The malignant bone tumor, osteosarcoma, which is more common in males, displays a bimodal peak in incidence in adolescence and later adulthood. [1], [2], [3] Osteosarcoma tumors are generally found in the long bones of the lower and upper extremities in children and the pelvis, spine, and skull in adults. [4] Despite the addition of chemotherapy alongside surgical resection in the 1970–80’s for treatment, osteosarcoma survival has remained at 60–70% 5-years post diagnosis with few treatment advancements in recent decades. [5] Osteosarcoma survival varies by tumor location. Tumors in the pelvis and spine result in 5-year survival <35% while tumors in the upper limbs and face/skull result in 5-year survival around 60%. [4] Osteosarcoma survival varies by age at diagnosis with individuals >60 years of age experiencing twice the risk of death as those <25 years of age at diagnosis. [4]

In children and adults, we and others have reported on the male excess in death following an osteosarcoma diagnosis of approximately 30–40% when compared to females. [6], [7], [8] Reasons behind observed differences in osteosarcoma survival by sex are likely manifold and depend on treatment received, response to therapy, and tumor biology. Our prior study in pediatric osteosarcoma attempted to parse contributors to the sex difference in survival. Sex differences in survival were largely independent of stage of disease among pediatric patients in our analysis of Surveillance, Epidemiology and End Results data. [6] Sex differences in the somatic tumor landscape may drive tumorigenicity and impact survival. As such, we recently identified over 1000 differentially expressed genes by sex in osteosarcoma tumors from males and females, which may underlie some of the observed differences in outcomes. [9] In previous analyses, [6], [9] we were unable to account for treatment received as it was not available. Therefore, in the present study we have examined long-term survival differences by sex for osteosarcoma in children and adults. Additionally, we have examined sex differences in osteosarcoma survival adjusting for and stratifying by treatment received to determine the role of treatment in the observed sex disparities.