Risk of solid subsequent malignant neoplasms after childhood Hodgkin lymphoma-Identification of high-risk populations to guide surveillance: A report from the Late Effects Study Group.

BACKGROUND: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations. METHODS: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow-up was 26.6 years. RESULTS: In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14-fold increased risk of developing an sSMN (95% confidence interval, 12.0-fold to 16.3-fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age <10 years were found to be at highest risk of developing lung cancer. Survivors of HL who were treated with abdominal/pelvic radiotherapy and high-dose alkylating agents were found to be at highest risk of developing colorectal cancer and females exposed to neck radiotherapy at age <10 years were at highest risk of thyroid cancer. By age 50 years, the cumulative incidence of breast, lung, colorectal, and thyroid cancer was 45.3%, 4.2%, 9.5%, and 17.3%, respectively, among those at highest risk. CONCLUSIONS: Survivors of childhood HL remain at an increased risk of developing sSMNs. In the current study, subgroups of survivors of HL at highest risk of specific sSMNs were identified, and evidence for screening provided.

Patterns and predictors of clustered risky health behaviors among adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Health complications related to childhood cancer may be influenced by risky health behaviors (RHBs), particularly when RHBs co-occur. To the authors' knowledge, only limited information is available describing how RHBs cluster among survivors of childhood cancer and their siblings and the risk factors for co-occurring RHBs. METHODS: Latent class analysis was used to identify RHB clusters using longitudinal survey data regarding smoking, alcohol use, and physical activity from adult survivors (4184 survivors) and siblings (1598 siblings) in the Childhood Cancer Survivor Study. Generalized logistic regression was used to evaluate associations between demographic characteristics, treatment exposures, psychological distress, health conditions, and cluster membership. RESULTS: Three RHB clusters were identified: a low-risk cluster, an insufficiently active cluster, and a high-risk cluster (tobacco and risky alcohol use and insufficient activity). Compared with siblings, survivors were more likely to be in the insufficiently active cluster (adjusted odds ratio [ORadj ], 1.17; 95% confidence interval [95% CI], 1.06-1.27) and were less likely to be in the high-risk cluster (ORadj , 0.79; 95% CI, 0.69-0.88). Risk factors for membership in the high-risk cluster included psychological distress (ORadj , 2.76; 95% CI, 1.98-3.86), low educational attainment (ORadj , 7.49; 95% CI, 5.15-10.88), income <$20,000 (ORadj , 2.62; 95% CI, 1.93-3.57), being divorced/separated or widowed (ORadj , 1.36; 95% CI, 1.03-1.79), and limb amputation (ORadj , 1.52; 95% CI, 1.03-2.24). Risk factors for the insufficiently active cluster included chronic health conditions, psychological distress, low education or income, being obese or overweight, female sex, nonwhite race/ethnicity, single marital status, cranial radiation, and cisplatin exposure. CONCLUSIONS: RHBs co-occur in survivors of childhood cancer and their siblings. Economic and educational disadvantages and psychological distress should be considered in screening and interventions to reduce RHBs. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2747-2756. © 2016 American Cancer Society.

Secondary malignant neoplasms after high-dose chemotherapy and autologous stem cell rescue for high-risk neuroblastoma.

BACKGROUND: Outcomes for high-risk neuroblastoma remain poor. Modern treatment protocols utilizing intense induction followed by myeloablative consolidation chemotherapy with autologous stem cell rescue (ASCR) have improved survival rates, but the long-term sequelae, including development of secondary malignant neoplasms (SMN), are just now surfacing. METHODS: We retrospectively reviewed data from 87 patients with high-risk neuroblastoma who were treated with intensive induction chemotherapy followed by ASCR between January 1991 and July 2011 following one of two institutional protocols: Chicago Pilot 1 (CP1; n = 12) and Chicago Pilot 2 (CP2; n = 75). RESULTS: The 15-year overall survival rate for all 87 patients was 33.9% (95% confidence interval [CI], 23.1-45.0%). The 10- and 15-year cumulative incidence of SMN was 16.5% (95%CI, 7.2-38.0%) and 34.2% (95%CI, 18.6-63.1%), respectively, without evidence of a plateau at 15 years. Six of the 10 patients (n = 2 in CP1 and n = 8 in CP2) who developed SMN had hematologic malignancies including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). Solid tumors included thyroid papillary carcinoma, chondrosarcoma, hepatocellular carcinoma, and biliary adenocarcinoma. CONCLUSION: A significantly higher incidence of SMN, especially hematological malignancies, was observed in this cohort compared to older neuroblastoma studies, potentially due to exposure to epipodophyllotoxins and a high cumulative dose of alkylating agents these patients received. The risk of developing an SMN continued to increase with survival time and did not reach the plateau at 15 years. Although the number of the patients is relatively small, our study emphasizes the need for life-long follow-up of survivors who were treated using modern therapy.

