Photon vs. Proton Radiotherapy in the Definitive Treatment of Nasopharyngeal Cancer: Single Institution Experience

Abstract

Definitive therapy for nasopharyngeal cancer includes chemotherapy and radiation (RT). Common toxicities such as xerostomia, mucositis, and hearing loss are correlated with the RT dose delivered to associated organs at risk. We hypothesized that compared to our historical experience with IMRT, the implementation of proton therapy (PT) would reduce radiation dose to organs at risks without compromising oncologic outcomes. A retrospective review of all non-metastatic stage II-IV nasopharyngeal carcinoma (SCC, lymphoepithelioma, undifferentiated carcinomas) treated with definitive therapy at our institution from 2012-2022. Disease parameters and the mean dose to organs at risk were evaluated. Statistical comparison was made with the chi square test for categorical and Wilcoxon rank sum test for continuous variables. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS), using a log-rank test to compare IMRT and PT. PFS was defined as the time from the start of treatment to the first of either disease progression, relapse or death from any cause. PT was delivered with pencil-beam scanning in all patients. IMRT included multi-field treatment and volumetric-modulated arc therapy. A total of 80 patients were included in analyses: 48 treated with IMRT and 32 with PT. Comparing IMRT to PT cohorts, there was no difference in the median age of patients (51 vs 55 years, p = 0.73), nor the distribution by T stage (p = 0.57) or N stage (p = 0.34) or in the percentage of patients with ECOG 2/3 performance status at presentation (p = 0.11). All but one patient received concurrent systemic therapy and there was no difference in the use of concurrent cisplatin between cohorts (83% vs 78%, p = 0.57). The most common non-cisplatin concurrent regimen was weekly carboplatin and paclitaxel. Induction chemotherapy was more commonly used in patients treated with PT (10.4% vs 25%, p = 0.04) while there was no difference in the use of adjuvant chemotherapy (10.4% vs 9.4%, p = 0.88). Among 42 cases initiating treatment since the opening of our proton center, 32 (76%) have received PT. Comparing IMRT and PT dosimetry, patients treated with PT received significantly lower mean dose to the better spared parotid gland (32.8 vs 25.7 Gy, p = 0.001), lesser spared parotid gland (35.5 vs 31.1 Gy, p = 0.047), better spared cochlea (31.5 vs 25.5 Gy, p = 0.004), lesser spared cochlea (41.8 vs 33.2 Gy, p = 0.004), larynx (44.5 vs 21.7 Gy, p<0.001), and oral cavity (42.6 vs 17.0 Gy, p<0.001). After a median follow-up time of 30 months (45 mos IMRT, 23 mos PT) the estimated 2-year PFS was 63.9% with IMRT and 90.3% with PT (p = 0.047). The estimate of 2-year overall survival was 86.8% with IMRT and 96.8% with PT (p = 0.17). Comparing patients by radiation treatment modality, PT was associated with a statistically significant reduction in mean radiation dose to the parotid glands, cochlea, larynx, and oral cavity with excellent initial oncologic outcomes.