Mixed-beam approach in locally advanced nasopharyngeal carcinoma: IMRT followed by proton therapy boost versus IMRT-only. Evaluation of toxicity and efficacy

Objective: To compare radiation-induced toxicity and dosimetry parameters in patients with locally advanced nasopharyngeal cancer (LANPC) treated with a mixed-beam (MB) approach (IMRT followed by proton therapy boost) with an historic cohort of patients treated with a full course of IMRT-only. Material and methods: Twenty-seven patients with LANPC treated with the MB approach were compared to a similar cohort of 17 patients treated with IMRT-only. The MB approach consisted in a first phase of IMRT up to 54-60 Gy followed by a second phase delivered with a proton therapy boost up to 70-74 Gy (RBE). The total dose for patients treated with IMRT-only was 69.96 Gy. Induction chemotherapy was administrated to 59 and 88% and concurrent chemoradiotherapy to 88 and 100% of the MB and IMRT-only patients, respectively. The worst toxicity occurring during the entire course of treatment (acute toxicity) and early-late toxicity were registered according to the Common Terminology Criteria Adverse Events V4.03. Results: The two cohorts were comparable. Patients treated with MB received a significantly higher median total dose to target volumes (p = .02). Acute grade 3 mucositis was found in 11 and 76% (p = .0002) of patients treated with MB and IMRT-only approach, respectively, while grade 2 xerostomia was found in 7 and 35% (p = .02) of patients treated with MB and IMRT-only, respectively. There was no statistical difference in late toxicity. Local progression-free survival (PFS) and progression-free survival curves were similar between the two cohorts of patients (p = .17 and p = .40, respectively). Local control rate was 96% and 81% for patients treated with MB approach and IMRT-only, respectively. Conclusions: Sequential MB approach for LANPC patients provides a significantly lower acute toxicity profile compared to full course of IMRT. There were no differences in early-late morbidities and disease-related outcomes (censored at two-years) but a longer follow-up is required to achieve conclusive results.