J.H.C. Chang

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

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.

Proton beam radiotherapy as part of comprehensive regional nodal irradiation for locally advanced breast cancer

PURPOSE This study evaluates acute toxicity outcomes in breast cancer patients treated with adjuvant proton beam therapy (PBT). METHODS From 2011 to 2016, 91 patients (93 cancers) were treated with adjuvant PBT targeting the intact breast/chest wall and comprehensive regional nodes including the axilla, supraclavicular fossa, and internal mammary lymph nodes. Toxicity was recorded weekly during treatment, one month following treatment, and then every 6months according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Charts were retrospectively reviewed to verify toxicities, patient parameters, disease and treatment characteristics, and disease-related outcomes. RESULTS Median follow-up was 15.5months. Median PBT dose was 50.4 Gray relative biological effectiveness (GyRBE), with subsequent boost as clinically indicated (N=61, median 10 GyRBE). Chemotherapy, when administered, was given adjuvantly (N=42) or neoadjuvantly (N=46). Grades 1, 2, and 3 dermatitis occurred in 23%, 72%, and 5%, respectively. Eight percent required treatment breaks owing to dermatitis. Median time to resolution of dermatitis was 32days. Grades 1, 2, and 3 esophagitis developed in 31%, 33%, and 0%, respectively. CONCLUSIONS PBT displays acceptable toxicity in the setting of comprehensive regional nodal irradiation.

Initial toxicity, quality-of-life outcomes, and dosimetric impact in a randomized phase 3 trial of hypofractionated versus standard fractionated proton therapy for low-risk prostate cancer

Purpose Randomized evidence for extreme hypofractionation in prostate cancer is lacking. We aimed to identify differences in toxicity and quality-of-life outcomes between standard fractionation and extreme hypofractionated radiation in a phase 3 randomized trial. Methods and materials We analyzed the results of the first 75 patients in our phase 3 trial, comparing 38 Gy relative biologic effectiveness (RBE) in 5 fractions (n = 46) versus 79.2 Gy RBE in 44 fractions (n = 29). Patients received proton radiation using fiducials and daily image guidance. We evaluated American Urological Association Symptom Index (AUASI), adverse events (AEs), and Expanded Prostate Index Composite (EPIC) domains. The primary endpoint of this interim analysis was the cumulative incidence of grade 2 (G2) or higher AEs. The randomized patient allocation scheme was a 2:1 ratio favoring the 38 Gy RBE arm. Results The median follow-up was 36 months; 30% of patients reached 48-month follow-up. AUASI scores differed <5 points (4.4 vs 8.6; P = .002) at 1 year, favoring the 79.2 Gy arm. Differences in AUASI were not significant at ≥18 months. EPIC urinary symptoms favored the 79.2 Gy arm at 1 year (92.3 vs 84.5; P = .009) and 18 months (92.3 vs 85.3; P = .03); bother scores were not significant at other time points. Cumulative ≥G2 genitourinary toxicity was similar between the 79.2 Gy and 38 Gy arms (34.5% vs 30.4%; P = .80). We found no differences in the EPIC domains of bowel symptoms, sexual symptoms, or bowel ≥G2 toxicities. Bladder V80 (79.2 Gy arm; P = .04) and V39 (38 Gy arm; P = .05) were predictive for cumulative G2 genitourinary AEs. Conclusions Low AE rates were seen in both study arms. Early temporary differences in genitourinary scores disappeared over time. Bladder constraints were associated with genitourinary AEs.

In Regard to Habl et al

tomographyecomputed tomography). The results are shown in Table 1. The data confirm that recurrences in a nontargeted level IB or RP are very rare. As Gunn and Garden point out, nontargeted level IB or RPs will to some extent receive dose, and we do not disagree that even fairly low levels of radiation may influence the risk of recurrence. However, the fact that patients with more advanced cancersmost likelywill receivemore unintentional dose to these regions because of the volume of disease makes analyses of this very difficult. A likely outcome of a retrospective analysis would be a correlation between the dose received (unintentionally) and a higher risk of recurrence. These issues are relevant for analyses of recurrence localization of all tumor types treated with modern, highly conformal radiation therapy. Moreover, unintentional irradiation of part of a lymph node region is not an argument for inclusion of the whole level. We aimed for a pragmatic approach to guide targeting, and other studies on elective nodal regions have used a similar methodology (3). Regarding hypopharyngeal carcinomas, Gunn and Garden read the data selectively. Although a low number of hypopharyngeal carcinoma patients become long-term survivors (often because of causes not directly related to their malignant disease), the cohort includes 120 hypopharyngeal cancers, which contribute time at risk of recurrence, and not 24 as stated in the comment. Recurrences in level IB and the retropharyngeal regions are rare, and the rationale of including these in elective radiation therapy is difficult to investigate in a setting in which these levels are included routinely. Thus, despite the concerns raised by Gunn and Garden, we believe that our dataset offers valuable information and supports a selective approach for the inclusion of level IB and the RPs.