Kirsten K. Ness

Clinical ascertainment of health outcomes among adults treated for childhood cancer.

IMPORTANCE Adult survivors of childhood cancer are known to be at risk for treatment-related adverse health outcomes. A large population of survivors has not been evaluated using a comprehensive systematic clinical assessment to determine the prevalence of chronic health conditions. OBJECTIVE To determine the prevalence of adverse health outcomes and the proportion associated with treatment-related exposures in a large cohort of adult survivors of childhood cancer. DESIGN, SETTING, AND PARTICIPANTS Presence of health outcomes was ascertained using systematic exposure-based medical assessments among 1713 adult (median age, 32 [range, 18-60] years) survivors of childhood cancer (median time from diagnosis, 25 [range, 10-47] years) enrolled in the St Jude Lifetime Cohort Study since October 1, 2007, and undergoing follow-up through October 31, 2012. MAIN OUTCOMES AND MEASURES Age-specific cumulative prevalence of adverse outcomes by organ system. RESULTS Using clinical criteria, the crude prevalence of adverse health outcomes was highest for pulmonary (abnormal pulmonary function, 65.2% [95% CI, 60.4%-69.8%]), auditory (hearing loss, 62.1% [95% CI, 55.8%-68.2%]), endocrine or reproductive (any endocrine condition, such as hypothalamic-pituitary axis disorders and male germ cell dysfunction, 62.0% [95% CI, 59.5%-64.6%]), cardiac (any cardiac condition, such as heart valve disorders, 56.4% [95% CI, 53.5%-59.2%]), and neurocognitive (neurocognitive impairment, 48.0% [95% CI, 44.9%-51.0%]) function, whereas abnormalities involving hepatic (liver dysfunction, 13.0% [95% CI, 10.8%-15.3%]), skeletal (osteoporosis, 9.6% [95% CI, 8.0%-11.5%]), renal (kidney dysfunction, 5.0% [95% CI, 4.0%-6.3%]), and hematopoietic (abnormal blood cell counts, 3.0% [95% CI, 2.1%-3.9%]) function were less common. Among survivors at risk for adverse outcomes following specific cancer treatment modalities, the estimated cumulative prevalence at age 50 years was 21.6% (95% CI, 19.3%-23.9%) for cardiomyopathy, 83.5% (95% CI, 80.2%-86.8%) for heart valve disorder, 81.3% (95% CI, 77.6%-85.0%) for pulmonary dysfunction, 76.8% (95% CI, 73.6%-80.0%) for pituitary dysfunction, 86.5% (95% CI, 82.3%-90.7%) for hearing loss, 31.9% (95% CI, 28.0%-35.8%) for primary ovarian failure, 31.1% (95% CI, 27.3%-34.9%) for Leydig cell failure, and 40.9% (95% CI, 32.0%-49.8%) for breast cancer. At age 45 years, the estimated cumulative prevalence of any chronic health condition was 95.5% (95% CI, 94.8%-98.6%) and 80.5% (95% CI, 73.0%-86.6%) for a serious/disabling or life-threatening chronic condition. CONCLUSIONS AND RELEVANCE Among adult survivors of childhood cancer, the prevalence of adverse health outcomes was high, and a systematic risk-based medical assessment identified a substantial number of previously undiagnosed problems that are more prevalent in an older population. These findings underscore the importance of ongoing health monitoring for adults who survive childhood cancer.

Social Outcomes in the Childhood Cancer Survivor Study Cohort

Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.

