Eight-year follow-up of patient-reported outcomes in patients with breast cancer participating in exercise studies during chemotherapy.

PURPOSE: Numerous randomized controlled trials (RCTs) have shown beneficial exercise effects on fatigue, anxiety and depression and health-related quality of life (HRQoL) in breast cancer (BC) patients during and shortly after treatment. Here, we investigated the long-term effects of exercise during chemotherapy for BC on these outcomes. METHODS: We invited participants of two highly comparable RCTs that investigated the effects of exercise (EX) (versus usual care (UC)) during chemotherapy in patients with non-metastatic BC (N = 357) to participate in an 8-year follow-up. In both trials, fatigue, anxiety and depression and HRQoL were assessed using the same questionnaires, at multiple timepoints. Linear mixed-effect models were used to compare study arms over time. RESULTS: In total, 156 participants (EX = 82; UC = 74) completed the follow-up questionnaires. EX reported comparable general (between-group difference 0.73, 95% confidence interval (- 0.35; 1.80), ES = 0.18) and physical fatigue (0.55 (- 0.55; 1.65), ES = 0.13), small but statistically significantly higher levels of anxiety (1.24 (0.47 to 2.00), ES = 0.39) and depression (1.10 (0.34; 1.85), ES = 0.38), significantly lower global HRQoL (- 5.99 (- 10.65; - 1.32), ES = 0.34) and comparable summary HRQoL (- 1.90 (- 4.70; 0.89), ES = 0.16) compared to UC. CONCLUSION: No long-term beneficial effects of exercise during chemotherapy on BC patients' fatigue, anxiety, depression or HRQoL were observed. The less favourable outcomes for mood and HRQoL that were observed 8 years after participation in an exercise intervention may be explained by selective loss-to-follow-up. IMPLICATIONS FOR CANCER SURVIVORS: The results highlight the need to incorporate strategies that promote physical activity maintenance after participation in an exercise programme to also counteract long-term detrimental side effects of cancer treatment.

Evaluating the Impact of Post-Esophagectomy Exercise on 2- and 5-Year Survival: Findings from the PERFECT Trial.

PURPOSE: Despite recent treatment advances, esophageal cancer still has poor survival and a high morbidity. Exploratory evidence suggests that exercise can reduce cancer-related mortality and recurrence rates. Here, we investigated the effects of an exercise intervention in the first year after esophagectomy on survival in participants of the Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT)-trial. METHODS: In the PERFECT-trial, esophageal cancer patients who had undergone esophagectomy were randomized to a 12-week exercise program (EX) or the control group (CG). We assessed 2- and 5-year (progression-free) survival. (Un)adjusted Cox Proportional-Hazards models were used to calculate hazard ratios (HRs) for comparison between the trial arms. Sensitivity analyses, excluding patients with events within the exercise intervention period, were performed. RESULTS: In total, 120 participants (EX = 61; CG = 59) were included in the PERFECT-trial. After 2-year follow-up, no significant difference in the risk of death or progression between EX and CG was found (adjusted HR = 1.65, 95% CI [0.75-3.63] and 1.38, 95% CI [0.76-2.50], respectively). After excluding patients with events during the intervention period (EX = 8; CG = 4), 2-year HRs for death (1.03, 95% CI [0.41-2.56]) and progression (1.26, 95% CI [0.64-2.48]) both decreased and remained insignificant. No significant effects were found on 5-year mortality (1.03, 95% CI [0.57-1.84]) and progression (1.21, 95% CI [0.72-2.04]) either. Sensitivity-analysis resulted in attenuated 5-year HRs for mortality (0.82, 95% CI [0.42-1.58]) and progression (1.08, 95% CI [0.61-1.92]). CONCLUSIONS: The results indicate no benefit of a 12-week exercise program in the first year post-esophagectomy on 2- and 5-year (progression-free) survival in esophageal cancer patients. The absence of beneficial effects may be explained by the relatively short exercise program, which was performed after treatment completion.

[A runner with a movement disorder]. / Een hardloopster met een bewegingsstoornis.

A 56-year old female runner is not able to run without tripping over anymore. Only whilst running her right foot repeatedly and involuntary makes an outward twist, which impedes her from continuing. She was diagnosed with Runner's Dystonia based on her presentation and virtually normal physical neurologic examination at rest.

Efficacy of Physical Exercise to Offset Anthracycline-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis of Clinical and Preclinical Studies.

Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. Conclusions Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019118218.