Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells.

The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resulted in the downregulation of many transcripts required for HSC maintenance. Genome-wide profiling by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex-binding sites at highly conserved regions in the promoters of genes involved in HSC maintenance. Our results identify a central role for Ldb1 in regulating the transcriptional program responsible for the maintenance of HSCs.

Economic evaluation of exercise interventions for individuals with cancer: A systematic review.

While there is good evidence that exercise is an effective adjunct therapy to cancer care, little is known about its value for money. The aim of this systematic review is to explore the available evidence pertaining to the cost-effectiveness of exercise interventions following cancer. A search of eight online databases (CINAHL, the Cochrane Library (NHSEED), Econlit, Embase, PsycInfo, PubMed, Scopus, Web of science) was first conducted on 26 March 2021 and updated on 8 March 2022. Only economic evaluations with results in the form of incremental cost-effectiveness ratio (ICER) were included. The Consolidated Health Economics Evaluation Reporting Standards (CHEERS) was used to appraise the quality of reporting in the studies. The study protocol was registered in PROSPERO. Sixteen studies comprising seven (44%) cost-utility analyses (CUA), one (6%) cost-effectiveness analyses (CEA) and eight (50%) combined CUA and CEA were identified. These studies explored exercise in five cancer types (breast, colon, lung, prostate, and blood), with half (50%) in breast cancer. Seven studies (44%) adopted societal perspectives. Exercise interventions were found to be cost-effective in five of ten (50%) trial-based economic evaluations and in five of the six (83%) model-based economic evaluations. Most exercise interventions included were supervised, while close supervision and individualized exercise sessions incurred higher costs. Exercise interventions in cancer care are cost-effective for various cancer types despite considerable heterogeneity in exercise delivery and the type of analysis used for economic evaluation. There is clear value in using decision-analytic modelling to account for the long-term benefits of exercise in cancer care.

Self-efficacy, motivation, and habits: psychological correlates of exercise among women with breast cancer.

PURPOSE: The purpose of this analysis was to explore associations between exercise behaviour among breast cancer survivors and three behavioural constructs from distinct theories: self-efficacy from social cognitive theory, motivation from self-determination theory, and habits from habit theory. METHODS: Breast cancer survivors (n = 204) completed a cross-sectional survey that collected demographic and disease characteristics, exercise levels, and self-efficacy, motivation, and habits. Multivariable linear regression models were used to identify constructs associated with total activity and resistance training. RESULTS: Participants were a mean (SD) age of 57.3 (10.8) years and most were diagnosed with early-stage disease (72%) and engaged in sufficient levels of total activity (94%), though only 45% completed ≥ 2 resistance training sessions/week. Identified motivation (ꞵ[95% CI] = 7.6 [3.9-11.3]) and habits (ꞵ[95% CI] = 4.4 [1.4-7.4]) were significantly associated with total activity (as were body mass index and disease stage), whilst identified motivation (ꞵ[95% CI] = 0.6 [0.3-0.9]) and coping self-efficacy (ꞵ[95% CI] = 0.02 [< 0.01-0.03]) were significantly associated with resistance training. The models explained 27% and 16% of variance in total activity and resistance training behaviour, respectively. CONCLUSION: Results suggest that incorporating strategies that support identified motivation, habits, and coping self-efficacy in future interventions could promote increased exercise behaviour among breast cancer populations. Future longitudinal research should examine associations with exercise in a more representative, population-based sample.

Efficacy of exercise interventions for women during and after gynaecological cancer treatment - a systematic scoping review.

