TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

Publisher: Springer Country of Publication: United States NLM ID: 9420840 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1534-4681 (Electronic) Linking ISSN: 10689265 NLM ISO Abbreviation: Ann Surg Oncol Subsets: MEDLINE

Publication: 2005- : New York, NY : Springer
Original Publication: New York, NY : Raven Press, c1994-

Breast Neoplasms*/radiotherapy ; Breast Neoplasms*/surgery; Follow-Up Studies ; Humans ; Intraoperative Care ; Mastectomy, Segmental ; Neoplasm Recurrence, Local/radiotherapy ; North America ; Prospective Studies ; Retrospective Studies

Background: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment.
Methods: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR).
Results: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%.
Conclusion: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Early 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;378:1707–16. (PMID: 10.1016/S0140-6736(11)61629-2)
Veronesi U, Luini A, Del Vecchio M, Greco M, Galimberti V, Merson M, et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med. 1993;328:1587–91. (PMID: 10.1056/NEJM199306033282202)
Fyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, et al. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004;351:963–70. (PMID: 10.1056/NEJMoa040595)
Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, 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;31:2382–7. (PMID: 10.1200/JCO.2012.45.2615)
Baum M, Vaidya JS, Mittra I. Multicentricity and recurrence of breast cancer. Lancet. 1997;349:208. (PMID: 10.1016/S0140-6736(05)60950-6)
Vaidya JS, Tobias JS, Baum M, Wenz F, Kraus-Tiefenbacher U, D’Souza D, et al. TARGeted Intraoperative radiotherapy (TARGIT): an innovative approach to partial-breast irradiation. Semin Radiat Oncol. 2005;15:84–91. (PMID: 10.1016/j.semradonc.2004.10.007)
Korzets Y, Fyles A, Shepshelovich D, Amir E, Goldvaser H. Toxicity and clinical outcomes of partial-breast irradiation compared to whole-breast irradiation for early-stage breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019;175:531–45. (PMID: 10.1007/s10549-019-05209-9)
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;376:91–102. (PMID: 10.1016/S0140-6736(10)60837-9)
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;383:603–13. (PMID: 10.1016/S0140-6736(13)61950-9)
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. (PMID: 10.1136/bmj.m2836)
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.
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;7:73–9. (PMID: 10.1016/j.prro.2016.09.007)
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;23:2809–15. (PMID: 10.1245/s10434-016-5240-1)
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;17:154–70. (PMID: 10.1016/j.brachy.2017.09.004)
Shah C, Vicini F, Wazer DE, Arthur D, Patel RR. The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation. Brachytherapy. 2013;12:267–77. (PMID: 10.1016/j.brachy.2013.02.001)
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;94:264–73. (PMID: 10.1016/j.radonc.2010.01.014)
Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, et al. Accelerated partial-breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74:987–1001. (PMID: 10.1016/j.ijrobp.2009.02.031)
(ASBrS). ASoBS. The American Society of Breast Surgery Consensus Statement for Accelerated Partial-Breast Irradiation. Retrieved 5 June 2018 at https://www.breastsurgeonsorg/docs/statements/Consensus-Statement-for-Accelerated-Partial-Breast-Irradiationpdf .
Abo-Madyan Y, Welzel G, Sperk E, Neumaier C, Keller A, Clausen S, et al. Single-center long-term results from the randomized phase 3 TARGIT-A trial comparing intraoperative and whole-breast radiation therapy for early breast cancer. Strahlenther Onkol. 2019;195:640–7. (PMID: 10.1007/s00066-019-01438-5)
