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

Abstract

Purpose/Objectives Re-irradiation (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-irradiation, interest in proton beam radiotherapy (PBRT) has increased. Herein, we report the first multi-institutional clinical experience using curative intent PBRT for re-RT in recurrent HNC. Materials/Methods A retrospective analysis of ongoing prospective data registries from 2-hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who had at least one prior course of definitive intent external beam RT were included. Acute and late toxicities were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and by 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 twelve-month freedom from distant metastasis (FFDM) and overall survival (OS) 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 (interquartile range, 5.3-17.5 months). The median time between last RT and PBRT was 34.4 months. There were 76 patients with one prior RT course and 16 with two or more courses. Median PBRT dose was 60.6 Gy (RBE). Eighty-five percent of patients had prior HNC RT for an oropharynx primary and 39% had salvage surgery prior to re-RT. The cumulative incidence of locoregional failure at 12-months, with death as a competing risk, was 25.1%. Actuarial 12-month FFDM and OS were 84.0% and 65.2%, respectively. Acute grade ≥3 toxicities included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was one death during PBRT secondary to disease progression. Grade 3 or greater late skin and dysphagia toxicity were noted in 6 (8.7%) and 4 (7.1%) of patients, respectively. Two patients had grade 5 toxicity secondary to treatment-related bleeding. Conclusions Proton beam re-irradiation of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely secondary to the decreased dose to the surrounding normal, albeit previously irradiated tissue, though longer follow up is needed to confirm these findings.

Burden of Oral Mucositis: A Systematic Review and Implications for Future Research

“…There were 7 studies covering 2 topics each [3,13,14,15,16,17,18] and 7 meta-analyses [19,20,21,22,23,24,25]. 20 studies (29.4%) were from Europe [3,5,9,10,11,12,15,22,26,27,28,29,30,31,32,33,34,35,36,37,38,] 20 from the US [4,14,17,19,20,24,39,40,41,42,43,44,45,46,47,48,49,50,51,52], 3 studies (4.4%) from US plus Europe [23,53,54], 6 studies (8.8%) from Japan [16,55,56,57,58,59], 6 studies (8.8%) from China [18,25,60,61,62,63], 2 studies (3.0%) from Hong Kong [13,64,65], 3 studies (4.4%) from Canada [66,67,68], 3 studies (4.4%) from India [21,69,70] and 5 studies (7.4%) from other countries [7,71,72,73,74]. 21 studies (30.9%) used the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale for assessment of OM.…”

“…1 Studies on oral mucositis (OM). Incidence of OM was investigated in patients with hematopoietic stem cell transplantation (HSCT) in 14 studies (32.6%) [3,5,14,17,19,28,31,36,37,39,44,56,62,67], in head and neck cancer (HNC) patients in 13 studies (30.2%) [18,21,29,40,50,51,55,59,60,61,63,70,73], in patients with chemotherapy in 13 studies (30.2%) [15,16,22,23,24,25,30,34,38,46,48,58,71], with mixed tumor types and treatment in 1 study (2.3%) [13] and with palliative care in 2 studies (4.7%) [32,57]. Cost related to OM in patients undergoing HSCT was the focus in 4 studies [7,14,17,54], in HNC patients in 2 studies [43,47], in patients with chemotherapy in 6 studies [9,10,11,12,42,49,68], and in patients with mixed tumor types and treatment in 2 studies [20,45].…”

“…In head and neck cancer (HNC) patients, OM incidence for all grades is reported to be from 59.4% [50] to 100% when follow-up after radiotherapy or chemoradiotherapy is included [29,40,51,60,61,73]. Special radiation techniques are used with the intention of reducing the severity of OM.…”

Proton Therapy in the Treatment of Head and Neck Cancer

“…In the largest multi-institutional series on proton reirradiation therapy, 92 patients with recurrent head and neck cancer previously treated with radiation were examined. 15 The cumulative index of 1 year locoregional failure was 25.1%, while OS was 65.2%. Acute grade ≥3 toxicity rates were very low and included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%).…”

Proton radiotherapy should be further developed in Poland

“…Because of how the dose is deposited, proton radiotherapy may be a valuable, and indeed the only means of re-irradiation, particularly in cases of recurrence localised within the brain or head and neck regions [46,47]. More long-term observations are however required, but above all else prospective studies are needed.…”