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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: 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]

Background: Survivors of pediatric cancer have elevated risks of mortality and morbidity. Many late adverse effects associated with cancer treatment (eg, second cancers and cardiac and pulmonary disease) are also associated with cigarette smoking, and this suggests that survivors who smoke may be at high risk for these conditions.Methods: This study examined the self-reported smoking status for 9397 adult survivors of childhood cancer across 3 questionnaires (median time interval, 13 years). The smoking prevalence among survivors was compared with the smoking prevalence among siblings and the prevalence expected on the basis of age-, sex-, race-, and calendar time-specific rates in the US population. Multivariable regression models examined characteristics associated with longitudinal smoking patterns across all 3 questionnaires.Results: At the baseline, 19% of survivors were current smokers, whereas 24% of siblings were current smokers, and 29% were expected to be current smokers on the basis of US rates. Current smoking among survivors dropped to 16% and 14% on follow-up questionnaires, with similar decreases in the sibling prevalence and the expected prevalence. Characteristics associated with consistent never-smoking included a higher household income (relative risk [RR], 1.16; 95% confidence interval [CI], 1.08-1.25), higher education (RR, 1.32; 95% CI, 1.22-1.43), and receipt of cranial radiation therapy (RR, 1.08; 95% CI, 1.03-1.14). Psychological distress (RR, 0.86; 95% CI, 0.80-0.92) and heavy alcohol drinking (RR, 0.64; 95% CI, 0.58-0.71) were inversely associated. Among ever-smokers, a higher income (RR, 1.17; 95% CI, 1.04-1.32) and education (RR, 1.23; 95% CI, 1.10-1.38) were associated with quitting, whereas cranial radiation (RR, 0.86; 95% CI, 0.76-0.97) and psychological distress (RR, 0.80; 95% CI, 0.72-0.90) were associated with not having quit. The development of adverse health conditions was not associated with smoking patterns.Conclusions: Despite modest declines in smoking prevalence, the substantial number of consistent current smokers reinforces the need for continued development of effective smoking interventions for survivors. [ABSTRACT FROM AUTHOR]