Intraoperative radiation therapy in the management of early stage breast cancer

Published:October 05, 2022DOI:


      Adjuvant radiotherapy (RT) following breast conserving surgery (BCS) is associated with an improvement in local control and a reduction in breast cancer mortality. While traditionally delivered with whole breast irradiation (WBI), novel approaches have looked to reduce the duration, target volume, and toxicity of adjuvant RT. One such approach is intraoperative radiation therapy (IORT), which delivers radiation at the time of surgery with 80–90% of patients not requiring additional WBI. The current review presents IORT techniques and outcomes from modern series evaluating IORT as monotherapy or as a tumor bed boost. Based on two randomized trials (TARGIT-A and ELIOT) with recent updates, concern regarding higher rates of local recurrence with IORT exist, whether using electrons or low-energy techniques. In contrast, data is promising regarding IORT used as a boost, with ongoing studies evaluating its role prospectively. With respect to toxicity, the data suggest IORT is associated with comparable to slightly lower rates of toxicity though there may be a higher risk of seroma requiring aspiration and fat necrosis with IORT. Given current data and guidelines, WBI or other partial breast techniques should remain the standard of care in early stage breast cancer patients, while IORT should not be utilized outside of prospective clinical trials at this time.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      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'


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


        • Darby S.
        • McGale P.
        • et al.
        • Early Breast Cancer Trialists' Collaborative G.
        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 randomized trials.
        Lancet. 2011; 378: 1707-1716
        • Celaya M.O.
        • Rees J.R.
        • Gibson J.J.
        • et al.
        Travel distance and season of diagnosis affect treatment choices for women with early-stage breast cancer in a predominantly rural population (United States).
        Cancer Causes Control. 2006; 17: 851-856
        • Nattinger A.B.
        • Kneusel R.T.
        • Hoffmann R.G.
        • Gilligan M.A.
        Relationship of distance from a radiotherapy facility and initial breast cancer treatment.
        J Natl Cancer Inst. 2001; 93: 1344-1346
        • Shah C.
        • Vicini F.
        • Shaitelman S.F.
        • et al.
        The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation.
        Brachytherapy. 2018; 17: 154-170
        • Showalter S.L.
        • Petroni G.
        • Trifiletti D.M.
        • et al.
        A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: results of a Prospective Phase I Clinical Trial.
        Int J Radiat Oncol Biol Phys. 2016; 96: 46-54
        • Silverstein M.J.
        • Fastner G.
        • Maluta S.
        • et al.
        Intraoperative radiation therapy: a critical analysis of the ELIOT and TARGIT trials. Part 2–TARGIT.
        Ann Surg Oncol. 2014; 21: 3793-3799
        • Tom M.C.
        • Joshi N.
        • Vicini F.
        • et al.
        The American Brachytherapy Society consensus statement on intraoperative radiation therapy.
        Brachytherapy. 2019; 18: 242-257
        • Dutta S.W.
        • Mehaffey J.H.
        • Sanders J.C.
        • et al.
        Implementation of an HDR brachytherapy-based breast IORT program: initial experiences.
        Brachytherapy. 2019; 18: 285-291
        • Cuzick J.
        Radiotherapy for breast cancer, the TARGIT-A trial.
        Lancet. 2014; 383: 1716
        • Vaidya J.S.
        • Bulsara M.
        • Saunders C.
        • et al.
        Effect of Delayed Targeted Intraoperative Radiotherapy vs. Whole-Breast Radiotherapy on Local Recurrence and Survival: long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer.
        JAMA Oncol. 2020; 6e200249
        • Shah C.
        Intraoperative radiation therapy for breast cancer: are we there yet?.
        Ann Surg Oncol. 2021; 28: 20-21
        • Bentzen S.M.
        • Haviland J.S.
        • Yarnold J.R.
        Targeted Intraoperative Radiotherapy for Early Breast Cancer.
        JAMA Oncol. 2020; 6: 1636
        • Valente S.A.
        • Tendulkar R.D.
        • Cherian S.
        • et al.
        TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.
        Ann Surg Oncol. 2021; 28: 2512-2521
        • Silverstein M.J.
        • Epstein M.S.
        • Chen P.
        • et al.
        Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT).
        Ann Surg Oncol. 2022; 29: 3726-3736
        • Zhang L.
        • Zhou Z.
        • Mei X.
        • et al.
        Intraoperative radiotherapy versus whole-breast external beam radiotherapy in early-stage breast cancer: a systematic review and meta-analysis.
        Medicine (Baltimore). 2015; 94: e1143
        • Wang L.
        • Sun M.
        • Yang S.
        • et al.
        Intraoperative radiotherapy is not a better alternative to whole breast radiotherapy as a therapeutic option for early-stage breast cancer.
        Front Oncol. 2021; 11737982
        • Vaidya J.S.
        • Bulsara M.
        • Wenz F.
        • et al.
        Reduced mortality with partial-breast irradiation for early breast Cancer:a meta-analysis of randomized trials.
        IntJ Radiat Oncol Biol Phys. 2016; 96: 259-265
        • Vaidya J.S.
        • Bulsara M.
        • Baum M.
        • et al.
        Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomized clinical trial.
        BMJ. 2020; 370: m2836
        • Veronesi U.
        • Orecchia R.
        • Maisonneuve P.
        • et al.
        Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomized controlled equivalence trial.
        Lancet Oncol. 2013; 14: 1269-1277
        • Leonardi M.C.
        • Maisonneuve P.
        • Mastropasqua M.G.
        • et al.
        How do the ASTRO consensus statement guidelines for the application of accelerated partial breast irradiation fit intraoperative radiotherapy? A retrospective analysis of patients treated at the European Institute of Oncology.
        Int J Radiat Oncol Biol Phys. 2012; 83: 806-813
        • Jacobs D.H.M.
        • Mast M.E.
        • Horeweg N.
        • et al.
        Accelerated partial breast irradiation using external beam or intraoperative electron radiation therapy: 5-year oncological outcomes of a prospective cohort study.
        Int J Radiat Oncol Biol Phys. 2022; 113: 570-581
        • Hughes K.S.
        • Schnaper L.A.
        • Bellon J.R.
        • et al.
        Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.
        J Clin Oncol. 2013; 31: 2382-2387
        • Kunkler I.H.
        • Williams L.J.
        • Jack W.J.
        • et al.
        Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomized controlled trial.
        Lancet Oncol. 2015; 16: 266-273
        • Bartelink H.
        • Maingon P.
        • Poortmans P.
        • et al.
        Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomized phase III trial.
        Lancet Oncol. 2015; 16: 47-56
        • Blank E.
        • Kraus-Tiefenbacher U.
        • Welzel G.
        • et al.
        Single-center long-term follow-up after intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage x-rays.
        Ann Surg Oncol. 2010; 17 (Suppl): 352-358
        • Fastner G.
        • Sedlmayer F.
        • Merz F.
        • et al.
        IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: long term results of an ISIORT pooled analysis.
        Radiother Oncol. 2013; 108: 279-286
        • Sedlmayer F.
        • Fastner G.
        • Merz F.
        • et al.
        IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: results of an ISIORT pooled analysis.
        Strahlenther Onkol. 2007; 183 (Spec No 2): 32-34
      1. A comparison of intra-operative radiotherapy boost with external beam radiotherapy boost in early breast cancer. (TARGIT-B). Available at: Accessed August 20, 2022.

