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.

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.

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.

Exercise-based oncology rehabilitation: leveraging the cardiac rehabilitation model.

PURPOSE: The value of exercise and rehabilitative interventions for cancer survivors is increasingly clear, and oncology rehabilitation programs could provide these important interventions. However, a pathway to create oncology rehabilitation has not been delineated. Community-based cardiac rehabilitation (CR) programs staffed by health care professionals with experience in providing rehabilitation and secondary prevention services to individuals with coronary heart disease are widely available and provide a potential model and location for oncology rehabilitation programs. Our purpose was to outline the rehabilitative needs of cancer survivors and demonstrate how oncology rehabilitation can be created using a CR model. METHODS: We identify the impairments associated with cancer and its therapy that respond to rehabilitative interventions. Components of the CR model that would benefit cancer survivors are described. An example of an oncology rehabilitation program using a CR model is presented. RESULTS: Cancer survivors have impairments associated with cancer and its therapy that improve with rehabilitation. Our experience demonstrates that effective rehabilitation services can be provided utilizing an existing CR infrastructure. Few adjustments to current CR models would be needed to provide oncology rehabilitation. Preliminary evidence suggests that cancer survivors participating in an oncology rehabilitation program experience improvements in psychological and physiologic parameters. CONCLUSIONS: Utilizing the CR model of rehabilitative services and disease management provides a much needed mechanism to bring oncology rehabilitation to larger numbers of cancer survivors.

Quantitative and morphologic change associated with breast cancer-related lymphedema. Comparison of 3.0T MRI to external measures.

UNLABELLED: Abstract Introduction: Lymphedema is a chronic disease of increasing importance to cancer survivors. A tape measurement tool used for lymphedema relies on indirect volume calculations based on external circumference, which may not reflect the true extent of abnormal fluid accumulation accurately. Fluid-sensitive MRI sequences may be able to delineate the severity of this condition more precisely and thus also monitor response to therapy. METHODS AND RESULTS: Eight patients being followed by physical therapy for clinically diagnosed breast cancer-related lymphedema were recruited to participate in this study. External measurements and upper extremity MRI were performed on all subjects. Arm circumference, arm volume, and lymphedema volumes were calculated for each method. MR imaging detected lymphedema in all study subjects. Correlation was found between external circumferential measurements and with the 3.0T MRI (r=0.9368). There was poor correlation between lymphedema volumes calculated from clinical measurements and MR imaging (r=0.5539). CONCLUSIONS: External measurements were not found to be an accurate measure of lymphedema volume associated with breast cancer lymphedema. MRI is a reliable means to obtain upper extremity circumferential and volume measurements. MRI is able to evaluate morphologic change associated with breast cancer-related lymphedema. Lymphedema research requires integrated use of tools to further describe the disease process over time, quantitate the distribution of tissue changes, and improve the sensitivity and specificity of the measurements.

Primary Care Provider Evaluation of Cancer Survivorship Care Plans Developed for Patients in their Practice.

OBJECTIVE: Survivorship care plans (SCP), which describe a cancer survivor's diagnosis, treatment and follow-up, are recommended. The study objective was to evaluate primary care providers' (PCP) responses to SCPs developed for breast and colorectal cancer survivors in their practice and to determine whether PCP response to the SCPs varied according to characteristics of the practitioner and their practice. METHOD: SCPs were created using the Journey Forward® Care Plan for breast and colorectal cancer patients in rural and urban settings. The SCP and a survey were sent to PCPs. PARTICIPANTS: Primary care physicians. MAIN MEASURES: Attitudes regarding survivorship care plans. RESULTS: Thirty-nine (70.9% response rate) surveys were completed. Most felt the SCP was useful (90%), that it enhanced understanding (75%) and that detail was sufficient (>80%). However, 15% disagreed that the care plan helped them understand their role, a perception especially prevalent among PCPs in the rural setting. Among PCPs with ≤ 18 years in practice, 95% agreed that the SCP would improve communication with patients, contrasted with 60% of those with >21 years in practice. The most common barrier to providing follow-up care was limited access to survivors. CONCLUSIONS: While SCPs appear to improve PCPs understanding of a cancer diagnosis and treatment, clear delineation of each provider's role in follow-up care is needed. Additional detail on which tests are needed and education on late and long term effects of cancer may improve coordination of care.

Barriers and facilitators to implementing cancer survivorship care plans.

PURPOSE/OBJECTIVES: To evaluate the process of survivorship care plan (SCP) completion and to survey oncology staff and primary care physicians (PCPs) regarding challenges of implementing SCPs. DESIGN: Descriptive pilot study. SETTING: Two facilities in Vermont, an urban academic medical center and a rural community academic cancer center. SAMPLE: 17 oncology clinical staff created SCPs, 39 PCPs completed surveys, and 58 patients (breast or colorectal cancer) participated in a telephone survey. METHODS: Using Journey Forward tools, SCPs were created and presented to patients. PCPs received the SCP with a survey assessing its usefulness and barriers to delivery. Oncology staff were interviewed to assess perceived challenges and benefits of SCPs. Qualitative and quantitative data were used to identify challenges to the development and implementation process as well as patient perceptions of the SCP visit. MAIN RESEARCH VARIABLES: SCP, healthcare provider perception of barriers to completion and implementation, and patient perception of SCP visit. FINDINGS: Oncology staff cited the time required to obtain information for SCPs as a challenge. Completing SCPs 3-6 months after treatment ended was optimal. All participants felt advanced practice professionals should complete and review SCPs with patients. The most common challenge for PCPs to implement SCP recommendations was insufficient knowledge of cancer survivor issues. Most patients found the care plan visit very useful, particularly within six months of diagnosis. CONCLUSIONS: Creation time may be a barrier to widespread SCP implementation. Cancer survivors find SCPs useful, but PCPs feel insufficient knowledge of cancer survivor issues is a barrier to providing best follow-up care. Incorporating SCPs in electronic medical records may facilitate patient identification, appropriate staff scheduling, and timely SCP creation. IMPLICATIONS FOR NURSING: Oncology nurse practitioners are well positioned to create and deliver SCPs, transitioning patients from oncology care to a PCP in a shared-care model of optimal wellness. Institution support for the time needed for SCP creation and review is imperative for sustaining this initiative. KNOWLEDGE TRANSLATION: Accessing complete medical records is an obstacle for completing SCPs. A 3-6 month window to develop and deliver SCPs may be ideal. PCPs perceive insufficient knowledge of cancer survivor issues as a barrier to providing appropriate follow-up care.

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.

Patient satisfaction with breast and colorectal cancer survivorship care plans.

Cancer survivors face several challenges following the completion of active treatment, including uncertainty about late effects of treatment and confusion about coordination of follow-up care. The authors evaluated patient satisfaction with personalized survivorship care plans designed to clarify those issues. The authors enrolled 48 patients with breast cancer and 10 patients with colorectal cancer who had completed treatment in the previous two months from an urban academic medical center and a rural community hospital. Patient satisfaction with the care plan was assessed by telephone interview. Overall, about 80% of patients were very or completely satisfied with the care plan, and 90% or more agreed that it was useful, it was easy to understand, and the length was appropriate. Most patients reported that the care plan was very or critically important to understanding an array of survivorship issues. However, only about half felt that it helped them better understand the roles of primary care providers and oncologists in survivorship care. The results provide evidence that patients with cancer find high value in personalized survivorship care plans, but the plans do not eliminate confusion regarding the coordination of follow-up care. Future efforts to improve care plans should focus on better descriptions of how survivorship care will be coordinated.