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Effect of physical exercise on cognitive function and brain measures after chemotherapy in patients with breast cancer (PAM study): protocol of a randomised controlled trial

INTRODUCTION: After treatment with chemotherapy, many patients with breast cancer experience cognitive problems. While limited interventions are available to improve cognitive functioning, physical exercise showed positive effects in healthy older adults and people with mild cognitive impairment. The Physical Activity and Memory study aims to investigate the effect of physical exercise on cognitive functioning and brain measures in chemotherapy-exposed patients with breast cancer with cognitive problems.METHODS AND ANALYTICS: One hundred and eighty patients with breast cancer with cognitive problems 2-4 years after diagnosis are randomised (1:1) into an exercise intervention or a control group. The 6-month exercise intervention consists of twice a week 1-hour aerobic and strength exercises supervised by a physiotherapist and twice a week 1-hour Nordic or power walking. The control group is asked to maintain their habitual activity pattern during 6 months. The primary outcome (verbal learning) is measured at baseline and 6 months. Further measurements include online neuropsychological tests, self-reported cognitive complaints, a 3-tesla brain MRI, patient-reported outcomes (quality of life, fatigue, depression, anxiety, work performance), blood sampling and physical fitness. The MRI scans and blood sampling will be used to gain insight into underlying mechanisms. At 18 months online neuropsychological tests, self-reported cognitive complaints and patient-reported outcomes will be repeated.ETHICS AND DISSEMINATION: Study results may impact usual care if physical exercise improves cognitive functioning for breast cancer survivors.TRIAL REGISTRATION NUMBER: NTR6104.

Tailoring of exercise and dietary interventions to adverse effects and existing comorbidities in patients with ovarian cancer receiving chemotherapy

Purpose: This study aims to capture the complex clinical reasoning process during tailoring of exercise and dietary interventions to adverse effects and comorbidities of patients with ovarian cancer receiving chemotherapy. Methods: Clinical vignettes were presented to expert physical therapists (n = 4) and dietitians (n = 3). Using the think aloud method, these experts were asked to verbalize their clinical reasoning on how they would tailor the intervention to adverse effects of ovarian cancer and its treatment and comorbidities. Clinical reasoning steps were categorized in questions raised to obtain additional information; anticipated answers; and actions to be taken. Questions and actions were labeled according to the evidence-based practice model. Results: Questions to obtain additional information were frequently related to the patients’ capacities, safety or the etiology of health issues. Various hypothetical answers were proposed which led to different actions. Suggested actions by the experts included extensive monitoring of symptoms and parameters, specific adaptations to the exercise protocol and dietary-related patient education. Conclusions: Our study obtained insight into the complex process of clinical reasoning, in which a variety of patient-related variables are used to tailor interventions. This insight can be useful for description and fidelity assessment of interventions and training of healthcare professionals.

Effects of physical exercise during adjuvant chemotherapy for breast cancer on long-term tested and perceived cognition

PurposeCancer-related cognitive impairment (CRCI) following chemotherapy is commonly reported in breast cancer survivors, even years after treatment. Data from preclinical studies suggest that exercise during chemotherapy may prevent or diminish cognitive problems; however, clinical data are scarce.MethodsThis is a pragmatic follow-up study of two original randomized trials, which compares breast cancer patients randomized to exercise during chemotherapy to non-exercise controls 8.5 years post-treatment. Cognitive outcomes include an online neuropsychological test battery and self-reported cognitive complaints. Cognitive performance was compared to normative data and expressed as age-adjusted z-scores.ResultsA total of 143 patients participated in the online cognitive testing. Overall, cognitive performance was mildly impaired on some, but not all, cognitive domains, with no significant differences between groups. Clinically relevant cognitive impairment was present in 25% to 40% of all participants, regardless of study group. We observed no statistically significant effect of exercise, or being physically active during chemotherapy, on long-term cognitive performance or self-reported cognition, except for the task reaction time, which favored the control group (β = -2.04, 95% confidence interval: -38.48; -2.38). We observed no significant association between self-reported higher physical activity levels during chemotherapy or at follow-up and better cognitive outcomes.ConclusionIn this pragmatic follow-up study, exercising and being overall more physically active during or after adjuvant chemotherapy for breast cancer was not associated with better tested or self-reported cognitive functioning, on average, 8.5 years after treatment. Future prospective studies are needed to document the complex relationship between exercise and CRCI in cancer survivors.

