Radiation-induced hypoglossal nerve palsy after definitive radiotherapy for nasopharyngeal carcinoma: Clinical predictors and dose-toxicity relationship.

Abstract

BACKGROUND AND PURPOSE\nRadiation-induced hypoglossal nerve palsy is a debilitating and irreversible late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC) and other skull base tumors. This study sets to evaluate its incidence and clinical predictive factors, and to propose relevant dosimetric constraints for this structure to guide radiotherapy planning.\n\n\nMATERIALS AND METHODS\nWe undertook a retrospective review of 797 NPC patients who underwent definitive intensity-modulated radiotherapy (IMRT) between 2003 and 2011. Cumulative incidence and clinical predictors for radiation-induced hypoglossal nerve palsy were evaluated. Archived radiotherapy plans were retrieved and 330 independent hypoglossal nerves were retrospectively contoured following standardized atlas. Optimal threshold analyses of dosimetric parameters (Dmax, D0.5cc, D1cc, D2cc, Dmean) were conducted using receiver operating characteristic curves. Normal tissue complication probability was generated with logistic regression modeling.\n\n\nRESULTS\nWith a median follow-up of 8.1\u202fyears, sixty-nine (8.7%) patients developed radiation-induced hypoglossal nerve palsy. High radiotherapy dose, premorbid diabetes, advanced T-stage and radiological hypoglossal canal involvement were independent clinical risk factors. Maximum dose received by 1\u202fcc volume (D1cc) was the best predictor for the development of radiation-induced nerve palsy (AUC\u202f=\u202f0.826) at 8\u202fyears after IMRT. Hypoglossal nerves with D1cc of 74\u202fGy EQD2 had an estimated palsy risk of 4.7%. Nerves with D1cc <74\u202fGy EQD2 had significantly lower risk of palsy than those ≥74\u202fGy EQD2 (2.4% vs 20.8%, p <0.001).\n\n\nCONCLUSION\nIncidence of radiation-induced hypoglossal nerve palsy was high after definitive IMRT for NPC. D1cc <74\u202fGy EQD2 can serve as a useful dose constraint to adopt during radiotherapy planning to limit palsy risk to <5% at 8\u202fyears after IMRT.