Exercise Intensity Among Older Adults Participating From Home in Remotely Delivered EnhanceFitness.

We aimed to examine exercise intensity among older adults participating from home in remotely delivered EnhanceFitness (Tele-EF). Exercise intensity was assessed through Fitbit-measured heart rate and the Borg 10-point rating of perceived exertion over 1 week of a 16-week exercise program. Outcomes included mean minutes spent at or above the heart rate reserve calculated threshold for moderate intensity and mean rating of perceived exertion. Pearson and Spearman rank correlations were used to examine associations between baseline characteristics with exercise intensity. During the 60-min classes, the 55 participants achieved moderate intensity for a mean of 21.0 min (SD = 13.5) and had a mean rating of perceived exertion of 4.9 (SD = 1.2). There were no significant associations between baseline characteristics and exercise intensity. Older adults can achieve sustained moderate-intensity exercise during Tele-EF supervised classes. Baseline physical function, physical activity, and other health characteristics did not limit ability to exercise at a moderate intensity, though further investigation is warranted.

Female cancer survivor perspectives on remote intervention components to support physical activity maintenance.

PURPOSE: Physical activity minimizes the side effects of cancer; yet, participation rates among cancer survivors are low. Technological innovations are promoted as efficient means for communication and remote monitoring, but little is known about acceptability among female cancer survivors. The purpose of this study was to examine female cancer survivor perspectives on remote monitoring and communication to support independent, physical activity maintenance after completing a structured, facility-based program. METHODS: Participants were 19 female cancer survivors (mean age 56.3) recruited after completing a 12-week exercise-based oncology rehabilitation program. Semi-structured interviews were conducted with participants following a 4-week pilot trial of a tailored text message, FitBit®, and health coach intervention to support independent physical activity maintenance. All interviews were audio-recorded and transcribed. Transcripts from the interviews were iteratively coded by two team members using a thematic analysis. RESULTS: Participants reported acceptance and satisfaction with remote monitoring and communication. Emergent themes related to technology-based support for physical activity maintenance included the following: (1) accountability to a remote partner; (2) plan Bs, planning for barriers; (3) the habit cycle; (4) convenience through technology; and (5) reclaiming health ownership following a cancer diagnosis. CONCLUSIONS: Participants attributed physical activity maintenance to accountability enabled by technology. Communication based on remote monitoring was perceived as encouraging and not intrusive, during the transition to a home program. IMPLICATIONS FOR CANCER SURVIVORS: This study highlights the importance of accountability and support for physical activity adherence and the positive role that technology can provide for female cancer survivors to regain control of health management.

Effects of an exercise-based oncology rehabilitation program and age on strength and physical function in cancer survivors.

PURPOSE: Cancer therapy diminishes strength and physical function in cancer survivors. Whether oncology rehabilitation (OR) exercise training following therapy can correct these deficits, and whether its effectiveness differs by age, is not clear. We examine the utility of a clinically based, 12-week, combined aerobic and resistance training intervention on muscle strength and physical function in two age groups of cancer survivors. METHODS: Strength and physical function measures were assessed in middle-aged (45 to 64 years) and older (≥ 65 years) patients following treatment for stage 0-III cancer before and after the OR training program. RESULTS: Older patients had lower physical function compared to middle-aged patients across a range of subjective and objective measures at baseline, and exercise improved all indices of physical function and strength in both age groups. Compared to the middle-aged individuals, older participants tended to have less improvement leg strength and the 5 time sit to stand (5TSTS) test as a result of OR. In models predicting post-intervention measures, older age contributed to less improvement in walking distance and power as well as the 5TSTS test. CONCLUSION: Prior to beginning the OR exercise program, middle-aged patients had higher physical function compared to older patients. However, a 12-week aerobic and resistance training intervention improved physical function across both age groups, although older age did limit responsiveness in some physical function measures. The physical function and strength of middle-aged and older cancer survivors improve in response to an exercise-based OR program after cancer treatment.

