High-intensity interval training and thromboembolic events during chemotherapy for testicular cancer: a retrospective analysis from the Body & Cancer cohort.

Background: Men with testicular cancer receiving platinum-based chemotherapy have an increased risk of thromboembolic events, with incidence rates between 8-24%. A recent trial evaluating the effect of high-intensity interval training (HIIT) prematurely closed as three out of nine participants (33%) in the intervention group developed a thromboembolic event. The purpose of this retrospective cohort study was: 1) (primary) to evaluate the incidence of thromboembolic events in men receiving chemotherapy for testicular cancer who had participated in HIIT during a 6-week exercise program (Body & Cancer) 2) to describe the feasibility of this program.Material and methods: Forty men who had participated in at least one HIIT session from February 2007 to February 2020 were included. Electronic medical records were searched for incident thromboembolic events (arterial and venous) during Body & Cancer and up to one-year post-chemotherapy. Attendance, cardiorespiratory fitness (VO2-peak), and upper and lower extremity muscular strength (1 repetition maximum (RM)) were obtained from the Body & Cancer database.Results: One participant developed a thromboembolic event during Body & Cancer. No participants developed a thromboembolic event in the follow-up period. In all, data represent 160 HIIT sessions with a median attendance of eight sessions [range 1-19]. Statistically significant increases in upper and lower extremity strength were observed (8.6 (4.2 to 13.0) and 26.0 (14.9 to 37.0) kg, respectively). No significant increase in cardiorespiratory fitness was found (0.14 (-0.03 to 0.31) l/min).Conclusion: While conclusions on the safety of HIIT cannot be drawn, data from the present study do not support previous findings cautioning avoidance of HIIT due to a possible added risk of thromboembolic events in men receiving platinum-based chemotherapy for testicular cancer. Considering the potential for positive effects on cardiovascular outcomes associated with HIIT, future studies with robust design should be performed in this population to confirm these observations.

Effects of football fitness training on lymphedema and upper-extremity function in women after treatment for breast cancer: a randomized trial.

BACKGROUND: Breast cancer survivors are encouraged to be physically active. A recent review suggests that football training is an effective exercise modality for women across the lifespan, positively influencing health variables such as strength, fitness and social well-being. However, football is a contact sport, potentially posing an increased risk of trauma-related injury. Against this backdrop, breast cancer survivors are advised to avoid trauma or injury to the affected or at-risk arm in order to protect against lymphedema onset or exacerbation. The aim of this study was therefore to evaluate the feasibility and safety of Football Fitness training in relation to lymphedema and upper-extremity function after treatment for breast cancer. MATERIAL AND METHODS: Sixty-eight women aged 18-75 years, who had received surgery for stage I-III breast cancer and completed (neo) adjuvant chemotherapy and/or radiotherapy within five years, were randomized (2:1) to a Football Fitness group (FFG, n = 46) or a control group (CON, n = 22) for twelve months. Secondary analyses using linear mixed models were performed to assess changes in upper-body morbidity, specifically arm lymphedema (inter-arm volume % difference, dual energy X-ray absorptiometry; extracellular fluid (L-Dex), bioimpedance spectroscopy), self-reported breast and arm symptoms (EORTC breast cancer-specific questionnaire (BR23) and upper-extremity function (DASH questionnaire) at baseline, six- and twelve-month follow-up. RESULTS: We observed similar point prevalent cases of lymphedema between groups at all time points, irrespective of measurement method. At the six-month post-baseline assessment, reductions in L-Dex (extracellular fluid) were found in FFG versus CON. These significant findings were not maintained at the twelve-month assessment. No difference between groups was observed for inter-limb volume difference %, nor any of the remaining outcomes. CONCLUSION: While superiority of Football Fitness was not observed, the results support that participation in Football Fitness training is feasible and suggests no negative effects on breast cancer-specific upper-body morbidity, including lymphedema. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov. NCT03284567.

Heavy-load resistance exercise during chemotherapy in physically inactive breast cancer survivors at risk for lymphedema: a randomized trial.