Medical Care in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

PURPOSE To evaluate whether childhood cancer survivors receive regular medical care focused on the specific morbidities that can arise from their therapy. PATIENTS AND METHODS We conducted a cross-sectional survey of health care use in 8,522 participants in the Childhood Cancer Survivor Study, a multi-institutional cohort of childhood cancer survivors. We assessed medical visits in the preceding 2 years, whether these visits were related to the prior cancer, whether survivors received advice about how to reduce their long-term risks, and whether screening tests were discussed or ordered. Completion of echocardiograms and mammograms were assessed in patients at high risk for cardiomyopathy or breast cancer. We examined the relationship between demographics, treatment, health status, chronic medical conditions, and health care use. RESULTS Median age at cancer diagnosis was 6.8 years (range, 0 to 20.9 years) and at interview was 31.4 years (range, 17.5 to 54.1 years). Although 88.8% of survivors reported receiving some form of medical care, only 31.5% reported care that focused on their prior cancer (survivor-focused care), and 17.8% reported survivor-focused care that included advice about risk reduction or discussion or ordering of screening tests. Among survivors who received medical care, those who were black, older at interview, or uninsured were less likely to have received risk-based, survivor-focused care. Among patients at increased risk for cardiomyopathy or breast cancer, 511 (28.2%) of 1,810 and 169 (40.8%) of 414 had undergone a recommended echocardiogram or mammogram, respectively. CONCLUSION Despite a significant risk of late effects after cancer therapy, the majority of childhood cancer survivors do not receive recommended risk-based care.

Behavioral and Social Outcomes in Adolescent Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

PURPOSE Adolescents, regardless of medical history, may face behavioral and social challenges. Cancer and related treatments represent additional challenges for teens navigating the transition from childhood to adulthood. This study was conducted to evaluate behavioral and social outcomes of adolescent childhood cancer survivors using data from the Childhood Cancer Survivor Study. PATIENTS AND METHODS We evaluated 2,979 survivors and 649 siblings of cancer survivors to determine the incidence of difficulty in six behavioral and social domains (depression/anxiety, headstrong, attention deficit, peer conflict/social withdrawal, antisocial behaviors, and social competence). Outcomes were determined by calculating parent-reported scores to questions from the behavior problem index. RESULTS Survivors and siblings were similar in age at the time of interview (mean: 14.8, survivors; 14.9, siblings; range, 12 to 17 years). Overall, multivariate analyses showed that survivors were 1.5 times (99% CI, 1.1 to 2.1) more likely than siblings to have symptoms of depression/anxiety and 1.7 times (99% CI, 1.3 to 2.2) more likely to have antisocial behaviors. Scores in the depression/anxiety, attention deficit, and antisocial domains were significantly elevated in adolescents treated for leukemia or CNS tumors when compared with siblings. In addition, survivors of neuroblastoma had difficulty in the depression/anxiety and antisocial domains. Treatments with cranial radiation and/or intrathecal methotrexate were specific risk factors. CONCLUSION Adolescent survivors of childhood cancer, especially those with a history of leukemia, CNS tumors, or neuroblastoma, may be at increased risk for adverse behavioral and social outcomes. Increased surveillance of this population, in combination with development of interventional strategies, should be a priority.

Metabolic Syndrome and Growth Hormone Deficiency in Adult Survivors of Childhood Acute Lymphoblastic Leukemia

The purpose of the study was to determine the prevalence of metabolic syndrome, growth hormone deficiency, and cardiovascular risk factors among adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with or without cranial irradiation.

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.

Health Behaviors, Medical Care, and Interventions to Promote Healthy Living in the Childhood Cancer Survivor Study Cohort

Childhood cancer survivors are at risk for medical and psychosocial late effects as a result of their cancer and its therapy. Promotion of healthy lifestyle behaviors and provision of regular risk-based medical care and surveillance may modify the evolution of these late effects. This manuscript summarizes publications from the Childhood Cancer Survivor Study (CCSS) that have examined health behaviors, risk-based health care, and interventions to promote healthy lifestyle practices. Long-term survivors use tobacco and alcohol and have inactive lifestyles at higher rates than is ideal given their increased risk of cardiac, pulmonary, and metabolic late effects. Nearly 90% of survivors report receiving some form of medical care. However, only 18% report medical visits related to their prior cancer that include discussion or ordering of screening tests or counseling on how to reduce the specific risks arising from their cancer. One low-cost, peer-driven intervention trial has been successful in improving smoking cessation within the CCSS cohort. On the basis of data from CCSS investigations, several trials to promote improved medical surveillance among high-risk groups within the cohort are underway. Despite their long-term risks, many survivors of childhood cancer engage in risky health behaviors and do not receive adequate risk-based medical care.