Exostoses as a long-term sequela after pediatric hematopoietic progenitor cell transplantation: potential causes and increase risk of secondary malignancies from Ann & Robert H. Lurie Children's Hospital of Chicago.

Allogeneic hematopoietic progenitor cell transplantation (HPCT) is a curative therapy for pediatric patients with both malignant and nonmalignant diseases. Single or multiple benign exostoses or osteochondromas have been reported after total body irradiation (TBI), as well as after focal irradiation. Patients exposed to TBI at a young age are at highest risk of developing exostoses. The objective of this institutional review board-approved study was to look at potential factors, besides radiation, that may play a role in development of exostoses. All patients who underwent allogeneic and autologous HPCT at a single institution between March 1992 and December 2003 and who developed an exostosis identified by clinical findings or as an incidental finding on a radiologic study were included. A case-control design matched patients with controls who had the same stem cell source.

Fractures among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Although reductions in bone mineral density are well documented among children during treatment for cancer and among childhood cancer survivors, little is known about the long-term risk of fracture. The objective of this study was to ascertain the prevalence of and risk factors for fractures among individuals participating in the Childhood Cancer Survivor Study (CCSS). METHODS: Analyses included 7414 ≥ 5-year survivors of childhood cancer diagnosed between 1970 and 1986 who completed the 2007 CCSS follow-up questionnaire and a comparison group of 2374 siblings. Generalized linear models stratified by sex were used to compare the prevalence of reported fractures between survivors and siblings. RESULTS: The median ages at follow-up among survivors and siblings were 36.2 years (range, 21.2-58.8 years) and 38.1 years (range, 18.4-62.6 years), respectively, with a median 22.7 years of follow-up after cancer diagnosis for survivors. Approximately 35% of survivors and 39% of siblings reported ≥ 1 fracture during their lifetime. The prevalence of fractures was lower among survivors than among siblings, both in males (prevalence ratio, 0.87; 95% confidence interval, 0.81-0.94; P < .001) and females (prevalence ratio, 0.94; 95% confidence interval, 0.86-1.04; P = .22). In multivariable analyses, increasing age at follow-up, white race, methotrexate treatment, and balance difficulties were associated with increased prevalence of fractures among female survivors (P = .015). Among males, only smoking history and white race were associated with an increased prevalence of fracture (P < .001). CONCLUSIONS: Findings from this study indicated that the prevalence of fractures among adult survivors did not increase compared with that of siblings. Additional studies of bone health among aging female cancer survivors may be warranted.

Anthracycline-induced cardiac toxicity more likely in underweight childhood cancer survivors.

BACKGROUND: We did a retrospective medical record and echocardiogram review of patients with history of anthracyclines and/or radiation seen in a long-term survivor clinic from 2000-2007. OBSERVATIONS: Three hundred eight out of three hundred seventy (83.2%) patients had received at least 1 screening echocardiogram, and 24/308 (7.8%) patients had an abnormal echocardiogram. Observed risk factors for a future abnormal echocardiogram included anthracycline dose > or =250 mg/m2 and underweight status (BMI <5th%) at follow-up. Age, gender, radiation, anthracycline type, history of relapse, and history of stem cell transplant were not risk factors. CONCLUSIONS: Our results confirm the dose-dependent risk of anthracyclines, and describe a novel association with underweight status.

Guidelines for identification of, advocacy for, and intervention in neurocognitive problems in survivors of childhood cancer: a report from the Children's Oncology Group.