Background: Due to long-standing concerns that heavy-load lifting could increase the risk of developing lymphedema, breast cancer survivors have been advised to refrain from resistance exercise with heavy loads. This study prospectively evaluated the effect of heavy-load resistance exercise on lymphedema development in women receiving chemotherapy for breast cancer.Material and Methods: Physically inactive women receiving adjuvant chemotherapy for breast cancer (n = 153) were randomized to a HIGH (supervised, multimodal exercise including heavy-load resistance exercise: 85-90% 1 repetition maximum [RM], three sets of 5-8 repetitions) versus LOW (pedometer and one-on-one consultations) 12-week intervention. Outcomes (baseline, 12 and 39 weeks) included lymphedema status (extracellular fluid [bioimpedance spectroscopy] and inter-arm volume % difference [dual-energy X-ray absorptiometry], lymphedema symptoms [numeric rating scale 0-10]), upper-extremity strength (1 RM), and quality of life domains (EORTC- BR23). Linear mixed models were used to evaluate equivalence between groups for lymphedema outcomes (equivalence margins for L-Dex, % difference and symptoms scale: ±5, ±3% and ±1, respectively). Superiority analysis was conducted for muscle strength and quality of life domains.Results: Postintervention equivalence between groups was found for extracellular fluid (0.4; 90% CI -2.5 to 3.2) and symptoms of heaviness (-0.2; -0.6 to 0.2), tightness (-0.1; -0.8 to 0.6) and swelling (0.2; -0.4 to 0.8). Nonequivalence was found for inter-arm volume % difference (-3.5%; -17.3 to 10.3) and pain (-0.7; -1.3 to 0), favoring HIGH. Strength gains were superior in the HIGH versus LOW group (3 kg; 1 to 5, p < .05). Further, clinically relevant reductions in breast (-11; -15 to -7) and arm (-6; -10 to -1) symptoms were found in the HIGH group.Conclusion: Findings suggest that physically inactive breast cancer survivors can benefit from supervised heavy-load resistance exercise during chemotherapy without increasing lymphedema risk. Trial registration: ISRCTN13816000.

A randomized cross-over trial to detect differences in arm volume after low- and heavy-load resistance exercise among patients receiving adjuvant chemotherapy for breast cancer at risk for arm lymphedema: study protocol.

BACKGROUND: In an effort to reduce the risk of breast cancer-related arm lymphedema, patients are commonly advised to avoid heavy lifting, impacting activities of daily living and resistance exercise prescription. This advice lacks evidence, with no prospective studies investigating arm volume changes after resistance exercise with heavy loads in this population. The purpose of this study is to determine acute changes in arm volume after a session of low- and heavy-load resistance exercise among women undergoing adjuvant chemotherapy for breast cancer at risk for arm lymphedema. METHODS/DESIGN: This is a randomized cross-over trial. PARTICIPANTS: Women receiving adjuvant chemotherapy for breast cancer who have undergone axillary lymph node dissection will be recruited from rehabilitation centers in the Copenhagen area. INTERVENTION: Participants will be randomly assigned to engage in a low- (two sets of 15-20 repetition maximum) and heavy-load (three sets of 5-8 repetition maximum) upper-extremity resistance exercise session with a one week wash-out period between sessions. OUTCOME: Changes in extracellular fluid (L-Dex score) and arm volume (ml) will be assessed using bioimpedance spectroscopy and dual-energy x-ray absorptiometry, respectively. Symptom severity related to arm lymphedema will be determined using a visual analogue scale (heaviness, swelling, pain, tightness). Measurements will be taken immediately pre- and post-exercise, and 24- and 72-hours post-exercise. SAMPLE SIZE: A sample size of 20 participants was calculated based on changes in L-Dex scores between baseline and 72-hours post exercise sessions. DISCUSSION: Findings from this study are relevant for exercise prescription guidelines, as well as recommendations regarding participating in activities of daily living for women following surgery for breast cancer and who may be at risk of developing arm lymphedema. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97332727 . Registered 12 February 2015.

