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Intraoperative Radiation Therapy for Breast Cancer

  • Clinical Trials (J Lang, Section Editor)
  • Published:
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Abstract

Purpose of Review

Adjuvant radiation represents a standard approach following breast conserving surgery. While traditionally delivered as whole breast irradiation (WBI), an alternative has emerged with the development of partial breast irradiation techniques. One such technique is intraoperative radiation therapy (IORT). The purpose of this review is to discuss the studies evaluating IORT as well as evaluating current guidelines and future directions.

Recent Findings

Review of two randomized trials (TARGIT-A and ELIOT) demonstrates that breast cancer patients treated with IORT had a higher risk of local recurrence (LR). However, patients with low-risk features and IORT performed at the time of surgery had similar rates of LR at 5 years, with longer follow-up needed. IORT as a boost is promising, and studies are ongoing.

Summary

Further studies are needed to validate the role of IORT and which patients are appropriate for IORT, and longer follow-up is needed.

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References

  1. Early Breast Cancer Trialists' Collaborative G, Darby S, McGale P, Correa C, Taylor C, Arriagada R, 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(9804):1707–16.

    Article  Google Scholar 

  2. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41.

    Article  Google Scholar 

  3. Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst. 2002;94(15):1143–50.

    Article  Google Scholar 

  4. Brunt AM, Haviland JS, Sydenham M, Agrawal RK, Algurafi H, Alhasso A, et al. Ten-year results of FAST: a randomized controlled trial of 5-fraction whole-breast radiotherapy for early breast cancer. J Clin Oncol. 2020;38(28):3261–72.

    Article  Google Scholar 

  5. Tuttle TM, Jarosek S, Habermann EB, Yee D, Yuan J, Virnig BA. Omission of radiation therapy after breast-conserving surgery in the United States: a population-based analysis of clinicopathologic factors. Cancer. 2012;118(8):2004–13.

    Article  Google Scholar 

  6. Bartelink H, Horiot JC, Poortmans P, Struikmans H, Van den Bogaert W, Barillot I, et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med. 2001;345(19):1378–87.

    Article  CAS  Google Scholar 

  7. Vaidya JS, Tobias JS, Baum M, Keshtgar M, Joseph D, Wenz F, et al. Intraoperative radiotherapy for breast cancer. Lancet Oncol. 2004;5(3):165–73.

    Article  Google Scholar 

  8. Shah C, Vicini F, Shaitelman SF, Hepel J, Keisch M, Arthur D, et al. The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation. Brachytherapy. 2018;17(1):154–70.

    Article  Google Scholar 

  9. Alvarado MD, Conolly J, Park C, Sakata T, Mohan AJ, Harrison BL, et al. Patient preferences regarding intraoperative versus external beam radiotherapy following breast-conserving surgery. Breast Cancer Res Treat. 2014;143(1):135–40.

    Article  Google Scholar 

  10. Keshtgar MR, Vaidya JS, Tobias JS, Wenz F, Joseph D, Stacey C, et al. Targeted intraoperative radiotherapy for breast cancer in patients in whom external beam radiation is not possible. Int J Radiat Oncol Biol Phys. 2011;80(1):31–8.

    Article  Google Scholar 

  11. Larson KE, Valente SA, Shah C, Tendulkar RD, Cherian S, Yanda C, et al. Are patients traveling for intraoperative radiation therapy? Int J Breast Cancer. 2017;2017:6395712.

    Article  Google Scholar 

  12. Vaidya JS, Baum M, Tobias JS, Morgan S, D'Souza D. The novel technique of delivering targeted intraoperative radiotherapy (Targit) for early breast cancer. Eur J Surg Oncol. 2002;28(4):447–54.

    Article  Google Scholar 

  13. Dickler A, Ivanov O, Francescatti D. Intraoperative radiation therapy in the treatment of early-stage breast cancer utilizing xoft axxent electronic brachytherapy. World J Surg Oncol. 2009;7:24.

    Article  Google Scholar 

  14. Orecchia R, Veronesi U. Intraoperative electrons. Semin Radiat Oncol. 2005;15(2):76–83.

    Article  Google Scholar 

  15. Intra M, Gatti G, Luini A, Galimberti V, Veronesi P, Zurrida S, et al. Surgical technique of intraoperative radiotherapy in conservative treatment of limited-stage breast cancer. Arch Surg. 2002;137(6):737–40.

