Acute Toxicity in Patients Treated With Proton vs. Photon Chemoradiotherapy for Locally Advanced Head and Neck Cancer

PURPOSE/OBJECTIVE(S) Patients undergoing concurrent chemoradiotherapy (CRT) for head and neck cancer often experience significant toxicities. Proton therapy permits decreased dose delivery to non-target structures and the potential for superior organs-at-risk sparing. The aim of this study was to evaluate if proton therapy is associated with decreased acute grade ≥3 toxicities compared to photon therapy in the setting of concurrent CRT for head and neck cancers. MATERIALS/METHODS This study included 654 adult patients with nonmetastatic, locally advanced head and neck cancer treated with definitive concurrent CRT from January 1, 2011 to April 30, 2019 at one institution. 90-day toxicity data were prospectively collected as defined by Common Terminology Criteria for Adverse Events, version 4. Acute toxicities were grouped into five categories for analysis: mucosal (mucosal infection, mucositis), oral cavity (dry mouth, dysgeusia), swallow (aspiration, dysphagia), constitutional (fatigue, anorexia, dehydration), and skin (dermatitis, edema, superficial soft tissue necrosis, alopecia) toxicities. Modified Poisson regression models with covariate adjustment were used to model toxicity risk following multiple imputation for missing covariate values. Ten hypotheses were tested. Thus, the Bonferroni multiple testing correction was applied and statistical significance was assessed at the 0.005 level. RESULTS One hundred and six patients received proton therapy and 548 received photon therapy. Patients receiving proton therapy were older (mean age [SD] 61.2 [12.2] vs 58.9 [9.30], P = 0.029) and were more likely to be HPV-positive (67.0% vs 57.0%, P = 0.036). Proton therapy patients had lower dose to the parotid glands (right mean [SD], 21.8 Gy [12.9] vs 27.9 [11.3], P < 0.001; left 23.1 Gy [12.7] vs 27.2 [11.0], P = 0.001), oral cavity (13.7 Gy [9.88] vs 28.8 [10.8], P < 0.001) and constrictor muscle (35.6 Gy [10.37] vs 43.7 [9.24], P < 0.001) compared to photon therapy patients. Charlson-Deyo comorbidity scores were similar for both groups (mean [SD] 6.18 [1.74] vs 6.40 [2.57], P = 0.39), as were the distributions for sex (P = 0.118), race (P = 0.16), cancer stage (P = 0.163), and baseline ECOG (P = 0.57). In covariate-adjusted analyses, proton therapy was associated with a significantly lower relative risk of any 90-day grade ≥3 toxicity (0.57, 95% CI 0.40-0.83, P = 0.003). For acute grade 2 toxicity proton therapy was associated with significantly reduced relative risk of oral cavity toxicity (0.74, 95% CI 0.61-0.90, P = 0.002) but higher skin toxicity (1.35, 95% CI 1.14-1.59, P = 0.0004). CONCLUSION Concurrent chemoradiotherapy with proton therapy for head and neck cancers was associated with lower dose to nontarget structures and significantly reduced acute grade ≥3 toxicity and acute grade 2 oral cavity toxicity compared to photon therapy. Grade 2 skin toxicity favored photon therapy.