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;26:454–7. (PMID: 10.1111/tbj.13574)
Melnik I, Yerushalmi R, Sobol Y, Magen A, Givon-Madhala O, Birinbaum Y, et al. Intraoperative radiation therapy for breast cancer: immediate and 30-month oncological outcomes. Breast J. 2019;26:946–51. (PMID: 10.1111/tbj.13708)
Fisher B, Bauer M, Margolese R, Poisson R, Pilch Y, Redmond C, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1985;312:665–73. (PMID: 10.1056/NEJM198503143121101)
Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, et al. Accelerated partial-breast irradiation using intensity-modulated radiotherapy versus whole-breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015;51:451–63. (PMID: 10.1016/j.ejca.2014.12.013)
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;394:2155–64. (PMID: 10.1016/S0140-6736(19)32514-0)
Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013;14:1269–77. (PMID: 10.1016/S1470-2045(13)70497-2)
Chirgwin JH, Giobbie-Hurder A, Coates AS, Price KN, Ejlertsen B, Debled M, et al. Treatment adherence and its impact on disease-free survival in the Breast International Group 1–98 trial of tamoxifen and letrozole, alone and in sequence. J Clin Oncol. 2016;34:2452–9. (PMID: 10.1200/JCO.2015.63.8619)
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;218:749–54. (PMID: 10.1016/j.amjsurg.2019.07.011)
Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol. 2009;27:2466–73. (PMID: 10.1200/JCO.2008.19.8424)
Goldberg M, Sutradhar R, Paszat L, Whelan TJ, Gu S, Fong C, et al. Patterns of adjuvant care and outcomes of elderly women with stage I breast cancer after breast-conserving surgery: a population-based analysis. Breast Cancer Res Treat. 2019;176:657–67. (PMID: 10.1007/s10549-019-05266-0)
Hershman DL, Unger JM, Hillyer GC, Moseley A, Arnold KB, Dakhil SR, et al. Randomized trial of text messaging to reduce early discontinuation of adjuvant aromatase inhibitor therapy in women with early-stage breast cancer: SWOG S1105. J Clin Oncol. 2020:JCO1902699.
Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134:459–78. (PMID: 10.1007/s10549-012-2114-5)
Sedlmayer F, Reitsamer R, Wenz F, Sperk E, Fussl C, Kaiser J, et al. Intraoperative radiotherapy (IORT) as boost in breast cancer. Radiat Oncol. 2017;12:23. (PMID: 10.1186/s13014-016-0749-9)
Shah C, Al-Hilli Z, Schwarz G. Oncoplastic surgery in breast cancer: don’t forget the boost! Ann Surg Oncol. 2018;25:2509–11. (PMID: 10.1245/s10434-018-6571-x)
London UC. A Comparison of Intraoperative Radiotherapy Boost With External Beam Radiotherapy Boost in Early Breast Cancer. (TARGIT-B). ClinicalTrialsgov Identifier: NCT01792726.
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;143:135–40. (PMID: 10.1007/s10549-013-2782-9)
Coombs NJ, Coombs JM, Vaidya UJ, Singer J, Bulsara M, Tobias JS, et al. Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer: data from UK TARGIT-A trial centres and two UK NHS hospitals offering TARGIT IORT. BMJ Open. 2016;6:e010703. (PMID: 10.1136/bmjopen-2015-010703)
Shah C, Lanni TB, Saini H, Nanavati A, Wilkinson JB, Badiyan S, et al. Cost-efficacy of acceleration partial-breast irradiation compared with whole-breast irradiation. Breast Cancer Res Treat. 2013;138:127–35. (PMID: 10.1007/s10549-013-2412-6)
University of California SF. Targeted Intraoperative Radiotherapy United States (TARGIT-US) Phase IV Registry Trial: A Registry Trial of Targeted Intraoperative Radiation Therapy Following Breast-conserving Surgery. ClinicalTrialsgov Identifier: NCT01570998.
Neumaier C, Elena S, Grit W, Yasser AM, Uta KT, Anke K, et al. TARGIT-E(lderly): prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer. BMC Cancer. 2012;12:171. (PMID: 10.1186/1471-2407-12-171)

Date Created: 20210112 Date Completed: 20210514 Latest Revision: 20210514

20221213

10.1245/s10434-020-09432-3

33433786