Skeletal muscle atrophy and dysfunction in breast cancer patients: role for chemotherapy-derived oxidant stress.

How breast cancer and its treatments affect skeletal muscle is not well defined. To address this question, we assessed skeletal muscle structure and protein expression in 13 women who were diagnosed with breast cancer and receiving adjuvant chemotherapy following tumor resection and 12 nondiseased controls. Breast cancer patients showed reduced single-muscle fiber cross-sectional area and fractional content of subsarcolemmal and intermyofibrillar mitochondria. Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused reductions in myosin expression, mitochondrial loss, and increased reactive oxygen species (ROS) production in C2C12 murine myotube cell cultures, supporting a role for chemotherapeutics in the atrophic and mitochondrial phenotypes. Additionally, concurrent treatment of myotubes with the mitochondrial-targeted antioxidant MitoQ prevented chemotherapy-induced myosin depletion, mitochondrial loss, and ROS production. In patients, reduced mitochondrial content and size and increased expression and oxidation of peroxiredoxin 3, a mitochondrial peroxidase, were associated with reduced muscle fiber cross-sectional area. Our results suggest that chemotherapeutics may adversely affect skeletal muscle in patients and that these effects may be driven through effects of these drugs on mitochondrial content and/or ROS production.

Comparative effectiveness of incorporating a hypothetical DCIS prognostic marker into breast cancer screening.

PURPOSE: Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. METHODS: A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. RESULTS: Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. CONCLUSION: A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Impact of a behaviorally-based weight loss intervention on parameters of insulin resistance in breast cancer survivors.

BACKGROUND: Breast cancer survivors with excess weight are more likely to have negative breast cancer outcomes. Biomarkers related to insulin resistance may help explain this negative association. Weight loss is associated with improvements in insulin sensitivity. Our goal was to identify the impact of a behaviorally based weight loss intervention on indices of insulin resistance. METHODS: Overweight, early stage breast cancer survivors who completed initial cancer therapy were enrolled in a 6 month behaviorally based weight loss intervention that included calorie reduction, exercise and behavior modification. Biomarkers related to insulin resistance were obtained at baseline and after the intervention. Results from participants who achieved ≥5% weight loss were compared to those who lost less weight. RESULTS: Despite not having diabetes as a preexisting diagnosis prior to the study, 69% of all participants were considered to have pre-diabetes or diabetes at baseline based on American Diabetes Association definitions. Participants who achieved ≥5% weight loss had significantly lower fasting insulin, AUC insulin, and insulin resistance as measured by HOMA-IR. Beta cell function decreased as anticipated when insulin resistance improved. Additionally, leptin levels declined. CONCLUSIONS: Breast cancer survivors who achieved ≥5% weight loss demonstrated significant improvements in indices of insulin resistance. Despite an exclusion criteria of diabetes at the time of enrolment, a high proportion met criteria for pre-diabetes or diabetes at baseline. Pre-diabetes appears to be under recognized in overweight breast cancer survivors. Behaviorally based weight loss interventions can result in weight loss and improvements in biomarkers related to breast cancer outcomes and additionally may decrease the chance of developing diabetes. TRIAL REGISTRATION: NCT01482702 4/12/2010 (retrospectively registered).  https://clinicaltrials.gov/ct2/show/NCT01482702?term=Dittus&rank=4.

Chemotherapy-related neuropathic symptom management: a randomized trial of an automated symptom-monitoring system paired with nurse practitioner follow-up.