    Article  Google Scholar 

  16. Orecchia R, Veronesi U, Maisonneuve P, Galimberti VE, Lazzari R, Veronesi P, et al. Intraoperative irradiation for early breast (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial. Lancet Oncol 2021 [Online ahead of print].

  17. Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet. 2010;376(9735):91–102.

    Article  Google Scholar 

  18. Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014;383(9917):603–13.

    Article  Google Scholar 

  19. Vaidya JS, Bulsara M, Saunders C, Flyger H, Tobias JS, Corica T, 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:e200249.

  20. Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, 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 randomised clinical trial. BMJ. 2020;370:m2836.

    Article  Google Scholar 

  21. Shah C, Wazer D, Vicini F. Targeted intraoperative radiotherapy for early breast cancer. JAMA Oncol. 2020.

  22. Cuzick J. Radiotherapy for breast cancer, the TARGIT-A trial. Lancet. 2014;383(9930):1716.

    Article  Google Scholar 

  23. Bentzen SM. Rapid Response: No apparent effect of 50kV intra-operative radiation therapy on loco-regional control after lumpectomy for early breast cancer. BMJ. 370:m2836. https://www.bmj.com/content/370/bmj.m2836/rr-4. Accessed 11 Apr 2021.

  24. Hess KR, Pusztai L, Buzdar AU, Hortobagyi GN. Estrogen receptors and distinct patterns of breast cancer relapse. Breast Cancer Res Treat. 2003;78(1):105–18.

    Article  CAS  Google Scholar 

  25. Valente SA, Tendulkar RD, Cherian S, O'Rourke C, Greif JM, Bailey L, et al. TARGIT-R (retrospective): North American experience with intraoperative radiation using low-kilovoltage X-rays for breast cancer. Ann Surg Oncol. 2016;23(9):2809–15.

    Article  Google Scholar 

  26. Broman K, Sun W, Zhou JM, Fridley B, Diaz R, Laronga C. Outcomes of selective whole breast irradiation following lumpectomy with intraoperative radiation therapy for hormone receptor positive breast cancer. Am J Surg. 2019;218(4):749–54.

  27. Obi E, Tom MC, Manyam BV, Grobmyer SR, Al-Hilli Z, Valente S, et al. Outcomes with intraoperative radiation therapy for early-stage breast cancer. Breast J. 2020;26(3):454–7.

    Article  CAS  Google Scholar 

  28. Silverstein MJ, Epstein M, Kim B, Lin K, Khan S, Snyder L, et al. Intraoperative Radiation Therapy (IORT): A Series of 1000 Tumors. Ann Surg Oncol. 2018;25(10):2987–93.

  29. Valente SA, Tendulkar RD, Cherian S, Shah C, Ross DL, Lottich SC, 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.

  30. Bartelink H, Maingon P, Poortmans P, Weltens C, Fourquet A, Jager J, 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 randomised phase 3 trial. Lancet Oncol. 2015;16(1):47–56.

    Article  Google Scholar 

  31. Vaidya JS, Baum M, Tobias JS, Wenz F, Massarut S, Keshtgar M, et al. Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery. Int J Radiat Oncol Biol Phys. 2011;81(4):1091–7.

    Article  Google Scholar 

  32. Kaiser J, Kronberger C, Moder A, Kopp P, Wallner M, Reitsamer R, et al. Intraoperative tumor bed boost with electrons in breast cancer of clinical stages I through III: updated 10-year results. Int J Radiat Oncol Biol Phys. 2018;102(1):92–101.

    Article  Google Scholar 

  33. Shah C, Al-Hilli Z, Schwarz G. Oncoplastic surgery in breast cancer: don't forget the boost! Ann Surg Oncol. 2018;25(9):2509–11.

    Article  Google Scholar 

  34. Kraus-Tiefenbacher U, Bauer L, Scheda A, Fleckenstein K, Keller A, Herskind C, et al. Long-term toxicity of an intraoperative radiotherapy boost using low energy X-rays during breast-conserving surgery. Int J Radiat Oncol Biol Phys. 2006;66(2):377–81.

  35. Vaidya JS. A comparison of intra-operative radiotherapy boost with external beam radiotherapy boost in early breast cancer. (TARGIT-B). ClinicalTrialsgov Identifier: NCT01792726.

  36. Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, et al. Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol. 2017;7(2):73–9.

    Article  Google Scholar 

  37. Polgar C, Van Limbergen E, Potter R, Kovacs G, Polo A, Lyczek J, 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(3):264–73.