        • Vaidya J.S.
        • Joseph D.J.
        • Tobias J.S.
        • et al.
        Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomized, non-inferiority phase III trial.
        Lancet. 2010; 376: 91-102
        • Corica T.
        • Nowak A.K.
        • Saunders C.M.
        • et al.
        Cosmesis and breast-related quality of life outcomes after intraoperative radiation therapy for early breast cancer: a substudy of the TARGIT-a trial.
        Int J Radiat Oncol Biol Phys. 2016; 96: 55-64
        • Engel D.
        • Schnitzer A.
        • Brade J.
        • et al.
        Are mammographic changes in the tumor bed more pronounced after intraoperative radiotherapy for breast cancer? Subgroup analysis from a randomized trial (TARGIT-A).
        Breast J. 2013; 19: 92-95
        • Pez M.
        • Keller A.
        • Welzel G.
        • et al.
        Long-term outcome after intraoperative radiotherapy as a boost in breast cancer.
        Strahlenther Onkol. 2020; 196: 349-355
        • Rivera R.
        • Smith-Bronstein V.
        • Villegas-Mendez S.
        • et al.
        Mammographic findings after intraoperative radiotherapy of the breast.
        Radiol Res Pract. 2012; 2012758371
        • Sedlmayer F.
        • Reitsamer R.
        • Wenz F.
        • et al.
        Intraoperative radiotherapy (IORT) as boost in breast cancer.
        Radiat Oncol. 2017; 12: 23
        • Burgos J.
        • Vega V.
        • Macias-Verde D.
        • et al.
        Hypofractionated whole breast irradiation after iort treatment is safe in patients receiving adjuvant chemotherapy.
        Clin Transl Oncol. 2021; : 2579-2583
        • Vaidya A.
        • Vaidya P.
        • Both B.
        • et al.
        Health economics of targeted intraoperative radiotherapy (TARGIT-IORT) for early breast cancer: a cost-effectiveness analysis in the United Kingdom.
        BMJ Open. 2017; 7e014944
      2. Alvarado M.D., Mohan A.J., Esserman L.J., et al. Cost-effectiveness analysis of intraoperative radiation therapy for early

        • Shah C.
        • Badiyan S.
        • Khwaja S.
        • et al.
        Evaluating radiotherapy options in breast cancer: does intraoperative radiotherapy represent the most cost-efficacious option?.
        Clin Breast Cancer. 2014; 14: 141-146
        • Deshmukh A.A.
        • Shirvani S.M.
        • Lal L.
        • et al.
        Cost-effectiveness analysis comparing conventional, hypofractionated, and intraoperative radiotherapy for early-stage breast cancer.
        J Natl Cancer Inst. 2017; 109
        • Shah C.
        • Vicini F.
        • Shaitelman S.F.
        • et al.
        The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation.
        Brachytherapy. 2018; 17: 154-170
        • Correa C.
        • Harris E.E.
        • Leonardi M.C.
        • et al.
        Accelerated Partial Breast Irradiation: executive summary for the update of an ASTRO Evidence-Based Consensus Statement.
        Pract Radiat Oncol. 2017; 7: 73-79
        • Polgar C.
        • Van Limbergen E.
        • Potter R.
        • et al.
        Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: recommendations of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009).
        Radiother Oncol. 2010; 94: 264-273