Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy

Abstract

IMPORTANCE Patients with nonmetastatic nasopharyngeal carcinoma (NPC) are primarily treated by radiotherapy with curative intent with or without chemotherapy and often experience substantial treatment-related toxic effects even with modern radiation techniques, such as intensitymodulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) may improve the toxicity profile; however, there is a paucity of data given the limited availability of IMPT in regions with endemic NPC. OBJECTIVE To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic NPC when treated with IMPT vs IMRT with or without chemotherapy. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study included 77 patients with newly diagnosed nonmetastatic NPC who received curative-intent radiotherapy with IMPT or IMRT at a tertiary academic cancer center from January 1, 2016, to December 31, 2019. Forty-eight patients with Epstein-Barr virus (EBV)-positive tumors were included in a 1:1 propensity score-matched analysis for survival outcomes. The end of the follow-up period was March 31, 2021.EXPOSURES IMPT vs IMRT with or without chemotherapy. MAIN OUTCOMES AND MEASURESThe main outcomes were the incidence of acute and chronic treatment-related adverse events (AEs) and oncologic outcomes, including locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS). RESULTSWe identified 77 patients (25 [32.5%] women; 52 [67.5%] men; median [interquartile range] age, 48.7 [42.2-60.3] years), among whom 28 (36.4%) were treated with IMPT and 49(63.6%) were treated with IMRT. Median (interquartile range) follow-up was 30.3 (17.9-41.5) months.On multivariable logistic regression analyses, IMPT was associated with lower likelihood of developing grade 2 or higher acute AEs compared with IMRT (odds ratio [OR], 0.15; 95% CI, 0.03-0.60; P = .01). Only 1 case (3.8%) of a chronic grade 3 or higher AE occurred in the IMPT group compared with 8 cases (16.3%) in the IMRT group (OR, 0.21; 95% CI, 0.01-1.21; P = .15). Propensity score matching generated a balanced cohort of 48 patients (24 IMPT vs 24 IMRT) and found similar PFS in the IMPT and IMRT groups (2-year PFS, 95.7% [95% CI, 87.7%-100%] vs 76.7% [95% CI, 60.7%-97.0%]; hazard ratio [HR], 0.31; 95% CI, 0.07-1.47; P = .14). No locoregional recurrence or death was observed in the IMPT group from the matched cohort. Two-year LRFS was 100% (95% CI, 100%-100%) in the IMPT group and 86.2% (95% CI, 72.8%-100%) in the IMRT group (P = .08).Three-year OS was 100% (95% CI, 100%-100%) in the IMPT group and 94.1% (95% CI, 83.6%-100%) in the IMRT group (P = .42). Smoking history was the only clinical factor significantly (continued) Key Points Question Is intensity-modulated proton therapy (IMPT) associated with fewer treatment-related adverse events and comparable oncologic outcomes for patients with nonmetastatic nasopharyngeal carcinoma (NPC) compared with patients treated with intensity-modulated radiation therapy (IMRT)? Findin...

Modern Radiation Oncology: From IMRT to Particle Therapy—Present Status and the Days to Come

“…Multiple dosimetric and phase II studies have shown improved disease control with proton therapy in sinonasal cancers, nonsquamous head and neck tumors like melanoma or adenoid cystic carcinomas, hepatobiliary malignancies, and low-grade gliomas. Owing to its favorable dose distribution profile and resultant excellent conformity, proton therapy has shown reduced treatment-induced toxicities in a wide range of cancers, including HNSCC, 35 mediastinal tumors, 36,37 pediatric medulloblastoma patients undergoing craniospinal irradiation, 38 low-grade or benign intracranial tumors, 39 and esophageal cancers. 40 A recent comparative study showed significantly improved toxicity profile with excellent oncologic outcomes with intensity-modulated proton therapy compared to that with IMRT in patients with nonmetastatic nasopharyngeal carcinoma.…”

“…40 A recent comparative study showed significantly improved toxicity profile with excellent oncologic outcomes with intensity-modulated proton therapy compared to that with IMRT in patients with nonmetastatic nasopharyngeal carcinoma. 35 Use of proton therapy is specially encouraged in pediatric patients, for possible reduction in second malignant neoplasms, attributable to the lower integral dose when actively scanned proton beams are used. 41 In certain sites (namely breast cancers, retroperitoneal sarcomas, gliomas, mediastinal tumors), comparative planning of photons with protons (including Normal Tissue Complication Probability [NTCP] modeling) is encouraged to determine probable benefit with protons.…”

Nasopharyngeal Carcinoma: Clinical Achievements and Considerations Among Treatment Options

“…Li et al compared the toxicity and survival outcomes of 77 patients with nonmetastatic NPC treated with IMPT or IMRT. The results showed that IMPT was associated with lower grade 2-4 acute adverse events and better oncological outcomes than IMRT, including 100% locoregional control at 2 years (21). Given the dosimetric advantages and reduced damage to normal tissue, proton therapy may be potentially suitable for patients with recurrences who received prior radiotherapy because reirradiation with photon-based therapy might result in a high risk of complications and morbidities (22).…”

Proton Radiation Therapy for Nasopharyngeal Cancer Patients: Dosimetric and NTCP Evaluation Supporting Clinical Decision

“…Planned comparison studies between IMPT and IMRT techniques have suggested that lower (mean) doses can be delivered to several organs at risk (OARs) in patients with NPC [ 10 , 11 , 12 , 13 ], without significant difference in target coverage, conformity, or homogeneity indexes [ 10 , 14 ]. A few small studies have shown a benefit in the clinical outcome when IMPT and IMRT were compared [ 11 , 15 ]. Nevertheless, due to the higher costs and relatively limited availability of IMPT with respect to conventional photon-based RT, PT should be reserved for patients that are likely to benefit the most in terms of toxicity risk reduction.…”