PURPOSE: To systematically synthesise evidence of exercise intervention efficacy for physical/psychosocial outcomes that matter to women during/following treatment for gynaecological cancer. METHODS: Five databases were searched (PubMed, EMBASE, CINAHL, PsychInfo, Scopus). Exercise-only intervention studies that included women during/ following treatment for any gynaecological cancer, with/ without control comparison, on any physical or psychosocial outcome(s), were included and qualitatively appraised using the Revised Cochrane Risk of Bias tool and a modified Newcastle-Ottawa Scale. RESULTS: Seven randomised controlled trials (RCTs), three single-arm pre-post studies, and one prospective cohort study satisfied were included (11 studies). Most studies were completed following treatment (91%), included combined (aerobic and resistance; 36%) and aerobic (36%) training, were fully/mostly (63%) unsupervised, and had a moderate-to-high risk of bias. Overall, 33 outcomes (64% objectively-measured) were assessed. Improvements were observed in aerobic capacity (V̇O2 Peak +1.6 mL/kg/min, 6-minute walk distance +20-27 m), lower- (30-second sit-to-stand +2-4 repetitions) and upper-limb strength (30-second arm curl +5 repetitions; 1RM grip strength/chest press +2.4-3.1 kg), and agility (timed up-and-go -0.6 seconds). However, changes in quality of life, anthropometry/body composition, balance and flexibility were inconsistent. There was no evidence to support worsening of outcomes. CONCLUSION: Preliminary research into the role of exercise post-gynaecological cancer suggests an improvement in exercise capacity, muscular strength, and agility which, in the absence of exercise, typically decline following gynaecological cancer. Future exercise trials involving larger and more diverse gynaecological cancer samples will improve understanding of the potential and magnitude of effect of guideline-recommended exercise on outcomes that matter to patients.

Burden of lymphedema in long-term breast cancer survivors by race and age.

BACKGROUND: Risk assessment for breast cancer-related lymphedema has emphasized upper-limb symptoms and treatment-related risk factors. This article examined breast cancer-related lymphedema after surgery, overall and in association with broader demographic and clinical features. METHODS: The Carolina Breast Cancer Study phase 3 followed participants for breast cancer-related lymphedema from baseline (on average, 5 months after breast cancer diagnosis) to 7 years after diagnosis. Among 2645 participants, 552 self-reported lymphedema cases were identified. Time-to-lymphedema curves and inverse probability weighted conditional Cox proportional hazards model were used to evaluate whether demographics and clinical features were associated with breast cancer-related lymphedema. RESULTS: Point prevalence of breast cancer-related lymphedema was 6.8% at baseline, and 19.9% and 23.8% at 2 and 7 years after diagnosis, respectively. Most cases had lymphedema in the arm (88%-93%), whereas 14% to 27% presented in the trunk and/or breast. Beginning approximately 10 months after diagnosis, younger Black women had the highest risk of breast cancer-related lymphedema and older non-Black women had the lowest risk. Positive lymph node status, larger tumor size (>5 cm), and estrogen receptor-negative breast cancer, as well as established risk factors such as higher body mass index, removal of more than five lymph nodes, mastectomy, chemotherapy, and radiation therapy, were significantly associated with increased hazard (1.5- to 3.5-fold) of lymphedema. CONCLUSIONS: Findings highlight that hazard of breast cancer-related lymphedema differs by demographic characteristics and clinical features. These factors could be used to identify those at greatest need of lymphedema prevention and early intervention. LAY SUMMARY: In this study, the aim was to investigate breast cancer-related lymphedema (BCRL) burden. This study found that risk of BCRL differs by race, age, and other characteristics.

Physical activity and exercise in adults diagnosed with primary brain cancer: a systematic review.

PURPOSE: The aims of this systematic review were to: (1) describe physical activity (PA) levels following diagnosis of primary brain cancer, (2) determine the relationship between PA levels and health outcomes, and (3) assess the effect of participating in an exercise intervention on health outcomes following a diagnosis of brain cancer. METHODS: PubMed, EMBASE, Scopus and CINAHL were searched for relevant articles published prior to May 1, 2020. Studies reporting levels of PA, the relationship between PA and health outcomes, and exercise interventions conducted in adults with brain cancer were eligible. The search strategy included terms relating to primary brain cancer, physical activity, and exercise. Two independent reviewers assessed articles for eligibility and methodological quality (according to Joanna Briggs Institute Critical Appraisal Tools). Descriptive statistics were used to present relevant data and outcomes. RESULTS: 15 studies were eligible for inclusion. Most adults with brain cancer were insufficiently active from diagnosis through to post-treatment. Higher levels of PA were associated with lower severity of brain cancer specific concerns and higher quality of life. Preliminary evidence suggests that exercise is safe, feasible and potentially beneficial to brain cancer symptom severity and interference, aerobic capacity, body composition and PA levels. However, the level of evidence to support these findings is graded as weak. CONCLUSIONS: Evidence suggests that it is likely appropriate to promote those with brain cancer to be as physically active as possible. The need or ability of those with brain cancer to meet current PA guidelines promoted to all people with cancer remains unclear.

