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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.
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Antineoplásicos , Supervivientes de Cáncer , Función Ejecutiva , Enfermedades del Sistema Nervioso Periférico , Humanos , Femenino , Masculino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Estudios Transversales , Supervivientes de Cáncer/psicología , Anciano , Función Ejecutiva/efectos de los fármacos , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológicoRESUMEN
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.
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Supervivientes de Cáncer , Neoplasias , Enfermedades del Sistema Nervioso Periférico , Humanos , Femenino , Anciano , Masculino , Función Ejecutiva , Estudios Transversales , Accidentes por Caídas , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Neoplasias/tratamiento farmacológicoRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Músculo Esquelético/patología , Fibras Musculares Esqueléticas/patología , Fuerza MuscularRESUMEN
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.
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Medicare , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos/epidemiología , Estudios Transversales , Envejecimiento , Velocidad al CaminarRESUMEN
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.
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Ejercicio Físico , Esfuerzo Físico , Humanos , Anciano , Esfuerzo Físico/fisiología , Frecuencia Cardíaca/fisiología , Prueba de EsfuerzoRESUMEN
Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies.
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Neoplasias de la Mama , Sustancia Gris , Humanos , Femenino , Sustancia Gris/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , EnvejecimientoRESUMEN
PURPOSE: The study aimed to determine the feasibility of remotely delivered exercise (tele-exercise) for older, rural cancer survivors and to explore the effects of tele-exercise on physical function, physical activity, and patient-reported outcomes. METHODS: Participants were rural cancer survivors age ≥ 60 years (79% female; mean age 70.4 ± 5.7) randomly assigned to the remotely delivered EnhanceFitness (tele-EF) exercise program, inclusive of aerobic, strength, and balance training and led by American Council on Exercise certified instructors for 1 h, 3 days/week for 16 weeks (n = 20) or to a waitlist control group (n = 19). We assessed feasibility, physical function, accelerometer-measured physical activity, and patient-reported outcomes at baseline and post intervention. RESULTS: Among those screened as eligible, 44 (64%) consented to participate with 39 randomized after completing baseline measures. Attrition was equivalent between groups (n = 1, each) with 95% completing the study. The median class attendance rate was 86.9% (interquartile range: 79-94%). Compared to controls, tele-EF participants had statistically significant improvement in the five-time sit-to-stand test (- 3.4 vs. - 1.1 s, p = 0.03, effect size = 0.44), mean daily light physical activity (+ 38.5 vs 0.5 min, p = 0.03, effect size = 0.72) and step counts (+ 1977 vs. 33, p = 0.01, effect size = 0.96). There were no changes in self-efficacy for exercise, fatigue, or sleep disturbance between groups. CONCLUSIONS: Findings indicate that tele-EF is feasible in older, rural cancer survivors and results in positive changes in physical function and physical activity. IMPLICATIONS FOR CANCER SURVIVORS: Tele-EF addresses common barriers to exercise for older, rural cancer survivors, including limited accessible opportunities for professional instruction and supervision.
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PURPOSE: Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR). METHODS: This review details the immediate challenges faced by hematology and oncology during the cyberattack. The impact and response on inpatient, outpatient, and special patient populations are described. Steps that other academic- and community-based oncology practices can take to lessen the brunt of such an assault are suggested. RESULTS: The two areas of immediate impact after the cyberattack were communications and lack of EMR access. The oncology-specific impact included loss of the individualized EMR chemotherapy plan templates and electronic safeguards built into multistep treatment preparation and delivery. With loss of access to schedules, basic patient information, encrypted communications platforms and radiology, and laboratory and pharmacy services, clinical outpatient care delivery was reduced by 40%. The infusion visit volume dropped by 52% in the first week and new patients could not access necessary services for timely diagnostic evaluation, requiring the creation of command centers to oversee ethical and transparent triage and allocation of systemic therapies and address new patient referrals. This included appropriate transfer of patients to alternate sites to minimize delays. Inpatient care including transitions of care was particularly challenging and addressing patient populations whose survival might be affected by delays in care. CONCLUSION: Oncology health care leaders and providers should be aware of the potential impact of a cyberattack on cancer care delivery and preventively develop processes to mitigate the impact.
