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Simple Summary: Tumors escape from the host immune control by upregulation of inhibitory immune checkpoints. Immune checkpoint inhibition (ICI) has become the standard of care for many cancer entities. However, several patients do not respond to ICI because of primary or secondary resistance. Patients not benefitting from checkpoint inhibitors frequently display an immunosuppressive tumor phenotype. Combination therapy with drugs enhancing immunosurveillance improves ICI efficacy. Since physical activity can boost immune response, exercise might be a promising combinatorial therapeutic approach for ICI. Here, we review preclinical and clinical data about the impact of exercise on anti-tumor immunity and checkpoint inhibitor therapy. Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor microenvironment. Exercise is known to promote immune cell circulation and improve immunosurveillance. Results of recent studies indicate that physical activity can induce mobilization and redistribution of immune cells towards the tumor microenvironment (TME) and therefore enhance anti-tumor immunity. This suggests a favorable impact of exercise on the efficacy of ICI. Our review delivers insight into possible molecular mechanisms of the crosstalk between muscle, tumor, and immune cells. It summarizes current data on exercise-induced effects on anti-tumor immunity and ICI in mice and men. We consider preclinical and clinical study design challenges and discuss the role of cancer type, exercise frequency, intensity, time, and type (FITT) and immune sensitivity as critical factors for exercise-induced impact on cancer immunosurveillance. [ABSTRACT FROM AUTHOR]

(1) Background: Strong evidence supports the persuasive positive effects of exercise for cancer patients and survivors. Different approaches of exercise programs have been established; however, the special interests of young adults (YAs) with cancer have rarely been considered in exercise interventions. Therefore, the study YOUng EXercisers (YOUEX) aimed to investigate exercise preferences in YAs. (2) Methods: YOUEX was a three-arm, patient preference-based non-randomized, longitudinal, pre–post exercise intervention, offering three different exercise modules to YAs during or after acute therapy (Module 1: online supervised group-based (M1); Module 2: online unsupervised (M2); Module 3: in-person supervised (M3)). The intervention period was 12 weeks with another 12-week follow-up period, the modules could be changed or amended after 6 and 12 weeks. (3) Results: 92 YAs were allocated to the study. At baseline, 50 YAs (54%) chose M2, 32 YAs (35%) M1 and 10 YAs (11%) M3. The analysis revealed high acceptability and feasibility of the online exercise programs (M1, M2). There was a high impact of the COVID-19 pandemic on the execution of M3. YAs showed diverse preferences in module selection due to differences in, e.g., cancer therapy status or favored level of supervision. (4) Conclusions: YAs need personalized exercise programs that consider their individual interests and needs. Online exercise programs can be a promising addition to existing exercise opportunities. They are an effective way to increase physical activity levels in YAs. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite numerous benefits of physical activity for cancer patients, the majority is insufficiently active. Previous research has shown that structural barriers negatively affect patients' physical activity behavior. Identifying underlying mechanisms could help to develop effective strategies that alleviate those barriers and increase physical activity levels. In the current survey study, we investigated whether cancer patients' self-efficacy, i.e., their confidence in their ability, and their intention to exercise mediated the relationship between structural barriers and physical activity. The results revealed a negative relation between structural barriers and patients' self-efficacy. Lower self-efficacy, in turn, decreased patients' intention and their likelihood to engage in physical activity. This mediating effect especially applied to those individuals who were sufficiently active before the diagnosis. Thus, the findings suggest that interventions directly addressing the perception of structural barriers or patients' self-efficacy in dealing with these barriers might be effective in improving the physical activity levels of cancer patients. Previous research has shown that structural barriers negatively influence the physical activity (PA) behavior of cancer patients, but underlying mechanisms are unclear. The aim of the current study was to explore the potential mediating role of social-cognitive factors, namely PA self-efficacy and PA intention in this context. A total of 856 cancer patients completed a questionnaire on sociodemographic and medical characteristics, pre- and post-diagnosis PA, PA self-efficacy, PA intention, and PA impediment by structural barriers. A serial mediation model was used to test whether the association between structural barriers and post-diagnosis PA was mediated by PA self-efficacy and/or PA intention, in the overall sample and in subsamples defined by individuals' pre-diagnosis PA. The results confirmed that structural barriers were not directly (95%CI [−0.45; 0.10]) but indirectly associated with post-diagnosis PA. Higher impediment by structural barriers decreased the likelihood of sufficient post-diagnosis PA via lower PA self-efficacy (95%CI [−0.25; −0.06]) and via the serial pathway of lower PA self-efficacy and lower PA intention (95%CI [−0.19; −0.05]). Investigating differences in these mediations by pre-diagnosis PA yielded significance only among previously active cancer patients. Both structural barriers and PA self-efficacy might hence be relevant target points for interventions aiming to improve PA behavior, especially among pre-diagnosis active cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It is experienced as numbness, tingling, pain, and cramping in the hands and/or feet and can interfere with daily living. Exercise is a promising treatment for CIPN but its underlying mechanisms are understudied. Herein, we discuss potential mechanisms underlying how exercise might treat CIPN (e.g., anti-inflammatory cytokines, self-efficacy, and social support) and what demographic (e.g., age and sex) and clinical characteristics (e.g., body mass index), and exercise routines (e.g., timing, intensity, and type of exercise) may moderate the effects of exercise on relieving CIPN. These details can help clinicians predict who will get CIPN, enable clinicians to tailor exercise programs to patients based on specific characteristics, and inform future research and biomarkers on the relationship between exercise and CIPN. Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of neurotoxic antineoplastic agents commonly used to treat cancer. Patients with CIPN experience debilitating signs and symptoms, such as combinations of tingling, numbness, pain, and cramping in the hands and feet that inhibit their daily function. Among the limited prevention and treatment options for CIPN, exercise has emerged as a promising new intervention that has been investigated in approximately two dozen clinical trials to date. As additional studies test and suggest the efficacy of exercise in treating CIPN, it is becoming more critical to develop mechanistic understanding of the effects of exercise in order to tailor it to best treat CIPN symptoms and identify who will benefit most. To address the current lack of clarity around the effect of exercise on CIPN, we reviewed the key potential mechanisms (e.g., neurophysiological and psychosocial factors), mediators (e.g., anti-inflammatory cytokines, self-efficacy, and social support), and moderators (e.g., age, sex, body mass index, physical fitness, exercise dose, exercise adherence, and timing of exercise) that may illuminate the relationship between exercise and CIPN improvement. Our review is based on the studies that tested the use of exercise for patients with CIPN, patients with other types of neuropathies, and healthy adults. The discussion presented herein may be used to (1) guide oncologists in predicting which symptoms are best targeted by specific exercise programs, (2) enable clinicians to tailor exercise prescriptions to patients based on specific characteristics, and (3) inform future research and biomarkers on the relationship between exercise and CIPN. [ABSTRACT FROM AUTHOR]

