Stop LCNP: High dose corticosteroid therapy for late radiation-associated lower cranial neuropathy: A report of the phase I dose finding trial and parallel prospective data registry

Purpose: Radiation-associated lower cranial neuropathy (LCNP) is a debilitating late complication among head and neck cancer (HNC) survivors, leading to progressive dysphagia, aspiration, and loss of nutritional independence. No proven therapies exist to reverse LCNP. This Phase I dose-finding trial (XXXX, XXXX) and parallel registry study prospectively evaluated the safety, feasibility, tolerability, and symptomatic response of high-dose corticosteroid therapy for radiation-associated LCNP. Methods and Materials: Eligible participants were disease-free oropharyngeal cancer survivors [≥]2 years post-radiotherapy with LCNP involving CN XII +/- X and no structural or malignant etiology. Phase I trial participants received oral prednisone 1 mg/kg (Dose 1, n = 3) or 3 mg/kg (Dose 2, n = 5) daily for 5 days followed by a 2-week taper. A parallel registry (n = 6) enrolled broader HNC survivors treated with 1 mg/kg. Phase I dose escalation decisions were based on the balance of tolerability and symptom response. The primary endpoint was change in MDASI-HN Top 5 mean symptom score from baseline to 1-2 weeks post-taper; a [≥] 1.315 unit decrease indicated clinically meaningful improvement. Secondary endpoints included clinician-graded measures of bulbar function, electromyography (EMG) and patient-report outcome measures. Results: All regimens were feasible and well tolerated. Insomnia (n = 4, Grade 1) was the most frequent adverse event and there were no treatment discontinuations. At 1-2 weeks post-taper, the median MDASI-HN Top 5 change was -0.2 in Dose 1 and -1.6 in Dose 2; three of five Dose 2 patients achieved clinically meaningful improvement versus one in Dose 1. By 6-10 weeks, symptom improvement persisted in a subset but diminished overall. Dose 2 met pre-specified criteria for Phase II progression. No consistent improvements were observed in objective functional or electrophysiologic measures, though exploratory trends favored higher dosing. Conclusions: High-dose corticosteroid therapy at 3 mg/kg/day was feasible and tolerable in long-term HNC survivors with LCNP and showed preliminary evidence of short-term symptomatic benefit. Phase II evaluation is warranted.