Catherine M. Alfano

Physical Activity, Biomarkers, and Disease Outcomes in Cancer Survivors: A Systematic Review

BACKGROUND Cancer survivors often seek information about how lifestyle factors, such as physical activity, may influence their prognosis. We systematically reviewed studies that examined relationships between physical activity and mortality (cancer-specific and all-cause) and/or cancer biomarkers. METHODS We identified 45 articles published from January 1950 to August 2011 through MEDLINE database searches that were related to physical activity, cancer survival, and biomarkers potentially relevant to cancer survival. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement to guide this review. Study characteristics, mortality outcomes, and biomarker-relevant and subgroup results were abstracted for each article that met the inclusion criteria (ie, research articles that included participants with a cancer diagnosis, mortality outcomes, and an assessment of physical activity). RESULTS There was consistent evidence from 27 observational studies that physical activity is associated with reduced all-cause, breast cancer-specific, and colon cancer-specific mortality. There is currently insufficient evidence regarding the association between physical activity and mortality for survivors of other cancers. Randomized controlled trials of exercise that included biomarker endpoints suggest that exercise may result in beneficial changes in the circulating level of insulin, insulin-related pathways, inflammation, and, possibly, immunity; however, the evidence is still preliminary. CONCLUSIONS Future research directions identified include the need for more observational studies on additional types of cancer with larger sample sizes; the need to examine whether the association between physical activity and mortality varies by tumor, clinical, or risk factor characteristics; and the need for research on the biological mechanisms involved in the association between physical activity and survival after a cancer diagnosis. Future randomized controlled trials of exercise with biomarker and cancer-specific disease endpoints, such as recurrence, new primary cancers, and cancer-specific mortality in cancer survivors, are warranted.

Cancer Survivors: A Booming Population

Background: In this first article of what is planned to be an annual series, we examine the history of cancer prevalence reporting and the role that these annual figures play in guiding the direction of cancer control research, and specifically the science of cancer survivorship. For this inaugural year, we focus on the confluence of the growing number of survivors and population aging, and the impact these combined trends will have on cancer survivorship in the future. Methods: State or metro area-level cancer incidence and prevalence data were collected from 9 registries via the Surveillance, Epidemiology, and End Results Program. The complete prevalence method was used to estimate prevalence for 2008 and the Prevalence, Incidence Approach Model method was used to project prevalence data through 2020, assuming flat cancer incidence and survival trends but dynamic U.S. population projections. Results: As of January 2008, the number of cancer survivors is estimated at 11.9 million. Approximately 60% of cancer survivors are age 65 or older, and by the year 2020, it is estimated that 63% of cancer survivors will be age 65 or older. Conclusions: Improved survival and population aging converge to generate a booming population of older adult cancer survivors, many of whom have multiple complex health conditions and unique survivorship needs. This demographic shift has important implications for future health care needs and costs of the U.S. population. Impact: The findings provide information critical for guiding cancer prevention and control research and service provision. Cancer Epidemiol Biomarkers Prev; 20(10); 1996–2005. ©2011 AACR.

American Society of Clinical Oncology Position Statement on Obesity and Cancer

Rates of obesity have increased significantly over the last three decades in the United States and globally. In addition to contributing to heart disease and diabetes, obesity is a major unrecognized risk factor for cancer. Obesity is associated with worsened prognosis after cancer diagnosis and also negatively affects the delivery of systemic therapy, contributes to morbidity of cancer treatment, and may raise the risk of second malignancies and comorbidities. Research shows that the time after a cancer diagnosis can serve as a teachable moment to motivate individuals to adopt risk-reducing behaviors. For this reason, the oncology care team--the providers with whom a patient has the closest relationships in the critical period after a cancer diagnosis--is in a unique position to help patients lose weight and make other healthy lifestyle changes. The American Society of Clinical Oncology is committed to reducing the impact of obesity on cancer and has established a multipronged initiative to accomplish this goal by 1) increasing education and awareness of the evidence linking obesity and cancer; 2) providing tools and resources to help oncology providers address obesity with their patients; 3) building and fostering a robust research agenda to better understand the pathophysiology of energy balance alterations, evaluate the impact of behavior change on cancer outcomes, and determine the best methods to help cancer survivors make effective and useful changes in lifestyle behaviors; and 4) advocating for policy and systems change to address societal factors contributing to obesity and improve access to weight management services for patients with cancer.

Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial.

Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N = 118), aerobic exercise (225 min/wk of moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte, and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity, and age. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53-1.31, P < 0.001) in the diet and 0.87 mg/L (0.51-1.23, P < 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13-0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15-0.49, P < 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 × 10(9)/L (0.09-0.54, P = 0.006) in the diet and 0.30 × 10(9)/L (0.09-0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with controls. The diet and diet + exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.

Mental and Physical Health–Related Quality of Life among U.S. Cancer Survivors: Population Estimates from the 2010 National Health Interview Survey

Background: Despite extensive data on health-related quality of life (HRQOL) among cancer survivors, we do not yet have an estimate of the percentage of survivors with poor mental and physical HRQOL compared with population norms. HRQOL population means for adult-onset cancer survivors of all ages and across the survivorship trajectory also have not been published. Methods: Survivors (N = 1,822) and adults with no cancer history (N = 24,804) were identified from the 2010 National Health Interview Survey. The PROMIS® Global Health Scale was used to assess HRQOL. Poor HRQOL was defined as 1 SD or more below the PROMIS® population norm. Results: Poor physical and mental HRQOL were reported by 24.5% and 10.1% of survivors, respectively, compared with 10.2% and 5.9% of adults without cancer (both P < 0.0001). This represents a population of approximately 3.3 million and 1.4 million U.S. survivors with poor physical and mental HRQOL. Adjusted mean mental and physical HRQOL scores were similar for breast, prostate, and melanoma survivors compared with adults without cancer. Survivors of cervical, colorectal, hematologic, short-survival, and other cancers had worse physical HRQOL; cervical and short-survival cancer survivors reported worse mental HRQOL. Conclusion: These data elucidate the burden of cancer diagnosis and treatment among U.S. survivors and can be used to monitor the impact of national efforts to improve survivorship care and outcomes. Impact: We present novel data on the number of U.S. survivors with poor HRQOL. Interventions for high-risk groups that can be easily implemented are needed to improve survivor health at a population level. Cancer Epidemiol Biomarkers Prev; 21(11); 2108–17. ©2012 AACR.

Survivors of Childhood Cancer in the United States: Prevalence and Burden of Morbidity

Background: No studies have estimated the population-level burden of morbidity in individuals diagnosed with cancer as children (ages 0–19 years). We updated prevalence estimates of childhood cancer survivors as of 2011 and burden of morbidity in this population reflected by chronic conditions, neurocognitive dysfunction, compromised health-related quality of life, and health status (general health, mental health, functional impairment, functional limitations, pain, and fear/anxiety). Methods: Surveillance, Epidemiology, and End Results (SEER) Program data from 1975 to 2011 were used to update the prevalence of survivors of childhood cancers in the United States. Childhood Cancer Survivor Study data were used to obtain estimates of morbidity burden indicators, which were then extrapolated to SEER data to obtain population-level estimates. Results: There were an estimated 388,501 survivors of childhood cancer in the United States as of January 1, 2011, of whom 83.5% are ≥5 years after diagnosis. The prevalence of any chronic condition among ≥5-year survivors ranged from 66% (ages 5–19) to 88% (ages 40–49). Estimates for specific morbidities ranged from 12% (pain) to 35% (neurocognitive dysfunction). Generally, morbidities increased by age. However, mental health and anxiety remained fairly stable, and neurocognitive dysfunction exhibited initial decline and then remained stable by time since diagnosis. Conclusions: The estimated prevalence of survivors of childhood cancer is increasing, as is the estimated prevalence of morbidity in those ≥5 years after diagnosis. Impact: Efforts to understand how to effectively decrease morbidity burden and incorporate effective care coordination and rehabilitation models to optimize longevity and well-being in this population should be a priority. Cancer Epidemiol Biomarkers Prev; 24(4); 653–63. ©2015 AACR.

