Delayed lower cranial neuropathy after oropharyngeal intensity-modulated radiotherapy: A cohort analysis and literature review

Abstract

Background: The purpose of this study was to examine swallowing-related lower cranial nerve palsy (LCNP) in oropharyngeal cancer (OPC) survivors after intensity-modulated radiotherapy (IMRT).

Methods: Patients treated with definitive IMRT (66-72 Gy) were pooled from institutional trial databases. Prospective analyses on parent trials included videofluoroscopy, clinical LCNP examination, and questionnaires pre-IMRT, 6 months post-IMRT, 12 months post-IMRT, and 24 months post-IMRT. Time-to-event and incidence of LCNP was estimated with competing risk methods. Literature review (1977-2015) summarized published LCNP outcomes.

Results: Three of 59 oropharyngeal cancer survivors with a minimum 2-year follow-up developed hypoglossal palsy ipsilateral to the index tumor (median latency 6.7 years; range 4.6-7.6 years). At a median of 5.7 years, cumulative incidence of LCNP was 5%. LCNP preceded progressive dysphagia in all cases. Published studies found median incidence of radiation-associated LCNP was 10.5% after NPC, but no OPC cancer-specific estimate.

Conclusion: Although uncommon, the potential for late LCNP preceding swallowing deterioration highlights the importance of long-term functional surveillance in OPC survivorship.

Keywords: cranial neuropathy; dysphagia; hypoglossal nerve; oropharyngeal cancer; radiotherapy.

FIGURE 1. Kaplan-Meier curve of overall survival

Median overall survival was not yet reached; 5- and 10-year overall survivor rates were 98.2% and 87.3% in this pooled cohort.

FIGURE 2. Cumulative incidence of LCNP

At a median follow-up of 5.7 years, cumulative incidence of delayed lower cranial neuropathy was 5%; 5- and 7-year LCNP rates were 2.1% and 6.1%, respectively.

FIGURE 3. LCNP case trajectories

Measures of swallowing function longitudinally plotted for each LCNP case using modified barium swallow (MBS) outcomes (Dynamic Imaging Grade of Swallowing Toxicity, DIGEST), perceived dysphagia per MD Anderson Dysphagia Inventory (MDADI) questionnaire, and standardized diet rating per Performance Status Scale of Head and Neck Cancer (PSSHN). Delayed LCNP preceded progressive late dysphagia (per fluoroscopy, diet, and self-report) in all 3 cases.

FIGURE 4. LCNP literature review

Incidence rates of LCNP after head and neck radiotherapy in published cohort studies are summarized by Forest Plot method. Median incidence rate of LCNP was 10.5% in long-term survivorship of NPC. While most cohorts observed incidence rates under 12%, two cohorts with long follow-up of survivors (minimum of 3.8 years) found more than 20% incidence of LCNP at median of 11.4Y follow-up. No OPC-specific incidence studies were identified in published data.