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Background The incidence of and risk factors for late-onset kidney failure among survivors over the very long term remains understudied. Materials and methods A total of 25,530 childhood cancer survivors (median follow-up 22.3 years, interquartile range 17.4–28.8) diagnosed between 1970 and 1999, and 5045 siblings from the Childhood Cancer Survivor Study were assessed for self-reported late-onset kidney failure, defined as dialysis, renal transplantation, or death attributable to kidney disease. Piecewise exponential models evaluated associations between risk factors and the rate of late-onset kidney failure. Results A total of 206 survivors and 10 siblings developed late-onset kidney failure, a 35-year cumulative incidence of 1.7% (95% confidence interval [CI] = 1.4–1.9) and 0.2% (95% confidence interval [CI] = 0.1–0.4), respectively, corresponding to an adjusted rate ratio (RR) of 4.9 (95% CI = 2.6–9.2). High kidney dose from radiotherapy (≥15Gy; RR = 4.0, 95% CI = 2.1–7.4), exposure to high-dose anthracycline (≥250 mg/m2; RR = 1.6, 95% CI = 1.0–2.6) or any ifosfamide chemotherapy (RR = 2.6, 95% CI = 1.2–5.7), and nephrectomy (RR = 1.9, 95% CI = 1.0–3.4) were independently associated with elevated risk for late-onset kidney failure among survivors. Survivors who developed hypertension, particularly in the context of prior nephrectomy (RR = 14.4, 95% CI = 7.1–29.4 hypertension with prior nephrectomy; RR = 5.9, 95% CI = 3.3–10.5 hypertension without prior nephrectomy), or diabetes (RR = 2.2, 95%CI = 1.2–4.2) were also at elevated risk for late-onset kidney failure. Conclusions Survivors of childhood cancer are at increased risk for late-onset kidney failure. Kidney dose from radiotherapy ≥15 Gy, high-dose anthracycline, any ifosfamide, and nephrectomy were associated with increased risk of late-onset kidney failure among survivors. Successful diagnosis and management of modifiable risk factors such as diabetes and hypertension may mitigate the risk for late-onset kidney failure. The association of late-onset kidney failure with anthracycline chemotherapy represents a novel finding that warrants further study.

PURPOSE: Adult childhood cancer survivors are frequently accompanied by a parent to survivorship clinic. From clinical evaluations among young adult survivors of childhood cancer we aimed to (1) investigate the association between accompaniment and the survivors’ health complexity; and (2) determine whether accompaniment is associated with adherence to recommended surveillance tests and follow-up in clinic. METHODS: This was a cross-sectional study of all patients ≥ 18 years old at their first visit to the regional Yale Childhood Cancer Survivorship Clinic from 2003 to 2018. Patients underwent standardized evaluations for medical, neurocognitive, and emotional late effects of therapy; individuals accompanying patients were documented. RESULTS: The 168 patients were a median of 12.0 (range: 0–17.9) years at diagnosis and 22.7 (range: 18.1–39.9) years at evaluation, and 45.8% were accompanied by a parent. In multivariable analyses, 18.0–24.99 years vs. 25.0–39.99 years at visit (OR = 3.43, p = 0.022) and central nervous system (CNS) tumor diagnosis (OR = 6.09 vs. leukemia/lymphoma diagnosis, p = 0.010) were significantly associated with parental accompaniment. Accompaniment was not associated with number and severity of medical late effects, neurocognitive impairment, or emotional distress. Accompaniment was not associated with completed surveillance tests or a clinic follow-up within 2 years. CONCLUSION: Forty-six percent of survivors were accompanied by a parent, and accompaniment was not associated with survivor health status. Accompaniment was not associated with adherence to recommended surveillance tests or clinic follow-up.

OBJECTIVE Assess the association between fine motor (FM) and visual-motor integration (VMI) skills and academic achievement in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS In this 28-site cross-sectional study of 256 children in first remission, a mean of 8.9 ± 2.2 years after treatment for standard-risk precursor-B ALL, validated measures of FM, VMI, reading, math, and intelligence were administered at mean follow-up age of 12.8 ± 2.5 years. RESULTS VMI was significantly associated with written math calculation ability (p

Purpose To determine the risk of subsequent carcinomas other than breast, thyroid, and skin, and to identify factors that influence the risk among survivors of childhood cancer. Patients and Methods Subsequent malignant neoplasm history was determined in 13,136 participants (surviving ≥ 5 years postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using Surveillance, Epidemiology, and End Results data. Results In 71 individuals, 71 carcinomas were diagnosed at a median age of 27 years and a median elapsed time of 15 years in the genitourinary system (35%), head and neck area (32%), gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%) had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in a previous radiotherapy field. Risk was significantly elevated following all childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas. Significantly elevated risk of head and neck carcinoma occurred in survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR = 20.9). Conclusion Young survivors of childhood cancers are at increased risk of developing subsequent carcinomas typical of later adulthood, underscoring the importance of long-term follow-up and risk-based screening. Follow-up of the cohort is ongoing to determine lifetime risk and delineate individual characteristics that contribute to risk.

Survival of childhood acute lymphoblastic leukemia (ALL) is one of the greatest medical success stories of the last four decades. Unfortunately, childhood ALL survivors experience medical late effects that increase their risk of morbidity and premature death, often due to heart and vascular disease. Research has helped elucidate the mechanisms and trajectory of direct damage to the heart from treatment exposure, particularly to anthracyclines, and has also contributed knowledge on the influences of related chronic conditions, such as obesity and insulin resistance on heart health in these survivors. This article summarizes the key issues associated with early morbidity and mortality from cardiac-related disease in childhood ALL survivors and suggests directions for interventions to improve long-term outcomes.

