Ahwon Lee

Prediction of homologous recombination deficiency from Oncomine Comprehensive Assay Plus correlating with SOPHiA DDM HRD Solution

Objective Poly(ADP-ribose) polymerase (PARP) inhibitors are used for targeted therapy for ovarian cancer with homologous recombination deficiency (HRD). In this study, we aimed to develop a homologous recombination deficiency prediction model to predict the genomic integrity (GI) index of the SOPHiA DDM HRD Solution from the Oncomine Comprehensive Assay (OCA) Plus. We also tried to a find cut-off value of the genomic instability metric (GIM) of the OCA Plus that correlates with the GI index of the SOPHiA DDM HRD Solution. Methods We included 87 cases with high-grade ovarian serous carcinoma from five tertiary referral hospitals in Republic of Korea. We developed an HRD prediction model to predict the GI index of the SOPHiA DDM HRD Solution. As predictor variables in the model, we used the HRD score, which included percent loss of heterozygosity (%LOH), percent telomeric allelic imbalance (%TAI), percent large-scale state transitions (%LST), and the genomic instability metric (GIM). To build the model, we employed a penalized logistic regression technique. Results The final model equation is -21.77 + 0.200 × GIM + 0.102 × %LOH + 0.037 × %TAI + 0.261 × %LST. To improve the performance of the prediction model, we added a borderline result category to the GI results. The accuracy of our HRD status prediction model was 0.958 for the test set. The accuracy of HRD status using GIM with a cut-off value of 16 was 0.911. Conclusion The Oncomine Comprehensive Assay Plus provides a reliable biomarker for homologous recombination deficiency.

Improved Prognostic Stratification With 2023 International Federation of Gynecology and Obstetrics Staging in Endometrial Cancer Reflecting Poor Prognosis of Aggressive Histological Types and p53 Abnormality

This study compares the distribution and prognostic impact of the 2009 and 2023 International Federation of Gynecology and Obstetrics (FIGO) staging systems for endometrial cancer and their impact on the 2022 European Society for Medical Oncology (ESMO) risk classification. Patients were restaged according to the 2009 FIGO staging system, the 2023 FIGO staging system, and the 2023 FIGO staging system with molecular classification. Risk groups were assigned according to the 2022 ESMO guidelines using each staging system. Among 679 patients, 139 (20.5%) experienced stage migration when transitioning from the 2009 FIGO staging system to the 2023 FIGO staging system with molecular classification, with 121 (17.8%) upstaged and 18 (2.7%) downstaged. Most changes were from FIGO stage I to stage II, primarily due to p53 abnormality, aggressive histological type, or extensive/substantial lymphovascular space invasion. Hazard ratios for overall survival, disease-free survival, and event-free survival increased with advancing stage groups in all systems, showing the greatest differences when the 2023 FIGO staging system with molecular classification was used. The newly introduced FIGO stages IC, IIC (both representing aggressive histological types), and IICmp53abn (associated with p53 abnormality) in the 2023 FIGO staging system were associated with worse outcomes, similar to FIGO stage III. The prognostic predictability of the 2022 ESMO risk group was minimally affected by the transition from the 2009 FIGO to the 2023 FIGO staging system, as the factors introduced in the new FIGO system were already incorporated into the 2022 ESMO risk classification. Only 17 (2.5%) patients experienced a change in their assigned risk group. The 2023 FIGO staging system showed improved prognostic stratification over the 2009 FIGO staging system, particularly by reflecting the poor prognosis of aggressive histological types and p53 abnormality.