Cardiovascular Risk Factors in Adult Survivors of Pediatric Cancer—A Report from the Childhood Cancer Survivor Study

Background: Childhood cancer survivors are at higher risk of morbidity and mortality from cardiovascular disease compared with the general population. Methods: Eight thousand five hundred ninety-nine survivors (52% male) and 2,936 siblings (46% male) from the Childhood Cancer Survivor Study, a retrospectively ascertained, prospectively followed study of persons who survived 5 years after childhood cancer diagnosed from 1970 to 1986, were evaluated for body mass index of ≥30 kg/m2 based on self-reported heights and weights and self-reported use of medications for hypertension, dyslipidemia, and impaired glucose metabolism. The presence of three or more of the above constituted Cardiovascular Risk Factor Cluster (CVRFC), a surrogate for Metabolic Syndrome. Results: Survivors were more likely than siblings to take medications for hypertension [odds ratio (OR), 1.9; 95% confidence interval (95% CI), 1.6-2.2], dyslipidemia (OR, 1.6; 95% CI, 1.3-2.0) or diabetes (OR, 1.7; 95% CI, 1.2-2.3). Among these young adults (mean age of 32 years for survivors and 33 years for siblings), survivors were not more likely than siblings to be obese or have CVRFC. In a multivariable logistic regression analysis, factors associated with having CVRFC included older age at interview [≥40 versus <30 years of age (OR, 8.2; 95% CI, 3.5-19.9)], exposure to total body irradiation (OR, 5.5; 95% CI, 1.5-15.8) or radiation to the chest and abdomen (OR, 2.3; 95% CI, 1.2-2.4), and physical inactivity (OR, 1.7; 95% CI, 1.1-2.6). Conclusions: Among adult survivors of pediatric cancer, older attained age, exposure to total body irradiation or abdominal plus chest radiation, and a sedentary life-style are associated with CVRFC. Cancer Epidemiol Biomarkers Prev; 19(1); 170–81

Screening Adult Survivors of Childhood Cancer for Cardiomyopathy: Comparison of Echocardiography and Cardiac Magnetic Resonance Imaging

PURPOSE To compare two-dimensional (2D) echocardiography, the current method of screening for treatment-related cardiomyopathy recommended by the Childrens Oncology Group Guidelines, to cardiac magnetic resonance (CMR) imaging, the reference standard for left ventricular (LV) function. PATIENTS AND METHODS Cross-sectional, contemporaneous evaluation of LV structure and function by 2D and three-dimensional (3D) echocardiography and CMR imaging in 114 adult survivors of childhood cancer currently median age 39 years (range, 22 to 53 years) exposed to anthracycline chemotherapy and/or chest-directed radiation therapy. RESULTS In this survivor population, 14% (n = 16) had an ejection fraction (EF) less than 50% by CMR. Survivors previously undiagnosed with cardiotoxicity (n = 108) had a high prevalence of EF (32%) and cardiac mass (48%) that were more than two standard deviations below the mean of normative CMR data. 2D echocardiography overestimated the mean EF of this population by 5%. Compared with CMR, 2D echocardiography (biplane method) had a sensitivity of 25% and a false-negative rate of 75% for detection of EF less than 50%, although 3D echocardiography had 53% and 47%, respectively. Twelve survivors (11%) had an EF less than 50% by CMR but were misclassified as ≥ 50% (range, 50% to 68%) by 2D echocardiography (biplane method). Detection of cardiomyopathy was improved (sensitivity, 75%) by using a higher 2D echocardiography cutoff (EF < 60%) to detect an EF less than 50% by the reference standard CMR. CONCLUSION CMR identified a high prevalence of cardiomyopathy among adult survivors previously undiagnosed with cardiac disease. 2D echocardiography demonstrated limited screening performance. In this high-risk population, survivors with an EF 50% to 59% by 2D echocardiography should be considered for comprehensive cardiac assessment, which may include CMR.

Body mass index in long-term adult survivors of childhood cancer: a report of the Childhood Cancer Survivor Study.

The goals of the current study were to determine the distribution of body mass index (BMI) of survivors of common pediatric malignancies and to identify factors associated with abnormal BMI.