Search

Simple Summary: This cross-sectional study analyzed how multilevel social factors affect patient-reported outcomes in children under 18 who survived cancer. Study participants include 293 pairs of these survivors who received survivorship care at a U.S.-based comprehensive cancer center between 2017 and 2018 and their primary caregivers. Findings indicate that higher caregiver anxiety is linked to worse depression, stress, fatigue, sleep problems, and lower positive affect in survivors of pediatric cancer. The study also found that family conflicts are associated with sleep issues in childhood cancer survivors. Furthermore, survivors living in socioeconomically deprived areas experience poorer sleep quality, and those residing in environments with high physical deprivation experience more psychological stress and fatigue, alongside reduced positivity and mobility. These results highlight the significant impact of parental, familial, and neighborhood factors on a range of patient-reported outcomes among young cancer survivors, suggesting these social factors as crucial targets for intervention. In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving treatment at St. Jude Children's Research Hospital who were <18 years of age during follow-up from 2017 to 2018 and their primary caregivers. Social determinants included family factors (caregiver-reported PROs, family dynamics) and county-level deprivation (socioeconomic status, physical environment via the County Health Rankings & Roadmaps). PROMIS measures assessed survivors' and caregivers' PROs. General linear regression tested associations of social determinants with survivors' PROs. We found that caregivers' higher anxiety was significantly associated with survivors' poorer depression, stress, fatigue, sleep issues, and reduced positive affect (p < 0.05); caregivers' sleep disturbances were significantly associated with lower mobility in survivors (p < 0.05). Family conflicts were associated with survivors' sleep problems (p < 0.05). Residing in socioeconomically deprived areas was significantly associated with survivors' poorer sleep quality (p < 0.05), while higher physical environment deprivation was associated with survivors' higher psychological stress and fatigue and lower positive affect and mobility (p < 0.05). Parental, family, and neighborhood factors are critical influences on young survivors' quality of life and well-being and represent new intervention targets. [ABSTRACT FROM AUTHOR]

The article examines the effects of financial toxicity on childhood cancer survivors. Topics discussed include individual-level drivers of financial toxicity, estimated childhood cancer survivors in the U.S. who potentially face decades more of indirect costs related to their childhood cancer, and multilevel interventions for financial toxicity.

The article focuses on the socioeconomic and health system factors of the population on childhood cancer medical care and screening including enrollment in the Childhood Cancer Survivor Study (CCSS) and individual-level factors from U.S. Area Health Resource File was reported.

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. [ABSTRACT FROM AUTHOR]

Background: Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data.Objective: To systematically assess cardiac outcomes among survivors of childhood cancer.Design: Cross-sectional study.Setting: St. Jude Children's Research Hospital.Patients: 1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier.Measurements: Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test.Results: One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in 1.4%). Nearly all survivors were asymptomatic. The prevalence of cardiac conditions increased with age at evaluation, ranging from 3% to 24% among survivors aged 30 to 39 years to 10% to 37% among those aged 40 years or older. In multivariable analysis, survivors exposed to anthracycline doses of 250 mg/m2 or more had greater odds of cardiomyopathy (odds ratio, 2.7 [95% CI, 1.1 to 6.9]) than those who were not exposed. Survivors exposed to heart radiation also had increased odds of cardiomyopathy (odds ratio, 1.9 [CI, 1.1 to 3.7]) compared with those who were not exposed. Radiation exposure greater than 1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings.Limitations: Sixty-one percent of survivors exposed to anthracycline chemotherapy or cardiac-directed radiation participated. A comparison group and longitudinal assessments were not available.Conclusion: Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer.Primary Funding Source: National Cancer Institute, American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to identify treatment and genetic factors associated with obesity among childhood cancer survivors.Methods: Participants included 1996 survivors who previously received treatment for cancer at St. Jude Children's Research Hospital and who survived ≥10 years from diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years). Obesity was defined as a body mass index ≥30 kg/m(2) . The factors associated with adult obesity were identified by subgroup-specific (cranial radiation [CRT] exposure status) multivariable logistic regression. Single nucleotide polymorphisms (SNPs) associated with obesity were identified by subgroup-specific, exploratory, genome-wide association analyses using a 2-stage resampling approach with a type I error rate of 5 × 10(-6) .Results: Forty-seven percent of survivors who received CRT and 29.4% of those who did not receive CRT were obese at evaluation. In multivariable analyses, abdominal/pelvic radiation exposure was associated with decreased prevalence of obesity among survivors regardless of CRT status (P < .0001). The odds of obesity were increased among survivors who received CRT who had also received glucocorticoids (P = .014) or who were younger at diagnosis (P = .013). Among the survivors who had received CRT, 166 SNPs were associated with obesity. The strongest association was observed with reference SNP rs35669975 (P = 3.3 × 10(-8) ) on segment 33.3 of the long arm of chromosome 13 (13q33.3), approximately 30 kb downstream of FAM155A (family with sequence similarity 155, member A). SNPs within the glycine receptor α3 (GLRA3) gene and near the sex-determining region Y box 11 (SOX11) and cadherin 18 type 2 (CDH18) genes also were identified. These genes have been implicated in neural growth, repair, and connectivity.Conclusions: Obesity in childhood cancer survivors remains associated with previous exposure to CRT and glucocorticoids. Genetic variants related to neural connectivity may modify the risk of obesity among survivors who receive CRT. Validation of these findings in independent cohorts is required. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lack of health insurance is a key barrier to accessing care for chronic conditions and cancer screening. The influence of insurance type (private, public, none) on survivor-focused and general preventive health care in adult survivors of childhood cancer was examined. METHODS: The Childhood Cancer Survivor Study is a retrospective cohort study of childhood cancer survivors diagnosed between 1970 and 1986. Among 8425 adult survivors, the relative risk (RR) and 95% confidence interval (CI) of receiving survivor-focused and general preventive health care were estimated for uninsured (n = 1390) and publicly insured (n = 640), compared with for the privately insured (n 1/4 6395) RESULTS: Uninsured survivors were less likely than those privately insured to report a cancer-related visit (adjusted RR, 0.83; 95% CI, 0.75-0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71-0.98). Uninsured survivors had lower levels of utilization in all measures of care in comparison with privately insured. In contrast, publicly insured survivors were more likely to report a cancer-related visit (adjusted RR, 1.22; 95% CI, 1.11-1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18-1.70) than were privately insured survivors. Although publicly insured survivors had similar utilization of general health examinations, they were less likely to report a Papanicolaou test or a dental examinations CONCLUSIONS: Among this large, socioeconomically diverse cohort, publicly insured survivors utilize survivor-focused health care at rates at least as high as survivors with private insurance. Uninsured survivors have lower utilization of both survivor-focused and general preventive health care. [ABSTRACT FROM AUTHOR]

Background: Women treated with therapeutic chest radiation may develop breast cancer. Purpose: To summarize breast cancer risk and breast cancer surveillance in women after chest radiation for pediatric or young adult cancer. Data Sources: Studies from MEDLINE, EMBASE, the Cochrane Library, and CINAHL (1966 to December 2008). Study Selection: Articles were selected to answer any of 3 questions: What is the incidence and excess risk for breast cancer in women after chest radiation for pediatric or young adult cancer? For these women, are the clinical characteristics of breast cancer and the outcomes after therapy different from those of women with sporadic breast cancer in the general population? What are the potential benefits and harms associated with breast cancer surveillance among women exposed to chest radiation? Data Extraction: Three investigators independently extracted data and assessed study quality. Data Synthesis: Standardized incidence ratios ranged from 13.3 to 55.5; cumulative incidence of breast cancer by age 40 to 45 years ranged from 13% to 20%. Risk for breast cancer increased linearly with chest radiation dose. Available limited evidence suggests that the characteristics of breast cancer in these women and the outcomes after diagnosis are similar to those of women in the general population; mammography can detect breast cancer, although sensitivity is limited. Limitation: The quality of evidence for key questions 2 and 3 is limited by substantial study heterogeneity, variation in study design, and small sample size. Conclusion: Women treated with chest radiation have a substantially elevated risk for breast cancer at a young age, which does not seem to plateau. In this high-risk population, there seems to be a benefit associated with early detection. Further research is required to better define the harms and benefits of lifelong surveillance. Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

The article discusses a study on behaviors and ultraviolet (UV) radiation exposure in a cohort of adult survivors of childhood and adolescent cancer in the U.S. The study examined the risk of skin cancer due to the exposure to radiation therapy, as shown by research from the Childhood Cancer Survivor Study (CCSS). The subjects of the study were childhood and adolescent cancer survivors and it found that they have an increased use of sunscreen and with lower tanning practices.

