Kevin C. Oeffinger

Obesity in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

PURPOSE To determine whether adult survivors (>or= 18 years of age) of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity and to assess patient and treatment variables that influence risk. PATIENTS AND METHODS A retrospective cohort of participants of the Childhood Cancer Survivor Study was used to compare 1,765 adult survivors of childhood ALL to 2,565 adult siblings of childhood cancer survivors. Body-mass index (BMI; kilograms per square meter), calculated from self-reported heights and weights, was used to determine the prevalence of being overweight (BMI, 25-29.9) or obese (BMI >or= 30.0). Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for being overweight or obese among ALL survivors relative to the sibling control group. RESULTS The age- and race-adjusted OR for being obese in survivors treated with cranial radiation doses >or= 20 Gy in comparison with siblings was 2.59 for females (95% CI, 1.88 to 3.55; P <.001) and 1.86 for males (95% CI, 1.33 to 2.57; P <.001). The OR for obesity was greatest among females diagnosed at 0 to 4 years of age and treated with radiation doses >or= 20 Gy (OR, 3.81; 95% CI, 2.34 to 5.99; P <.001). Obesity was not associated with treatment consisting of chemotherapy only or with cranial radiation doses of 10 to 19 Gy. CONCLUSION Cranial radiotherapy >or= 20 Gy is associated with an increased prevalence of obesity, especially in females treated at a young age. It is imperative that healthcare professionals recognize this risk and develop strategies to enhance weight control and encourage longitudinal follow-up.

American Cancer Society lung cancer screening guidelines

Answer questions and earn CME/CNE

Models for Delivering Survivorship Care

Survivors of adult cancer face lifetime health risks that are dependent on their cancer, cancer treatment exposures, comorbid health conditions, genetic predispositions, and lifestyle behaviors. Content, intensity, and frequency of health care that addresses these risks vary from survivor to survivor. The aims of this article are to provide a rationale for survivor health care and to articulate a taxonomy of models of survivor care that is applicable to both community practices and academic institutions.

Health Care of Young Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study

BACKGROUND We wanted to determine the type of outpatient medical care reported by young adult survivors of childhood cancer and to examine factors associated with limited medical care. METHODS We analyzed data from 9,434 adult childhood cancer survivors enrolled in a retrospective cohort study who completed a baseline questionnaire. They had a mean age of 26.8 years (range 18 to 48 years), 47% were female, 12% were minorities, and 16% were uninsured. Four self-reported outcome measures were used to determine outpatient medical care in a 2-year period: general contact with the health care system, general physical examination, cancer-related medical visit, and medical visit at a cancer center. RESULTS Eighty-seven percent reported general medical contact, 71.4% a general physical examination, 41.9% a cancer-related visit, and 19.2%, a visit at a cancer center. Factors associated with not reporting a general physical examination, a cancer-related visit, or a cancer center visit included no health insurance (odds ratio [OR] = 2.34; 95% confidence interval [CI], 1.97–2.77), male sex (OR = 1.65; 95% CI, 1.44–1.88), lack of concern for future health (OR = 1.57; 95% CI, 1.36–1.82), and age 30 years or older in comparison with those 18 to 29 years (OR = 1.56; 95% CI, 1.35–1.81). The likelihood of reporting a cancer-related visit or a general physical examination decreased significantly as the survivor aged or the time from cancer diagnosis increased. This trend was also significant for those treated with therapies associated with substantial risk for cardiovascular disease or breast cancer. CONCLUSIONS Primary care physicians provide health care for most of this growing high-risk population. To optimize risk-based care, it is critical that cancer centers and primary care physicians develop methods to communicate effectively and longitudinally.

Long-term Complications Following Childhood and Adolescent Cancer: Foundations for Providing Risk-based Health Care for Survivors

Survivors of childhood and adolescent cancer are one of the higher risk populations seen by health care professionals. The curative therapy administered for the cancer also affects growing and developing tissues. Following chemotherapy, radiation therapy, and surgery, many survivors will experience chronic or late‐occurring health problems, often not becoming clinically apparent until decades after therapy. Survivors face an increased risk of morbidity, mortality, and diminished quality of life associated with their previous cancer therapy. Risk is further modified by the survivors genetics, lifestyle habits, and comorbid health conditions. Over their lifetime, survivors will see health care professionals from an array of specialties and disciplines. The aim of this review is threefold: (1) to convey a sense of the risk faced by survivors to clinicians unfamiliar with the population; (2) to provide an up‐to‐date tool for clinicians, regardless of specialty or discipline, when providing care for a survivor; and (3) to complement the recently completed recommendations for screening, prevention, and management of childhood cancer survivors.