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Hematología , Neoplasias , Atención Ambulatoria , Humanos , Oncología Médica , Neoplasias/terapia , Derivación y ConsultaRESUMEN
Executive function (EF) impacts behavior associated with health outcomes. EF can be measured using self-report and/or performance measures, but the correlations between these types of measures are mixed in the extant literature. This study examined self-report and performance-based measures of EF using data from 6 studies, including community and clinical populations (410 participants, ages 19-80, 71% female). Partial correlations revealed significant relationships between performance on the Trail making, Delay Discounting, and Stop Signal tasks with self-reported EF (p < .006 after controlling for age). Mood scores were significantly related to all self-reported domains of EF (p < .0001), and mood and EF scores were correlated over time. When also controlling for mood, correlations between delay discounting and stop signal tasks with self-reported EF remained significant (p < .006). Finally, examining EF scores in participants with and without clinically elevated mood scores showed a wider distribution of self-reported EF scores among those with clinically elevated mood symptoms than among those without. We conclude that self-reported EF is associated with tasks measuring delay discounting and response inhibition in our large, heterogenous population and that assessing EF may be particularly important for those with high levels of mood symptoms.
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Función Ejecutiva , Análisis y Desempeño de Tareas , Adulto , Afecto/fisiología , Anciano , Anciano de 80 o más Años , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Adulto JovenRESUMEN
Exercise has numerous benefits for patients with cancer, but implementation is challenging because of practical and logistical hurdles. This study examined whether neuromuscular electrical stimulation (NMES) can serve as a surrogate for classic exercise by eliciting an exercise training response in skeletal muscle of women diagnosed with breast cancer undergoing chemotherapy. Patients (n = 22) with histologically confirmed stage I, II, or III breast cancer scheduled to receive neoadjuvant or adjuvant chemotherapy were randomized to 8 wk of bilateral neuromuscular electrical stimulation (NMES; 5 days/wk) to their quadriceps muscles or control. Biopsy of the vastus lateralis was performed at baseline and after 8 wk of intervention to assess muscle fiber size, contractility, and mitochondrial content. Seventeen patients (8 control/9 NMES) completed the trial and were included in analyses. NMES promoted muscle fiber hypertrophy (P < 0.001), particularly in fast-twitch, myosin heavy chain (MHC) IIA fibers (P < 0.05) and tended to induce fiber type shifts in MHC II fibers. The effects of NMES on single-muscle fiber contractility were modest, and it was unable to prevent declines in the function in MHC IIA fibers. NMES did not alter intermyofibrillar mitochondrial content/structure but was associated with reductions in subsarcolemmal mitochondria. Our results demonstrate that NMES induces muscle fiber hypertrophy and fiber type shifts in MHC II fibers but had minimal effects on fiber contractility and promoted reductions in subsarcolemmal mitochondria. Further studies are warranted to evaluate the utility of NMES as an exercise surrogate in cancer patients and other conditions.NEW & NOTEWORTHY This is the first study to evaluate whether neuromuscular electrical stimulation (NMES) can be used as an exercise surrogate to improve skeletal muscle fiber size or function in cancer patients receiving treatment. We show that NMES promoted muscle fiber hypertrophy and fiber type shifts but had minimal effects on single-fiber contractility and reduced subsarcolemmal mitochondria.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Estimulación Eléctrica , Femenino , Humanos , Contracción Muscular , Fibras Musculares Esqueléticas , Músculo Esquelético , Músculo CuádricepsRESUMEN
PURPOSE: We aimed to determine the effect of a health coach, text message, and Fitbit intervention on moderate-to-vigorous physical activity (MVPA) maintenance in cancer survivors following a supervised exercise program compared to provision of a Fitbit alone. METHODS: Participants were recruited during the last month of an exercise-based oncology rehabilitation program and randomly assigned to the full intervention (n = 34) or Fitbit-only control groups (n = 32). In total, 59 cancer survivors completed the program (81% female; mean age 61.4 ± 9.0). Group by time differences in accelerometer-measured MVPA was assessed using linear mixed models. Additionally, we examined mean weekly Fitbit-derived MVPA levels. RESULTS: Intervention participants maintained weekly MVPA from pre- (295.7 ± 139.6) to post-intervention (322.0 ± 199.4; p = 0.37), whereas those in the Fitbit-only group had a significant decrease in MVPA (305.5 ± 181.1 pre vs 250.7 ± 166.5 post; p = 0.03, effect size 0.57). The intervention participants maintained recommended levels of MPVA for health benefits during the 8-week intervention, whereas the Fitbit-only control group did not. CONCLUSIONS: The findings demonstrate that a remote intervention delivered through health coaching, text messages, and Fitbit can promote maintenance of MVPA after a structured program for cancer survivors. However, use of a Fitbit alone was not sufficient to prevent expected decline in MVPA. Additional research is warranted to examine long-term impacts and efficacy in a more diverse population of cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Use of a wearable tracker alone may not be sufficient for exercise maintenance among cancer survivors after transition to an independent program. Additional planning for relapse prevention is recommended.
