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

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

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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.

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.

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Authors and Affiliations

  1. Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Yasser Abo-Madyan MD, Grit Welzel M.Sc., Elena Sperk MD, Christian Neumaier MD, Anke Keller, Sven Clausen PhD, Frank Schneider PhD, Michael Ehmann MD & Frederik Wenz MD

  2. Department of Obstetrics and Gynecology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Marc Sütterlin MD

Authors
  1. Yasser Abo-Madyan MD
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  2. Grit Welzel M.Sc.
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  3. Elena Sperk MD
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  4. Christian Neumaier MD
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  5. Anke Keller
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  8. Michael Ehmann MD
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  9. Marc Sütterlin MD
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  10. Frederik Wenz MD
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Corresponding author

Correspondence to Yasser Abo-Madyan MD.

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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.

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Abo-Madyan, Y., Welzel, G., Sperk, E. 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 195, 640–647 (2019). https://doi.org/10.1007/s00066-019-01438-5

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