Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life: the EFFECT study
Anouk E. Hiensch,
Evelyn M. Monninkhof,
Martina E. Schmidt,
Eva M. Zopf,
Kate A. Bolam,
Neil K. Aaronson,
Jon Belloso,
Wilhelm Bloch,
Dorothea Clauss,
Johanna Depenbusch,
Milena Lachowicz,
Mireia Pelaez,
Helene Rundqvist,
Elzbieta Senkus,
Martijn M. Stuiver,
Mark Trevaskis,
Ander Urruticoechea,
Friederike Rosenberger,
Elsken van der Wall,
G. Ardine de Wit,
Philipp Zimmer,
Yvonne Wengström,
Karen Steindorf,
Anne M. May
Affiliations
Anouk E. Hiensch
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University
Evelyn M. Monninkhof
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University
Martina E. Schmidt
Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg
Eva M. Zopf
Mary MacKillop Institute for Health Research, Australian Catholic University
Kate A. Bolam
Division of Nursing, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet
Neil K. Aaronson
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute
Jon Belloso
R&D department, Fundación Onkologikoa
Wilhelm Bloch
Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne
Dorothea Clauss
Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg
Johanna Depenbusch
Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg
Milena Lachowicz
Department of Oncology and Radiotherapy, Medical University of Gdańsk
Mireia Pelaez
R&D department, Fundación Onkologikoa
Helene Rundqvist
Department of Laboratory Medicine, Karolinska Institutet
Elzbieta Senkus
Department of Oncology and Radiotherapy, Medical University of Gdańsk
Martijn M. Stuiver
Center for Quality of Life and Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute
Mark Trevaskis
Mary MacKillop Institute for Health Research, Australian Catholic University
Ander Urruticoechea
R&D department, Fundación Onkologikoa
Friederike Rosenberger
Department of Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg University Hospital
Elsken van der Wall
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University
G. Ardine de Wit
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University
Philipp Zimmer
Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne
Yvonne Wengström
Cabrini Cancer Institute, The Szalmuk Family Department of Medical Oncology, Cabrini Health
Karen Steindorf
Division of Physical Activity, Prevention and Cancer, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg
Anne M. May
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University
Abstract Background Many patients with metastatic breast cancer experience cancer- and treatment-related side effects that impair activities of daily living and negatively affect the quality of life. There is a need for interventions that improve quality of life by alleviating fatigue and other side effects during palliative cancer treatment. Beneficial effects of exercise have been observed in the curative setting, but, to date, comparable evidence in patients with metastatic breast cancer is lacking. The aim of this study is to assess the effects of a structured and individualized 9-month exercise intervention in patients with metastatic breast cancer on quality of life, fatigue, and other cancer- and treatment-related side effects. Methods The EFFECT study is a multinational, randomized controlled trial including 350 patients with metastatic breast cancer. Participants are randomly allocated (1:1) to an exercise or control group. The exercise group participates in a 9-month multimodal exercise program, starting with a 6-month period where participants exercise twice a week under the supervision of an exercise professional. After completing this 6-month period, one supervised session is replaced by one unsupervised session for 3 months. In addition, participants are instructed to be physically active for ≥30 min/day on all remaining days of the week, while being supported by an activity tracker and exercise app. Participants allocated to the control group receive standard medical care, general written physical activity advice, and an activity tracker, but no structured exercise program. The primary outcomes are quality of life (EORTC QLQ-C30, summary score) and fatigue (EORTC QLQ-FA12), assessed at baseline, 3, 6 (primary endpoint), and 9 months post-baseline. Secondary outcomes include physical fitness, physical performance, physical activity, anxiety, depression, pain, sleep problems, anthropometric data, body composition, and blood markers. Exploratory outcomes include quality of working life, muscle thickness, urinary incontinence, disease progression, and survival. Additionally, the cost-effectiveness of the exercise program is assessed. Adherence and safety are monitored throughout the intervention period. Discussion This large randomized controlled trial will provide evidence regarding the (cost-) effectiveness of exercise during treatment of metastatic breast cancer. If proven (cost-)effective, exercise should be offered to patients with metastatic breast cancer as part of standard care. Trial registration ClinicalTrials.gov NCT04120298 . Registered on October 9, 2019.