PURPOSE: The purpose of this study was to evaluate a new care model to reduce chemotherapy-induced neuropathic symptoms. Neuropathic symptom usual care was prospectively compared to an automated symptom-monitoring and coaching system, SymptomCare@Home (SCH), which included nurse practitioner follow-up triggered by moderate to severe symptoms. METHODS: Patients beginning chemotherapy were randomized to usual care (UC) or to the SCH intervention. This sub-analysis included only taxane/platin therapies. Participants called the automated telephone symptom-monitoring system daily to report numbness and tingling. The monitoring system recorded patient-reported neuropathic symptom severity, distress, and activity interference on a 0-10 scale. UC participants were instructed to call their oncologist for symptom management. SCH participants with symptom severity of ≥ 4 received automated self-care strategies, and a nurse practitioner (NP) provided guideline-based care. RESULTS: There were 252 participants, 78.6% of which were female. Mean age was 55.1 years. Mean follow-up was 90.2 ± 39.9 days (81.1 ± 40.3 calls). SCH participants had fewer days of moderate (1.8 ± 4.0 vs. 8.6 ± 17.3, p < 0.001) and severe chemotherapy-induced peripheral neuropathy symptoms (0.3 ± 1.0 vs. 1.1 ± 5.2, p = 0.006). SCH participants had fewer days with moderate and severe symptom-related distress (1.4 ± 3.7 vs. 6.9 ± 15.0, p < 0.001; 0.2 ± 0.9 vs. 1.5 ± 6.1, p = 0.001) and trended towards less activity interference (3.3 ± 1.9 vs. 3.8 ± 2.1, p = 0.08). Other neuropathic symptoms were addressed in 5.8-15.4% of SCH follow-up calls. CONCLUSIONS: The SCH system effectively identified neuropathic symptoms and their severity and, paired with NP follow-up, reduced symptom prevalence, severity, and distress compared to usual care.

When Clinical Trial Participation Is Not an Option in the Era of Personalized Medicine: The Case of Two Patients.

The combination of personalized therapy with immunotherapy might lead to rapid complete remission in patients who are too sick to be eligible for clinical trials. We report 2 such extraordinary responders. A discussion on the use and purpose of clinical trials in this new era of very active anticancer drug discovery concludes that a paradigm shift is urgently needed.

Exercise interventions for individuals with advanced cancer: A systematic review.

Despite improvements in therapy a large proportion of individuals with cancer will have a shortened life expectancy because of advanced or metastatic disease. Advances in therapy have however, extended life in those with advanced cancer thus heightening the importance of living well and preventing decline. The burdens of disease and cancer therapy impair aerobic fitness, strength, physical function and quality of life (QOL). Fatigue, the most common side effect of cancer and cancer therapy can further deteriorate QOL. Exercise has the potential to improve aerobic fitness, physical function, control fatigue and enhance QOL. However, exercise interventions are not routinely provided to those with advanced cancer. We present a systematic literature review of outcomes from interventions that include exercise for patients with advanced cancer. Studies were reviewed if they included an advanced cancer population and an intervention with a component of exercise. Overall, exercise containing interventions resulted in improvements in measures of aerobic capacity (14 of 19 studies) strength (11 of 12 studies), and components of physical function (9 of 9 studies). Fatigue and QOL were identified to improve in slightly over half of all evaluated studies (11 of 19 studies and 10 of 19 studies for fatigue and QOL respectively). The numbers of total participants reporting improvements in QOL (60%) were greater than fatigue (45%). Exercise provided to individuals with advanced cancer maintains or improves fitness and physical function and may diminish fatigue and enhance QOL and should be considered as an intervention to prevent further health complications.

Efficacy, feasibility, and acceptability of a novel technology-based intervention to support physical activity in cancer survivors.

PURPOSE: Physical activity is known to minimize the long-term side effects of cancer treatment. Yet, rates of physical activity participation by cancer survivors are significantly lower compared to the general population. The purpose of this pilot study was to examine the efficacy, feasibility, and acceptability of a technology-based intervention to promote maintenance of physical activity after completing an exercise-based oncology rehabilitation program. METHODS: The pre-post 4-week intervention included support delivered through tailored text messages, Fitbit® self-monitoring, and brief health coaching sessions. The primary outcome measure was accelerometer-assessed physical activity levels. Self-efficacy, self-regulation, social support, fatigue, sleep disturbance, depression, and Fitbit® step counts were assessed as secondary outcomes. RESULTS: Twenty-four participants (20 females; mean age = 57.9 years ± 10.4) completed the intervention. Mean daily step counts and weekly minutes of moderate-to-vigorous intensity physical activity were maintained after the intervention, as compared to baseline levels achieved at the end of 12 weeks of exercise-based oncology rehabilitation. Both self-regulation (goal setting, relapse prevention) and fatigue severity increased significantly post intervention as compared to baseline (p = 0.05 and p = 0.02, respectively). Qualitative responses demonstrated overall satisfaction with intervention components. CONCLUSIONS: Results demonstrate efficacy of the intervention for maintenance of physical activity levels achieved during exercise-based oncology rehabilitation. Low attrition and high satisfaction provide evidence for both the acceptability and feasibility of the intervention components. Exercise interventions post oncology treatment provide multiple benefits for cancer survivors, yet continued maintenance after program completion is challenging. Technological options offer low-cost, accessible modes to deliver continued monitoring and support beyond traditional facility-based programs.

Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ.

BACKGROUND: The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. METHODS: Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. RESULTS: DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. CONCLUSIONS: Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society.

Health behavior change following a diagnosis of ductal carcinoma in situ: An opportunity to improve health outcomes.

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that comprises approximately 20% of new breast cancer diagnoses. DCIS is predominantly detected by screening mammography prior to the development of any clinical symptoms. Prognosis following a DCIS diagnosis is excellent, due to both the availability of effective treatments and the frequently benign nature of the disease. However, a DCIS diagnosis and its treatment have psychological and physical impacts that often lead to adverse changes in health-related behaviors, including changes in physical activity, body weight, alcohol intake, and smoking, which may represent a greater threat to the woman's overall health than the DCIS itself. Depending on age at diagnosis, women diagnosed with DCIS are 3-13 times more likely to die from non-breast cancer related causes, such as cardiovascular disease, than from breast cancer. Thus, the maintenance and improvement of healthy behaviors that influence a variety of outcomes after diagnosis may warrant increased attention during DCIS management. This may also represent an important opportunity to promote the adoption of healthy behaviors, given that DCIS carries the psychological impact of a cancer diagnosis but also a favorable prognosis. Particular focus is needed to address these issues in vulnerable patient subgroups with pre-existing higher rates of unhealthy behaviors and demonstrated health disparities.

The association of chemotherapy-induced peripheral neuropathy with reduced executive function in chemotherapy-treated cancer survivors: A cross-sectional study.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is common and disabling among cancer survivors. Little is known about the association of CIPN with other measures of the nervous system's integrity, such as executive dysfunction. We compared measures of executive function in older chemotherapy-treated cancer survivors with and without CIPN. MATERIALS AND METHODS: This cross-sectional study enrolled 50 chemotherapy-treated cancer survivors (65.6 ± 11.5 years, 88% female) post-chemotherapy treatment who were previously referred for outpatient rehabilitation at the request of the cancer survivor or a medical provider. Twenty-two participants (44%) had CIPN defined by patient-reported distal paresthesia or numbness, which began with chemotherapy and continued to the time of cognitive testing. Measures of executive function included Trails-B, Stroop, and rapid reaction accuracy (RRA) and were evaluated between cancer survivors with and without CIPN using t-tests. Multivariable models were then used to determine whether CIPN was an independent determinant of the measures of executive function (Trails-B, Stroop Incongruent, and RRA). Models were adjusted for age, sex, history of anxiety, and benzodiazepine use due to their known associations with CIPN and executive function. RESULTS: Cancer survivors with CIPN (CIPN+) had reduced executive function compared to survivors without CIPN (CIPN-) on Trails-B (CIPN+: 84.9 s ± 44.1 s, CIPN-: 59.1 s ± 22.5 s, p = 0.01), Stroop (CIPN+: 100.6 s ± 38.2 s, CIPN-: 82.1 s ± 17.3 s, p = 0.03), and RRA (CIPN+: 60.3% ± 12.9%, CIPN-: 70.6% ± 15.7%, p = 0.01). There were no differences in cancer stage severity or functional status by patient report or sit-to-stand function. The association between CIPN and reduced executive function was found in multivariable models after adjusting for age, sex, anxiety, and benzodiazepine use for Trails-B (ß:17.9, p = 0.046), Stroop (ß:16.9, p = 0.02), and RRA (ß:-0.072, p = 0.03). DISCUSSION: In this population, CIPN is associated with reduced executive function in older cancer survivors treated with chemotherapy. Future research is required to further understand this preliminary association, the causality, and the potential risk factors.