Late-Occurring Stroke Among Long-Term Survivors of Childhood Leukemia and Brain Tumors: A Report From the Childhood Cancer Survivor Study

PURPOSE This report examines the incidence of and risk factors for strokes that occur in > or = 5-year survivors of childhood leukemia and brain tumors. PATIENTS AND METHODS The rate of first occurrence of self-reported late-occurring strokes was determined for leukemia survivors (n = 4,828), brain tumor survivors (n = 1,871), and a comparison group of a random sample of cancer survivor siblings (n = 3,846). Relative risks (RRs) and 95% confidence intervals (CIs) of stroke by treatment exposures were examined by multivariate analyses. RESULTS Thirty-seven leukemia survivors and 63 brain tumor survivors reported a late-occurring stroke. The rate of late-occurring stroke for leukemia survivors was 57.9 per 100,000 person-years (95% CI, 41.2 to 78.7). The RR of stroke for leukemia survivors compared with the sibling comparison group was 6.4 (95% CI, 3.0 to 13.8; P < .0001). The rate of late-occurring stroke for brain tumor survivors was 267.6 per 100,000 person-years (95% CI, 206.8 to 339.2). The RR of stroke for brain tumor survivors compared with the sibling comparison group was 29.0 (95% CI, 13.8 to 60.6; P < .0001). Mean cranial radiation therapy (CRT) dose of > or = 30 Gy was associated with an increased risk in both leukemia and brain tumor survivors in a dose-dependent fashion, with the highest risk after doses of > or = 50 Gy CRT. CONCLUSION Survivors of childhood leukemia and brain tumors, particularly those with brain tumors treated with CRT at doses of greater than 30 Gy, are at an increased risk of stroke.

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.

Chronic Disease in the Childhood Cancer Survivor Study Cohort: A Review of Published Findings

A primary objective of the Childhood Cancer Survivor Study (CCSS) is to characterize the major chronic health conditions faced by childhood cancer survivors, and to determine the risk factors for those conditions. In order to characterize these conditions, at entry into the study, participants completed questionnaires that documented self-reported chronic illnesses, symptoms, and medications. Over time, follow-up questionnaires (administered approximately every 2 to 3 years) have allowed analysis of changes in symptoms and disease burden. To date, analyses have been completed which describe the profile of chronic disease in the cohort at first entry into the study and for specific subgroups, defined by primary cancer, by specific exposures, and by demographic factors.1,2 Generally, these analyses estimate risk of chronic disease by calculating a risk estimate for self-reported symptoms or conditions. Relative risks for chronic disease or specific conditions are calculated comparing the survivor cohort with the sibling cohort or population norms. In addition, relative risk for an outcome in a subgroup with a specific treatment exposure or demographic characteristic is calculated relative to a comparison group without that specific factor of interest. Cumulative incidence of specific chronic illnesses is estimated in many of the reports, and analyses of chronic illnesses in each of the survivor groups by primary diagnosis are completed (acute lymphoblastic leukemia [ALL],3 acute myeloid leukemia [AML],4 and rhadbdomyosarcoma5) or in progress (neuroblastoma, bone sarcoma, renal tumors, lymphomas, and brain tumors). This review presents the completed analyses of overall chronic illness in the original cohort and then describes findings by organ system. Specific chronic diseases reported here will include: endocrinologic disorders (including thyroid disease, disorders of growth, weight, and pubertal regulation), osteonecrosis, cardiac disease, pulmonary conditions, and neurosensory/neurologic adverse outcomes. Adverse outcomes in some domains which might be considered chronic illnesses—secondary cancers, emotional and psychological disorders, pain—are not covered herein, but are reviewed separately in other articles within this issue of Journal of Clinical Oncology. For some outcomes, only subsets of the cohort have been analyzed, often because a hypothesis regarding a specific exposure or disease (eg, weight regulation in leukemia survivors or stroke after neck radiation therapy [RT]) has been explored. Analyses in progress, and not included in this report, include risk of renal and urinary disorders, gastrointestinal diseases, and more in depth cohort-wide characterizations of cardiovascular disease. Additional studies to characterize further longitudinal changes in risk as the cohort ages are planned.

Twenty-five–year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study

Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late effects of cancer therapy. Five-year ALL survivors (< 21 years at diagnosis; n = 5760 eligible, 4151 participants), diagnosed from 1970 to 1986 were compared with the general population and a sibling cohort (n = 3899). Cumulative mortality of 5760 5-year survivors was 13% at 25 years from diagnosis. Recurrent ALL (n = 483) and second neoplasms (SNs; n = 89) were the major causes of death. Among 185 survivors, 199 SNs occurred, 53% in the CNS. Survivors reported more multiple chronic medical conditions (CMCs; odds ratio [OR], 2.8; 95% CI, 2.4-3.2) and severe or life-threatening CMCs (OR, 3.6; 95% CI, 3.0-4.5) than siblings. Cumulative incidence of severe CMCs, including death, 25 years from diagnosis was 21.3% (95% CI, 18.2-24.4; 23.3% [95% CI, 19.4-27.2] and 13.4% [95% CI, 8.4-18.4] for irradiated and nonirradiated survivors, respectively). Survivors reported more adverse general and mental health, functional impairment, and activity limitations compared with siblings (P < .001). Rates of marriage, college graduation, employment, and health insurance were all lower compared with sibling controls (P < .001). Long-term survivors of childhood ALL exhibit excess mortality and morbidity. Survivors who received radiation therapy as part of their treatment or had a leukemia relapse are at greatest risk for adverse outcomes.

Modifiable risk factors and major cardiac events among adult survivors of childhood cancer.

PURPOSE To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. PATIENTS AND METHODS Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models. RESULTS Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all P(trend) < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7). CONCLUSION Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.