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Supervivientes de Cáncer/psicología , Ejercicio Físico/psicología , Medios de Comunicación Sociales/normas , Envío de Mensajes de Texto/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
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.
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Supervivientes de Cáncer/psicología , Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Fuerza Muscular/fisiología , Neoplasias/rehabilitación , Entrenamiento de Fuerza/métodos , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
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Supervivientes de Cáncer/psicología , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Neoplasias/psicología , Neoplasias/rehabilitación , Adulto , Anciano , Terapia por Ejercicio , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Envío de Mensajes de TextoRESUMEN
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.
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Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Caquexia/genética , Atrofia Muscular/genética , Peroxiredoxina III/genética , Anciano , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Caquexia/inducido químicamente , Caquexia/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/inducido químicamente , Atrofia Muscular/patología , Miosinas/genética , Miosinas/metabolismo , Compuestos Organofosforados/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Ubiquinona/análogos & derivados , Ubiquinona/farmacologíaRESUMEN
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.
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Control de la Conducta , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/metabolismo , Supervivientes de Cáncer , Resistencia a la Insulina , Pérdida de Peso , Adulto , Biomarcadores , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Calidad de VidaRESUMEN
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.
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Antineoplásicos/efectos adversos , Monitoreo Fisiológico/métodos , Enfermedades del Sistema Nervioso Periférico/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermeras Practicantes , Enfermedades del Sistema Nervioso Periférico/patología , Estudios ProspectivosRESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Carcinoma Intraductal no Infiltrante/diagnóstico , Detección Precoz del Cáncer/métodos , Pruebas Genéticas/métodos , Adulto , Anciano , Neoplasias de la Mama/economía , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/economía , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/patología , Estudios de Cohortes , Análisis Costo-Beneficio , Progresión de la Enfermedad , Detección Precoz del Cáncer/economía , Femenino , Pruebas Genéticas/economía , Humanos , Mamografía/economía , Persona de Mediana Edad , Modelos Biológicos , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Sensibilidad y EspecificidadRESUMEN
Cancer survivors are at increased risk of chronic disease and diminished quality of life. The presence of overweight and obesity can exacerbate these health risks. Fortunately, even small weight losses have been found to produce clinically meaningful health outcomes. However, effective obesity treatment is difficult to access, and recently, efforts have been made to disseminate interventions using eHealth or distantly delivered technology. This review aims to focus on the efficacy and limitations of these technologies for female cancer survivors. Suggestions are also provided to encourage further meaningful work in this area.
Asunto(s)
Supervivientes de Cáncer/psicología , Obesidad/terapia , Calidad de Vida/psicología , Telemedicina/métodos , Pérdida de Peso , Índice de Masa Corporal , Manejo de la Enfermedad , Femenino , Humanos , Obesidad/psicologíaRESUMEN
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.