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.

Physical activity levels among ovarian cancer survivors: a prospective longitudinal cohort study.

OBJECTIVE: Physical activity following cancer diagnosis is associated with improved outcomes, including potential survival benefits, yet physical activity levels among common cancer types tend to decrease following diagnosis and remain low. Physical activity levels following diagnosis of less common cancers, such as ovarian cancer, are less known. The objectives of this study were to describe physical activity levels and to explore characteristics associated with physical activity levels in women with ovarian cancer from pre-diagnosis to 2 years post-diagnosis. METHODS: As part of a prospective longitudinal study, physical activity levels of women with ovarian cancer were assessed at multiple time points between pre-diagnosis and 2 years post-diagnosis. Physical activity levels and change in physical activity were described using metabolic equivalent task hours and minutes per week, and categorically (sedentary, insufficiently, or sufficiently active). Generalized Estimating Equations were used to explore whether participant characteristics were related to physical activity levels. RESULTS: A total of 110 women with ovarian cancer with a median age of 62 years (range 33-88) at diagnosis were included. 53-57% of the women were sufficiently active post-diagnosis, although average physical activity levels for the cohort were below recommended levels throughout the 2-year follow-up period (120-142.5min/week). A decrease or no change in post-diagnosis physical activity was reported by 44-60% of women compared with pre-diagnosis physical activity levels. Women diagnosed with stage IV disease, those earning a lower income, those receiving chemotherapy, and those currently smoking or working were more likely to report lower physical activity levels and had increased odds of being insufficiently active or sedentary. CONCLUSIONS: Interventions providing patients with appropriate physical activity advice and support for behavior change could potentially improve physical activity levels and health outcomes.

A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer - ENDO-3: ANZGOG trial 1911/2020.

BACKGROUND: Sentinel node biopsy is a surgical technique to explore lymph nodes for surgical staging of endometrial cancer, which has replaced full retroperitoneal lymph node dissection. However, the effectiveness of sentinel node biopsy, its value to patients, and potential harms compared with no-node dissection have never been shown in a randomized trial. PRIMARY OBJECTIVES: Stage 1 will test recovery from surgery. Stage 2 will compare disease-free survival at 4.5 years between patients randomized to sentinel node biopsy versus no retroperitoneal node dissection. STUDY HYPOTHESIS: The primary hypothesis for stage 1 is that treatment with sentinel node biopsy will not cause detriment to patient outcomes (lymphedema, morbidity, loss of quality of life) and will not increase treatment-related morbidity or health services costs compared with patients treated without a retroperitoneal node dissection at 12 months after surgery. The primary hypothesis for stage 2 is that disease-free survival at 4.5 years after surgery in patients without retroperitoneal node dissection is not inferior to those receiving sentinel node biopsy. TRIAL DESIGN: This phase III, open-label, two-arm, multistage, randomized non-inferiority trial (ENDO-3) will determine the value of sentinel node biopsy for surgical management of endometrial cancer. Patients with endometrial cancer are randomized to receive: (1) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy with sentinel node biopsy or (2) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection. In stage 1, 444 patients will be enrolled to demonstrate feasibility and quality of life. If this is demonstrated, we will enroll another 316 patients in stage 2. MAJOR INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria include women aged 18 years or older with histologically confirmed endometrial cancer; clinical stage 1, who meet the criteria for laparoscopic or robotic total hysterectomy and bilateral salpingo-oophorectomy. Patients with uterine mesenchymal tumors are excluded. PRIMARY ENDPOINTS: The endpoint for stage 1 is surgical recovery, with the proportion of patients returning to usual daily activities at 3 months post-surgery as measured with the EQ-5D. Stage 2 is disease-free survival at 4.5 years. SAMPLE SIZE: 760 participants (both stages). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Stage 1 commenced in January 2021 and is planned to be completed in December 2024 when 444 participants have completed 12 months' follow-up. Stage 2 will enroll a further 316 participants for a total of 760 patients. TRIAL REGISTRATION: NCT04073706.

