Hypofractionated Nodal Radiation Therapy for Breast Cancer Was Not Associated With Increased Patient-Reported Arm or Brachial Plexopathy Symptoms


      To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx.

      Methods and Materials

      Two cancer registries were used to identify subjects who received computed tomography–planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χ2 analysis, and multivariate ordinal regression.


      Of 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P<.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P<.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy.


      Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared with CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.
      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


        • Tyldesley S.
        • Delaney G.
        • Foroudi F.
        • et al.
        Estimating the need for radiotherapy for patients with prostate, breast, and lung cancers: Verification of model estimates of need with radiotherapy utilization data from British Columbia.
        Int J Radiat Oncol Biol Phys. 2011; 79: 1507-1515
        • Whelan T.J.
        • Olivotto I.A.
        • Parulekar W.R.
        • et al.
        Regional nodal irradiation in early-stage breast cancer.
        N Engl J Med. 2015; 373: 307-316
        • Poortmans P.M.
        • Collette S.
        • Kirkove C.
        • et al.
        Internal mammary and medial supraclavicular irradiation in breast cancer.
        N Engl J Med. 2015; 373: 317-327
        • Thorsen L.B.
        • Offersen B.V.
        • Danø H.
        • et al.
        DBCG-IMN: A population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer.
        J Clin Oncol. 2016; 34: 314-320
        • Darby S.
        • McGale P.
        • Correa C.
        • et al.
        Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10 801 women in 17 randomised trials.
        Lancet. 2011; 378: 1707-1716
        • Ragaz J.
        • Olivotto I.A.
        • Spinelli J.J.
        • et al.
        Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial.
        J Natl Cancer Inst. 2005; 97: 116-126
        • Overgaard M.
        • Jensen M.B.
        • Overgaard J.
        • et al.
        Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial.
        Lancet. 1999; 353: 1641-1648
        • Early Breast Cancer Trials Collaborative Group
        Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials.
        Lancet. 2005; 365: 1687-1717
        • Whelan T.J.
        • Julian J.
        • Wright J.
        • et al.
        Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis.
        J Clin Oncol. 2000; 18: 1220-1229
        • Wai E.S.
        • Lesperance M.
        • Speers C.H.
        • et al.
        Increased use of regional radiotherapy is associated with improved outcome in a population-based cohort of women with breast cancer with 1-3 positive nodes.
        Radiother Oncol. 2010; 97: 301-306
        • Belkacemi Y.
        • Kaidar-Person O.
        • Poortmans P.
        • et al.
        Patterns of practice of regional nodal irradiation in breast cancer: Results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.
        Ann Oncol. 2015; 26: 529-535
        • Kwan W.
        • Jackson J.
        • Weir L.M.
        • et al.
        Chronic arm morbidity after curative breast cancer treatment: Prevalence and impact on quality of life.
        J Clin Oncol. 2002; 20: 4242-4248
        • Kori S.H.
        • Foley K.M.
        • Posner J.B.
        Brachial plexus lesions in patients with cancer: 100 cases.
        Neurology. 1981; 31: 45-50
        • Johansson S.
        • Svensson H.
        • Denekamp J.
        Dose response and latency for radiation-induced fibrosis, edema, and neuropathy in breast cancer patients.
        Int J Radiat Oncol Biol Phys. 2002; 52: 1207-1219
        • Killer H.E.
        • Hess K.
        Natural history of radiation-induced brachial plexopathy compared with surgically treated patients.
        J Neurol. 1990; 237: 247-250
        • Bajrovic A.
        • Rades D.
        • Fehlauer F.
        • et al.
        Is there a life-long risk of brachial plexopathy after radiotherapy of supraclavicular lymph nodes in breast cancer patients?.
        Radiother Oncol. 2004; 71: 297-301
        • Pritchard J.
        • Anand P.
        • Broome J.
        • et al.
        Double-blind randomized phase II study of hyperbaric oxygen in patients with radiation-induced brachial plexopathy.
        Radiother Oncol. 2001; 58: 279-286
        • Whelan T.J.
        • Pignol J.P.
        • Levine M.N.
        • et al.
        Long-term results of hypofractionated radiation therapy for breast cancer.
        N Engl J Med. 2010; 362: 513-520