Exercise-oncology research: Past, present, and future

Abstract Significant progress has been made in the field of exercise-oncology research over the past two decades. As the field continues to forge ahead, it is time to reflect on past accomplishments in order to inform and define the critical unanswered questions postulated to have the largest impact on the field and on clinical care. Against this background, we overview the extant literature base together with ongoing/planned studies examining the role of exercise therapy following a cancer diagnosis with a view towards identifying major gaps in the knowledge. Method. We adapted the Physical Exercise Across the Cancer Experience (PEACE) organizational framework to systematically overview published as well as ongoing studies of exercise therapy across the cancer survivorship continuum [i.e. 1) pretreatment; 2) during treatment; and 3) post-treatment]. To overview ongoing studies, we performed a systematic review of all exercise trials in adult cancer patients registered in Clinical Trials.Gov and the International Standard Randomized Controlled Trial Number Register. Results. Data from published studies provides relatively strong evidence that exercise therapy is a well-tolerated and safe adjunct therapy that can mitigate several common treatment-related side effects among cancer patients across the PEACE framework. In addition, observational studies suggest that higher levels of exercise may be associated with improved prognosis in patients with solid tumors. Regarding ongoing studies, a total of 82 independent clinical studies were identified. Consistent with prior work, most ongoing studies are being conducted either during or following adjuvant therapy in women with breast cancer with exercise interventions following standard exercise prescription guidelines. Across all studies, there were a total of approximately 51 different primary endpoints; in two-thirds of studies, quality of life, fatigue, or physical functioning was the primary endpoint. Conclusion. There have been significant leaps in knowledge regarding the role and efficacy of exercise therapy in cancer survivors over the past 25 years. On the platform of this evidence base, it is now time to launch the next generation of research to ensure continued progress in this emergent field. This work will continue to contribute to the ultimate goal of improving both the quantity and quality of life of persons diagnosed with cancer.

Dietary weight loss and exercise interventions effects on quality of life in overweight/obese postmenopausal women: a randomized controlled trial

BackgroundAlthough lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior, few studies have compared individual and combined effects of diet and/or exercise interventions on health-related quality of life (HRQOL). In addition, the mechanisms of how these lifestyle interventions affect HRQOL are unknown. The primary aim of this study was to examine the individual and combined effects of dietary weight loss and/or exercise interventions on HRQOL and psychosocial factors (depression, anxiety, stress, social support). The secondary aim was to investigate predictors of changes in HRQOL.MethodsThis study was a randomized controlled trial. Overweight/obese postmenopausal women were randomly assigned to 12 months of dietary weight loss (n = 118), moderate-to-vigorous aerobic exercise (225 minutes/week, n = 117), combined diet and exercise (n = 117), or control (n = 87). Demographic, health and anthropometric information, aerobic fitness, HRQOL (SF-36), stress (Perceived Stress Scale), depression [Brief Symptom Inventory (BSI)-18], anxiety (BSI-18) and social support (Medical Outcome Study Social Support Survey) were assessed at baseline and 12 months. The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance, adjusting for baseline scores. Multiple regression was used to assess predictors of changes in HRQOL.ResultsTwelve-month changes in HRQOL and psychosocial factors differed by intervention group. The combined diet + exercise group improved 4 aspects of HRQOL (physical functioning, role-physical, vitality, and mental health), and stress (p ≤ 0.01 vs. controls). The diet group increased vitality score (p < 0.01 vs. control), while HRQOL did not change differently in the exercise group compared with controls. However, regardless of intervention group, weight loss predicted increased physical functioning, role-physical, vitality, and mental health, while increased aerobic fitness predicted improved physical functioning. Positive changes in depression, stress, and social support were independently associated with increased HRQOL, after adjusting for changes in weight and aerobic fitness.ConclusionsA combined diet and exercise intervention has positive effects on HRQOL and psychological health, which may be greater than that from exercise or diet alone. Improvements in weight, aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.Trial RegistrationClinical Trials, ClinicalTrials.gov register, NCT00470119

Parental cancer and the family: a population-based estimate of the number of US cancer survivors residing with their minor children.

Cancer diagnosis and treatment of a parent has considerable impact on the lives of their minor children, family caregivers, and patients themselves. Understanding the number and characteristics of the population of cancer survivors with children younger than 18 years of age would help to better target services for these survivors and their children and to stimulate and inform research on these understudied families.

Risk factors for smoking among adolescents with asthma

PURPOSE To examine the prevalence of smoking among youth with asthma and explore potential risk factors for smoking among these youth, compared with youth without asthma. METHODS In March 1997, a questionnaire assessing risk factors for smoking was administered to students attending public high school in Memphis, Tennessee. The sample (n = 3234) ranged from 15 to 18 years of age, was predominately African-American (76.7%), and 56.7% female. Based on a single self-reported item, 15.7% of youth reported having asthma. Logistic regression analyses assessed asthma status differences in current smoking and the association between risk factors and smoking. RESULTS Nearly 20% of youth reported current smoking. Adolescents with asthma (current or past) were nearly 1.5 times more likely to smoke than peers without asthma. The association between risk factors and current cigarette smoking was equivalent for youth regardless of whether they had asthma and did not differ for those youth with current vs. past asthma. CONCLUSIONS Results suggest that adolescents with or without asthma smoke for similar reasons. Research is needed to elucidate whether there are unique risk factors, not examined here, for smoking among adolescents with asthma. Smoking prevention and cessation programs are needed for youth with asthma.