Translating research into practice: outcomes from the Healthy Living after Cancer partnership project.

BACKGROUND: Healthy Living after Cancer (HLaC) was a national dissemination and implementation study of an evidence-based lifestyle intervention for cancer survivors. The program was imbedded into existing telephone cancer information and support services delivered by Australian state-based Cancer Councils (CC). We report here the reach, effectiveness, adoption, implementation, and maintenance of the program. METHODS: In this phase IV study (single-group, pre-post design) participants - survivors of any type of cancer, following treatment with curative intent - received up to 12 nurse/allied health professional-led telephone health coaching calls over 6 months. Intervention delivery was grounded in motivational interviewing, with emphasis on evidence-based behaviour change strategies. Using the RE-AIM evaluation framework, primary outcomes were reach, indicators of program adoption, implementation, costs and maintenance. Secondary (effectiveness) outcomes were participant-reported anthropometric, behavioural and psychosocial variables including: weight; physical activity; dietary intake; quality-of-life; treatment side-effects; distress; and fear of cancer recurrence and participant satisfaction. Changes were evaluated using linear mixed models, including terms for timepoint (0/6 months), strata (Cancer Council), and timepoint x strata. RESULTS: Four of 5 CCs approached participated in the study. In total, 1183 cancer survivors were referred (mostly via calls to the Cancer Council telephone information service). Of these, 90.4% were eligible and 88.7% (n = 791) of those eligible consented to participate. Retention rate was 63.4%. Participants were mostly female (88%), aged 57 years and were overweight (BMI = 28.8 ± 6.5 kg/m2). Improvements in all participant-reported outcomes (standardised effect sizes of 0.1 to 0.6) were observed (p < 0.001). The program delivery costs were on average AU$427 (US$296) per referred cancer survivor. CONCLUSIONS: This telephone-delivered lifestyle intervention, which was feasibly implemented by Cancer Councils, led to meaningful and statistically significant improvements in cancer survivors' health and quality-of-life at a relatively low cost. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12615000882527 (registered on 24/08/2015).

Physical activity and exercise in women with ovarian cancer: A systematic review.

OBJECTIVE: A consistent body of evidence supports participating in physical activity (PA) post-cancer diagnosis as beneficial to function, quality-of-life and potentially survival. However, diagnosis of late stage disease, poor prognosis, receipt of high doses of adjuvant therapy and presence of severe acute and persistent treatment-related side-effects may alter how these findings translate to women with ovarian cancer. Therefore, the objectives of this review were to (I) describe PA levels post-diagnosis of ovarian cancer, (II) explore the relationship between PA levels and health outcomes, and (III) evaluate the effect of exercise interventions for women with ovarian cancer. METHODS: PubMed, EMBASE, Scopus and CINAHL were systematically searched to December 31, 2019. Two independent reviewers assessed articles for eligibility. Studies were eligible if they evaluated the relationship between PA levels or an exercise intervention and health outcomes following ovarian cancer. Methodological quality was assessed by two independent reviewers using the Joanna Briggs Institute Critical Appraisal Tools. Descriptive statistics were used to collate relevant data. RESULTS: 34 articles were eligible for inclusion. Results demonstrated that most women decrease PA from pre- to post-diagnosis and remain insufficiently active following diagnosis. Higher levels of PA were associated with higher health-related quality-of-life (HRQOL), and lower levels of anxiety and depression. Exercise appears safe and feasible during and following treatment and leads to improvements in HRQOL, fatigue and additional physical and psychological outcomes. CONCLUSIONS: Findings suggest that PA is relevant to health outcomes for women with ovarian cancer. Interventions that aid women to stay or become sufficiently active, including through exercise interventions during or following treatment have potential to improve the lives of those with ovarian cancer. Future work evaluating targeted interventions that can accommodate disease-specific challenges is now required to ensure scientific findings can translate into improved ovarian cancer care.