Background: The purpose of the current study was to evaluate the activity and toxicity of dexamethasone, high-dose cytarabine, and carboplatin (DAC) combination therapy in children with newly diagnosed large-cell non-Hodgkin lymphoma (NHL) and to estimate the event-free and overall survival rates achieved when DAC is incorporated into a conventional regimen.Methods: From 1991 to 1997, 20 boys and 5 girls aged 4.2 to 17.7 years who had stage III (according to the St. Jude staging system) (n = 21) or stage IV (n = 4) large-cell NHL were treated in this study. DAC therapy was administered at the beginning of the induction phase in 2 sequential cycles and incorporated throughout a continuation phase (modified from the ACOP+ regimen, which features doxorubicin, cyclophosphamide, vincristine, and prednisone) with doxorubicin, cyclophosphamide, vincristine, and dexamethasone. The total duration of treatment was approximately 10 months.Results: DAC therapy yielded a response in 22 of 25 patients (88%; 95% confidence interval [95% CI], 68%-97%): complete remission in 13 cases (52%), and partial response in 9 (36%). After additional treatment with doxorubicin, cyclophosphamide, vincristine, and dexamethasone, complete remission was attained in 18 patients (72%) and partial remission in 3 (12%). The event-free survival rate (+/- the standard error [SE]) was 64% +/- 9% and the overall survival rate was 80% +/- 8% at 5 years.Conclusions: The results of the current study indicate that the DAC regimen is well tolerated and effective for pediatric patients with large-cell NHL. [ABSTRACT FROM AUTHOR]

About 1,700 children in the United States are diagnosed yearly with lymphomas; Hodgkin's disease accounts for approximately half of these cases, or 6% of all childhood cancers. Contemporary therapy allows for the achievement of remission in the majority of cases. The fusion of positron emission tomography (PET) with CT provides the most accurate imaging method for disease characterization and treatment response. However, experience with 18F-FDG PET-CT is limited in pediatric Hodgkin's disease. Numerous non-oncologic processes can mimic recurrent or residual tumor. This pictorial addresses mimickers of disease such as uptake in normal structures, infections, transforming germinal canters and effects of therapy on normal tissues. It is essential for radiologists to be familiar with these findings in order to stage disease activity and therapeutic response accurately. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Reports on health issues surrounding survivors of childhood cancer in the U.S. as of September 2002. Factors that should be considered in the approach and evaluation of childhood cancer survivors; Dental abnormalities that may develop due to chemotherapy; Number of children diagnosed with cancer in 1999.

Simple Summary: Childhood cancer patients receiving treatment containing alkylating agents are at risk of infertility, yet inter-individual variability in treatment-related ovarian damage is observed. Alkylating agents are metabolized by cytochrome P450 (CYP450) enzymes and polymorphisms in these CYP450 enzymes may explain this variability in ovarian damage. This study on genetic variation in CYP450 enzymes of chemotherapy-induced gonadotoxicity, using anti-Müllerian hormone (AMH) levels as a proxy for ovarian reserve, in female childhood cancer survivors (CCSs) may identify patients at risk of infertility. This unique global collaboration of two large CCS studies shows the significant gonadotoxic effect of enzyme CYP3A4*3 and significant protective effect of CYP2B6*2 on gonadal function in CCSs receiving alkylating agents. Genetic variation in CYP3A4 and CYP2B6 have previously been associated with gonadotoxicity after cancer treatment. These findings could guide risk prediction models determining patients at risk of chemotherapy-induced gonadal impairment. Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. Methods: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743; age (years): median 25.8, interquartile range (IQR) 22.1–30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort (n = 391; age (years): median 31.3, IQR 26.6–37.4). Results: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): −0.706 (−1.11–−0.298), p-value = 7 × 10−4) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126–0.928), p-value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m2 CED. Conclusions: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatment-related risk of infertility and fertility preservation options. [ABSTRACT FROM AUTHOR]

Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk.Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15-25), the 20-year cumulative incidence of at least one grade 3-5 chronic condition decreased significantly from 33·2% (95% CI 32·0-34·3) in those diagnosed 1970-79 to 29·3% (28·4-30·2; p<0·0001) in 1980-89, and 27·5% (26·4-28·6; p=0·012 vs 1980-89) in 1990-99. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition in 5051 siblings was 4·6% (95% CI 3·9-5·2). The 15-year cumulative incidence of at least one grade 3-5 condition was lower for survivors diagnosed 1990-99 compared with those diagnosed 1970-79 for Hodgkin lymphoma (17·7% [95% CI 15·0-20·5] vs 26·4% [23·8-29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0-19·7] vs 23·8% [19·9-27·7]; p=0.0053), astrocytoma (30·5% [27·8-33·2] vs 47·3% [42·9-51·7]; p<0·0001), Wilms tumour (11·9% [9·5-14·3] vs 17·6% [14·3-20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5-33·1] vs 36·5% [31·5-41·4]; p=0·021), and osteosarcoma (65·6% [60·6-70·6] vs 87·5% [84·1-91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-99 vs 1970-79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4-63·3] vs 42·9% [34·9-50·9]; p=0·00060), and neuroblastoma (25·0% [21·8-28·2] vs 18·0% [14·5-21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64-0·92; HR with treatment in the model=0·89, 95% CI 0·72-1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65-0·85; HR with treatment=0·91, 95% CI 0·73-1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970-79 to survivors diagnosed 1990-99 were noted for endocrinopathies (5·9% [5·3-6·4] vs 2·8% [2·5-3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3-3·1] vs 1·9% [1·6-2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2-6·4] vs 3·3% [2·9-3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0-2·7] vs 1·5% [1·3-1·8]; p=0·00037), while hearing loss increased (3·0% [2·6-3·5] vs 5·7% [5·2-6·1]; p<0·0001).Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population.Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Background: The magnitude of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is not known. Using medically ascertained data, we applied the cumulative burden metric to compare chronic cardiovascular health conditions in survivors of Hodgkin's lymphoma and general population controls.Methods: For this study, participant data were obtained from two ongoing cohort studies at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE) and the St Jude Long-term Follow-up Study (SJLTFU). SJLIFE is a cohort study initiated on April 27, 2007, to enable longitudinal clinical evaluation of health outcomes of survivors of childhood cancer treated or followed at St Jude Children's Research Hospital, and SJLTFU is an administrative system-based study initiated in 2000 to collect outcome and late toxicity data for all patients treated at the hospital for childhood cancer. The patient cohort for our study was defined as patients treated at St Jude Children's Research Hospital who reached 18 years of age and were at least 10 years post-diagnosis of pathologically confirmed primary Hodgkin's lymphoma. Outcomes in the Hodgkin's lymphoma survivors were compared with a sample of SJLIFE community control participants, aged 18 years or older at the time of assessment, frequency-matched based on strata defined by 5-year age blocks within each sex, who were selected irrespective of previous medical history. All SJLIFE participants underwent assessment for 22 chronic cardiovascular health conditions. Direct assessments, combined with retrospective clinical reviews, were used to assign severity to conditions using a modified Common Terminology Criteria of Adverse Events (CTCAE) version 4.03 grading schema. Occurrences and CTCAE grades of the conditions for eligible non-SJLIFE participants were accounted for by multiple imputation. The mean cumulative count (treating death as a competing risk) was used to estimate cumulative burden.Findings: Of 670 survivors treated at St Jude Children's Research Hospital, who survived 10 years or longer and reached age 18 years, 348 were clinically assessed in the St Jude Lifetime Cohort Study (SJLIFE); 322 eligible participants did not participate in SJLIFE. Age and sex frequency-matched SJLIFE community controls (n=272) were used for comparison. At age 50 years, the cumulative incidence of survivors experiencing at least one grade 3-5 cardiovascular condition was 45·5% (95% CI 36·6-54·3), compared with 15·7% (7·0-24·4) in community controls. The survivor cohort at age 50 experienced a cumulative burden of 430·6 (95% CI 380·7-480·6) grade 1-5 and 100·8 (77·3-124·3) grade 3-5 cardiovascular conditions per 100 survivors; these numbers were appreciably higher than those in the control cohort (227·4 [192·7-267·5] grade 1-5 conditions and 17·0 [8·4-27·5] grade 3-5 conditions per 100 individuals). Myocardial infarction and structural heart defects were the major contributors to the excess grade 3-5 cumulative burden in survivors. High cardiac radiation dose (≥35 Gy) was associated with an increased proportion of grade 3-5 cardiovascular burden, whereas increased anthracyline dose was not.Interpretation: The true effect of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is reflected in the cumulative burden. Survivors aged 50 years will experience more than two times the number of chronic cardiovascular health conditions and nearly five times the number of more severe (grade 3-5) cardiovascular conditions compared with community controls and, on average, have one severe, life-threatening, or fatal cardiovascular condition. The cumulative burden metric provides a more comprehensive approach for assessing overall morbidity compared with currently used cumulative incidence based analytic methodologies, and will assist clinical researchers when designing future trials and refining general practice screening guidelines.Funding: US National Cancer Institute, St Baldrick's Foundation, and American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Background: Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects.Methods: We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals.Results: Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor.Conclusions: The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer. (Funded by the National Cancer Institute and the American Lebanese-Syrian Associated Charities.). [ABSTRACT FROM AUTHOR]

Importance: Employment is an important factor in quality of life and provides social and economic support. Longitudinal data on employment and associations with chronic health conditions for adult survivors of childhood cancer are lacking., Objective: To evaluate longitudinal trends in employment among survivors of childhood cancer., Design, Setting, and Participants: Retrospective cohort study of 5-year cancer survivors diagnosed at age 20 years or younger between 1970 and 1986 enrolled in the multi-institutional Childhood Cancer Survivor Study (CCSS). Sex-stratified employment status at baseline (2002 to 2004) and follow-up (2014 to 2016) was compared with general population rates from the Behavioral Risk Factor Surveillance System cohort. Data were analyzed from July 2021 to June 2022., Exposures: Cancer therapy and preexisting and newly developed chronic health conditions., Main Outcomes and Measures: Standardized prevalence ratios of employment (full-time or part-time, health-related unemployment, unemployed, not in labor force) among adult (aged ≥25 years) survivors between baseline and follow-up compared with the general population. Longitudinal assessment of negative employment transitions (full-time to part-time or unemployed at follow-up)., Results: Female participants (3076 participants at baseline; 2852 at follow-up) were a median (range) age of 33 (25-53) years at baseline and 42 (27-65) years at follow-up; male participants (3196 participants at baseline; 2557 at follow-up) were 33 (25-54) and 43 (28-64) years, respectively. The prevalence of full-time or part-time employment at baseline and follow-up was 2215 of 3076 (71.3%) and 1933 of 2852 (64.8%) for female participants and 2753 of 3196 (85.3%) and 2079 of 2557 (77.3%) for male participants, respectively, with declining standardized prevalence ratios over time (female participant baseline, 1.01; 95% CI, 0.98-1.03; follow-up, 0.94; 95% CI, 0.90-0.98; P < .001; male participant baseline, 0.96; 95% CI, 0.94-0.97; follow-up, 0.92; 95% CI, 0.89-0.95; P = .02). While the prevalence of health-related unemployment increased (female participants, 11.6% to 17.2%; male participants, 8.1% to 17.1%), the standardized prevalence ratio remained higher than the general population and declined over time (female participant baseline, 3.78; 95% CI, 3.37-4.23; follow-up, 2.23; 95% CI, 1.97-2.51; P < .001; male participant baseline, 3.12; 95% CI, 2.71-3.60; follow-up, 2.61; 95% CI, 2.24-3.03; P = .002). Among survivors employed full-time at baseline (1488 female participants; 1933 male participants), 285 female participants (19.2%) and 248 male participants (12.8%) experienced a negative employment transition (median [range] follow-up, 11.5 [9.4-13.8] years). Higher numbers and grades of chronic health conditions were significantly associated with these transitions., Conclusions and Relevance: In this retrospective analysis of adult survivors of childhood cancer, significant declines in employment and increases in health-related unemployment among cancer survivors compared with the general population were identified. A substantial portion of survivors in the midcareer age range fell out of the workforce. Awareness among clinicians, caregivers, and employers may facilitate clinical counseling and occupational provisions for supportive work accommodations.