        • Haviland J.S.
        • Owen J.R.
        • Dewar J.A.
        • et al.
        The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials.
        Lancet Oncol. 2013; 14: 1086-1094
        • Wang E.H.
        • Mougalian S.S.
        • Soulos P.R.
        • et al.
        Adoption of hypofractionated whole-breast irradiation for early-stage breast cancer: A national cancer data base analysis.
        Int J Radiat Oncol Biol Phys. 2014; 90: 993-1000
        • Jagsi R.
        • Falchook A.D.
        • Hendrix L.H.
        • et al.
        Adoption of hypofractionated radiation therapy for breast cancer after publication of randomized trials.
        Int J Radiat Oncol Biol Phys. 2014; 90: 1001-1009
        • Rajagopalan M.S.
        • Flickinger J.C.
        • Heron D.E.
        • et al.
        Changing practice patterns for breast cancer radiation therapy with clinical pathways: An analysis of hypofractionation in a large, integrated cancer center network.
        Pract Radiat Oncol. 2015; 5: 63-69
        • Smith B.D.
        • Bentzen S.M.
        • Correa C.R.
        • et al.
        Fractionation for whole breast irradiation: An American Society for Radiation Oncology (ASTRO) evidence-based guideline.
        Int J Radiat Oncol Biol Phys. 2011; 81: 59-68
        • Powell S.
        • Cooke J.
        • Parsons C.
        Radiation-induced brachial plexus injury: Follow-up of two different fractionation schedules.
        Radiother Oncol. 1990; 18: 213-220
        • Galecki J.
        • Hicer-Grzenkowicz J.
        • Grudzien-Kowalska M.
        • et al.
        Radiation-induced brachial plexopathy and hypofractionated regimens in adjuvant irradiation of patients with breast cancer-a review.
        Acta Oncol (Madr). 2006; 45: 280-284
        • Gunderson L.
        • Tepper J.
        Breast Cancer in Clinical Radiation Oncology.
        3rd ed. W.B. Saunders Company, Philadelphia, Pennsylvania2012
        • Fathers E.
        • Thrush D.
        • Huson S.M.
        • et al.
        Radiation-induced brachial plexopathy in women treated for carcinoma of the breast.
        Clin Rehabil. 2002; 16: 160-165
        • Bates T.D.
        The 10-year results of a prospective trial of post-operative radiotherapy delivered in 3 fractions per week versus 2 fractions per week in breast carcinoma.
        Br J Radiol. 1988; 61: 625-630
        • Rodger A.
        • Jack W.J.L.
        • Kerr G.
        A change in postmastectomy radiotherapy fractionation: An audit of tumour control, acute and late morbidity.
        Breast. 1996; 5: 244-250
        • Nesvold I.L.
        • Fosså S.D.
        • Naume B.
        • et al.
        Kwan's arm problem scale: Psychometric examination in a sample of stage II breast cancer survivors.
        Breast Cancer Res Treat. 2009; 117: 281-288
        • Bellefqih S.
        • Elmajjaoui S.
        • Aarab J.
        • et al.
        Hypofractionated regional nodal irradiation for women with node-positive breast cancer.
        Int J Radiat Oncol Biol Phys. 2017; 97: 563-570
        • Ragaz J.
        • Jackson S.M.
        • Le N.
        • et al.
        Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer.
        N Engl J Med. 1997; 337: 956-962
        • Stokes E.L.
        • Tyldesley S.
        • Woods R.
        • et al.
        Effect of nodal irradiation and fraction size on cardiac and cerebrovascular mortality in women with breast cancer treated with local and locoregional radiotherapy.
        Int J Radiat Oncol. 2011; 80: 403-409
        • Chan E.K.
        • Woods R.
        • Virani S.
        • et al.
        Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer.
        Radiother Oncol. 2015; 114: 73-78
        • Cote R.
        • Giuliano A.
        • Hawes D.
        • et al.
        ACOSOG Z0010: A multicenter prognostic study of sentinel node (SN) and bone marrow (BM) micrometastases in women with clinical T1/T2 N0 M0 breast cancer.
        J Clin Oncol. 2010; 28: CRA504
        • Giuliano A.E.
        • Hunt K.K.
        • Ballman K.V.
        • et al.
        Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: A randomized clinical trial.
        JAMA. 2011; 305: 569-575
        • Mazor K.M.
        • Clauser B.E.
        • Field T.
        • et al.
        A demonstration of the impact of response bias on the results of patient satisfaction surveys.
        Health Serv Res. 2002; 37: 1403-1417
        • Lundstedt D.
        • Gustafsson M.
        • Steineck G.
        • et al.
        Radiation therapy to the plexus brachialis in breast cancer patients: Analysis of paresthesia in relation to dose and volume.
        Int J Radiat Oncol Biol Phys. 2015; 92: 277-283


      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.