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- Hiensch, Anouk E, et al.
(författare)
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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.
- 2022
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1, s. 610-
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Tidskriftsartikel (refereegranskat)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.
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| 3. |
- Reuten, Raphael, et al.
(författare)
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Basement membrane stiffness determines metastases formation
- 2021
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Ingår i: Nature Materials. - : Springer Science and Business Media LLC. - 1476-4660 .- 1476-1122.
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Tidskriftsartikel (refereegranskat)abstract
- The basement membrane (BM) is a special type of extracellular matrix and presents the major barrier cancer cells have to overcome multiple times to form metastases. Here we show that BM stiffness is a major determinant of metastases formation in several tissues and identify netrin-4 (Net4) as a key regulator of BM stiffness. Mechanistically, our biophysical and functional analyses in combination with mathematical simulations show that Net4 softens the mechanical properties of native BMs by opening laminin node complexes, decreasing cancer cell potential to transmigrate this barrier despite creating bigger pores. Our results therefore reveal that BM stiffness is dominant over pore size, and that the mechanical properties of ‘normal’ BMs determine metastases formation and patient survival independent of cancer-mediated alterations. Thus, identifying individual Net4 protein levels within native BMs in major metastatic organs may have the potential to define patient survival even before tumour formation. The ratio of Net4 to laminin molecules determines BM stiffness, such that the more Net4, the softer the BM, thereby decreasing cancer cell invasion activity.
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