Nomogram to Predict the Benefit of Intensive Treatment for Locoregionally Advanced Head and Neck Cancer

Purpose: Previous studies indicate that the benefit of therapy depends on patients' risk for cancer recurrence relative to noncancer mortality (omega ratio). We sought to test the hypothesis that patients with head and neck cancer (HNC) with a higher omega ratio selectively benefit from intensive therapy. Experimental Design: We analyzed 2,688 patients with stage III-IVB HNC undergoing primary radiotherapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522). We used generalized competing event regression to stratify patients according to omega ratio and compared the effectiveness of intensive therapy as a function of predicted omega ratio (i.e., omega score). Intensive therapy was defined as treatment on an experimental arm with altered fractionation and/or multiagent concurrent systemic therapy. A nomogram was developed to predict patients' omega score on the basis of tumor, demographic, and health factors. Analysis was by intention to treat. Results: Decreasing age, improved performance status, higher body mass index, node-positive status, P16-negative status, and oral cavity primary predicted a higher omega ratio. Patients with omega score >= 0.80 were more likely to benefit from intensive treatment [5-year overall survival (OS), 70.0% vs. 56.6%; HRof 0.73, 95% confidence interval (CI): 0.57-0.94; P = 0.016] than those with omega score <0.80 (5-year OS, 46.7% vs. 45.3%; HR of 1.02, 95% CI: 0.92-1.14; P = 0.69; P = 0.019 for interaction). In contrast, the effectiveness of intensive therapy did not depend on risk of progression. Conclusions: Patients with HNC with a higher omega score selectively benefit from intensive treatment. A nomogram was developed to help select patients for intensive therapy.