Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes

Abstract

Purpose: Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC.

Methods and materials: A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method.

Results: Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding.

Conclusions: Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.

Figure 1

Cumulative incidence of locoregional failure with death as a competing risk.

Figure 2

(2a) actuarial distant metastasis free survival and (2b) overall survival both with 95% confidence interval and number needed to treat.

Figure 2

(2a) actuarial distant metastasis free survival and (2b) overall survival both with 95% confidence interval and number needed to treat.

Figure 3

Representative isodose plans for patients under going re-RT for (3a) recurrent poorly differentiated carcinoma with squamous features previously treated to 48Gy with concurrent cisplatin and etoposide after a superficial parotidectomy who developed a local recurrence ~3 years later who underwent re-irradiation with PBRT to 66Gy (RBE) in 33 fractions with concurrent cisplatin in the post-operative setting for a positive margin after a right parotidectomy with right masseter muscle resection, rectus abdominus free flap reconstruction, and selective right neck dissection and (3b) recurrent olfactory neuroblastoma previously treated to 55.8 Gy after endoscopic resection who developed a local recurrence ~2.5 years later who underwent re-irradiation with PBRT to 66Gy (RBE) in 33 fractions in the post-operative setting for a positive margin after a right maxillectomy, extranasal ethmoidectomy, dacryocystorhinostomy, and right modified neck dissection for a positive margin, cortical bone invasion, perineural invasion, and four positive nodes with extracapsular extension. The PTV is in magenta and CTV is in red.