Background & Aims Children who receive cancer therapy experience numerous acute gastrointestinal (GI) toxicities. However, the long-term GI consequences have not been extensively studied. We evaluated the incidence of long-term GI outcomes and identified treatment-related risk factors. Methods Upper GI, hepatic, and lower GI adverse outcomes were assessed in cases from participants in the Childhood Cancer Survivor Study, a study of 14,358 survivors of childhood cancer who were diagnosed between 1970 and 1986; data were compared with those from randomly selected siblings. The median age at cancer diagnosis was 6.8 years (range, 0–21.0 years), and the median age at outcome assessment was 23.2 years (5.6–48.9 years) for survivors and 26.6 years (1.8–56.2 years) for siblings. Rates of self-reported late GI complications (occurred 5 or more years after cancer diagnosis) were determined and associated with patient characteristics and cancer treatments, adjusting for age, sex, and race. Results Compared with siblings, survivors had increased risk of late-onset complications of the upper GI tract (rate ratio [RR], 1.8; 95% confidence interval [CI], 1.6–2.0), liver (RR, 2.1; 95% CI, 1.8–2.5), and lower GI tract (RR, 1.9; 95% CI, 1.7–2.2). The RRs for requiring colostomy/ileostomy, liver biopsy, or developing cirrhosis were 5.6 (95% CI, 2.4–13.1), 24.1 (95% CI, 7.5–77.8), and 8.9 (95% CI, 2.0–40.0), respectively. Older age at diagnosis, intensified therapy, abdominal radiation, and abdominal surgery increased the risk of certain GI complications. Conclusions Individuals who received therapy for cancer during childhood have an increased risk of developing GI complications later in life.

Background/Objective: Adult survivors of childhood cancer can have altered social functioning. We sought to identify factors that predict marriage and divorce outcomes in this growing population. Methods: This was a retrospective cohort study of 8,928 ≥5-year adult survivors of childhood malignancy and 2,879 random sibling controls participating in the Childhood Cancer Survivor Study. Marital status, current health, psychological status, and neurocognitive functioning were determined from surveys and validated instruments. Results: Survivors were more likely to be never-married than siblings [relative risk (RR), 1.21; 95% confidence interval (95% CI), 1.15-1.26] and the U.S. population (RR, 1.25; 95% CI, 1.21-1.29), after adjusting for age, gender, and race. Patients with central nervous system tumors were at greatest risk of not marrying (RR, 1.50; 95% CI, 1.41-1.59). Married survivors divorced at frequencies similar to controls. In multivariable regression analysis, nonmarriage was most associated with cranial radiation (RR, 1.15; 95% CI, 1.02-1.31 for >2,400 centigray). In analysis of neurobehavioral functioning, nonmarriage was associated with worse task efficiency (RR, 1.27; 95% CI, 1.20-1.35), but not with emotional distress, or problems with emotional regulation, memory, or organization. Physical conditions predictive of nonmarriage included short stature (RR, 1.27; 95% CI, 1.20-1.34) and poor physical function (RR, 1.08; 95% CI, 1.00-1.18). Structural equation modeling suggested that cranial radiation influenced marriage status through short stature, cognitive problems, and poor physical function. Conclusions: Childhood cancer survivors married at lower frequencies compared with peers. Patients with central nervous system tumors, cranial radiation, impaired processing efficiency, and short stature were more likely to never marry. Divorce patterns in survivors were similar to peers. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2626–35)

Purpose Osteonecrosis (ON) is a potentially serious complication of therapy in survivors of childhood cancer. Our goals were to describe the incidence of ON and identify patient and treatment characteristics associated with elevated risk. Patients and Methods The rate of self-reported ON was determined for 9,261 patients enrolled onto the Childhood Cancer Survivor Study, a cohort of 5-year survivors of childhood cancer diagnosed from 1970 to 1986, and compared with the rate in a random sample of 2,872 siblings of survivors. Survivors with positive responses were reinterviewed to confirm the diagnosis. Results Fifty-two cancer survivors reported ON in 78 joints, yielding 20-year cumulative incidence of 0.43% and a rate ratio (RR) of 6.2 (95% CI, 2.3 to 17.2) compared with siblings, adjusted for age and sex; 44% developed ON in a previous radiation field. The RR was greatest among survivors of stem-cell transplantation for acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (RR = 26.9, 66.5, and 93.1, respectively). Nontransplantation patients with ALL (RR = 6.5; 95% CI, 2.2 to 19.4), AML (RR = 11.2; 95% CI, 2.1 to 61.2), and bone sarcoma (RR = 7.3; 95% CI, 2.0 to 26.2) were at higher risk for ON. Older age at diagnosis, shorter elapsed time, older treatment era, exposure to dexamethasone (± prednisone), and gonadal and nongonadal radiation were independently associated with ON. Conclusion ON among long-term survivors of childhood cancer is rare. However, compared with siblings, childhood cancer survivors have a significantly increased relative rate of ON, particularly those who were older at diagnosis and who received dexamethasone or radiation therapy. Future studies are needed to better delineate our findings, particularly the increased risk after gonadal radiation.