Heavy resistance training and lymphedema: prevalence of breast cancer-related lymphedema in participants of an exercise intervention utilizing heavy load resistance training.

BACKGROUND: There is limited knowledge regarding progressive resistance training during adjuvant chemotherapy and the risk of developing breast cancer-related lymphedema (BCRL). Furthermore, no studies have investigated the safety of resistance training with heavy loads (> 80% 1 repetition maximum) in this population. 'Body and Cancer' is a six-week, nine-hour weekly, supervised, multimodal exercise intervention utilizing progressive resistance training with heavy loads for cancer patients undergoing chemotherapy. The purpose of the present study was to estimate the prevalence of BCRL in former participants, and identify associations between progressive resistance training with heavy loads, and the development of BCRL. MATERIAL AND METHODS: This was a descriptive study. POPULATION: Women treated for breast cancer (n = 149), who had participated in the 'Body and Cancer' exercise intervention between 1 January 2010 and 31 December 2011 participated in a structured telephone interview. The average follow-up time was 14 months (range 4-26). A clinical diagnosis of BCRL reported by the participant was the primary outcome. RESULTS: A total of 27.5% reported that they had been diagnosed with BCRL by a clinician. This was true for 44.4% with axillary node dissection. No statistically significant association between strength gains during the exercise intervention, and the development of BCRL was observed, nor was self-reported participation in progressive resistance training with heavy loads up to three months post-intervention. CONCLUSION: The prevalence of BCRL among former "Body and Cancer" participants at follow-up was 27.5%. There appears to be no association between performing heavy resistance training during adjuvant treatment (chemotherapy/radiotherapy), and the development of BCRL. However randomized controlled trials should be performed to confirm this observation.

Prospective Surveillance for Breast Cancer-Related Arm Lymphedema: A Systematic Review and Meta-Analysis.

PURPOSE: The call to integrate prospective surveillance for lymphedema into cancer care pathways is building momentum to enable early intervention and prevent the progression of the condition. We offer a critical evaluation of the literature on prospective surveillance and early management for cancer-related lymphedema and evaluate the effect of such programs in preventing chronic lymphedema (CRD42019137965). METHODS: Five databases and two registries were searched for randomized controlled trials or observational studies that assessed the incidence or prevalence of lymphedema associated with participation in a prospective surveillance program, published until February 26, 2021. Numbers triggered for early lymphedema management, resolved, and chronic lymphedema were extracted. Pooled relative risk (trials) and pooled rate (cumulative incidence; observational studies) of chronic lymphedema was calculated. Subgroup analyses assessed the effect of study design, length of follow-up, and extent of axillary surgery. RESULTS: Twenty-three studies were included, of which 21 studies evaluated breast cancer-related arm lymphedema (BCRaL). Participation in prospective surveillance with early management reduced the risk of chronic BCRaL versus usual care (relative risk 0.31; 95% CI, 0.10 to 0.95; two randomized controlled trials; N = 106). The pooled rate of chronic BCRaL was 4% (95% CI, 3 to 6; 15 observational studies; N = 3,545), and 6% (95% CI, 4 to 9) when restricted to participants with axillary lymph node dissection (12 studies; N = 1,527). CONCLUSION: The findings suggest that participation in prospective surveillance with early management reduces the risk of chronic BCRaL. Only a minority of patients at high risk of lymphedema because of axillary surgery developed chronic lymphedema. More robust research is needed to determine whether prospective surveillance with early management can reduce the risk of chronic lymphedema, particularly among cancer survivors other than breast cancer.

The Effect of Exercise for the Prevention and Treatment of Cancer-Related Lymphedema: A Systematic Review with Meta-analysis.

