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

Published:February 16, 2016DOI:


      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.


      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.


      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.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Glenny A.M.
        • Furness S.
        • Worthington H.V.
        • et al.
        Interventions for the treatment of oral cavity and oropharyngeal cancer: Radiotherapy.
        Cochrane Database Syst Rev. 2010; : CD006387
        • Brizel D.M.
        • Albers M.E.
        • Fisher S.R.
        • et al.
        Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer.
        N Engl J Med. 1998; 338: 1798-1804
        • Vokes E.E.
        • Weichselbaum R.R.
        • Lippman S.M.
        • et al.
        Head and neck cancer.
        N Engl J Med. 1993; 328: 184-194
        • Riaz N.
        • Hong J.C.
        • Sherman E.J.
        • et al.
        A nomogram to predict loco-regional control after re-irradiation for head and neck cancer.
        Radiother Oncol. 2014; 111: 382-387
        • Salama J.K.
        • Vokes E.E.
        Concurrent chemotherapy and re-irradiation for locoregionally recurrent head and neck cancer.
        Semin Oncol. 2008; 35: 251-261
        • Jensen A.D.
        • Nikoghosyan A.
        • Ellerbrock M.
        • et al.
        Re-irradiation with scanned charged particle beams in recurrent tumours of the head and neck: Acute toxicity and feasibility.
        Radiother Oncol. 2011; 101: 383-387
        • Lowe V.J.
        • Boyd J.H.
        • Dunphy F.R.
        • et al.
        Surveillance for recurrent head and neck cancer using positron emission tomography.
        J Clin Oncol. 2000; 18: 651
        • Langer C.J.
        • Harris J.
        • Horwitz E.M.
        • et al.
        Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: Results of Radiation Therapy Oncology Group protocol 9911.
        J Clin Oncol. 2007; 25: 4800-4805
        • Lee N.
        • Chan K.
        • Bekelman J.E.
        • et al.
        Salvage re-irradiation for recurrent head and neck cancer.
        Int J Radiat Oncol Biol Phys. 2007; 68: 731-740
        • Sulman E.P.
        • Schwartz D.L.
        • Le T.T.
        • et al.
        IMRT reirradiation of head and neck cancer—Disease control and morbidity outcomes.
        Int J Radiat Oncol Biol Phys. 2009; 73: 399-409
        • Sher D.J.
        • Haddad R.I.
        • Norris C.M.
        • et al.
        Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer.
        Cancer. 2010; 116: 4761-4768
        • Mendenhall N.P.
        • Malyapa R.S.
        • Su Z.
        • et al.
        Proton therapy for head and neck cancer: Rationale, potential indications, practical considerations, and current clinical evidence.
        Acta Oncol. 2011; 50: 763-771
        • Lin R.
        • Slater J.D.
        • Yonemoto L.T.
        • et al.
        Nasopharyngeal carcinoma: Repeat treatment with conformal proton therapy—Dose-volume histogram analysis 1.
        Radiology. 1999; 213: 489-494
        • Kaplan E.L.
        • Meier P.
        Nonparametric estimation from incomplete observations.
        J Am Stat Assoc. 1958; 53: 457-481
        • Corry J.
        • Peters L.J.
        • Costa I.D.
        • et al.
        The ‘quad shot’—A phase II study of palliative radiotherapy for incurable head and neck cancer.
        Radiother Oncol. 2005; 77: 137-142
        • Wang T.J.
        • Riaz N.
        • Tam M.
        • et al.
        Patterns of failure after salvage re-irradiation for recurrent head and neck cancer: Implications for field design and consolidation therapy.
        J Radiat Oncol. 2014; 3: 139-145
        • Romesser P.B.
        • Romanyshyn J.C.
        • Schupak K.D.
        • et al.
        Percutaneous endoscopic gastrostomy in oropharyngeal cancer patients treated with intensity-modulated radiotherapy with concurrent chemotherapy.
        Cancer. 2012; 118: 6072-6078
        • Frank S.J.
        • Rosenthal D.I.
        • Ang K.
        • et al.
        Gastrostomy tubes decrease by over 50% with intensity modulated proton therapy (IMPT) during the treatment of oropharyngeal cancer patients: A case–control study.
        Int J Radiat Oncol Biol Phys. 2013; 87 ([abstract]): S144
        • Chen H.Y.
        • Ma X.M.
        • Ye M.
        • et al.
        Effectiveness and toxicities of intensity-modulated radiotherapy for patients with locally recurrent nasopharyngeal carcinoma.
        PLoS One. 2013; 8: e73918
        • Pryzant R.M.
        • Wendt C.D.
        • Delclos L.
        • et al.
        Re-treatment of nasopharyngeal carcinoma in 53 patients.
        Int J Radiat Oncol Biol Phys. 1992; 22: 941-947
        • Mizumoto M.
        • Okumura T.
        • Ishikawa E.
        • et al.
        Reirradiation for recurrent malignant brain tumor with radiotherapy or proton beam therapy.
        Strahlenther Onkol. 2013; 189: 656-663
        • Chan A.W.
        • Liebsch N.J.
        Proton radiation therapy for head and neck cancer.
        J Surg Oncol. 2008; 97: 697-700
        • Glimelius B.
        • Ask A.
        • Bjelkengren G.
        • et al.
        Number of patients potentially eligible for proton therapy.
        Acta Oncol. 2005; 44: 836-849
        • Cozzi L.
        • Fogliata A.
        • Lomax A.
        • et al.
        A treatment planning comparison of 3D conformal therapy, intensity modulated photon therapy and proton therapy for treatment of advanced head and neck tumours.
        Radiother Oncol. 2001; 61: 287-297


      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.