With modern therapies and supportive care, survival of childhood cancer has increased considerably. Patients who have survived cancers involving the central nervous system or who have received therapy toxic to the developing brain are at risk of long-term neurocognitive sequelae. Negative outcomes are observed most frequently in survivors of acute lymphoblastic leukemia and brain tumors. The Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer has generated risk-based, exposure-related guidelines designed to direct the follow-up care of survivors of pediatric malignancies based on a comprehensive literature review and expert opinion. This article expands on these guidelines by reviewing the risk factors for the development of neurocognitive sequelae and describing the expected pattern of these disabilities. We herein present recommendations for the screening and management of neurocognitive late effects and outline important areas of school and legal advocacy for survivors with disabilities. Finally, we list resources that can guide patients, their parents, and their medical caregivers as they face the long-term neurocognitive consequences of cancer therapy.

Cancer survivors and infertility: a review of a new problem and novel answers.

Improvements in cancer treatment have changed the way in which cancer is viewed and experienced. However, these same treatments have led to numerous early and late effects, including the loss of fertility. Infertility can influence the biologic and psychologic health of both male and female survivors. Reproductive science can now offer methods to address this concern and provide promising new approaches that may eliminate or mitigate this treatment-related outcome. For current and future reproductive options to serve the needs of survivors more fully, health providers must understand the complexities of infertility as well as their role in delivering answers their patients require. This review will discuss what is known about the causes and experience of infertility among cancer survivors as well as the forms of fertility preservation available.

Effectiveness of a Multicomponent Sun Protection Program for Young Children: A Randomized Clinical Trial.

IMPORTANCE: Emphasizing sun protection behaviors among young children may minimize sun damage and foster lifelong sun protection behaviors that will reduce the likelihood of developing skin cancer, especially melanoma. OBJECTIVE: To determine whether a multicomponent sun protection program delivered in pediatric clinics during the summer could increase summertime sun protection among young children. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled clinical trial with 4-week follow-up that included 300 parents or relatives (hereafter simply referred to as caregivers [mean age, 36.0 years]) who brought the child (2-6 years of age) in their care to an Advocate Medical Group clinic during the period from May 15 to August 14, 2015. Of the 300 caregiver-child pairs, 153 (51.0%) were randomly assigned to receive a read-along book, swim shirt, and weekly text-message reminders related to sun protection behaviors (intervention group) and 147 (49.0%) were randomly assigned to receive the information usually provided at a well-child visit (control group). Data analysis was performed from August 20 to 30, 2015. INTERVENTION: Multicomponent sun protection program composed of a read-along book, swim shirt, and weekly text-message reminders related to sun protection behaviors. MAIN OUTCOMES AND MEASURES: Outcomes were caregiver-reported use of sun protection by the child (seeking shade and wearing sun-protective clothing and sunscreen) using a 5-point Likert scale, duration of outdoor activities, and number of children who had sunburn or skin irritation. The biologic measurement of the skin pigment of a child's arm was performed with a spectrophotometer at baseline and 4 weeks later. RESULTS: Of the 300 caregiver-child pairs, the 153 children in the intervention group had significantly higher scores related to sun protection behaviors on both sunny (mean [SE], 15.748 [0.267] for the intervention group; mean [SE], 14.780 [0.282] for the control group; mean difference, 0.968) and cloudy days (mean [SE], 14.286 [0.282] for the intervention group; mean [SE], 12.850 [0.297] for the control group; mean difference, 1.436). Examination of pigmentary changes by spectrophotometry revealed that the children in the control group significantly increased their melanin levels, whereas the children in the intervention group did not have a significant change in melanin level on their protected upper arms (P < .001 for skin type 1, P = .008 for skin type 2, and P < .001 for skin types 4-6). CONCLUSIONS AND RELEVANCE: A multicomponent intervention using text-message reminders and distribution of read-along books and swim shirts was associated with increased sun protection behaviors among young children. This was corroborated by a smaller change in skin pigment among children receiving the intervention. This implementable program can help augment anticipatory sun protection guidance in pediatric clinics and decrease children's future skin cancer risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02376517.

Tobacco-related documentation in pediatric practice.

