1(st) week, followed by 2GyX5 daily fractions in the 2(nd) week). SETTINGS AND DESIGN: Prospective randomized controlled two-arm unblinded trial. MATERIALS AND METHODS: Patients with locally advanced oropharyngeal, laryngeal, and hypopharyngeal cancers treated with a minimum of two cycles of taxane, platinum, and fluorouracil-based IC were eligible if residual disease volume amounted <30 cm(3). Kaplan-Meier survival curves were compared by the log-rank test. Response rates were compared using the unpaired t-test. Quality of life (QOL) was measured via patient reported questionnaires. RESULTS: Of the initially enrolled 51 patients, 45 patients (24 from standard arm, and 21 from the hybrid arm) were eligible for analysis. Despite being underpowered to attain statistical significance, there still seemed to be a trend towards improvement in progression-free (Hazard ratio (HR) for progression: 0.5966; 95% CI 0.3216-1.1066) and overall survival (HR for death: 0.6062; 95% CI 0.2676-1.3734) with the hybrid arm when compared to the standard arm. Benefits were also observed with regards to response rates and QOL. Rate of complications were similar in both arms. CONCLUSIONS: In comparison to the routinely used palliative fractionation scheme of 30 Gray (Gy) in 10 fractions (Fr), the use of hybrid fractionation which integrates hypofractionation in the 1(st) week, followed by conventional fractionation in the 2(nd) week, could possibly offer better response rates, QOL increments, and potential survival benefits among LAHNSCC patients even after failing to respond to IC.