Comparison of Clinical and Toxicity Outcomes of Adenoid Cystic Carcinomas Treated With Intensity Modulated Radiation Therapy vs. Proton Radiotherapy.

Purpose/Objective(s) Adenoid cystic carcinomas (ACC) are indolent malignancies with a predilection for perineural invasion (PNI), often requiring complex multimodal care. This study compares clinical and toxicity outcomes in patients treated with either intensity modulated radiation therapy (IMRT) or proton therapy (IMPT). Materials/Methods 48 ACC patients treated with definitive or adjuvant RT from 2013-2020 at a single institution were included in this IRB approved analysis. Acute and chronic toxicity (CTCAE 4) was prospectively recorded weekly through treatment and at each follow-up appointment. Multivariate, bivariate, and Kaplan Meier analyses were utilized. Results IMRT (N = 25) and IMPT (N = 23) groups were matched for gender (44 vs 52% F), age (56 vs 53 yr), primary site presentation (56 vs 57% major salivary glands), AJCC stage (8 vs 13% (I), 24 vs 22% (II), 32 vs 22% (III), and 36 vs 43% (IV)), and treatment intent (84 vs 78% adjuvant). Median follow-up was 43.7 mo (IMRT) and 23.8 mo (IMPT). IMPT use tended to favor primary site location including and superior to the palate (56% vs 24%) while IMRT use tended to favor locations below the palate (60% vs 22%). There was no difference in treatment modality selection for a lateral primary site location (22% IMPT vs 16% IMRT), most of which were parotid (N = 8/9). 44% of IMRT patients received RT to cervical lymph nodes in comparison to only 13% with IMPT (P = 0.03). Patients treated with IMPT tended to have a higher overall dose (median 6 vs 6.6 Gy; P = 0.01). Clinical outcomes at last follow-up were similar between the 2 cohorts: locoregional control (88% IMRT vs 91% PT); metastasis-free (72% IMRT vs 91% IMPT) and overall survival (96% IMRT vs 94% IMPT at 2 years). No difference was observed in acute or chronic grade 2 (G2; 88 vs 87% acute, 39 vs 33% chronic) or grade 3 (G3; 20 vs 22% acute, 17 vs 14% chronic) toxicity profiles. Acute toxicities included pain, mucositis, fatigue, and dermatitis, while chronic toxicities were xerostomia, dysphagia, pain, and dysgeusia. There were no reports of symptomatic neurological toxicities including neuropathy and encephalopathy. Reports of ≥2 acute G2 toxicity were associated with histological evidence of PNI (OR = 27, P = 0.001), while ≥2 chronic G2 toxicities were associated with clinical evidence of PNI and positive margins (OR = 10.1, P = 0.007; OR = 11, P = 0.03). Factors that were assessed and found not to be associated with toxicity profiles included stage, LN radiation, cranial nerve tracking, lymphovascular invasion, tumor volume and location. Conclusion Patients treated with both IMRT and IMPT appear to have acceptable clinical outcomes and toxicity profiles. IMPT selection in this series appeared to favor subsites near the base of skull and higher dose yet resulted in similar toxicity profiles as those patients treated with IMRT. Longer follow up is needed.