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Strahlentherapie und Onkologie

, Volume 195, Issue 7, pp 640–647 | Cite as

Single-center long-term results from the randomized phase-3 TARGIT-A trial comparing intraoperative and whole-breast radiation therapy for early breast cancer

  • Yasser Abo-MadyanEmail author
  • Grit Welzel
  • Elena Sperk
  • Christian Neumaier
  • Anke Keller
  • Sven Clausen
  • Frank Schneider
  • Michael Ehmann
  • Marc Sütterlin
  • Frederik Wenz
Original Article
  • 259 Downloads

Abstract

Purpose

Partial breast irradiation using intraoperative radiotherapy (IORT) after breast-conserving surgery could be sufficient for a selected group of breast cancer patients. We report the results of a cohort of patients from a single center treated as part of the randomized phase-3 TARGIT-A trial.

Methods

Patients (≥50 years) with cT1 cN0 cM0 and invasive ductal histology on biopsy were randomized between IORT with 20 Gy (arm-A) or postoperative whole-breast RT (WBRT) up to 56 Gy in 2 Gy fractions (arm-B). Postoperatively, patients in arm-A with multifocality, lymphovascular invasion, nodal invasion, extensive intraductal component, invasive lobular carcinoma, or resection margins <1 cm received additional postoperative WBRT.

Results

Between 2002 and 2012, 184 patients were randomized, of whom 90 in arm-A and 90 in arm-B were evaluated. Median follow-up was 8.5 years. The 5‑year overall survival was 94.4% in arm-A and 93.3% in arm-B (p = 0.73). Two local recurrences were observed: one at 70.3 months in an arm-A patient who received IORT + WBRT and another at 4.5 months in an arm-B patient who refused all forms of adjuvant treatment, thus resulting in a 5-year local recurrence of 0% in arm-A and 1.1% in arm-B. The 5‑year in-breast recurrence (outside of the index quadrant) was 0% in arm-A and 1.2% in arm-B. Salvage mastectomy was performed successfully in all patients with relapse.

Conclusion

Long-term follow-up of this single-center cohort consolidates the earlier reports of low local recurrence rates after single-dose IORT. Our results are in line with non-inferiority of risk-adapted IORT for selected patients with early breast cancer.

Keywords

Early breast cancer Overall survival Local recurrence Risk-adapted therapy Partial breast irradiation 

Single-Center-Langzeitergebnisse der randomisierten Phase-3-TRAGIT-A-Studie im Vergleich mit intraoperativer und Ganzbrustbestrahlung bei frühem Brustkrebs

Zusammenfassung

Ziel

Eine Teilbrustbestrahlung mittels intraoperativer Strahlentherapie (IORT) nach einer brusterhaltenden Operation könnte für eine ausgewählte Gruppe von Brustkrebspatientinnen ausreichend sein. Wir berichten über die Ergebnisse der Kohorte von Patientinnen unseres Zentrums, die im Rahmen der randomisierten Phase-3-TARGIT-A-Studie behandelt wurden.

Methoden

Patienten (≥50 Jahre) mit dem Stadium cT1 cN0 cM0 und invasiver duktaler Histologie eines Mammakarzinoms in der Biopsie wurden zwischen IORT mit 20 Gy (Arm A) oder postoperativer Ganzbrust-RT (WBRT) bis zu einer Dosis von 50 Gy in 2‑Gy-Fraktionen (Arm B) randomisiert. Postoperativ erhielten Patientinnen in Arm A bei Multifokalität, lymphovaskulärer Invasion, Lymphknotenmetastasen, umfangreicher intraduktaler Komponente, invasivem lobulärem Karzinom oder Resektionsrändern <1 cm eine zusätzliche postoperative WBRT.

Ergebnisse

Zwischen 2002 und 2012 wurden 184 Patientinnen randomisiert. Hiervon konnten 90 Patientinnen in Arm A und 90 in Arm B ausgewertet werden. Die mediane Nachbeobachtungszeit betrug 8,5 Jahre. Das 5‑Jahres-Gesamtüberleben betrug 94,4% in Arm A und 93,3% in Arm B (p = 0,73). Zwei Lokalrezidive wurden beobachtet: eines nach 70,3 Monaten bei einer Patientin im Studienarm A, die eine IORT und eine WBRT erhalten hat, sowie eines nach 4,5 Monaten bei einer Arm-B-Patientin, die alle Formen der adjuvanten Behandlung ablehnte. Damit beträgt die 5‑Jahres-Lokalrezidivrate 0% in Arm A und 1,1% in Arm B. Die 5‑Jahres-In-Brust-Rezidivrate (außerhalb des Indexquadranten) beträgt 0% in Arm A und 1,2% in Arm B. Bei allen Patientinnen mit Rezidiv konnte eine Salvage-Mastektomie erfolgreich durchgeführt werden.