Incidence and risk factors for lower limb lymphedema associated with endometrial cancer: Results from a prospective, longitudinal cohort study.

BACKGROUND: Evidence on the incidence and risk factors for lower limb lymphedema (LLL) associated with endometrial cancer is limited. Our objective was to use data from a prospective, longitudinal gynecological cancer cohort study to determine LLL incidence up to 24 months post-diagnosis of endometrial cancer and to explore the relationship between personal and treatment-related factors and risk of developing LLL. METHODS: Women recently diagnosed with endometrial cancer (n = 235) were evaluated at regular intervals post-diagnosis (up to 3-monthly) using bioimpedance spectroscopy (BIS) and self-reported leg swelling (SRLS). RESULTS: Incidence of LLL at 24 months post-diagnosis was 33% and 45% according to BIS and SRLS, respectively. When analyses were restricted to obese women, incidence at 24 months post-diagnosis increased to 67% (BIS) and 54% (SRLS). Following adjusted analyses, higher body mass index was associated with higher odds of baseline lymphedema (BIS: OR 1.91, 95% CI 1.47-2.49, p < .01; SRLS: OR 1.06, 95% CI 1.00-1.12, p < .01) and LLL incidence by 24 months post-diagnosis (BIS: OR 1.29, 95% CI: 0.99-1.68, p = .055; SRLS: OR 1.06, 95% CI 1.02-1.11, p = .008). According to SRLS, presence of comorbidities was also associated with baseline lymphedema (OR: 1.43, 95% CI: 1.15-1.78, p = .001), and more extensive lymph node dissection (OR 1.06, 95% CI: 1.01-1.12, p = .026) and receipt of chemotherapy (OR: 2.65, 95% CI: 1.12-6.29, p = .027) were identified as risk factors for lymphedema incidence. CONCLUSIONS: These findings suggest that LLL following endometrial cancer is common, particularly in women with high body mass index, or comorbidities, and those requiring more extensive lymph node dissection or chemotherapy. Future studies should examine the potential of weight loss intervention as a strategy to reduce LLL incidence.

Exercise and colorectal cancer: a systematic review and meta-analysis of exercise safety, feasibility and effectiveness.

BACKGROUND: This meta-analysis evaluated the safety, feasibility and effect of exercise among individuals with colorectal cancer. METHODS: A database search (CINAHL, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing, Science Direct) for randomised, controlled, exercise trials involving individuals with colorectal cancer, published before January 1, 2020 was undertaken. Safety (adverse events), feasibility (withdrawal and adherence rates) and effect data (health outcomes including quality of life, QoL) were abstracted. Risk difference (RD) and standardised mean differences (SMD) were calculated to compare safety and effects between exercise and usual care (UC). Subgroup analyses were conducted to assess whether outcomes differed by exercise mode, duration, supervision and treatment. Risk of bias was assessed using the Physiotherapy Evidence Database tool. RESULTS: For the 19 trials included, there was no difference in adverse event risk between exercise and UC (RD = 0.00; 95% CI:-0.01, 0.01, p = 0.92). Median withdrawal rate was 12% (0-22%) and adherence was 86% (42-91%). Significant effects of exercise compared to UC were observed for QoL, fatigue, aerobic fitness, upper-body strength, depression, sleep and reduced body fat (SMD = 0.21-0.66, p < 0.05). Subgroup analyses suggested larger benefits (p < 0.05) for QoL and fatigue for supervised interventions; for QoL, aerobic fitness and reduced body fat for ≥12-week interventions; and for aerobic fitness when interventions were during chemotherapy. CONCLUSION: Although reporting of safety and compliance data was lacking in most trials, findings support that exercise is safe and feasible in colorectal cancer. Further, participation in mixed-mode exercise, including unsupervised exercise, leads to improvements in various health-related outcomes.

A systematic review and meta-analysis of sarcopenia as a prognostic factor in gynecological malignancy.