OBJECTIVE: The goal of this study was to evaluate tobacco-related documentation in children's medical records. METHOD: A cross-sectional, consecutive sample of 4216 parents at 13 primary care practices was surveyed on demographics, health habits, and smoking status of household members. The medical records of 2085 children from a subsample of 1149 families (all households with smokers and a sample of nonsmoking households) were reviewed for tobacco-related documentation at the first visit to the practice and visits in the 14 months preceding recruitment. Relationships of documentations with visit type, household smoking status, and use of charting prompts were examined. RESULTS: Most children (93%) had > or =1 visit during the reviewed period (77% had a health supervision visit), 23% were aged > or =11 years, 52% were Medicaid/uninsured, and 70% lived with smokers; 30.6% of children had family tobacco use status documented at a first visit to the practice and 15.4% had prenatal tobacco use status documented. Among children with a visit in the reviewed period, 39.3% with a health supervision visit and 9.6% without had a tobacco-related notation at a visit (P < .001). Overall, 15.2% of children living with a smoker had a visit notation indicating that someone in the household smoked. In households with smokers, documentation of household tobacco use status often disagreed with parent survey. Charting prompts significantly increased rates of identification of family tobacco use history and prenatal tobacco use history. CONCLUSIONS: Correct identification of household smoking status was absent for most children living with smokers. Improved documentation systems may facilitate tobacco-related surveillance and counseling.

Heritability and environmental factors affecting vitamin D status in rural Chinese adolescent twins.

CONTEXT: Factors associated with the high prevalence of vitamin D deficiency in China are not well described, especially among Chinese adolescents. OBJECTIVES: The aim of the study was to examine important environmental or sociodemographic factors influencing 25-hydroxyvitamin D [25(OH)D] levels and estimate its heritability. DESIGN: A sample of 226 male and female adolescent twins aged 13-20 yr from a large prospective twin cohort of rural Chinese children and adolescents that has been followed for 6 yr were evaluated. MAIN OUTCOME MEASURE(S): Blood level of 25(OH)D was measured using tandem mass spectrometry methodology. RESULTS: The overall mean (SD) 25(OH)D level was 18.0 (9.4) ng/ml, with wide variation by gender and season. In males (47.4% of subjects), the mean (SD) 25(OH)D level was 12.1 (4.2) ng/ml in non-summer and 27.4 (8.8) ng/ml in summer; in females, it was 10.1 (4.1) ng/ml in non-summer and 19.5 (6.3) ng/ml in summer. A multivariate model that included gender, age, season, physical activity, and student status demonstrated that male gender, summer season, and high physical activity significantly increased 25(OH)D levels. Summer season and male gender also significantly decreased the risk of being in the lowest 25(OH)D tertile. Overall, 68.9% of the variability in 25(OH)D level was attributable to additive genetic influence. Stratification by gender found that in males, 85.9% of the variability in 25(OH)D level was attributable to such influence, but in females, it was only 17%. CONCLUSION: In this sample of rural Chinese adolescents, 25(OH)D level was influenced by gender, season, and physical activity level. There was a strong genetic influence on 25(OH)D level in males only.

Identification of overweight status is associated with higher rates of screening for comorbidities of overweight in pediatric primary care practice.

OBJECTIVES: The goals were to determine whether primary care provider identification of children as overweight was associated with additional screening or referrals and whether the types and numbers of visits to primary care differed for overweight and nonoverweight children. METHODS: Sequential parents/guardians at 13 diverse pediatric practices completed an in-office survey addressing health habits and demographic features. Medical records of each child from a sample of families were reviewed. Data were abstracted from the first visit and from all visits in the 14-month period before study enrollment. Analyses were limited to children > or = 2 years of age for whom BMI percentile could be calculated. RESULTS: The analytic sample included 1216 children (mean age: 7.9 years; 51% male) from 777 families (parents were 43% white, 18% black, 34% Hispanic, and 5% other; 49% of families had a child receiving Medicaid/uninsured). Among overweight children (BMI of > or = 95th percentile; n = 248), 28% had been identified as such in the record. Screening or referral for evaluation of comorbidities was more likely among overweight children who were identified in the record (54%) than among overweight children who were not identified (17%). Among children at risk of overweight (BMI of 85th to 94th percentile; n = 186), 5% had been identified as such in the record and overall 15% were screened/referred. In logistic regression modeling, the children identified as overweight/at risk of overweight had 6 times greater odds of receiving any management for overweight. CONCLUSIONS: Low rates of identification of overweight status and evaluation or referrals for comorbidities were found. Identification of overweight status was associated with a greatly increased rate of screening for comorbidities.