Fatigue following radiotherapy of low-risk early breast cancer - a randomized controlled trial of intraoperative electron radiotherapy versus standard hypofractionated whole-breast radiotherapy: the COSMOPOLITAN trial (NCT03838419)

Tobias Forster, Cornelia Jäkel, Sati Akbaba, David Krug, Robert Krempien, Matthias Uhl, Matthias Felix Häfner, Laila König, Stefan Alexander Koerber, Semi Harrabi, Denise Bernhardt, Rouven Behnisch, Johannes Krisam, Andre Hennigs, Christof Sohn, Jörg Heil, Jürgen Debus, Juliane Hörner-Rieber, Tobias Forster, Cornelia Jäkel, Sati Akbaba, David Krug, Robert Krempien, Matthias Uhl, Matthias Felix Häfner, Laila König, Stefan Alexander Koerber, Semi Harrabi, Denise Bernhardt, Rouven Behnisch, Johannes Krisam, Andre Hennigs, Christof Sohn, Jörg Heil, Jürgen Debus, Juliane Hörner-Rieber

Abstract

Background: Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients.

Methods: This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size < 2,5 cm, ER pos. Her2neu neg., age > 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale.

Discussion: The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance.

Trial registration: The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. "Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)".

Study status: Ongoing study. Start of recruitment was December 2019.

Keywords: Breast cancer; Fatigue; Intraoperative electron radiotherapy; Radiotherapy; Whole-breast radiotherapy.

Conflict of interest statement

This trial is financially supported by IntraOP Medical, 570 Del Rey Avenue, Sunnyvale, CA 94085. IntraOP Medical is not involved in the design of the study, nor the collection, storage or analysis of the data gathered in this study. All authors declare that there is no conflict of interest in connection with the implementation and evaluation of this study.

Figures

Fig. 1
Fig. 1
Trial flow-chart

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