Association between computed tomography assessment of skeletal muscle index and muscle attenuation and chemotherapy intolerance in patients with head and neck cancer: preliminary results

Low muscle mass is associated with early termination of chemotherapy related to toxicity in patients with head and neck cancer

BACKGROUND & AIMS: We studied whether low pre-treatment muscle mass, measured with CT at thoracic (T4) or lumbar level (L3) associates with early termination of chemotherapy related to toxicity in head and neck cancer (HNC) patients.METHODS: This was a retrospective chart and image review. Adult HNC patients treated with (surgery and) platinum-based chemo-radiotherapy were included if a pre-treatment CT scan at T4 or L3 level was available. Muscle mass was evaluated by assessment of skeletal muscle index (SMI; cm2/m2). T4 and L3 SMI measurements were corrected for deviation from their respective means and were merged into one score for SMI difference (cm2/m2). All cases were assessed for presence of toxicity-related unplanned early termination of chemotherapy ('early termination'). Univariate and multivariate logistic regression models were used to investigate associations between pooled SMI and early termination.RESULTS: 213 patients (age: 57.9 ± 10.3 y, male: 77%, T4 image: 45%) were included. A significant association between SMI as a continuous variable and early termination was found, both in the univariate analysis (p = 0.007, OR = 0.96 [0.94-0.99]) and the multivariate analysis (p = 0.021, OR 0.96 [0.92-0.99]). The multivariate models identified potential associations with type of chemotherapy, presence of co-morbidity, a combination of (former) smoking and alcohol consumption, and sex.CONCLUSION: Lower muscle mass was robustly associated with higher odds of early termination of chemotherapy in HNC patients. Further prospective studies are required to tailor the care for patients with low muscle mass and to avoid early termination of chemotherapy.

Physical Fitness and Chemotherapy Tolerance in Patients with Early-Stage Breast Cancer

INTRODUCTION: An optimal relative dose intensity (RDI) of adjuvant chemotherapy is associated with better survival in patients with breast cancer. Little is known about the role of physical fitness in attaining an adequate RDI in patients with early stage breast cancer. We investigated the association between pre-treatment physical fitness and RDI in this population.METHODS: We pooled individual patient data from two randomized exercise trials that studied exercise programs in early breast cancer: the PACES (n = 230) and the PACT (N = 204) study. Logistic regression models were used to evaluate the association between pre-treatment fitness and achieving an optimal RDI (≥85%). In addition, we added an interaction term to the model to explore the potential moderating effect of participating in an exercise program.RESULTS: Data were available for 419 patients (mean age at diagnosis 50.0 ± 8.6 years). In the total sample, lower pre-treatment physical fitness was associated with significantly lower odds of achieving ≥85% RDI: age-adjusted OR 0.66 [95%CI 0.46-0.94]. In patients allocated to the supervised exercise intervention during chemotherapy (n = 173), the association between pretreatment physical fitness and RDI was almost completely mitigated (OR 0.95 (95%CI 0.54-1.56)), while it was more pronounced in patients who received care as usual (n = 172, OR 0.31 (95%CI 0.13-0.63) pinteraction: 0.022).CONCLUSION: Early stage breast cancer patients with relatively lower levels of pretreatment physical fitness have lower odds of achieving an optimal dose of chemotherapy. Given that physical fitness is modifiable and our results suggest that following a moderate-to-high intensity exercise training during chemotherapy could improve treatment completion, clinicians should not refrain from referring patients to supportive exercise programs because of low fitness.