Simple Summary: Previous research indicates that the outcomes of irradiation of spinal metastases can be improved through exercise. After this was demonstrated for metastases of low fracture risk, we conducted the first study in patients with spinal metastases of high fracture risk to investigate exercise feasibility. An exercise group performed four spinal stabilization exercises daily over two weeks of radiotherapy, while a control group received relaxation. Patients in the exercise group attended 90% of training sessions, compared to 80% in the control group. No injuries occurred. However, about half of the patients could not perform two out of the four exercises due to pain, weakness or immobility. Nevertheless, they increased exercise time and training-specific strength. Altogether, exercise is well accepted and enhances muscle strength in these patients, but frequent individual adaptations of the training program are needed. This knowledge is a prerequisite for larger studies addressing exercise effects on health. Exercise concomitant to radiotherapy for stable spinal metastases was demonstrated to increase bone density and reduce pain. In the DISPO-II study, the feasibility of exercise concomitant to radiotherapy for unstable spinal metastases was investigated. Here, a detailed analysis of the training program is presented. Cancer patients with spinal metastases (Taneichi score ≥ D) were randomly assigned to an intervention group (INT, n = 27, 62 ± 9 years) or control group (CON, n = 29, 61 ± 9 years). INT performed spinal stabilization exercises ("all fours"/"plank"/"swimmer"/"band exercise"), and CON received relaxation, daily concomitant to radiotherapy. Exercise attendance rate was 90% in INT and 80% in CON (p = 0.126). Within INT, exercise dose increased significantly (p < 0.001). 54% of patients could not perform "swimmer" in some or all sessions. 42% could not perform "plank" in some or all sessions. 13 and 25% could not perform "all fours" and "band exercise" in some sessions. "Plank" holding time increased in INT and remained unchanged in CON with different development between groups (p = 0.022). Handgrip strength did not develop differently between groups (p = 0.397). The exercise intervention demonstrated high acceptability but required frequent modifications due to pain, weakness and immobility to be feasible for the majority of participants. It enhanced specific muscle strength. Larger trials should now investigate exercise effects on health. [ABSTRACT FROM AUTHOR]

Background: Isometric paravertebral muscle training (IPMT) may improve mobility, pain, and quality of life (QOL) in cancer patients with spinal metastases. However, this regimen remains unproven in patients with unstable spinal metastases (USM), a population at high risk for clinical exacerbation with such interventions. Thus, we conducted this exploratory, non-blinded, randomized controlled trial (NCT02847754) to evaluate the safety/feasibility of IPMT and secondarily assess pain, bone density, pathologic fracture rate, and QOL. Methods: All patients had histologically/radiologically confirmed USM (per Taneichi score) and underwent non-operative management with 5–10 fractions of palliative radiotherapy (RT). Randomization (1:1) groups were IPMT (intervention, INT) or muscle relaxation (control, CON); both lasted 15 min/day and started concurrently with radiotherapy. The primary endpoint was feasibility (completion of training programs three months post-RT). Secondary endpoints were pain response (Visual Analog Scale) and opioid consumption, bone density and pathologic fracture rate, and QOL (European Organization for Research and Treatment of Cancer, EORTC questionnaires). Results: Sixty patients were randomized and 56 received protocol therapy. Mean survival in both groups was 4.4 months. There were no adverse events with either training regimen. Altogether, ≥80% of the planned sessions were completed by 55% (n = 16/29) in CON and 67% (n = 18/27) in INT. Regarding the post-radiotherapy home-based training, ≥80% of planned sessions were completed by 64% (n = 9/14) of the INT cohort. There were no differences in pain scores, opioid consumption, or bone density between arms (p > 0.05 for all). No difference was observed between groups regarding new pathological fractures (INT: n = 1 vs. CON: n = 3) after three months (p = 0.419). There were no QOL differences between arms (all parameters p > 0.05). Conclusions: IPMT is potentially feasible for high-risk USM patients. Future trials adequately powered for relevant endpoints are thus recommended. [ABSTRACT FROM AUTHOR]