Purpose: To investigate racial/ethnic-related disparities by insurance status in "forgoing needed medical care in the last year due to finances" in childhood cancer survivors., Methods: Our study included 3310 non-Hispanic/Latinx White, 562 non-Hispanic/Latinx Black, and 92 Hispanic/Latinx survivors from the St. Jude Lifetime Cohort Study. Logistic regression analyses, guided by Andersen's Healthcare Utilization Model, were adjusted for "predisposing" (survey age, sex, childhood cancer diagnosis and treatment, and treatment era) and "need" (perceived health status) factors. Additional adjustment for household income/education and chronic health conditions was considered., Results: Risk of forgoing care was highest among non-Hispanic/Latinx Blacks and lowest among Hispanics/Latinxs for each insurance status. Among privately insured survivors, relative to non-Hispanic/Latinx Whites, non-Hispanic/Latinx Blacks were more likely to forgo care (adjusted OR: 1.82, 95% CI: 1.30-2.54): this disparity remained despite additional adjustment for household income/education (adjusted OR: 1.43, 95% CI: 1.01-2.01). In contrast, publicly insured survivors, regardless of race/ethnicity, had similar risk of forgoing care as privately insured non-Hispanic/Latinx Whites. All uninsured survivors had high risk of forgoing care. Additional chronic health condition adjustment did not alter these results., Conclusions: Provision of public insurance to all childhood cancer survivors may diminish racial/ethnic disparities in forgoing care that exist among the privately insured and reduce the risk of forgoing care among uninsured survivors to that of privately insured non-Hispanic/Latinx Whites., Implications for Cancer Survivors: Under public insurance, childhood cancer survivors had low risk of forgoing care, at the similar level to privately insured non-Hispanic/Latinx Whites, regardless of race/ethnicity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Young survivors of cancer are at increased risk for cancers that are related to human papillomavirus (HPV), primarily caused by oncogenic HPV types 16 and 18. We aimed to examine the immunogenicity and safety of the three-dose series of HPV vaccine in young survivors of cancer., Methods: We conducted an investigator-initiated, phase 2, single-arm, open-label, non-inferiority trial at five National Cancer Institute-designated comprehensive cancer centres in the USA. Eligible participants were survivors of cancer who were HPV vaccine-naive, were aged 9-26 years, in remission, and had completed cancer therapy between 1 and 5 years previously. Participants received three intramuscular doses of either quadrivalent HPV vaccine (HPV4; enrolments on or before March 1, 2016) or nonavalent HPV vaccine (HPV9; enrolments after March 1, 2016) over 6 months (on day 1, at month 2, and at month 6). We also obtained data from published clinical trials assessing safety and immunogenicity of HPV4 and HPV9 in 9-26-year-olds from the general population, as a comparator group. The primary endpoint was antibody response against HPV types 16 and 18 at month 7 in the per-protocol population. A response was deemed non-inferior if the lower bound of the multiplicity-adjusted 95% CI was greater than 0·5 for the ratio of anti-HPV-16 and anti-HPV-18 geometric mean titres (GMTs) in survivors of cancer versus the general population. Responses were examined separately in male and female participants by age group (ie, 9-15 years and 16-26 years). Safety was assessed in all participants who received at least one vaccine dose and for whom safety data were available. This study is registered with ClinicalTrials.gov, NCT01492582. This trial is now completed., Findings: Between Feb 18, 2013, and June 22, 2018, we enrolled 453 survivors of cancer, of whom 436 received one or more vaccine doses: 203 (47%) participants had survived leukaemia, 185 (42%) were female, and 280 (64%) were non-Hispanic white. Mean age at first dose was 15·6 years (SD 4·6). 378 (83%) of 453 participants had evaluable immunogenicity data; main reasons for exclusion from per-protocol analysis were to loss to follow-up, patient reasons, and medical reasons. Data were also obtained from 26 486 general population controls. The ratio of mean GMT for anti-HPV types 16 and 18 in survivors of cancer versus the general population was more than 1 for all subgroups (ie, aged 9-15 years, aged 16-26 years, male, and female groups) in both vaccine cohorts (ranging from 1·64 [95% CI 1·12-2·18] for anti-HPV type 16 in female participants aged 9-15 years who received HPV9, to 4·77 [2·48-7·18] for anti-HPV type 18 in male participants aged 16-26 years who received HPV4). Non-inferiority criteria were met within each age and sex subgroup, except against HPV type 18 in female participants aged 16-26 years receiving HPV9 (4·30 [0·00-9·05]). Adverse events were reported by 237 (54%) of 435 participants; injection site pain was most common (174 [40%] participants). One serious adverse event (ie, erythema nodosum) was possibly related to vaccine (HPV9; 16-26 year female cohort)., Interpretation: Immunogenicity and safety of HPV vaccine three-dose series in survivors of cancer is similar to that in the general population, providing evidence for use in this clinically vulnerable population., Funding: US National Cancer Institute, Merck, Sharp & Dohme, and American Lebanese Syrian Associated Charities., Competing Interests: Declaration of interests JAC reports payment for a consulting or advisory role for X4 Pharmaceuticals. ARG reports payment for membership of a scientific advisory board and global advisory board for, honoraria from, and funds to their institution to conduct research studies unrelated to this research from Merck Sharp & Dohme. MMH reports payment for a consulting or advisory role for the Oncology Research Information Exchange Network Patient Advisory Committee, Princess Maxima Center Scientific Advisory Board, and SurvivorLink. WL reports non-financial support (provision of vaccine and laboratory analysis) to their institution related to this research from Merck Sharp & Dohme and payment for a consulting or advisory role for SurvivorLink. ML reports payment for consulting for Oncoceutics. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: Kevin R. KrullPatents, Royalties, Other Intellectual Property: Royalties from Wolters Kluwer Melissa M. HudsonConsulting or Advisory Role: Oncology Research Information Exchange Network, Princess Máxima CenterNo other potential conflicts of interest were reported.

Purpose: To determine the incidence of serious chronic health conditions among survivors of pediatric Hodgkin lymphoma (HL), compare by era of therapy and by selected cancer therapies, and provide estimates of risks associated with contemporary therapy., Methods: Assessing 2,996 5-year HL survivors in the Childhood Cancer Survivor Study diagnosed from 1970 to 1999, we examined the cumulative incidence of severe to fatal chronic conditions (grades 3-5) using self-report conditions, medically confirmed subsequent malignant neoplasms, and cause of death based on the National Death Index. We used multivariable regression models to estimate hazard ratios (HRs) per decade and by key treatment exposures., Results: HL survivors were of a mean age of 35.6 years (range, 12-58 years). The cumulative incidence of any grade 3-5 condition by 35 years of age was 31.4% (95% CI, 29.2 to 33.5). Females were twice as likely (HR, 2.1; 95% CI, 1.8 to 2.4) to have a grade 3-5 condition compared with males. From the 1970s to the 1990s, there was a 20% reduction (HR, 0.8; 95% CI, 0.7 to 0.9) in decade-specific risk of a grade 3-5 condition ( P trend = .002). In survivors who had a recurrence and/or hematopoietic cell transplant, the risk of a grade 3-5 condition was substantially elevated, similar to that of survivors treated with high-dose, extended-field radiotherapy (HR, 1.2; 95% CI, 0.9 to 1.5). Compared with survivors treated with chest radiotherapy ≥ 35 Gy in combination with an anthracycline or alkylator, a contemporary regimen for low-intermediate risk HL was estimated to lead to a 40% reduction in risk of a grade 3-5 condition (HR, 0.6; 95% CI, 0.4 to 0.8)., Conclusion: This study demonstrates that risk-adapted therapy for pediatric HL has resulted in a significant reduction in serious long-term outcomes.

Purpose: Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL., Methods: Open-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov (identifier: NCT01920932)., Results: Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy., Conclusion: The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes., Competing Interests: Monika L. MetzgerResearch Funding: Seattle Genetics Michael P. LinkConsulting or Advisory Role: Incyte, ADC Therapeutics, Lilly, Steba Biotech, Mesoblast, GlaxoSmithKline, SyndaxResearch Funding: Seattle Genetics, Janssen Oncology Jamie FlerlageResearch Funding: Seattle Genetics Matthew J. EhrhardtHonoraria: Optum Torunn I. YockConsulting or Advisory Role: Huron Consulting Services, LLCResearch Funding: MIM Software Sue C. KasteStock and Other Ownership Interests: GE Healthcare Barry ShulkinConsulting or Advisory Role: Navidea Melissa M. HudsonConsulting or Advisory Role: Oncology Research Information Exchange Network, Princess Máxima Center Matthew J. KrasinConsulting or Advisory Role: Debiopharm GroupNo other potential conflicts of interest were reported.