INTRODUCTION: The purpose of this systematic review and meta-analysis was to evaluate the effects of exercise on (i) the prevention of cancer-related lymphedema (CRL) and (ii) the treatment of CRL, lymphedema-associated symptoms, and other health outcomes among individuals with CRL. METHODS: An electronic search was undertaken for exercise studies measuring lymphedema and involving individuals at risk of developing or with CRL. The Effective Public Health Practice Project Quality scale was used to assess study quality, and overall quality of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses were performed to evaluate effects of exercise on CRL incidence, existing CRL status, lymphedema-associated symptoms, and health outcomes. RESULTS: Twelve studies ( n = 1955; 75% moderate-high quality) and 36 studies ( n = 1741; 58% moderate-high quality) were included in the prevention and treatment aim, respectively. Relative risk of developing CRL for those in the exercise group compared with the nonexercise group was 0.90 (95% confidence interval (CI), 0.72 to 1.13) overall and 0.49 (95% CI, 0.28 to 0.85) for those with five or more lymph nodes removed. For those with CRL in the exercise group, the standardized mean difference (SMD) before to after exercise of CRL was -0.11 (95% CI, -0.22 to 0.01), and compared with usual care postintervention, the SMD was -0.10 (95% CI, -0.24 to 0.04). Improvements after intervention were observed for pain, upper-body function and strength, lower-body strength, fatigue, and quality of life for those in the exercise group (SMD, 0.3-0.8; P < 0.05). CONCLUSIONS: Findings support the application of exercise guidelines for the wider cancer population to those with or at risk of CRL. This includes promotion of aerobic and resistance exercise, and not just resistance exercise alone, as well as unsupervised exercise guided by symptom response.

Physical deterioration and adaptive recovery in physically inactive breast cancer patients during adjuvant chemotherapy: a randomised controlled trial.

Cardiorespiratory fitness is an independent risk factor for cardiovascular disease and shortened life expectancy in breast cancer survivors. This randomised controlled trial (n = 153) was designed for patients with a physically inactive lifestyle prediagnosis and concurrently referred to adjuvant chemotherapy. We compared two 12-week exercise interventions aimed at physiological and patient-reported outcomes (cardiorespiratory fitness, muscle strength, metabolic markers, physical activity, pain, fatigue), including a 39-week follow-up. A supervised hospital-based moderate to high intensity group exercise intervention was compared to an instructed home-based individual pedometer intervention. The two 12-week interventions included oncologists' recommendations and systematic health counselling. Outcomes were measured at baseline and week 6, 12 and 39. Primary outcome cardiorespiratory fitness declined significantly during chemotherapy and was restored in both interventions at follow-up. The interventions effectively engaged breast cancer patients in sustaining physical activities during and following adjuvant treatment. A composite metabolic score improved significantly. Positive cardiorespiratory fitness responders had improved clinical effects on fatigue, pain and dyspnoea versus negative responders. We conclude that a loss of cardiorespiratory fitness among physically inactive breast cancer patients may be restored by early initiated interventions and by adapting to physical activity recommendations, leading to a decreased cardiovascular risk profile in breast cancer survivors.

Heavy-Load Lifting: Acute Response in Breast Cancer Survivors at Risk for Lymphedema.

PURPOSE: Despite a paucity of evidence, prevention guidelines typically advise avoidance of heavy lifting in an effort to protect against breast cancer-related lymphedema. This study compared acute responses in arm swelling and related symptoms after low- and heavy-load resistance exercise among women at risk for lymphedema while receiving adjuvant taxane-based chemotherapy. METHODS: This is a randomized, crossover equivalence trial. Women receiving adjuvant taxane-based chemotherapy for breast cancer who had undergone axillary lymph node dissection (n = 21) participated in low-load (60%-65% 1-repetition maximum, two sets of 15-20 repetitions) and heavy-load (85%-90% 1-repetition maximum, three sets of 5-8 repetitions) upper-extremity resistance exercise separated by a 1-wk wash-out period. Swelling was determined by bioimpedance spectroscopy and dual-energy x-ray absorptiometry, with breast cancer-related lymphedema symptoms (heaviness, swelling, pain, tightness) reported using a numeric rating scale (0-10). Order of low- versus heavy-load was randomized. All outcomes were assessed before, immediately after, and 24 and 72 h after exercise. Generalized estimating equations were used to evaluate changes over time between groups, with equivalence between resistance exercise loads determined using the principle of confidence interval inclusion. RESULTS: The acute response to resistance exercise was equivalent for all outcomes at all time points irrespective of loads lifted, with the exception of extracellular fluid at 72 h after exercise with less swelling after heavy loads (estimated mean difference, -1.00; 95% confidence interval, -3.17 to 1.17). CONCLUSIONS: Low- and heavy-load resistance exercise elicited similar acute responses in arm swelling and breast cancer-related lymphedema symptoms in women at risk for lymphedema receiving adjuvant taxane-based chemotherapy. These represent important preliminary findings, which can be used to inform future prospective evaluation of the long-term effects of repeated exposure to heavy-load resistance exercise.