INTRODUCTION: Sarcopenia is a condition described as the progressive generalized loss of muscle mass and strength. While sarcopenia has been linked with poorer outcomes following a variety of malignancies, its relationship with all gynecological cancer clinical outcomes has, to date, not been evaluated. This review interrogates the concept of sarcopenia as a prognostic tool for oncological outcomes and adverse effects of treatments in all primary gynecological malignancies. METHODS: This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines, searching PubMed, Embase, and CINAHL without date or language restriction for studies reporting on sarcopenia and gynecological malignancies. Random effects meta-analysis models were used to determine the effects of sarcopenia on progression-free survival, overall survival, and treatment-related adverse events. RESULTS: Data were analyzed from 13 studies, including 2446 patients (range 60-323) with ovarian cancer (n=1381), endometrial cancer (n=354), or cervical cancer (n=481). Sarcopenia was associated with lower progression-free survival (HR 1.69, 95% CI 1.03 to 2.76), overall survival (HR 1.33, 95% CI 1.08 to 1.64), and no increase in adverse events (HR 1.28, 95% CI 0.69 to 2.40). The risk of bias of the studies was mostly rated unclear, and Begg's and Egger's test revealed a potential publication bias for progression-free survival and overall survval, although the HRs remained significant when adjusting for it. CONCLUSION: Sarcopenia is associated with worse progression-free survival and overall survival in gynecological oncology malignancies. Further research is warranted to validate these findings in larger and prospective samples using standardized methodology and to examine if an intervention could reverse its effect in gynecological oncology trials.

Physical activity trajectories following gynecological cancer: results from a prospective, longitudinal cohort study.

BACKGROUND: Participating in physical activity after a diagnosis of cancer is associated with reduced morbidity and improved outcomes. However, declines in, and low levels of, physical activity are well documented in the broader cancer population, but with limited evidence following gynecological cancer. OBJECTIVE: To describe physical activity levels from before and up to 2 years after gynecological cancer surgery; to explore the relationship between physical activity patterns and quality of life; and to describe characteristics associated with physical activity trajectories post-gynecological cancer. METHODS: Women with gynecological cancer (n=408) participated in a prospective study that assessed physical activity and quality of life pre-surgery (baseline), at 6 weeks, and 3, 6, 9, 12, 15, 18 and 24 months post-surgery. Validated questionnaires were used to assess physical activity (Active Australia Survey) and quality of life outcomes (Functional Assessment of Cancer Therapy-General). Generalized estimating equation modeling, group-based trajectory analysis, and analysis of variance were used to identify physical activity levels over time, to categorize women into physical activity trajectory groups, and to assess the relationship between physical activity levels and quality of life, respectively. RESULTS: Women had a mean±SD age of 60±11.4 years at diagnosis, with the majority diagnosed with endometrial cancer (n=235, 58%) or stage I disease (n=241, 59%). Most women (80%) started with and maintained low levels of physical activity (1-10 metabolic equivalent task hours per week), reported no physical activity throughout the follow-up period, or reduced physical activity levels over time. Only 19% of women maintained or doubled physical activity levels, so that by 24 months post-diagnosis they were engaging in sufficient levels of physical activity. Women with endometrial cancer (58% of the sample) were more likely to be overweight or obese and to report low levels of physical activity or none at all. Higher physical activity levels were associated with higher quality of life (p<0.05). CONCLUSION: The low baseline and surveillance levels of physical activity show that the vast majority of gynecological cancer survivors have the ability to improve their physical activity levels. Integration of physical activity advice and support into standard care could lead to gains in quality of life during gynecological cancer survivorship.

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.

Effects and moderators of exercise on muscle strength, muscle function and aerobic fitness in patients with cancer: a meta-analysis of individual patient data.