Background: The impact of specific treatment modalities on long-term renal function and blood pressure among adult survivors of Wilms tumor (WT) has not been well documented., Methods: Among 40 WT survivors and 35 noncancer controls, we estimated the glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations with and without cystatin C, obtained 24-hour ambulatory blood pressure readings, and, among survivors only, measured 99m Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. Survivors were treated with unilateral nephrectomy and nonnephrotoxic chemotherapy. Twenty received whole abdomen radiation therapy (WART) [median -16.5 Gray (Gy)], and 20 received no radiation therapy. Pairwise comparisons between survivors treated with and without WART, and each group to controls were performed using two-sample t tests., Results: Twenty-six (65%) WT survivors were female, and 33 (83%) were non-Hispanic white. GFR estimated with creatinine or creatinine + cystatin C was decreased among irradiated survivors compared with controls. No irradiated or unirradiated participant had an eGFR (creatinine + cystatin C) < 60 mL/min/1.73 m 2 . The prevalence of hypertension was significantly increased among unirradiated (25%) and irradiated survivors (35%) compared with controls (0%). Of the 24-hour ambulatory blood pressure monitoring parameters evaluated, only mean sleep period diastolic blood pressure load of those who received WART was significantly different from that of controls., Conclusions: Chronic kidney disease was infrequent in long-term survivors of unilateral nonsyndromic WT, whether treated with WART or no radiation. The prevalence of hypertension was increased in both groups compared with controls, emphasizing the need for ongoing monitoring of renal and cardiovascular health., (© 2020 Wiley Periodicals, Inc.)

Purpose: To estimate the absolute number of adult survivors of childhood cancer in the U.S. population who carry a pathogenic or likely pathogenic variant in a cancer predisposition gene., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated the number of childhood cancer survivors on December 31, 2016 for each childhood cancer diagnosis, multiplied this by the proportion of carriers of pathogenic/likely pathogenic variants in the St. Jude Lifetime Cohort (SJLIFE) study, and projected the resulting number onto the U.S., Results: Based on genome sequence data, 11.8% of 2450 SJLIFE participants carry a pathogenic/likely pathogenic variant in one of 156 cancer predisposition genes. Given this information, we estimate that 21 800 adult survivors of childhood cancer in the United States carry a pathogenic/likely pathogenic variant in one of these genes. The highest estimated absolute number of variant carriers are among survivors of central nervous system tumors (n = 4300), particularly astrocytoma (n = 1800) and other gliomas (n = 1700), acute lymphoblastic leukemia (n = 4300), and retinoblastoma (n = 3500). The most frequently mutated genes are RB1 (n = 3000), NF1 (n = 2300), and BRCA2 (n = 800)., Conclusion: Given the increasing number of childhood cancer survivors in the United States, clinicians should counsel survivors regarding their potential genetic risk, consider referral for genetic counseling and testing, and, as appropriate, implement syndrome-specific cancer surveillance or risk-reducing measures., (© 2019 Wiley Periodicals, Inc.)

Purpose: To examine prevalence and predictors of neurocognitive outcomes, social attainment, emotional distress, and health-related quality of life (HRQOL) in long-term survivors of pediatric Wilms tumor (WT)., Methods: One hundred fifty-eight WT survivors (59% female; mean [SD] age 33 [9.1] years; time since diagnosis 29 [9.1] years) and 354 community controls (55.6% female; 35 [10.2] years) completed comprehensive neuropsychological testing and physical examination, including echocardiography/electrocardiography, pulmonary function tests, and endocrine evaluation. Self-report of emotional distress, HRQOL, and social attainment were collected. Impairment was defined in relation to both controls and normative data. Generalized linear models were developed to examine impact of treatment and chronic health conditions on outcomes., Results: WT survivors performed poorer than norms and controls in 6 of 16 cognitive variables and 1 of 8 HRQOL variables, with scores ranging from - 0.64 (mathematics) to - 0.21 (verbal fluency) standard deviations below expectations. Compared to controls, WT survivors were less likely to graduate college (odds ratio 2.23, 95% confidence interval 1.46-3.41) and had more moderate to severe neurologic conditions (18.4% vs 8.2%, p < 0.001), which were associated with poor memory (β = - 0.90, p < 0.001), attention (β = - 1.02, p < 0.001), and HRQOL general health (β = - 0.80, p = 0.0015). Treatment variables and cardiopulmonary morbidity (higher in survivors) were not associated with outcomes., Conclusions: Survivors of WT demonstrate impairment in neurocognitive function and have lower social attainment during adulthood, with poorer neurocognitive function associated with neurologic morbidity., Implications for Cancer Survivors: Survivors of WT should be offered neurocognitive evaluations and rehabilitation. Neurologic conditions should be routinely assessed, and appropriate support offered to reduce risk for functional limitations.

Background: The impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT)., Methods: Adult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4-62.2 years) completed neurocognitive tests and self-reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin-like growth factor1 level less than -2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high-dose intravenous methotrexate were included as covariates in multivariable linear regression models., Results: Of the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT (P = .002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z-score, -0.84 vs -0.61; P = .02), processing speed (z-score, -0.49 vs -0.30; P = .04), cognitive flexibility (z-score, -1.37 vs -0.94; P = .01), and verbal fluency (z-score, -0.74 vs -0.44; P = .001), and they self-reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P = .01; vitality, P = .01; mental health, P = .01); and CRT dose accounted for the lower neurocognitive outcomes., Conclusions: Adult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD., (© 2019 American Cancer Society.)

Purpose Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed the contribution of pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes to their SN risk. Patients and Methods Whole-genome sequencing (30-fold) was performed on samples from childhood cancer survivors who were ≥ 5 years since initial cancer diagnosis and participants in the St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Germline mutations in 60 genes known to be associated with autosomal dominant cancer predisposition syndromes with moderate to high penetrance were classified by their pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Relative rates (RRs) and 95% CIs of SN occurrence by mutation status were estimated using multivariable piecewise exponential regression stratified by radiation exposure. Results Participants were 3,006 survivors (53% male; median age, 35.8 years [range, 7.1 to 69.8 years]; 56% received radiotherapy), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 P/LP mutations were identified in 5.8% (95% CI, 5.0% to 6.7%) of survivors. Mutations were associated with significantly increased rates of breast cancer (RR, 13.9; 95% CI, 6.0 to 32.2) and sarcoma (RR, 10.6; 95% CI, 4.3 to 26.3) among irradiated survivors and with increased rates of developing any SN (RR, 4.7; 95% CI, 2.4 to 9.3), breast cancer (RR, 7.7; 95% CI, 2.4 to 24.4), nonmelanoma skin cancer (RR, 11.0; 95% CI, 2.9 to 41.4), and two or more histologically distinct SNs (RR, 18.6; 95% CI, 3.5 to 99.3) among nonirradiated survivors. Conclusion The findings support referral of all survivors for genetic counseling for potential clinical genetic testing, which should be prioritized for nonirradiated survivors with any SN and for those with breast cancer or sarcoma in the field of prior irradiation.

