ESTRO 2024 - Abstract Book

S1059

Clinical - Gynaecology

ESTRO 2024

Material/Methods:

This retrospective cohort study incorporated the largest available EC patients’ datasets including AACR Project GENIE (n=5,087), Memorial Sloan Kettering-Metastatic Events and Tropisms (n=1,315) and The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC, n=517), collected from 2015-2023, 2013-2021 and 2006-2012, respectively. The prevalence and prognostic significance of POLE or POLD1 mutations in EC were evaluated across self-reported racial groups.

Results:

Patients with POLD1 mutations exhibited an excellent prognosis regardless of race, histology and TP53 mutation status. 23% of POLE mutated cases co-existed with POLD1 mutations. The majority of pathogenic POLE mutations are P286R (71 cases) and V411L[DE1] /M (60 cases), accounting for 69.3% of all the cases with pathogenic mutations. Tumors with both POLE and POLD1 mutations (POLE/POLD1) showed higher tumor mutation burden (TMB) than either mutation alone, with a median TMB of 374.4, as compared with 44.1 and 105.5 for POLD1 only and POLE only, respectively (p<0.001). Patients with both POLE/POLD1 mutated vs. POLE mutated alone vs. POLD1 mutated alone showed similar favorable survival rates (p=0.2, Fig.1). In a total of 6,919 EC cases were studied, of whom 444, 694 and 4,869 patients were self-described as Asian, Black and White, respectively. Within these large data sets, Black patients with EC exhibited a lower weighted average prevalence of pathogenic POLE mutations (0.5%, 3 out of 590 cases), as compared to Asian (6.1%; 26 out of 424) or White (4.6%; 204 out of 4,520) patients. By contrast, the prevalence of POLD1 pathogenic mutations was 5.0%, 3.2%, and 5.6%; in Asian, Black and White EC patients, respectively. As compared with TCGA/Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) EC risk classification algorithm, the composite biomarker panel of POLE or POLD1 mutations identified more Asian, Black and White EC good prognosis than using POLE alone (10% vs. 5.4%; 6.7% vs. 1.5%; 9.6% vs. 7.4%, respectively). For Black EC patients, the panel identified 17 Black EC patients from clinically annotated datasets, with only 1 event at [SJ2] 70 months follow up.