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

doi:10.1186/s13014-020-01581-9

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)

Radiat Oncol. 2020 Jun 1;15(1):134. doi: 10.1186/s13014-020-01581-9.

Authors

Tobias Forster^{1

2

3}, Cornelia Jäkel^{1

2

3

4}, Sati Akbaba^{1

2

3}, David Krug^{1

5}, Robert Krempien⁶, Matthias Uhl^{1

2

3}, Matthias Felix Häfner^{1

2

3}, Laila König^{1

2

3}, Stefan Alexander Koerber^{1

2

3}, Semi Harrabi^{1

2

3}, Denise Bernhardt^{1

2

3}, Rouven Behnisch⁷, Johannes Krisam⁷, Andre Hennigs⁸, Christof Sohn⁸, Jörg Heil⁸, Jürgen Debus^{1

2

3

4

9

10}, Juliane Hörner-Rieber^{11

12

13

14}

Affiliations

¹ Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg University, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
² Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
³ National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁴ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Department of Radiation Oncology, University Hospital Schleswig Holstein, Kiel, Germany.
⁶ Department of Radiation Oncology, Helios Hospital Berlin-Buch, Berlin, Germany.
⁷ Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany.
⁸ Department of Gynecology and Obstetrics, Heidelberg University, 69115, Heidelberg, Germany.
⁹ Heidelberg Ion-Beam Therapy Center (HIT), Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
¹⁰ German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany.
¹¹ Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg University, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. [email protected].
¹² Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany. [email protected].
¹³ National Center for Tumor Diseases (NCT), Heidelberg, Germany. [email protected].
¹⁴ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [email protected].

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.

Publication types

Clinical Trial, Phase II
Multicenter Study
Randomized Controlled Trial

MeSH terms

Aged
Breast Neoplasms / radiotherapy*
Breast Neoplasms / surgery
Fatigue / epidemiology
Fatigue / etiology*
Female
Humans
Intraoperative Period
Middle Aged
Radiation Dose Hypofractionation
Radiotherapy, Adjuvant / adverse effects*
Radiotherapy, Adjuvant / methods*
Radiotherapy, High-Energy / methods
Radiotherapy, Intensity-Modulated / methods
Research Design

Associated data

ClinicalTrials.gov/NCT03838419