Toxicity and Pharyngeal Dysphagia Outcomes from Intensity Modulated Proton Therapy for Oropharyngeal Squamous Cell Cancer

Abstract

To report acute and chronic toxicities, including swallowing outcomes, from intensity modulated proton therapy (IMPT) in patients treated for oropharynx squamous cell carcinoma (OPSCC). This study combines 2 prospective protocols evaluating IMPT in head and neck cancer. This analysis included OPSCC patients treated with IMPT as first course irradiation treated from May 2012 to July 2016. Toxicities were graded as per Common Terminology Criteria for Adverse Events version 4.01. In patients who underwent post-treatment modified barium swallow (MBS), the summary of pharyngeal dysphagia grade using the dynamic imaging grade of swallowing toxicity (DIGEST) scale, scoring swallowing function from 0 (no dysphagia) to 4 (very severe dysphagia). Overall survival (OS), locoregional control (LRC) and disease free survival (DFS) were estimated using the Kaplan Meier Method. 103 patients met the inclusion criteria. Median age was 61 years (range 37-84), 85% of patients were male, 92% had HPV-associated disease, and 44% were never smokers. Seventy percent of patients had concurrent chemotherapy, 30% had induction chemotherapy, and 7% had robotic surgery before IMPT; only 22% had IMPT monotherapy. As per AJCC 8th Ed, 63%, 19%, 10%, 7% and 1% of patients had stage I, II, III, IVA and IVB, respectively; while as per AJCC 7th Ed, 1%, 1%, 17%, 77% and 5% of patients had stage I, II, III, IVA and IVB, respectively. Median follow-up was 3.3 years (range 0.5-7.0 years). Acute toxicities were: grade 3 mucositis, grade 3 dermatitis, and grade 3 dysphagia in 46%, 43%, and 15% of patients. There were no grade 4-5 toxicities. Rate of gastrostomy (feeding) tube during therapy was 26%, for a median duration of 106 days (range 28-624). Rates of aspiration pneumonia and hospitalization per-treatment were 16% and 7%. In 41 patients who had post-therapy MBS, worst post-treatment DIGEST score was 0, 1, 2 and 3 in 29%, 37%, 27% and 7% of patients. OS, LRC, and DFS were 96% , 93%, and 93% at 3-years and 80%, 90%, and 77% at 5-years. 5%, 6% and 3% of patients has local, neck and distant failure. Stage I disease and absence of tobacco smoking history were associated with improved OS and DFS. This large prospective report of patients with OPSCC treated with IMPT demonstrates a safe toxicity profile with favorable swallowing outcomes. Our results support that IMPT for OPCSCC is well tolerated and yields excellent long-term cancer control outcomes.