Schlussfolgerung

Die Langzeitnachbeobachtung dieser Single-Center-Kohorte konsolidiert die früheren Berichte einer niedrigen Lokalrezidivrate nach IORT. Unsere Ergebnisse stimmen mit den vorhandenen Ergebnissen der Nichtunterlegenheit einer risikoadaptierten IORT für ausgewählte Patientinnen mit frühem Brustkrebs überein.

Schlüsselwörter

Mammakarzinom im Frühstadium Gesamtüberleben Lokalrezidiv Risikoadaptierte Therapie Partielle Radiotherapie der Mamma 

Notes

Compliance with ethical guidelines

Conflict of interest

Y. Abo-Madyan reports personal fees from Carl-Zeiss Meditec, personal fees from Merck-Serono, and non-financial support from Elekta outside the submitted work. G. Welzel reports non-financial support from Carl-Zeiss Meditec and personal fees from Roche outside the submitted work. E. Sperk reports non-financial support from Carl-Zeiss Meditec outside the submitted work. S. Clausen reports personal fees from Carl-Zeiss Meditec and personal fees from Medical Solutions outside the submitted work. F. Schneider reports personal fees from Carl-Zeiss Meditec outside the submitted work. M. Ehmann reports personal fees from Carl-Zeiss Meditec, personal fees from Elekta, and personal fees from Siemens outside the submitted work. M. Sütterlin reports personal fees and non-financial support from Carl-Zeiss Meditec outside the submitted work. F. Wenz reports grants, personal fees, and non-financial support from Carl-Zeiss Meditec during the conduct of the study; personal fees and non-financial support from Elekta, grants and non-financial support from IBA outside the submitted work. C. Neumaier and A. Keller declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y, Early Breast Cancer Trialists’ Collaborative Group (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106.  https://doi.org/10.1016/S0140-6736(05)67887-7 CrossRefPubMedGoogle Scholar
  2. 2.
    Early Breast Cancer Trialists’ Collaborative G, Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R (2011) 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 378(9804):1707–1716.  https://doi.org/10.1016/S0140-6736(11)61629-2 CrossRefGoogle Scholar
  3. 3.
    Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sutterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M (2010) Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 376(9735):91–102.  https://doi.org/10.1016/S0140-6736(10)60837-9 CrossRefPubMedGoogle Scholar
  4. 4.
    Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Keshtgar M, Flyger HL, Massarut S, Alvarado M, Saunders C, Eiermann W, Metaxas M, Sperk E, Sutterlin M, Brown D, Esserman L, Roncadin M, Thompson A, Dewar JA, Holtveg HM, Pigorsch S, Falzon M, Harris E, Matthews A, Brew-Graves C, Potyka I, Corica T, Williams NR, Baum M, TARGIT trialists’ group (2014) 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 383(9917):603–613.  https://doi.org/10.1016/S0140-6736(13)61950-9 CrossRefPubMedGoogle Scholar
  5. 5.
    Vaidya JS, Wenz F, Bulsara M, Tobias JS, Joseph DJ, Saunders C, Brew-Graves C, Potyka I, Morris S, Vaidya HJ, Williams NR, Baum M (2016) An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial). Health Technol Assess 20(73):1–188.  https://doi.org/10.3310/hta20730 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Valente SA, Tendulkar RD, Cherian S, O’Rourke C, Greif JM, Bailey L, Uhl V, Bethke KP, Donnelly ED, Rudolph R, Pederson A, Summer T, Lottich SC, Ross DL, Laronga C, Loftus L, Abbott AM, Kelemen P, Hermanto U, Friedman NB, Bedi GC, Joh JE, Thompson WA 3rd, Hoefer RA, Wilson JP, Kang SK, Rosen B, Ruffer J, Bravo L, Police A, Escallon JM, Fyles AW, McCready DR, Graves GM, Rohatgi N, Eaker JA, Graves J, Willey SC, Tousimis EA, Collins BT, Shaw CM, Riley L, Deb N, Kelly T, Andolino DL, Boisvert ME, Lyons J, Small W Jr., Grobmyer SR (2016) TARGIT-R (retrospective): north American experience with intraoperative radiation using low-kilovoltage X‑rays for breast cancer. Ann Surg Oncol 23(9):2809–2815.  https://doi.org/10.1245/s10434-016-5240-1 CrossRefPubMedGoogle Scholar
  7. 7.