Background: To compare associations of symptom prevalence, chronic conditions, and health-related quality of life (HRQOL) between cancer survivors and non-cancer individuals using the U.S. National Health Interview Survey. Methods: Study samples comprised 604 survivors and 6,166 non-cancer individuals. Symptoms included sensation abnormality, pain, fatigue, cognitive disturbance, depression, and anxiety. Physical and mental HRQOL was measured by the Patient-Reported Outcomes Measurement Information System. Results: Compared with non-cancer individuals, survivors had higher prevalence in sensation abnormality (OR = 2.4; 95% CI = 1.9 to 3.0), pain (OR = 2.1; 95% CI = 1.7 to 2.6), fatigue (OR = 1.4; 95% CI = 1.1 to 1.8), and decremented physical HRQOL (difference = -3.7; 95% CI = -4.7 to -2.6). The prevalence of individual symptoms was significantly associated with decremented physical HRQOL [range = -5.9 (anxiety) to -8.9 (pain)] and mental HRQOL [range = -4.7 (sensation) to -8.4 (depression)]. The association between cancer experience and physical and mental HRQOL was chiefly explained by the prevalence of six symptoms and presence of chronic conditions. Pain (β = -4.0; 95% CI = -4.5 to -3.6) and ≥2 chronic conditions (β = -9.2; 95% CI = -10.2 to -8.2) significantly decremented physical HRQOL. Depression (β = -5.2; 95% CI = -5.8 to -4.6) and ≥2 chronic conditions (β = -3.3; 95% CI = -4.4 to -2.3) significantly decremented mental HRQOL. Conclusions: Cancer survivors experience more symptom burden than non-cancer individuals, which is associated with more chronic conditions and impaired HRQOL. Impacts: Interventions to manage symptom prevalence especially for older cancer survivors and survivors with more chronic conditions may improve their HRQOL outcomes. Cancer Epidemiol Biomarkers Prev; 26(7); 1124-32. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Purpose: To assess the prevalence and severity of neurocognitive impairment in adult survivors of pediatric CNS tumors and to examine associated treatment exposures., Patients and Methods: Participants included 224 survivors of CNS tumors who were treated at St Jude Children's Research Hospital (current median age [range], 26 years [19 to 53 years]; time from diagnosis, 18 years [11 to 42 years]) and completed neurocognitive testing. Information on cranial radiation therapy (CRT) doses and parameters of delivery were abstracted from medical records. The prevalence of severe impairment (ie, at least two standard deviations below normative mean) was compared across radiation treatment groups (no CRT, focal irradiation, craniospinal irradiation) using the χ(2) test. Log-binomial models were used to estimate risk ratios (RRs) and corresponding 95% CIs for severe impairment., Results: In multivariable models, craniospinal irradiation was associated with a 1.5- to threefold increased risk of severe impairment compared with no CRT (eg, intelligence: RR = 2.70; 95% CI, 1.37 to 5.34; memory: RR = 2.93; 95% CI, 1.69 to 5.08; executive function: RR = 1.74; 95% CI, 1.24 to 2.45). Seizures were associated with impaired academic performance (RR = 1.48; 95% CI, 1.02 to 2.14), attention (RR = 1.54; 95% CI, 1.12 to 2.13), and memory (RR = 1.44; 95% CI, 1.04 to 1.99). Hydrocephalus with shunt placement was associated with impaired intelligence (RR = 1.78; 95% CI, 1.12 to 2.82) and memory (RR = 1.42; 95% CI, 1.03 to 1.95). Differential follow-up time contributed to variability in prevalence estimates between survivors treated with older nonconformal and those treated with more contemporary conformal radiation therapy methods. Neurocognitive impairment was significantly associated with lower educational attainment, unemployment, and nonindependent living., Conclusion: Survivors of pediatric CNS tumors are at risk of severe neurocognitive impairment in adulthood. The prevalence of severe impairment is greater than expected in the general population, even in the absence of CRT, and is associated with disrupted attainment of adult social milestones., (© 2016 by American Society of Clinical Oncology.)

Importance: This study provides the first objective data documenting neurocognitive impairment in long-term survivors of childhood osteosarcoma., Objective: To examine neurocognitive, neurobehavioral, emotional, and quality-of-life outcomes in long-term survivors of childhood osteosarcoma., Design, Setting, and Participants: Cross-sectional cohort study at an academic research hospital, with prospective treatment and chronic health predictors. Outcome data were collected from June 2008 to August 2014. Data analysis was completed in April 2015. Survivors of osteosarcoma recruited from the St Jude Lifetime Cohort Study were compared with community controls., Main Outcomes and Measures: Neurocognitive function, neurobehavioral symptoms, emotional distress, and quality of life. Outcomes were examined in relation to pharmacokinetic indices of methotrexate exposure and current chronic health conditions, which were assessed through medical examination and coded according to Common Terminology Criteria for Adverse Events, Version 4.03., Results: Eighty survivors of osteosarcoma (mean [SD] age, 38.9 [7.6] years; time since diagnosis, 24.7 [6.6] years; 42% female) were compared with 39 community controls (age, 39.0 [11.7] years; 56% female). Survivors demonstrated lower mean scores in reading skills (-0.21 [95% CI, -0.32 to -0.10] vs 0.05 [95% CI, -0.13 to 0.23]; P = .01), attention (-0.78 [95% CI, -1.32 to -0.24] vs 0.24 [95% CI, -0.07 to 0.55]; P = .002), memory (-0.24 [95% CI, -0.48 to 0] vs 0.27 [95% CI, -0.08 to 0.62]; P = .01), and processing speed (-0.15 [95% CI, -0.35 to 0.05] vs 0.74 [95% CI, 0.44 to 1.03]; P < .001). Results of pharmacokinetic analysis showed that high-dose methotrexate maximum plasma concentration (estimate = 0; P = .48), median clearance (estimate = -0.11; P = .76), and median/cumulative exposure (estimate = 0; P = .45) were not associated with neurocognitive outcomes. Any grade 3 or 4 Common Terminology Criteria for Adverse Events cardiac, pulmonary, or endocrine condition was associated with poorer memory (t = 2.93; P = .006) and slower processing speed (t = 3.03; P = .002). Survivor-reported poor general health was associated with decreased sustained attention (estimate = 0.24; P = .05) and processing speed (estimate = 0.34; P = .005)., Conclusions and Relevance: Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. Prospective longitudinal studies are needed to identify onset and progression of impairment to inform optimal interventions.

Background: Childhood cancer survivors (CCSs) are at risk for obesity. The purpose of this project was to determine which clinical measures of body composition are most accurate among CCSs in comparison with dual-energy x-ray absorptiometry (DXA)., Methods: The agreement between the body mass index (BMI), skinfold percent body fat, and waist-to-height ratio (WHtR) and DXA was evaluated among 1361 CCSs (mean age, 32.4 ± 7.7 years) 10 or more years after the diagnosis. The sensitivity and specificity of BMI, skinfold, and WHtR obesity classifications were calculated with respect to DXA. Log-binomial regression, stratified by sex, was used to evaluate treatment-related factors for misclassification as nonobese by BMI, skinfolds, and WHtR., Results: The mean body fat values were 23.3% ± 7.7% (males) and 32.3% ± 8.1% (females) for skinfolds and 26.9% ± 7.4% (males) and 38.4% ± 7.7% (females) for DXA. Pearson correlations between skinfolds and DXA were high (R = 0.83 for males, R = 0.84 for females). Skinfolds incorrectly classified 34.5% of obese males and 27.3% of obese females. BMI measures were the least sensitive with false-negative rates of 46.4% (males) and 53.1% (females). Males exposed to abdominal/pelvic radiation were at increased risk for misclassification as nonobese by BMI (relative risk, 1.57; 95% confidence interval, 1.25-1.95). The percentages classified as obese were highest with DXA (males, 63.1%; females, 84.8%) and lowest with BMI (males, 35.7%; females, 39.7%). Although skinfolds and WHtR underestimated the percentage classified as obese in comparison with DXA, the differences were not as large., Conclusions: Findings suggest that skinfolds and WHtR are better than BMI for obesity classification in CCSs. Clinicians should be aware of the high risk of misclassifying obese CCSs as nonobese., (© 2015 American Cancer Society.)

