Molecular characterization of long-term and short-term survivors of metastatic uterine leiomyosarcoma.

11542 Background: While some metastatic uterine leiomyosarcomas (uLMS) are clinically aggressive, others have a more indolent disease pace, suggesting biologic heterogeneity. Our objective was to determine whether the molecular characteristics of metastatic uLMS tumors differed between long-term survivors (LS) and short-term survivors (SS). Methods: Patients with metastatic uLMS between 1/1/2000 – 11/31/2020 who received care at our institution and had tumor tissue available were included. uLMSs were subjected to a targeted DNA next-generation sequencing panel of up to 505 cancer-related genes. Metastatic overall survival (mOS) was calculated from the date of diagnosis of metastatic disease until the date of death or last follow-up. LS was defined as mOS >2 years and SS as mOS 0.05 for both). Most BRCA2alterations (92%) were homozygous deletions. Levels of chromosomal instability as quantified by the fraction of genome altered was similar between groups (median 27.3% in LS versus 22.9% in SS, p=0.26). Tumor mutational burden was low in both groups. Conclusions: While uLMS from LS and SS have similar levels of chromosomal instability and tumor mutational burden, uLMS in LS have lower rates of TP53 alterations compared to SS patients, as well as compared to previously reported rates in uLMS. Rates of RB1alterations were higher in LS compared to SS. Interestingly, the rate of BRCA2alterations in both LS and SS is higher than previously reported and provides rationale for next-generation sequencing in patients with metastatic uLMS. Further studies in larger cohorts to validate these findings are warranted. Table: see text