Rethinking exercise identity: a qualitative study of physically inactive cancer patients' transforming process while undergoing chemotherapy.

OBJECTIVE: To explore physically inactive breast and colon cancer patients' prediagnosis exercise history and attitudes to physical activity (PA) and experiences in initiating PA while undergoing adjuvant chemotherapy. DESIGN: An explorative qualitative study guided the interpretive analysis of semistructured, open-ended interviews conducted at initiation of chemotherapy and after 12 weeks. The study was embedded in a pilot randomised controlled trial. SETTING: Participants were recruited from the Oncological Department at a hospital in Copenhagen, Denmark. PARTICIPANTS: 33 patients with cancer, median age 49 years: 25 patients with breast cancer and 8 with colon cancer, 72% with a low cardiac respiratory fitness level and the majority with a high level of education. Patients received adjuvant chemotherapy, oncologist's PA recommendation and exercise, cancer nurse specialist's counselling prior to allocation to PA interventions or waitlist control group. RESULTS: Prediagnosis exercise had been excluded from patients' daily lives due to perceptions of exercise as boring, lack of discipline and stressful work conditions for both genders. Recommendations from oncologists and nurses inspired the patients to reconsider their attitudes and behaviour by accepting recruitment and participation in PA interventions during chemotherapy. Despite extensive side effects, most patients adhered to their PA commitment due to their perception of the bodily, emotional and social benefits and support of healthcare professionals, peers and family. CONCLUSION: The patients' attitude towards exercise transformed from having no priority in patients' daily lives prediagnosis to being highly prioritised. This study identified four important phases in the exercise transformation process during the patients' treatment trajectory of relevance to clinicians in identifying, motivating and supporting physically inactive patients with cancer at long-term risk. Clinicians should address young, highly educated patients with cancer at onset of adjuvant chemotherapy due to their specific risk of a sedentary lifestyle resulting from being in stressful, ambitious careers. TRIAL REGISTRATION NUMBER: Current Controlled Trials (ISRCTN24901641), Stage: Qualitative results.

The challenge of preserving cardiorespiratory fitness in physically inactive patients with colon or breast cancer during adjuvant chemotherapy: a randomised feasibility study.

INTRODUCTION: Anti-neoplastic treatment is synonymous with an inactive daily life for a substantial number of patients. It remains unclear what is the optimal setting, dosage and combination of exercise and health promoting components that best facilitate patient adherence and symptom management in order to support cardio-respiratory fitness and lifestyle changes in an at-risk population of pre-illness physically inactive cancer patients. METHODS: Patients with breast or colon cancer referred to adjuvant chemotherapy and by the oncologists pre-screening verified as physically inactive were eligible to enter a randomised three-armed feasibility study comparing a 12-week supervised hospital-based moderate to high intensity exercise intervention or alternate an instructive home-based12-week pedometer intervention, with usual care. RESULTS: Using a recommendation based physical activity screening instrument in order to correspond with cardio-respiratory fitness (VO2 peak) proved to be an applicable method to identify pre-illness physically inactive breast and colon cancer patients. The study demonstrated convincing recruitment (67%), safety and intervention adherence among breast cancer patients; while the attendance rate for colon cancer patients was notably lower (33%). VO2-peak declined on average 12% across study groups from baseline to 12 weeks though indices towards sustaining watt performance and reduce fat mass favoured the hospital-based intervention. Pedometer use was well adapted in both breast and colon cancer patients. CONCLUSIONS: Despite a fair adherence and safety, the current study calls into question whether aerobic exercise, regardless of intensity, is able to increase VO2-peak during texane-based chemotherapy in combination with Neulasta in physically inactive breast cancer patients. TRIAL REGISTRATION: ISRCTN24901641.

