Cardiovascular training for fatigue in people with cancer.

Rationale: Cancer-related fatigue (CRF) is the most prevalent and severe symptom among people with cancer. It can be attributed to the cancer itself or to anticancer therapies. CRF affects the individual physically and mentally, and cannot be alleviated by rest. Studies show a positive effect of exercise on CRF.

Objectives: To evaluate the effects of cardiovascular training on cancer-related fatigue (CRF), quality of life (QoL), adverse events, anxiety, and depression in people with cancer, with regard to their stage of anticancer therapy (before, during, or after), up to 12 weeks, up to six months, or longer, postintervention.

Search methods: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and World Health Organization ICTRP to identify studies that are included in the review. The latest search date was October 2023.

Eligibility criteria: We included randomised controlled trials (RCTs) evaluating cardiovascular training for CRF or QoL, or both, in people with cancer. Trials were eligible if training was structured, included at least five sessions, and instruction was face-to-face (via video tools or in person). We excluded studies with fewer than 20 randomised participants per group and where only an abstract was available.

Outcomes: Our critical outcomes were: short-, medium-, long-term CRF and QoL. Important outcomes were adverse events, and short-, medium-, long-term anxiety and depression.

Risk of bias: We used the Cochrane RoB 1 tool to assess bias in RCTs.

Synthesis methods: We used standard Cochrane methodology. We synthesised results for each outcome using meta-analysis where possible (inverse variance or Mantel-Haenszel; random-effects model). We pooled data for the respective assessment periods above. We used GRADE to assess certainty of evidence for each outcome.

Included studies: We included 23 RCTs with 2135 participants, of whom 96.6% originated from high-income countries; 1101 participants were randomised to cardiovascular training and 1034 to no training. Studies included mostly females who were diagnosed with breast cancer. We also identified 36 ongoing and 12 completed studies that have not yet published (awaiting assessment). We only present findings on CRF, QoL and adverse events. For details regarding anxiety and depression, see full text.

Synthesis of results: Cardiovascular training before anticancer therapy versus no training for people with cancer We identified no studies for inclusion in this comparison. Cardiovascular training during anticancer therapy versus no training for people with cancer We included 10 studies (1026 participants); eight studies contributed data to quantitative analyses (860 participants). Cardiovascular training probably reduces short-term CRF slightly (mean difference (MD) 2.85, 95% confidence interval (CI) 1.16 to 4.55, on the Functional Assessment of Cancer Therapy - Fatigue (FACT-F), scale 0 to 52, higher values mean better outcome; minimally important difference (MID) 3; 6 studies, 593 participants) and probably results in little to no difference in short-term QoL (MD 3.56, 95% CI 0.21 to 6.90, on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C-30), scale 0 to 100, higher values mean better outcome, MID 10; 6 studies, 612 participants) (both moderate-certainty evidence). We are uncertain about the effects on medium-term CRF (MD 2.67, 95% CI -2.58 to 7.92, on FACT-F; MID 3; 1 study, 62 participants), long-term CRF (MD 0.41, 95% CI -2.24 to 3.05, on FACT-F; MID 3; 2 studies, 230 participants), medium-term QoL (MD 6.79, 95% CI -4.39 to 17.97, on EORTC QLQ C-30; MID 10; 1 study, 62 participants), and long-term QoL (MD 1.51, 95% CI -3.40 to 6.42, on EORTC QLQ C-30; MID 10; 2 studies, 230 participants) (all very low-certainty evidence). For adverse events (any grade and follow-up), we did not perform meta-analysis due to heterogeneous definitions, reporting, and measurement (9 RCTs, 955 participants; very low-certainty evidence). Cardiovascular training after anticancer therapy versus no training for people with cancer We included 13 studies (1109 participants); nine studies contributed data to quantitative analyses (756 participants). We are uncertain about the effects of cardiovascular training on short-term CRF (MD 3.62, 95% CI 0 to 7.13, on FACT-F; MID 3; 6 studies, 497 participants), long-term CRF (MD -0.80, 95% CI -1.72 to 0.13, on the Fatigue Symptom Inventory (FSI), scale 1 to 10, higher values mean worse outcome; MID 1; 2 studies, 262 participants), short-term QoL (MD 3.70, 95% CI -0.14 to 7.41, on the Functional Assessment of Cancer Therapy - General (FACT-G), scale 0 to 108, higher values mean better outcome; MID 4; 8 studies, 642 participants), long-term QoL (MD 3.10, 95% CI -1.12 to 7.32, on FACT-G; MID 4; 1 study, 201 participants), and adverse events (risk ratio (RR) 2.71, 95% CI 0.58 to 12.67; 1 study, 50 participants) (all very low-certainty evidence). There were no data for medium-term CRF and QoL.

Authors' conclusions: Moderate-certainty evidence shows that cardiovascular training by people with cancer during their anticancer therapy slightly reduces short-term CRF and results in little to no difference in short-term QoL. We do not know whether cardiovascular training increases or decreases medium-term CRF/QoL, and long-term CRF/QoL. There is very low-certainty evidence (due to heterogeneous definitions, reporting and measurement) evaluating whether the training increases or decreases adverse events. In people with cancer who perform cardiovascular training after anticancer therapy, we are uncertain about the effects on short-term CRF/QoL, long-term CRF/QoL, and adverse events. We identified a lack of evidence concerning cardiovascular training before anticancer therapy and on safety outcomes. The 36 ongoing and 12 completed, but unpublished, studies could help close this gap, and could contribute to improving the effect estimates and certainty.

Funding: This Cochrane review was funded by the Federal Ministry of Education and Research of Germany, grant number: FKZ 01KG2017.

Registration: Protocol available via DOI: 10.1002/14651858.CD015211.