Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99: a report from the Childhood Cancer Survivor Study cohort

Abstract

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 the American Lebanese-Syrian Associated Charities.