Age acceleration among adolescent and young adult patients with Ewing sarcoma and osteosarcoma.

11051 Background: Ewing sarcoma (ES) and osteosarcoma (OS) are two common bone malignancies affecting adolescent and young adult (AYA) patients, often requiring intensive and multi-modal therapy. Cancer and its associated treatments may accelerate the aging process, as reflected in phenotypic age acceleration (PAA), leading to increased risk for developing chronic health conditions typically ascribed in older individuals.We conducted a pilot study to evaluate the impact of treatment completion for ES and OS on age acceleration among an AYA cohort using the validated phenotypic age (PheAge) instrument. Methods: This pilot study included participants who completed treatment at Vanderbilt University Medical Center from 2012-present for either ES or OS between age 20 and 39 years. Phenotypic age at diagnosis and end of treatment was derived using a modified PheAge equation, which was validated for patients age ≥20 years and based on chronological age and eight clinical biochemistry measurements, including albumin, creatinine, glucose, lymphocyte percent, mean cell volume, red cell distribution width, alkaline phosphatase, and white blood cell count. PAA was then calculated as the difference between PheAge and chronologic age. A positive PAA indicates an individual’s phenotypic age is older than their chronological age, signifying accelerated aging. A descriptive analysis of PAA across patient demographics and disease strata was then conducted. Results: Among 30 AYA participants included in our study, 15 participants were diagnosed with ES and 15 with OS. The mean age at diagnosis was 23.8 (Q1 21.8, Q3 27.5). There was an overall male predominance of 19 participants (63.3%). Among participants with ES, the median PAA was 16.1 years (13.8, 18.1) at diagnosis and 18.4 years (13.6, 25.8) at end of therapy. Among participants with OS, the median PAA was 16.0 years (12.9, 20.7) at diagnosis and 15.9 years (13.9, 19.7) at end of therapy. Conclusions: This pilot study suggests that AYA patients with ES and OS had accelerated aging at diagnosis and ES patients may endure further age acceleration following treatment, while patients with OS had shown a nearly unchanged PAA. These results highlight the need for a larger and more comprehensive investigation into the contributing factors of PAA, including an evaluation of genetics, environmental exposures, cancer characteristics, treatment modalities, as well as acute and chronic toxicities of therapy. Such knowledge will contribute to understanding the etiology and cumulative and long-term impact of these common bone malignancies among AYAs.