At cancer diagnosis: a 'window of opportunity' for behavioural change towards physical activity. A randomised feasibility study in patients with colon and breast cancer.

INTRODUCTION: Challenges exist in identifying, recruiting and motivating sedentary patients with cancer to initiate physical activity towards recommended levels. We hypothesise that the onset period of adjuvant chemotherapy can be 'the open window of opportunity' to identify and motivate sedentary patients with breast and colon cancers, at risk for developing coronary heart disease, to initiate and sustain lifestyle changes. AIMS: To investigate the feasibility of oncologists/nurses screening for physical inactivity, in order to identify and recruit an at-risk population of sedentary patients with breast or colon cancer at the onset of adjuvant chemotherapy. Furthermore, the study will examine the adherence to one of two multimodal exercise interventions lasting 12 weeks; (1) hospital-based, high intensity, group exercise intervention (2) home-based, low intensity, individual, pedometer intervention. Both arms will be compared with a control group. METHODS AND ANALYSES: All newly referred patients will be screened for sedentary behaviour, using national recommendations. Testing at baseline, 6, 12 and 39 weeks will include; (1) physiological testing (VO2-peak, one repetition maximum muscle strength and lung function (2) fasting full body dual-energy X-ray absorptiometry scan (3) fasting blood glucose, insulin, lipids and cholesterols, (4) psychometric questionnaires (general well-being, quality of life, anxiety and depression, motivational readiness). The randomised controlled trial feasibility design is selected in order to examine barriers for recruitment, programme adherence, safety aspects and potential efficacy to the interventions during adjuvant chemotherapy. ETHICS AND DISSEMINATION: The Scientific Committee of the Capital Region (case No. H-1-2011-131) and the Danish Data Protection Agency (j. No. 2011-41-6349) approved the study. Data will be entered and locked into a database hosted by the Copenhagen Trial Unit, Rigshosptialet. Data will be available for analyses to project members and the trial statistician after the 45 included patients have completed the 12-week test. Results will be published in peer-reviewed scientific journals. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24901641.

The effects of a six-week supervised multimodal exercise intervention during chemotherapy on cancer-related fatigue.

PURPOSE: Cancer related fatigue (CRF) is a common problem for cancer patients across diagnoses during chemotherapy and is associated with physical inactivity, lower functional level and lack of energy. Few RCT exercise intervention studies have included cancer patients undergoing chemotherapy. The objective of this study is to evaluate whether a six-week supervised multimodal exercise intervention, adjunct to chemotherapy and standard care, can reduce the patient's CRF level. METHODS: Data is based on analyses of a prospective randomised controlled trial 'The Body & Cancer Trial'. 213 cancer patients with different diagnoses were randomised into an intervention group or wait-list control group. The primary outcome, Fatigue score (CRF), was evaluated by the Functional Assessment of Cancer Therapy-Anaemia Questionnaire (FACT-An-) (FACT-G score & FACT-An Anemia subscale). INTERVENTION: Supervised exercise, comprising high-intensity cardiovascular and heavy resistance training, relaxation- and body awareness training and massage, 9 h weekly for 6 weeks. RESULTS: CRF was significantly reduced in the intervention group, corresponding to a Fatigue score reduction of 3.04 (effect size of 0.44, 95% CI 0.17-0.72) (P = .002), the FACT-An score by 5.40 (P = .015), the FACT-An Toi score by 5.22 (P = .009) and the Anaemia-ANS by 3.76 (P = .002). There was no statistically significant effect on the General Quality of Life score (FACT-G) or on any of the individual wellbeing scores; Physical (P = .13), Emotional (P = .87), Social (P = .83) and Functional (P = .26). CONCLUSION: In summary, this six-week supervised multimodal exercise intervention can lead to significant reduction in self-reported CRF in cancer patients undergoing chemotherapy.