Physician Graded Toxicity Profiles and Survival Outcomes among Patients with Non-Metastatic Oropharyngeal Carcinoma Treated with Proton Therapy vs. Intensity-Modulated Radiation Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Proton therapy (PT) has a potential advantage over intensity-modulated radiation therapy (IMRT) in the treatment of oropharyngeal carcinoma (OPC) due to reduction of dose to the surrounding organs at risk. Our objective was to compare adverse effects and oncologic outcomes in patients with OPC treated with PT vs. IMRT <h3>Materials/Methods</h3> This retrospective cohort study included 292 consecutive patients with newly diagnosed non-metastatic OPC who received curative-intent radiation with PT or IMRT from 2018 to 2021. Clinical and demographic details were compared between the two groups. The main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs), and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). <h3>Results</h3> 58 PT and 234 IMRT patients were included. The median follow-up for all patients was 26 months (2-88mo). Median RT dose was 70 CGE (Gy) (range 66-78 CGE, 64-76 Gy). There were no imbalances in patient/tumor characteristics except for smoking pack-years (PY) (mean 7.4 PYs PT and 13.2Pys IMRT, p=.002), and N-stage (N0 17% PT versus 7% IMRT, N1 5% PT versus 15% IMRT, p=.04). There were no significant differences in T-stage or use of concurrent chemotherapy between PT and IMRT groups. 98% of patients in PT group were p16 or HPV+ versus 92% in the IMRT group. Statistically significant differences were not observed in 3 year overall-survival (91% IMRT, 97% PT, p=0.166), PFS (86% IMRT, 82% PT, p=.984) or LRR (3% IMRT, 5% PT, p=0.369).Using chi-square analysis, acute toxicities were statistically significantly higher for IMRT compared to PT for acute grade ≥2 oral pain (92.8% IMRT vs 72.4%PT p<.001), acute grade ≥2 xerostomia (29 % IMRT versus 21% PT, p<.001), acute grade ≥2 dysgeusia (57% IMRT versus 28% PT, p<.001), grade 3 dysphagia (12% (29) IMRT versus 7% (4) PT p<.001), grade ≥3 mucositis (70% IMRT versus 53% PT, p=.003), grade ≥2 nausea (7.7% IMRT versus 0% PT, p=.04), and grade ≥2 weight loss (59% IMRT, versus 37% PT, p<.001). When excluding patients with follow-up less than 6 months, 221 IMRT and 43 PT patients remain. There were no significant differences in grade ≥2 late toxicities between the two groups. When looking at the presence of any toxicity, at ≥ 6 months follow-up, there was a significant difference in the presence of xerostomia (77% IMRT versus 61% PT, p=.026). Four patients (1.7%) in the IMRT group, versus 1 patient (1.7%) in PT group had a PEG at a follow-up of at least 6 months. All late PEG tubes were due to recurrent/refractory disease <h3>Conclusion</h3> PT for non-metastatic OPC reduces acute toxicity burden in comparison with IMRT with similar oncologic outcomes. Prospective randomized comparisons of these two technologies in the treatment of OPC along with patient-reported outcomes are warranted to confirm our results.