A Retrospective Analysis of 235 Patients and 281 Radiotherapy Plans for Sialorrhea Treatment in Amyotrophic Lateral Sclerosis and Parkinson Patients

Abstract

To evaluate the efficacy and safety of radiotherapy (RT) of the primary salivary glands in a large series of patients with amyotrophic lateral sclerosis (ALS) and Parkinson's disease with sialorrhea.Patients treated in our institution between 2010 and 2020 were retrospectively analyzed, including the first 50 patients prospectively analyzed. All patients included were refractory to conventional sialorrhea drug treatments. RT was delivered by a conventional LINAC, with 2 opposite beams including the two submandibular glands and two thirds of the two parotid glands before 2014, and from 2015 2 lateral beams including the submaxillary glands, and 2 opposite oblique beams directed to each parotid gland, with reduced oral cavity irradiation. The total dose delivered was 10 Gy in 2 fractions or 20 Gy in 4 fractions. RT efficacy was assessed using the 9-item Sialorrhea Scoring Scale (SSS), prospectively validated as the most effective and sensitive tool for measuring sialorrhea in ALS patients.A total of 235 patients were included, and 281 treatments (45 reirradiations, 1 patient received 3 irradiations). Median age was 69 years (range: 38 - 95), 127 women (54%) and 126 men (46%), 212 had ALS (90%), 17 had Parkinson's disease (7%), and 5 patients (3%) had another neurological disorder. Median interval between the first and second radiotherapy course was 7.5 months (range: 1 - 37). The median SSS score before radiation therapy was 8 (range: 6 - 9), and the median SSS score at 1 month of irradiation was 2 (range: 1 - 6). There was no toxicity of > grade 1. At the end of RT, all but one patient had an improvement in SSS score: 272 had a complete response (CR) (97%, SSS 1-3) and 8 had a partial response (PR) (3%, SSS 4-5); one patient had a stable SSS score (< 1%). A 1-month CR after RT was achieved in 96% of the 235 patients who underwent a primary RT, and 100% of the 45 patients who received re-irradiation. Patients treated with 20Gy versus 10Gy during the first RT treatment were more likely to have a CR at 1 month (99% vs. 91%, P = 0.007), and had a greater decrease in SSS score (mean difference -6 vs. -5 points, P < 0.001). Also, the 45 patients who received reirradiation were more frequently previously treated with the RT 10Gy protocol (25/45 patients, 55%) versus 60/191 (31%) in patients who did not require reirradiation (P < 0.001). The 3-beam irradiation technique, used from 2014 and beyond, did not significantly improve treatment efficacy (reduction of the SSS score by -5.8 points on average versus -5.6 points previously, P = 0.3). Nevertheless, it reduced 1 month toxicity, in particular decreased saliva thickening discomfort (P < 0.001).A 20 Gy irradiation in 4 fractions is an effective treatment for ALS patients with sialorrhea, with minimal toxicity, particularly by separately targeting parotid and submaxillary glands. A shorter RT (10 Gy in 2 fractions) may be proposed in patients with poor medical condition, subject to its lower efficacy and the greater need for reirradiation.