Cranial Neuropathies in Advanced Nasopharyngeal Carcinoma: Neurological Recovery and Prognosis After Modern Radiotherapy and Systemic Chemotherapy

Abstract

Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. This study sets to evaluate the prognostic factors and recovery pattern of cranial neuropathies, using longitudinal clinical data from two tertiary oncology centers in endemic areas.Case records of consecutive T4 NPC patients who received definitive IMRT in 2004-2019 were reviewed. Distribution of cranial neuropathies at disease presentation were recorded. Time to partial and full neurological recovery, time from neurological recovery to re-palsy, relapse-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors for neurological recovery were analyzed using multivariable Cox regression.During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was 2 months (IQR, 1-4 months). All patients completed definitive IMRT, and 94% of patients received chemotherapy. The 5-year RFS and OS of the combined cohort were 50.8% and 60.1% respectively. Median RFS of patients with single versus multiple neuropathies were 5.8 years and 4.2 years (P = 0.62). Cranial nerves (CN) VI (56.4%), V2 (47.9%) and V3 (29.2%) were most frequently involved. Over a median follow-up of 6.4 years, 111 (22%) and 289 (57.3%) neuropathies attained partial and full recovery respectively, and 86% of the recoveries occurred within the first year after definitive radiotherapy. CN III, IV, VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), CN XII (48.6%), and CN II (18.2%) (P < 0.001). Positive smoking history, optic nerve involvement, and long duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences at the base of skull.Rate and durability of cranial neuropathy recovery in this contemporary NPC cohort compared favorably with data from the 2D radiotherapy era. Both patient and disease factors affected the chance of nerve recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.