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Hyperthermic chest wall re-irradiation in recurrent breast cancer: a prospective observational study

Hyperthermie und Rebestrahlung der Brustwand bei rezidivierendem Brustkrebs: eine prospektive Beobachtungsstudie

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Abstract

Purpose

To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC).

Methods

Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50–50.4 Gy, with a boost up to 60–60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40–42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated.

Results

20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy.

Conclusion

Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.

Zusammenfassung

Ziel

Prospektive Untersuchung der Rolle der Rebestrahlung (re-RT) kombiniert mit Hyperthermie (HT) in einer aktuellen Kohorte von Patientinnen mit lokal rezidiviertem Mammakarzinom (RBC).

Methoden

In der prospektiven HT-03-Registerstudie wurden Patientinnen mit RBC nach Resektion und vorangegangener Bestrahlung eingeschlossen. Es erfolgte eine re-RT der Rezidivregion mit 50–50,4 Gy mit sequenziellem Boost bis zu 60–60,4 Gy auf die positive Resektionsränder(R1/R2)-Regionen. Parallel zur re-RT erfolgte die HT mit 40–42 ℃. Neben dem primären Endpunkt lokale Kontrolle (LC) wurden akute und späte Toxizität, Gesamtüberleben, krebsspezifisches (CSS) und progressionsfreies (PFS) Überleben analysiert.

Ergebnisse

Ausgewertet wurden 20 Patientinnen mit 21 RBC-Läsionen. Es wurden eine mediane re-RT-Dosis von 50,4 Gy und im median 11 HT-Sitzungen pro Patient appliziert. Die Behandlung mit re-RT+HT wurde gut vertragen. Drei Patientinnen zeigten eine akute Hautreaktion vom Grad 3 (G3). Es wurden keine ≥G3-Spättoxizitäten beobachtet. Bei einer mittleren Nachbeobachtungszeit von 24,7 Monaten traten zwei Lokalrezidive auf. Zehn Patientinnen zeigten eine regionäre und/oder distante Metastasierung. Fünf Patientinnen verstarben, davon vier an Mammakarzinom. Ein längeres PFS bestand bei Patientinnen, die im ersten Rezidiv mit re-RT+HT und mit Dosen von 60 Gy behandelt wurden. Ein Trend zu besserem CSS bestand für Patientinnen mit negativem oder knappem Resektionsrand und Dosen von 60 Gy.

Schlussfolgerung

Die Kombination re-RT+HT ist für Patientinnen mit RBC gut verträglich und führt zu guter LC. Bereits beim ersten Rezidiv sollte re-RT+HT erwogen werden. Es sollten re-RT-Dosen von 60 Gy angestrebt werden. Das prospektive Register wird fortgeführt, um eine größere Anzahl an Patientinnen mit längerer Nachbeobachtungszeit auszuwerten.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital and Medical Faculty Tübingen, Eberhard Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    C. De-Colle, N. Weidner, V. Heinrich, K. MacMillan, U. Lamprecht, S. Gaupp, O. Voigt & D. Zips

  2. Department of Women’s Health, University Hospital and Medical Faculty Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany

    S. Brucker & M. Hahn

  3. German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) partner site Tübingen, Tübingen, Germany

    D. Zips

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  1. C. De-Colle
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  2. N. Weidner
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  3. V. Heinrich
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  9. O. Voigt
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Corresponding author

Correspondence to C. De-Colle.

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Conflict of interest

Dr. Sennewald Medizintechnik has financially supported scientific symposia organized by the University Department of Radiation Oncology Tübingen. C. De-Colle, N. Weidner, V. Heinrich, S. Brucker, M. Hahn, K. MacMillan, U. Lamprecht, S. Gaupp, O. Voigt, and D. Zips declare that they have no competing interests.

Ethical standards

The present study was approved by the ethics committee of the Medical Faculty of Tübingen (UKT-HT-03, Nr. 277/2012BO). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975 (in its most recently amended version). Informed consent was obtained from all patients included in the study.

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De-Colle, C., Weidner, N., Heinrich, V. et al. Hyperthermic chest wall re-irradiation in recurrent breast cancer: a prospective observational study. Strahlenther Onkol 195, 318–326 (2019). https://doi.org/10.1007/s00066-018-1414-z

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