Platelets, coagulation and fibrinolysis in breast cancer progression.

The progression of breast cancer from early-stage to metastatic disease results from a series of events during which malignant cells invade and travel within the bloodstream to distant sites, leading to a clonogenic accumulation of tumor cells in non-breast tissue. While mechanistically complex, an emerging literature supports hemostatic elements as an important patient factor that facilitates the metastatic potential of breast cancer. Hemostatic elements involved include platelets, coagulation, and fibrinolysis. Key steps in breast tumor progression, including cellular transformation, proliferation, tumor cell survival, and angiogenesis, can be mediated by components of the hemostatic system. Thus, the hemostatic system provides potential targets for novel therapeutic approaches to breast cancer therapy with drugs in current use and in development. The present article provides a comprehensive overview of the evidence and mechanisms supporting the roles played by platelets, coagulation activation, and the fibrinolytic system in breast cancer progression.

Skeletal muscle adaptations to cancer and its treatment: their fundamental basis and contribution to functional disability.

Cancer is a physically disabling condition. Functional disability, defined as an inability or impaired ability to perform simple tasks of daily life, afflicts a large majority of the cancer population and dramatically impacts patient well-being, negatively affecting treatment decisions, quality of life, and clinical outcomes. Our current understanding of the fundamental mechanisms underlying physical disability in cancer patients, however, is limited. This review will evaluate how cancer and cancer treatments and their pathological sequelae alter skeletal muscle structure and function to promote functional disability. Briefly, factors associated with cancer and its treatment can diminish skeletal muscle size and contractile function, which lead to a reduced physiological capacity for work and, in turn, functional disability. We outline the clinical evidence for the involvement of each of these factors in disability in cancer patients and then review structural and functional evidence at various anatomic levels to explore the tissue, cellular, and molecular mechanisms underlying cancer-related disability.

Mammographic screening interval in relation to tumor characteristics and false-positive risk by race/ethnicity and age.

BACKGROUND: Biennial screening mammography retains most of the benefits of annual breast cancer screening with reduced harms. Whether screening guidelines based on race/ethnicity and age would be more effective than age-based guidelines is unknown. METHODS: Mammography data from the Breast Cancer Surveillance Consortium were linked to pathology and tumor databases. The authors identified women aged 40 to 74 years who underwent annual, biennial, or triennial screening mammography between 1994 and 2008. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of adverse tumor characteristics among 14,396 incident breast cancer cases and 10-year cumulative risks of false-positive recall and biopsy recommendation among 1,276,312 noncases. RESULTS: No increased risk of adverse tumor characteristics associated with biennial versus annual screening were noted in white women, black women, Hispanic women aged 40 to 49 years, or Asian women aged 50 to 74 years. Hispanic women aged 50 to 74 years who screened biennially versus annually were found to have an increased risk of late-stage disease (OR, 1.6; 95% CI, 1.0-2.5) and large tumors (OR, 1.6; 95% CI, 1.1-2.4). Asian women aged 40 to 49 years who underwent biennial screening had an elevated risk of positive lymph nodes (OR, 3.1; 95% CI, 1.3-7.1). No elevated risks were associated with triennial versus biennial screening. Cumulative false-positive risks decreased markedly with a longer screening interval. CONCLUSIONS: The authors found limited evidence of elevated risks of adverse tumor characteristics with biennial versus annual screening, whereas cumulative false-positive risks were lower. However, elevated risks of late-stage disease in Hispanic women and lymph node-positive disease in younger Asian women who screened less often than annually warrant consideration and replication.

Impact of mammography screening interval on breast cancer diagnosis by menopausal status and BMI.