Purpose: To compare age-dependent changes in health status among childhood cancer survivors and a sibling cohort., Methods: Adult survivors of childhood cancer and siblings, all participants of the Childhood Cancer Survivor Study, completed three surveys assessing health status. At each of three time points, participants were classified as having poor outcomes in general health, mental health, function, or daily activities if they indicated moderate to extreme impairment. Generalized linear mixed models were used to compare survivors with siblings for each outcome as a function of age and to identify host- and treatment-related factors associated with age-dependent worsening health status., Results: Adverse health status outcomes were more frequent among survivors than siblings, with evidence of a steeper trajectory of age-dependent change among female survivors with impairment in at least one health status domain (P = .01). In adjusted models, survivors were more likely than siblings to report poor general health (prevalence ratio [PR], 2.37; 95% CI, 2.09 to 2.68), adverse mental health (PR, 1.66; 95% CI, 1.52 to 1.80), functional impairment (PR, 4.53; 95% CI, 3.91 to 5.24), activity limitations (PR, 2.38; 95% CI, 2.12 to 2.67), and an adverse health status outcome in any domain (PR, 2.10; 95% CI, 1.97 to 2.23). Cancer treatment and health behaviors influence the magnitude of differences by age groups. Chronic conditions were associated with adverse health status outcomes across organ systems., Conclusion: The prevalence of poor health status is higher among survivors than siblings, increases rapidly with age, particularly among female participants, and is related to an increasing burden of chronic health conditions., (© 2014 by American Society of Clinical Oncology.)

Cancer is the leading disease-related cause of death in adolescents and young adults (AYAs). This population faces many short- and long-term health and psychosocial consequences of cancer diagnosis and treatment, but many programs for cancer treatment, survivorship care, and psychosocial support do not focus on the specific needs of AYA cancer patients. Recognizing this health care disparity, the National Cancer Policy Forum of the Institute of Medicine convened a public workshop to examine the needs of AYA patients with cancer. Workshop participants identified many gaps and challenges in the care of AYA cancer patients and discussed potential strategies to address these needs. Suggestions included ways to improve access to care for AYAs, to deliver cancer care that better meets the medical and psychosocial needs of AYAs, to develop educational programs for providers who care for AYA cancer survivors, and to enhance the evidence base for AYAs with cancer by facilitating participation in research., (©AlphaMed Press.)

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., (© 2014 by American Society of Clinical Oncology.)

Background: Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols., Methods: We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population., Findings: We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living., Interpretation: The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted., Funding: National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: The first generation of childhood cancer survivors is now aging into their fourth and fifth decades of life, yet health risks across the aging spectrum are not well established., Methods: Analyses included 14,359 5-year survivors from the Childhood Cancer Survivor Study, who were first diagnosed when they were younger than 21 years old and who received follow-up for a median of 24.5 years after diagnosis (range, 5.0 to 39.3 years) along with 4,301 of their siblings. Among the survivors, 5,604 were at least 35 years old (range, 35 to 62 years) at last follow-up. Severe, disabling, life-threatening, and fatal health conditions more than 5 years from diagnosis were classified using the Common Terminology Criteria for Adverse Events, grades 3 to 5 (National Cancer Institute)., Results: The cumulative incidence of a severe, disabling, life-threatening, or fatal health condition was greater among survivors than siblings (53.6%; 95% CI, 51.5 to 55.6; v 19.8%; 95% CI, 17.0 to 22.7) by age 50 years. When comparing survivors with siblings, hazard ratios (HR) were significantly increased within the age group of 5 to 19 years (HR, 6.8; 95% CI, 5.5 to 8.3), age group of 20 to 34 years (HR, 3.8; 95% CI, 3.2 to 4.5), and the ≥ 35 years group (HR, 5.0; 95% CI, 4.1 to 6.1), with the HR significantly higher among those ≥ 35 years versus those 20 to 34 years old (P = .03). Among survivors who reached age 35 years without a previous grade 3 or 4 condition, 25.9% experienced a subsequent grade 3 to 5 condition within 10 years, compared with 6.0% of siblings (P < .001)., Conclusion: Elevated risk for morbidity and mortality among survivors increases further beyond the fourth decade of life, which affects the future clinical demands of this population relative to ongoing surveillance and interventions.

Purpose: To examine posttraumatic stress disorder and posttraumatic stress symptoms (PTSD/PTSS) in children with cancer using methods that minimize focusing effects and allow for direct comparison to peers without a history of cancer., Patients and Methods: Children with cancer (n = 255) stratified by time since diagnosis, and demographically matched peers (n = 101) were assessed for PTSD using structured diagnostic interviews by both child and parent reports, and survey measures of PTSS and psychological benefit/growth by child report., Results: Cancer was identified as a traumatic event by 52.6% of children with cancer, declining to 23.8% in those ≥ 5 years from diagnosis. By diagnostic interview, 0.4% of children with cancer met criteria for current PTSD, and 2.8% met lifetime criteria by self-report. By parent report, 1.6% of children with cancer met current criteria and 5.9% met lifetime criteria for PTSD. These rates did not differ from controls (all Ps >.1). PTSS levels were descriptively lower in children with cancer but did not differ from controls when all were referring to their most traumatic event (P = .067). However, when referring specifically to cancer-related events, PTSS in the cancer group were significantly lower than in controls (P = .002). In contrast, perceived growth was significantly higher in the cancer group when referring to cancer (P < .001)., Conclusion: These findings suggest no evidence of increased PTSD or PTSS in youths with cancer. Although childhood cancer remains a significant and challenging event, these findings highlight the capacity of children to adjust, and even thrive, in the face of such challenge.

Purpose: Frailty, a phenotype reported among 9.9% of individuals 65 years old and older (9.6% of women; 5.2% of men), has not been assessed among adult childhood cancer survivors (CCS). We estimated the prevalence of frailty and examined associations with morbidity and mortality., Methods: Participants included 1,922 CCS at least 10 years from original cancer diagnosis (men, 50.3%; mean age, 33.6 ± 8.1 years) and a comparison population of 341 participants without cancer histories. Prefrailty and frailty were defined as two and ≥ three of the following conditions: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Morbidity was defined as grade 3 to 4 chronic conditions (Common Terminology Criteria for Adverse Events version 4.0). Fisher's exact tests were used to compare, by frailty status, percentages of those with morbidity. In a subset of 162 CCS who returned for a second visit, Poisson regression was used to evaluate associations between frailty and new onset morbidity. Cox proportional hazards regression was used to evaluate associations between frailty and death., Results: The prevalence of prefrailty and frailty were 31.5% and 13.1% among women and 12.9% and 2.7% among men, respectively, with prevalence increasing with age. Frail CCS were more likely than nonfrail survivors to have a chronic condition (82.1% v 73.8%). In models adjusted for existing chronic conditions, baseline frailty was associated with risk of death (hazard ratio, 2.6; 95% CI, 1.2 to 6.2) and chronic condition onset (relative risk, 2.2; 95% CI, 1.2 to 4.2)., Conclusion: The prevalence of frailty among young adult CCS is similar to that among adults 65 years old and older, suggesting accelerated aging.

