Abstract 4196: Survival differences between males and females diagnosed with childhood cancer
Authors: Williams Lindsay A. , Spector Logan G. 
Published: August 2019

Abstract
Childhood cancer survival differs by sex, but few reports exist characterizing this relationship using modern tumor type classifications for main cancer types. Using the SEER 18 registries (2000-2014), we estimated survival differences between sexes among children aged 0-19 years. We used Kaplan Meier survival curves and Log-Rank p-values to characterize overall survival differences. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) as the measure of association between sex and risk of death by tumor type classified using the International Classification of Childhood Cancer 3rdedition. We used an inverse odds weighting method to determine whether the association between sex and risk of death by tumor type was mediated by stage of disease for solid tumors with significant total effects.
Males and females had similar racial distributions by tumor type. Males were more frequently diagnosed with distant stage of disease than females for Hodgkin lymphoma (33% female, 40% male), Non-Hodgkin lymphoma (45% female, 49% male), neuroblastoma (49% female, 56% male), and osteosarcoma (20% female, 24% male). Males had lower 5-year survival than females for acute lymphoblastic leukemia (ALL) (88% female, 85% male), ependymoma (78% female, 71% male), neuroblastoma (78% female, 74% male), hepatoblastoma (82% female, 77% male), osteosarcoma (71% female, 64% male), and Ewing tumor of the bone (71% female, 67% male). Males had worse overall survival for ALL, ependymoma, neuroblastoma, and osteosarcoma (all Log-Rank p-values&lt;0.02). Males had a higher risk of death than females for ALL (crudeHR:1.24, 95% CI:1.12-1.37), ependymoma (crudeHR:1.36, 95% CI:1.05-1.77), neuroblastoma (crudeHR:1.28, 95% CI:1.09-1.51), and osteosarcoma (crudeHR:1.29, 95% CI:1.08-1.53). Results were similar after adjusting for age at and year of diagnosis, and stage of disease. Among solid tumors with a significant total effect, the association between sex and the risk of death was mediated by stage of disease for neuroblastoma (indirectHR:1.12, 95% CI:1.05-1.19) and was suggestive for osteosarcoma (indirectHR:1.06, 95% CI:1.00-1.12), but not ependymoma. Results were similar in mediation analyses adjusted for age and year of diagnosis.
Sex differences in survival, particularly for ALL, neuroblastoma, osteosarcoma, and ependymoma, may depend to some degree on sex differences in tumor biology or response to treatment. ALL, ependymoma, neuroblastoma, and osteosarcoma account for 1/3 of new cancer diagnoses and ~40% of deaths among children and adolescents. If the five-year survival percentages were the same between sexes for these four cancers, ~18% of male deaths and ~11% of total deaths due to these cancers could be avoided; therefore, studies with detailed molecular tumor and clinical data will be important for identifying mechanisms underlying the observed sex differences in survival.
Citation Format: Lindsay A. Williams, Logan G. Spector. Survival differences between males and females diagnosed with childhood cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4196.