BACKGROUND: Controversy remains regarding the frequency of screening mammography. Women with different risks for developing breast cancer because of body mass index (BMI) may benefit from tailored recommendations. OBJECTIVE: To determine the impact of mammography screening interval for women who are normal weight (BMI < 25), overweight (BMI 25-29.9), or obese (BMI ≥ 30), stratified by menopausal status. DESIGN: Two cohorts selected from the Breast Cancer Surveillance Consortium. Patient and mammography data were linked to pathology databases and tumor registries. PARTICIPANTS: The cohort included 4,432 women aged 40-74 with breast cancer; the false-positive analysis included a cohort of 553,343 women aged 40-74 without breast cancer. MAIN MEASURES: Stage, tumor size and lymph node status by BMI and screening interval (biennial vs. annual). Cumulative probability of false-positive recall or biopsy by BMI and screening interval. Analyses were stratified by menopausal status. KEY RESULTS: Premenopausal obese women undergoing biennial screening had a non-significantly increased odds of a tumor size > 20 mm relative to annual screeners (odds ratio [OR] = 2.07; 95 % confidence interval [CI] 0.997 to 4.30). Across all BMI categories from normal to obese, postmenopausal women with breast cancer did not present with higher stage, larger tumor size or node positive tumors if they received biennial rather than annual screening. False-positive recall and biopsy recommendations were more common among annually screened women. CONCLUSION: The only negative outcome identified for biennial vs. annual screening was a larger tumor size (> 20 mm) among obese premenopausal women. Since annual mammography does not improve stage at diagnosis compared to biennial screening and false-positive recall/biopsy rates are higher with annual screening, women and their primary care providers should weigh the harms and benefits when deciding on annual versus biennial screening.

Physical function in older adults with and without a cancer history: Findings from the National Health and Aging Trends Study.

BACKGROUND: Previous studies identified physical function limitations in older cancer survivors, but few have included objective measures and most focused on breast and prostate cancer survivors. The current study compared patient-reported and objective physical function measures between older adults with and without a cancer history. METHODS: Our cross-sectional study used a nationally representative sample of community-dwelling, Medicare beneficiaries from the 2015 National Health and Aging Trends Study (n = 7495). Data collected included patient-reported physical function, including a composite physical capacity score and limitations in strength, mobility, and balance, and objectively measured physical performance metrics, including gait speed, five time sit-to-stand, tandem stand, and grip strength. All analyses were weighted to account for the complex sampling design. RESULTS: Thirteen percent of participants (n = 829) reported a history of cancer, of which more than half (51%) reported a diagnosis other than breast or prostate cancer. In models adjusted for demographics and health history, older cancer survivors had lower Short Physical Performance Battery scores (unstandardized beta [B] = -0.36; 95% CI: -0.64, -0.08), slower gait speed (B = -0.03; 95% CI: -0.05, -0.01), reduced grip strength (B = -0.86; 95% CI: -1.44, -0.27), worse patient-reported composite physical capacity (B = -0.43; 95% CI: -0.67, -0.18) and patient-reported upper extremity strength (B = 1.27; 95% CI: 1.07, 1.50) compared to older adults without cancer. Additionally, the burden of physical function limitations was greater in women than in men, which may be explained by cancer type. CONCLUSIONS: Our results extend studies in breast and prostate cancer to show worse objective and patient-reported physical function outcomes in older adults with a range of cancer types compared to those without a cancer history. Moreover, these burdens seem to disproportionately affect older adult women, underscoring the need for interventions to address functional limitations and prevent further health consequences of cancer and its treatment.

Skeletal muscle adaptations in patients with lung cancer: Longitudinal observations from the whole body to cellular level.