Background: Chronic health conditions are common among long-term childhood cancer survivors, but hospitalization rates have not been reported. The objective of this study was to determine overall and cause-specific hospitalization rates among survivors of childhood cancer and compare rates to the U.S. population., Procedure: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort of 5+ year survivors of childhood malignancies treated at 26 participating centers. Self-reported hospitalizations from 10,366 survivors (diagnosed 1970-1986) were compared to U.S. population rates using age- and sex-stratified standardized incidence ratios (SIRs). Reasons for hospitalization were evaluated and associations between demographic, cancer and treatment-related risk factors with hospitalization were investigated., Results: Survivors were, on average, 20.9 years from cancer diagnosis (SD: 4.6, range: 13-32) and 28.6 years of age (SD: 7.7, range: 13-51). Survivor hospitalization rates were 1.6 times the U.S. population (95% CI: 1.6; 1.7). Increased hospitalization rates were noted irrespective of gender, age at follow-up and cancer diagnosis, with highest SIRs noted among male (SIR = 2.6, 95% CI: 2.2; 3.0) and female (SIR = 2.7, 95% CI: 2.4; 3.1) survivors aged 45-54. Female gender, an existing chronic health condition and/or a second neoplasm, and prior treatment with radiation were associated with an increased risk of non-obstetrical hospitalization., Conclusions: Survivors of childhood cancer demonstrate substantially higher hospitalization rates. Additional research is needed to further quantify the healthcare utilization and economic impact of treatment-related complications as this population ages., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: Carbonyl reductases (CBRs) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR1 and CBR3 influence synthesis of these metabolites. We examined whether single nucleotide polymorphisms in CBR1 (CBR1 1096G>A) and/or CBR3 (CBR3 V244M) modified the dose-dependent risk of anthracycline-related cardiomyopathy in childhood cancer survivors., Patients and Methods: One hundred seventy survivors with cardiomyopathy (patient cases) were compared with 317 survivors with no cardiomyopathy (controls; matched on cancer diagnosis, year of diagnosis, length of follow-up, and race/ethnicity) using conditional logistic regression techniques., Results: A dose-dependent association was observed between cumulative anthracycline exposure and cardiomyopathy risk (0 mg/m(2): reference; 1 to 100 mg/m(2): odds ratio [OR], 1.65; 101 to 150 mg/m(2): OR, 3.85; 151 to 200 mg/m(2): OR, 3.69; 201 to 250 mg/m(2): OR, 7.23; 251 to 300 mg/m(2): OR, 23.47; > 300 mg/m(2): OR, 27.59; P(trend) < .001). Among individuals carrying the variant A allele (CBR1:GA/AA and/or CBR3:GA/AA), exposure to low- to moderate-dose anthracyclines (1 to 250 mg/m(2)) did not increase the risk of cardiomyopathy. Among individuals with CBR3 V244M homozygous G genotypes (CBR3:GG), exposure to low- to moderate-dose anthracyclines increased cardiomyopathy risk when compared with individuals with CBR3:GA/AA genotypes unexposed to anthracyclines (OR, 5.48; P = .003), as well as exposed to low- to moderate-dose anthracyclines (OR, 3.30; P = .006). High-dose anthracyclines (> 250 mg/m(2)) were associated with increased cardiomyopathy risk, irrespective of CBR genotype status., Conclusion: This study demonstrates increased anthracycline-related cardiomyopathy risk at doses as low as 101 to 150 mg/m(2). Homozygosis for G allele in CBR3 contributes to increased cardiomyopathy risk associated with low- to moderate-dose anthracyclines, such that there seems to be no safe dose for patients homozygous for the CBR3 V244M G allele. These results suggest a need for targeted intervention for those at increased risk of cardiomyopathy.

Background: Post-treatment attention problems experienced by pediatric cancer survivors have been described as similar to symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) experienced in physically healthy children. Accordingly, the objectives of this study were to: (a) estimate the rate of occurrence of ADHD and secondary ADHD (SADHD) in a sample of pediatric cancer survivors, (b) compare the rate of ADHD/SADHD among survivors to the prevalence of ADHD in the general population, and (c) examine clinical correlates of ADHD/SADHD in this sample., Procedure: Survivors of pediatric ALL or brain tumor (n = 100) participated in an assessment of attention including a Computerized Performance Measure [Conners' Continuous Performance test-II (CPT-II)], parent and self-report measures (Conners 3), and a structured diagnostic interview for ADHD and other psychological disorders [Diagnostic Interview for Children and Adolescents-IV (DICA-IV)]., Results: Binomial tests revealed that the rate of ADHD/SADHD in our sample (9%) was significantly greater than the lower limits of ADHD prevalence among children in the US (3%; P < 0.001), while no difference was identified compared to the upper limits of ADHD prevalence (7%; P > 0.05). Many additional survivors (>25% of the sample) obtained clinical elevations on Conners 3 scales but did not meet ADHD/SADHD criteria., Conclusions: Attentional deficits experienced by pediatric cancer survivors do not appear to resemble the clinical presentation of ADHD or SADHD. Many survivors with cognitive and behavioral difficulties related to attention were not identified using this diagnostic approach. Findings offer needed clarification to guide researchers and clinicians in conceptualizing, assessing, and intervening on attentional late effects., (Copyright © 2011 Wiley-Liss, Inc.)

The contribution of specific cancer therapies, comorbid medical conditions, and host factors to mortality risk after pediatric Hodgkin lymphoma (HL) is unclear. We assessed leading morbidities, overall and cause-specific mortality, and mortality risks among 2742 survivors of HL in the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study of survivors diagnosed from 1970 to 1986. Excess absolute risk for leading causes of death and cumulative incidence and standardized incidence ratios of key medical morbidities were calculated. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of risks for overall and cause-specific mortality. Substantial excess absolute risk of mortality per 10,000 person-years was identified: overall 95.5; death due to HL 38.3, second malignant neoplasms 23.9, and cardiovascular disease 13.1. Risks for overall mortality included radiation dose ≥ 3000 rad ( ≥ 30 Gy; supra-diaphragm: HR, 3.8; 95% CI, 1.1-12.6; infradiaphragm + supradiaphragm: HR, 7.8; 95% CI, 2.4-25.1), exposure to anthracycline (HR, 2.6; 95% CI, 1.6-4.3) or alkylating agents (HR, 1.7; 95% CI, 1.2-2.5), non-breast second malignant neoplasm (HR, 2.6; 95% CI 1.4-5.1), or a serious cardiovascular condition (HR, 4.4; 95% CI 2.7-7.3). Excess mortality from second neoplasms and cardiovascular disease vary by sex and persist > 20 years of follow-up in childhood HL survivors.

Background: Adult childhood cancer survivors report high levels of unemployment, although it is unknown whether this is because of health or employability limitations., Objectives: We examined 2 employment outcomes from 2003 in the Childhood Cancer Survivor Study (CCSS): (1) health-related unemployment and (2) unemployed but seeking work. We compared survivors with a nearest-age CCSS sibling cohort and examined demographic and treatment-related risk groups for each outcome., Methods: We studied 6339 survivors and 1967 siblings ≥25 years of age excluding those unemployed by choice. Multivariable generalized linear models evaluated whether survivors were more likely to be unemployed than siblings and whether certain survivors were at a higher risk for unemployment., Results: Survivors (10.4%) reported health-related unemployment more often than siblings (1.8%; Relative Risk [RR], 6.07; 95% Confidence Interval [CI], 4.32-8.53). Survivors (5.7%) were more likely to report being unemployed but seeking work than siblings (2.7%; RR, 1.90; 95% CI, 1.43-2.54). Health-related unemployment was more common in female survivors than males (Odds Ratio [OR], 1.73; 95% CI, 1.43-2.08). Cranial radiotherapy doses ≥25 Gy were associated with higher odds of unemployment (health-related: OR, 3.47; 95% CI, 2.54-4.74; seeking work: OR, 1.77; 95% CI, 1.15-2.71). Unemployed survivors reported higher levels of poor physical functioning than employed survivors, and had lower education and income and were more likely to be publicly insured than unemployed siblings., Conclusions: Childhood cancer survivors have higher levels of unemployment because of health or being between jobs. High-risk survivors may need vocational assistance.

Late effects of therapy for childhood cancer are frequent and serious. Fortunately, many late effects are also modifiable. Proactive and anticipatory risk-based care can reduce the frequency and severity of treatment-related morbidity. The primary care clinician should be an integral component in risk-based care of survivors. Continued communication between the "late effects" staff at the cancer center and the primary care clinician is essential for optimum care of this high-risk population.

Background: Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups., Methods: We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided., Results: Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage., Conclusions: Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines.

Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.