title: Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Memorial Sloan Kettering Cancer Center, Radiation Oncology, New York, New York.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Romesser
authors.affiliation: Memorial Sloan Kettering Cancer Center, Radiation Oncology, New York, New York; ProCure Proton Therapy Center, Somerset, New Jersey.
authors.forename: Oren
authors.initials: O
authors.lastname: Cahlon
authors.affiliation: Memorial Sloan Kettering Cancer Center, Radiation Oncology, New York, New York.
authors.forename: Eli D
authors.initials: ED
authors.lastname: Scher
authors.affiliation: ProCure Proton Therapy Center, Somerset, New Jersey.
authors.forename: Eugen B
authors.initials: EB
authors.lastname: Hug
authors.affiliation: ProCure Proton Therapy Center, Somerset, New Jersey.
authors.forename: Kevin
authors.initials: K
authors.lastname: Sine
authors.affiliation: Memorial Sloan Kettering Cancer Center, Radiation Oncology, New York, New York.
authors.forename: Carl
authors.initials: C
authors.lastname: DeSelm
authors.affiliation: Montefiore Medical Center, Radiation Oncology, Bronx, New York.
authors.forename: Jana L
authors.initials: JL
authors.lastname: Fox
authors.affiliation: ProCure Proton Therapy Center, Somerset, New Jersey.
authors.forename: Dennis
authors.initials: D
authors.lastname: Mah
authors.affiliation: Montefiore Medical Center, Radiation Oncology, Bronx, New York.
authors.forename: Madhur K
authors.initials: MK
authors.lastname: Garg
authors.affiliation: Northwestern Medicine Chicago Proton Center, Warrenville, Illinois.
authors.forename: John
authors.initials: J
authors.lastname: Han-Chih Chang
authors.affiliation: Memorial Sloan Kettering Cancer Center, Radiation Oncology, New York, New York. Electronic address: leen2@mskcc.org.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000532:radiotherapy; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000532:radiotherapy; D003680:Deglutition Disorders / Q000209:etiology; D004941:Esophagitis / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000532:radiotherapy; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy*; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011832:Radiation Injuries; D011855:Radiodermatitis; D000069475:Re-Irradiation / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D012509:Sarcoma / Q000401:mortality; D000077195:Squamous Cell Carcinoma of Head and Neck; D013280:Stomatitis / Q000209:etiology; D013997:Time Factors