    Article  Google Scholar 

  38. (ASBrS) ASoBS. Consensus guideline on accelerated partial breast irradiation. 2018. https://www.breastsurgeons.org/resources/statements. Accessed 11 Apr 2021.

  39. University of California SF. Intraoperative radiation therapy in treating patients with breast cancer undergoing breast-conserving surgery. https://clinicaltrials.gov/ct2/show/NCT01570998.NCT01570998. Accessed 11 Apr 2021.

  40. Mannheim U. TARGIT-C(consolidation) prospective phase IV study of IORT in patients with small breast cancer (TARGIT-C). https://clinicaltrials.gov/ct2/show/NCT02290782.NCT02290782. Accessed 11 Apr 2021.

  41. Mannheim U. Prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer (TARGIT-E). https://clinicaltrials.gov/ct2/show/NCT01299987.NCT01299987. Accessed 11 Apr 2021.

  42. Showalter SL, Petroni G, Trifiletti DM, Libby B, Schroen AT, Brenin DR, et al. A novel form of breast intraoperative radiation therapy with CT-guided high-dose-rate brachytherapy: results of a prospective phase 1 clinical trial. Int J Radiat Oncol Biol Phys. 2016;96(1):46–54.

    Article  Google Scholar 

  43. Kaidar-Person O, Poortmans P, Klimberg S, Haviland J, Offersen B, Audisio R, et al. Haste makes waste: are the data regarding TARGIT-A IORT ready for prime time? Breast Cancer Res Treat. 2014;147(1):221–2.

    Article  Google Scholar 

  44. Vaidya JS, Bulsara M, Wenz F, Joseph D, Saunders C, Massarut S, et al. In regard to Hepel and Wazer. Int J Radiat Oncol Biol Phys. 2015;92(5):953–4.

    Article  Google Scholar 

  45. Vaidya JS, Bulsara M, Wenz F, Joseph D, Saunders C, Massarut S, et al. Pride, prejudice, or science: attitudes towards the results of the TARGIT-A trial of targeted intraoperative radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys. 2015;92(3):491–7.

    Article  Google Scholar 

  46. Hepel J, Wazer DE. A flawed study should not define a new standard of care. Int J Radiat Oncol Biol Phys. 2015;91(2):255–7.

    Article  Google Scholar 

  47. Meattini I, Marrazzo L, Saieva C, Desideri I, Scotti V, Simontacchi G, et al. Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence trial. J Clin Oncol. 2020:JCO2000650.

  48. Strnad V, Hildebrandt G, Potter R, Hammer J, Hindemith M, Resch A, et al. Accelerated partial breast irradiation: 5-year results of the German-Austrian multicenter phase II trial using interstitial multicatheter brachytherapy alone after breast-conserving surgery. Int J Radiat Oncol Biol Phys. 2011;80(1):17–24.

    Article  Google Scholar 

  49. Polgar C, Major t, Takacsi-Nagy Z, Fodor J. Breast-conserving surgery followed by partial or whole breast irradiation: Twenty-year results of a phase 3 clinical study. Int J Radiat Oncol Biol Phys 2021;109:998–1006.

  50. Vicini FA, Cecchini RS, White JR, Arthur DW, Julian TB, Rabinovitch RA, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019;394(10215):2155–64.

    Article  Google Scholar 

  51. Whelan TJ, Julian JA, Berrang TS, Kim DH, Germain I, Nichol AM, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165–72.

    Article  Google Scholar 

  52. Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017;390(10099):1048–60.

    Article  Google Scholar 

  53. Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020;395(10237):1613–26.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of General Surgery, Division of Breast Surgery, Cleveland Clinic, 9500 Euclid Ave, A80, Cleveland, OH, 44195, USA

    Stephanie A. Valente

  2. Department of Radiation Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA

    Chirag Shah

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  1. Stephanie A. Valente
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  2. Chirag Shah
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Correspondence to Stephanie A. Valente.

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Conflict of Interest

Stephanie Valente is a member of the TARGIT Collaborative Group, on advisory board for Impedimed and speaker for Pacira. Chirag Shah reports personal fees from Impedimed, grants and personal fees from PreludeDX, grants from Varian Medical Systems, grants from PreludeDX, and grants from VisionRT, outside the submitted work.

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Valente, S.A., Shah, C. Intraoperative Radiation Therapy for Breast Cancer. Curr Breast Cancer Rep 13, 157–163 (2021). https://doi.org/10.1007/s12609-021-00411-5

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