BACKGROUND: Cancer and its treatment can adversely affect skeletal muscle, impacting physical function, treatment response and survival. No studies, however, have comprehensively characterized these muscle adaptations longitudinally in human patients at the cellular level. METHODS: We examined skeletal muscle size and function from the whole body to the sub-cellular level in 11 patients with non-small cell lung cancer (NSCLC; 6 male/5 female, mean age 58 ± 3 years) studied over a 2-month observation period starting during their first cycle of standard of care cancer treatment and in 11 age- and sex-matched healthy controls (HC) without a current or past history of cancer. Biopsies of the vastus lateralis were performed to assess muscle fibre size, contractility and mitochondrial content, along with assessments of physical function, whole muscle size and function, and circulating cytokines. RESULTS: Body weight, composition and thigh muscle area and density were unaltered over time in patients with NSCLC, while muscle density was lower in patients with NSCLC versus HC (P = 0.03). Skeletal muscle fibre size decreased by 18% over time in patients (all P = 0.02) and was lower than HC (P = 0.02). Mitochondrial fractional area and density did not change over time in patients, but fractional area was lower in patients with NSCLC compared with HC (subsarcolemmal, P = 0.04; intermyofibrillar, P = 0.03). Patients with NSCLC had higher plasma concentrations of IL-6 (HC 1.40 ± 0.50; NSCLC 4.71 ± 4.22; P < 0.01), GDF-15 (HC 569 ± 166; NSCLC 2071 ± 1168; P < 0.01) and IL-8/CXCL8 (HC 4.9 ± 1.8; NSCLC 10.1 ± 6.0; P = 0.02) compared with HC, but there were no changes in inflammatory markers in patients with NSCLC over time. No changes were observed in markers of satellite cell activation or DNA damage in patients and no group differences were noted with HC. Whole-muscle strength was preserved over time in patients with NSCLC coincident with improved single fibre contractility. CONCLUSIONS: This study is the first to comprehensively examine longitudinal alterations in skeletal muscle fibre size and function in patients with NSCLC and suggests that muscle fibre atrophy occurs during cancer treatment despite weight stability and no changes in conventional clinical measurements of whole body or thigh muscle size over this period.

Executive function is associated with balance and falls in older cancer survivors treated with chemotherapy: A cross-sectional study.

INTRODUCTION: Balance decrements and increased fall risk in older cancer survivors have been attributed to chemotherapy-induced peripheral neuropathy (CIPN). Cognition is also affected by chemotherapy and may be an additional contributing factor to poor balance through changes in executive functioning. We examined the association of executive function with balance and falls in older cancer survivors who had been treated with chemotherapy. MATERIALS AND METHODS: Fifty cancer survivors (aged 65.6 ± 11.5 years; 88% female) who were all treated with chemotherapy were included in this cross-sectional study at a tertiary medical center. Executive function was measured by Trails-B, Stroop, and rapid reaction accuracy, a measure emphasizing rapid inhibitory function. Balance was measured by five sit-to-stand time (5STS), repetitions of sit-to-stand in thirty seconds (STS30), and unipedal stance time (UST), which was the primary balance outcome measure. Self-reported falls in the past year were also recorded and was a secondary outcome. Bivariate analyses were conducted between executive function measures and balance variables. Multivariable models were constructed for UST and falls outcomes and included covariates of age and chemotherapy induced peripheral neuropathy status. RESULTS: Pearson correlations demonstrated significant relationships between two executive function measures (rapid reaction accuracy, Trails-B) and all the balance measures assessed (UST, STS30, and 5STS). Rapid reaction accuracy correlations were stronger than Trails-B. The Stroop measure correlated solely with UST. In multivariable models, rapid reaction accuracy was associated with better UST (standardized regression coefficient: 64.1, p < 0.01), decreased any fall (odds ratio = 0.000901, p = 0.04), and decreased recurrent falls (odds ratio = 0.0000044, p = 0.01). The interaction of CIPN with the inhibitory measures in the prediction of balance was not significant. DISCUSSION: Measures of executive function were associated with balance, but among the executive function tests, rapid reaction accuracy had the strongest correlations to balance and was independently associated with falls. The findings suggest that executive function should be considered when assessing fall risk and developing interventions intended to reduce fall risk in older chemotherapy-treated cancer survivors.