Background: Treatments for childhood cancer have evolved in recent decades, with the goal of maximizing cure rates while minimizing the adverse effects of therapy. We aimed to evaluate 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 prospective follow-up of 5-year survivors of childhood cancer diagnosed from 1970-1999 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. Multivariable regression models estimated hazard ratios per diagnosis decade, and addition of treatment variables assessed whether treatment changes attenuated associations between diagnosis decade and chronic disease risk. Findings: Among 23,601 survivors (median age 28, range 5-63 years; 46% female), 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 1970-1979 to 29·3% (95% CI, 28·4%-30·2%, p<0·0001) in 1980-1989, and 27·5% (95% CI, 26·4%-28·6%, p=0·012 vs. 1980-1989) in 1990-1999. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition among 5,051 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 1990-1999 compared to 1970-1979 for Hodgkin lymphoma (17·7% vs. 26·4%, p<0·0001), non-Hodgkin lymphoma (16·9% vs. 23·8%, p=0.0053), astrocytoma (30·5% vs. 47·3%, p<0·0001), Wilms tumor (11·9% vs. 17·6%, p=0·034), soft tissue sarcoma (28·3% vs. 36·5%, p=0·021), and osteosarcoma (65·6% vs. 87·5%, p<0·0001). In contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-1999 vs. 1970-1979) for medulloblastoma/PNET (58·9% vs. 42·9%, p=0·00060) and neuroblastoma (25·0% vs. 18·0%, p=0·0045). Results were consistent with changes in treatment as a mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma, Hodgkin lymphoma, and non-Hodgkin lymphoma. Temporal decreases were observed for endocrinopathies, subsequent malignant neoplasms, musculoskeletal conditions, and gastrointestinal conditions, while hearing loss increased. Interpretation: Our results provide novel evidence that more recently treated survivors of childhood cancer have experienced improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximize cure while reducing risk of late effects. Continuing advances in cancer therapy offer promise of further reducing the risk of late effects. However, achieving a cure for childhood cancer continues to come at a cost for many survivors, emphasizing the importance of long-term follow-up care for this population. Funding: National Cancer Institute and t...

Sex and race were associated with maturation-specific differences in cortical BMD and dimensions that were not fully explained by differences in bone length or muscle. No race or sex differences in the functional muscle bone unit were identified.

Purpose The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures. Patients and Methods We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children’s Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings. Results The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P < .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P < .001), and men demonstrated higher prevalence of testosterone replacement (P < .001) after cyclophosphamide equivalent dose of 20 g/m2 or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P < .001 for all). Conclusion Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.

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