    Neumaier C, Elena S, Grit W, Yasser AM, Uta KT, Anke K, Axel G, Marc S, Frederik W (2012) TARGIT-E(lderly)—prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer. BMC Cancer 12:171.  https://doi.org/10.1186/1471-2407-12-171 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, White J, Harris JR (2017) Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract Radiat Oncol 7(2):73–79.  https://doi.org/10.1016/j.prro.2016.09.007 CrossRefPubMedGoogle Scholar
  9. 9.
    Polgar C, Van Limbergen E, Potter R, Kovacs G, Polo A, Lyczek J, Hildebrandt G, Niehoff P, Guinot JL, Guedea F, Johansson B, Ott OJ, Major T, Strnad V, group G‑Ebcw (2010) 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 94(3):264–273.  https://doi.org/10.1016/j.radonc.2010.01.014 CrossRefPubMedGoogle Scholar
  10. 10.
    Sautter-Bihl ML, Budach W, Dunst J, Feyer P, Haase W, Harms W, Sedlmayer F, Souchon R, Wenz F, Sauer R (2007) DEGRO practical guidelines for radiotherapy of breast cancer I: breast-conserving therapy. Strahlenther Onkol 183(12):661–666.  https://doi.org/10.1007/s00066-007-1811-1 CrossRefPubMedGoogle Scholar
  11. 11.
    Blamey RW, Bates T, Chetty U, Duffy SW, Ellis IO, George D, Mallon E, Mitchell MJ, Monypenny I, Morgan DA, Macmillan RD, Patnick J, Pinder SE (2013) Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial. Eur J Cancer 49(10):2294–2302.  https://doi.org/10.1016/j.ejca.2013.02.031 CrossRefPubMedGoogle Scholar
  12. 12.
    Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC (2013) 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 31(19):2382–2387.  https://doi.org/10.1200/JCO.2012.45.2615 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM, PRIME II investigators (2015) Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol 16(3):266–273.  https://doi.org/10.1016/S1470-2045(14)71221-5 CrossRefPubMedGoogle Scholar
  14. 14.
    Fisher B, Bryant J, Dignam JJ, Wickerham DL, Mamounas EP, Fisher ER, Margolese RG, Nesbitt L, Paik S, Pisansky TM, Wolmark N (2002) Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol 20(20):4141–4149.  https://doi.org/10.1200/JCO.2002.11.101 CrossRefPubMedGoogle Scholar
  15. 15.
    Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P, Salvadori B, Zucali R (2001) Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term results of a randomized trial. Ann Oncol 12(7):997–1003CrossRefPubMedGoogle Scholar
  16. 16.
    Matuschek C, Bolke E, Haussmann J, Mohrmann S, Nestle-Kramling C, Gerber PA, Corradini S, Orth K, Kammers K, Budach W (2017) The benefit of adjuvant radiotherapy after breast conserving surgery in older patients with low risk breast cancer—a meta-analysis of randomized trials. Radiat Oncol 12(1):60.  https://doi.org/10.1186/s13014-017-0796-x CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Keshtgar MR, Williams NR, Bulsara M, Saunders C, Flyger H, Cardoso JS, Corica T, Bentzon N, Michalopoulos NV, Joseph DJ (2013) Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: results from a randomised controlled trial. Breast Cancer Res Treat 140(3):519–525.  https://doi.org/10.1007/s10549-013-2641-8 CrossRefPubMedGoogle Scholar
  18. 18.
    Corica T, Nowak AK, Saunders CM, Bulsara MK, Taylor M, Williams NR, Keshtgar M, Joseph DJ, Vaidya JS (2018) Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A Trial. Radiat Oncol 13(1):68.  https://doi.org/10.1186/s13014-018-0998-x CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Sperk E, Welzel G, Keller A, Kraus-Tiefenbacher U, Gerhardt A, Sutterlin M, Wenz F (2012) Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A. Breast Cancer Res Treat 135(1):253–260.  https://doi.org/10.1007/s10549-012-2168-4 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yasser Abo-Madyan
    • 1
    Email author
  • Grit Welzel
    • 1
  • Elena Sperk
    • 1
  • Christian Neumaier
    • 1
  • Anke Keller
    • 1
  • Sven Clausen
    • 1
  • Frank Schneider
    • 1
  • Michael Ehmann
    • 1
  • Marc Sütterlin
    • 2
  • Frederik Wenz
    • 1
  1. 1.Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty MannheimHeidelberg UniversityMannheimGermany
  2. 2.Department of Obstetrics and Gynecology, Universitätsmedizin Mannheim, Medical Faculty MannheimHeidelberg UniversityMannheimGermany

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