The impact of frailty on mortality in non-surgical head and neck cancer treatment: Shifting the clinical paradigm.

OBJECTIVE:Compare survival of head and neck cancer (HNC) patients treated with surgical or non-surgical management according to frailty, quantify frailty with the Risk Analysis Index (RAI), a validated 14-item instrument. MATERIALS AND METHODS:Prospective cohort study of newly diagnosed HNC patients (≥18 years) who had frailty assessment from April 13, 2016 to September 30, 2016. Primary outcome was overall survival at 1- and 3-years. Cox proportional hazard models were utilized to examine mortality with predictor variables. Adjusted and unadjusted (Kaplan-Meier) survival curves stratified by either RAI scores or treatment modality were plotted. Kruskal-Wallis and likelihood ratio chi-square tests were used for comparing clinicodemographic variables. RESULTS:Of 165 patients, 54 (32.7%) were managed non-surgically, 49 (29.7%) were treated with definitive surgery only, and 62 (37.6%) were treated with multimodality (surgery + adjuvant) therapy. Among the full cohort and subgroup analysis of the frail/very frail (RAI ≥ 37), non-surgical patients had worse or similar 3-year survival than those treated with surgery +/- adjuvant therapy. Multivariable Cox proportional hazard models demonstrate that frail patients treated non-surgically experienced worse survival than their counterparts treated with surgery (HR = 2.50, p = 0.015, 95% CI: 1.19, 5.23) or multimodality therapy (HR = 3.91, p < 0.001, 95% CI: 1.94-7.89). CONCLUSION:Across all levels of frailty, long term survival of HNC patients treated without surgery is either worse than or like those treated with surgery. These findings (1) challenge current practices of steering patients "too frail for surgery" towards non-surgical, "non-invasive" therapy, and (2) suggest equipoise warranting randomized trials to clarify treatment of frail patients.