OBJECTIVE: To optimally target exercise interventions for patients with cancer, it is important to identify which patients benefit from which interventions. DESIGN: We conducted an individual patient data meta-analysis to investigate demographic, clinical, intervention-related and exercise-related moderators of exercise intervention effects on physical fitness in patients with cancer. DATA SOURCES: We identified relevant studies via systematic searches in electronic databases (PubMed, Embase, PsycINFO and CINAHL). ELIGIBILITY CRITERIA: We analysed data from 28 randomised controlled trials investigating the effects of exercise on upper body muscle strength (UBMS) and lower body muscle strength (LBMS), lower body muscle function (LBMF) and aerobic fitness in adult patients with cancer. RESULTS: Exercise significantly improved UBMS (ß=0.20, 95% Confidence Interval (CI) 0.14 to 0.26), LBMS (ß=0.29, 95% CI 0.23 to 0.35), LBMF (ß=0.16, 95% CI 0.08 to 0.24) and aerobic fitness (ß=0.28, 95% CI 0.23 to 0.34), with larger effects for supervised interventions. Exercise effects on UBMS were larger during treatment, when supervised interventions included ≥3 sessions per week, when resistance exercises were included and when session duration was >60 min. Exercise effects on LBMS were larger for patients who were living alone, for supervised interventions including resistance exercise and when session duration was >60 min. Exercise effects on aerobic fitness were larger for younger patients and when supervised interventions included aerobic exercise. CONCLUSION: Exercise interventions during and following cancer treatment had small effects on UBMS, LBMS, LBMF and aerobic fitness. Demographic, intervention-related and exercise-related characteristics including age, marital status, intervention timing, delivery mode and frequency and type and time of exercise sessions moderated the exercise effect on UBMS, LBMS and aerobic fitness.

Clinical Oncology Society of Australia position statement on exercise in cancer care.

INTRODUCTION: Clinical research has established exercise as a safe and effective intervention to counteract the adverse physical and psychological effects of cancer and its treatment. This article summarises the position of the Clinical Oncology Society of Australia (COSA) on the role of exercise in cancer care, taking into account the strengths and limitations of the evidence base. It provides guidance for all health professionals involved in the care of people with cancer about integrating exercise into routine cancer care. Main recommendations: COSA calls for: exercise to be embedded as part of standard practice in cancer care and to be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment; all members of the multidisciplinary cancer team to promote physical activity and recommend that people with cancer adhere to exercise guidelines; and best practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care. Changes in management as a result of the guideline: COSA encourages all health professionals involved in the care of people with cancer to: discuss the role of exercise in cancer recovery; recommend their patients adhere to exercise guidelines (avoid inactivity and progress towards at least 150 minutes of moderate intensity aerobic exercise and two to three moderate intensity resistance exercise sessions each week); and refer their patients to a health professional who specialises in the prescription and delivery of exercise (ie, accredited exercise physiologist or physiotherapist with experience in cancer care).

A Systematic Review and Meta-Analysis of the Safety, Feasibility, and Effect of Exercise in Women With Stage II+ Breast Cancer.

OBJECTIVE: To systematically evaluate the safety, feasibility, and effect of exercise among women with stage II+ breast cancer. DATA SOURCES: CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, Science Direct and SPORTDiscus were searched for articles published before March 1, 2017. STUDY SELECTION: Randomized, controlled, exercise trials involving at least 50% of women diagnosed with stage II+ breast cancer were included. DATA EXTRACTION: Risk of bias was assessed and adverse event severity was classified using the Common Terminology Criteria. Feasibility was evaluated by computing median (range) recruitment, withdrawal, and adherence rates. Meta-analyses were performed to evaluate exercise safety and effects on health outcomes only. The influence of intervention characteristics (mode, supervision, duration and timing) on exercise outcomes were also explored. DATA SYNTHESIS: There were no differences in adverse events between exercise and usual care (risk difference: <0.01 ([95% CI: -0.01, 0.01], P=0.38). Median recruitment rate was 56% (1%-96%), withdrawal rate was 10% (0%-41%) and adherence rate was 82% (44%-99%). Safety and feasibility outcomes were similar, irrespective of exercise mode, supervision, duration, or timing. Effects of exercise for quality of life, fitness, fatigue, strength, anxiety, depression, body mass index and waist circumference compared with usual care were significant (standardized mean difference range: 0.17-0.77, P<0.05). CONCLUSION: The findings support the safety, feasibility, and effects of exercise for those with stage II+ breast cancer, suggesting that national and international exercise guidelines appear generalizable to women with local, regional, and distant breast cancer.