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( Junsik Park ),( Jung Chul Kim ),( Miran Lee ),( Joohyang Lee ),( Yoo-na Kim ),( Yong Jae Lee ),( Jung-yun Lee ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-
Objective: Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are becoming the standard of care options for epithelial ovarian cancer (EOC). In the current study, we investigated the immunologic effects of PAPRi on circulating Treg cells during PARPi maintenance therapy. Furthermore, we explored ways in which the addition of PD-1 blockade to PAPRi maintenance therapy enhances survival outcomes in recurrent EOC. Methods: We collected serial peripheral blood mononuclear cells (PBMCs) from EOC patients who responded to their most recent platinum-based chemotherapy (n=27). Peripheral blood was collected before treatment and at 1, 3, and 6 months after treatment initiation. Olaparib or niraparib was used as maintenance therapy. We also collected serial PBMCs from patients treated with PAPRi+anti-PD-1 (n=26, NCT04361370). The peripheral Treg cells were analyzed according to treatment responses using multi-color flow cytometry. PARPi responses were defined according to BRCA status and duration of PARPi treatment. Results: The expression of CTLA-4 and CCR8 on Treg cells significantly decreased after 6 months of PAPRi mono-treatment. PAPRi decreased the expression of FoxP3, CTLA-4, TIGIT, CD39, and CCR8 on Treg cells in vitro, but did not change PD-1 expression. Patients with high percentages of PD-1+Treg cells before PAPRi therapy showed significantly poorer progression-free survival (PFS). In a cohort of individuals treated with PAPRi+anti-PD-1 treatment, the expression of PD-1 on Treg cells was significantly decreased after the addition of anti-PD-1. Among patients with high percentages of PD-1+Treg cells between the two cohorts, those in the PAPRi+anti-PD-1 cohort had significantly longer PFS than those in the PAPRi monotherapy cohort. Conclusion: Peripheral PD-1+Treg cell amounts before PAPRi treatment could predict clinical responses, and targeting PD-1+Treg cells with additional PD-1 blockade during PAPRi treatment could potentially improve survival outcomes.
( Yoo-na Kim ),( Yun Soo Chung ),( Junsik Park ),( Yong Jae Lee ),( Jung-yun Lee ),( Eun Ji Nam ),( Sang Wun Kim ),( Sunghoon Kim ),( Young Tae Kim ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-
Objective: HER2 targeted drugs are increasingly introduced in non-breast cancers, yet studies on HER2 expression in ovarian cancer patients is lacking. Therefore, we studied HER2 receptor status and its dynamic change in ovarian cancer patients, a subset of whom also underwent next-generation sequencing (NGS). Methods: Ovarian cancer patients who underwent HER2 testing between January 2015 and May 2021 at Yonsei Cancer Hospital were identified. Clinical information, including histology, germline BRCA status, and immunohistochemistry (IHC) profile were noted. For patients receiving multiple time-lagged biopsies, each anatomical location, timing, and HER2 expression were counted. Results: A total of 200 patients with ovarian cancer, mostly advanced stage and high-grade serious histology, were identified. HER2 expressions of 2+ and 3+ were found in 28% and 6% respectively. A total of 33 patients (16.5%) received targeted therapy including Herceptin in 16 patients. With respect to histology, HER2 3+ rate was 23% in mucinous, 11% in endometrioid, 9% in clear cell, and 5% in high-grade serous type. HER2 3+ was exclusively identified in BRCA wildtype, mismatch repair proficient, or PD-L1 low expressing patients. Genomic analysis showed that in HER2 2+ or 3+ patients the TP53 mutation rate was lower and other mutations such as ARID1A, KRAS, PIK3CA were relatively more common, compared to HER2 0 or 1+ patients. CNV analysis showed that 4 out of 5 patients with HER2 3+ showed ERBB2 amplification on NGS. With respect to anatomical distribution, HER2+ and 3+ were frequently identified in ovary and breast biopsy specimen. Out of 20 patients with multiple time-lagged biopsy, 9 patients showed an increase in HER2 expression in the later biopsy sample. Conclusion: Ovarian cancer patients with HER2 overexpression show a distinct histological, IHC, and genomic profile. HER2 targeting agent may serve as a potential option for BRCA wildtype patients, especially in the later lines of treatment.
( Tae Kyung Lee ),( Na Young Kim ),( Kyunghwa Han ),( Junsik Park ),( Yong Jae Lee ),( Jung-yun Lee ),( Dae Chul Jung ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-
Objective: Efforts should be made to achieve complete cytoreduction during interval debulking surgery(IDS) after neoadjuvant chemotherapy(NAC) to treat ovarian cancer, due to optimal cytoreduction being an important prognostic factor. This study aimed to create a new model to predict optimal cytoreduction using computed tomography (CT) imaging before IDS. Methods: Preoperative CT scans of 72 patients who underwent IDS were retrospectively reviewed. We classified the abdominal cavity according to Sugarbaker's peritoneal cancer index (PCI) and scored the tumor size and degree of tumor invasiveness from 0 to 5 points for each CT feature. Residual disease measuring < 0.5 cm in maximal diameter after IDS was considered optimal cytoreduction. We developed a model using each scores to predict the residual disease, logistic regression and random forest were employed. A new model was created using the random forest that has been confirmed to have higher predictive power. The performance of the novel model has been reported, and the correlation between residual disease and progression-free survival (PFS) has been assessed. Results: The rate of optimal cytoreduction in the total study population was 59.7% (n = 43). Patients with optimal cytoreduction after IDS had significantly longer PFS than other patients (p = 0.04). CA125 levels before IDS did not affect residual disease (Area under the ROC curve (AUC) = 0.584, 95% CI: 0.450-0.719). Multivariable analysis resulted in a prediction model that included disease features of greater omentum, ascending colon and right paracolic gutter invasion with an AUC of 0.651 (95% CI: 0.539, 0.763). Using random forest, the top three CT features were selected with a threshold of 0.1; the greater omentum, pelvis, and lesser sac/lesser omentum. The top three features achieved an AUC of 0.729 (95% CI: 0.622-0.833). Conclusion: A low CT disease score of disease at top three CT features can be a strong predictor for optimal cytoreduction in IDS using out model.
박명화,최은정,정미리,Nayoung Lee,Minjung Kwak,Mihyun Lee,Eun-Chung Lim,Haesung Nam,김동일,구한울,Bong Seok Yang,Junsik Na,Ji Young Kim,Wonpyo Lee 대한의료정보학회 2019 Healthcare Informatics Research Vol.25 No.4
Objectives: This study developed an information and communication technology (ICT)-based comprehensive health and social-needs assessment (CHSNA) system based on the International Classification of Functioning, Disability, and Health (ICF) with the aim of enhancing person-centered community care for community residents and supporting healthcare professionals and social workers who provide healthcare and social services in the community. Methods: Items related to a CHSNA tool were developed and mapped with ICF codes. Experts validated the CHSNA system design and process using the Delphi method, and a pilot test of the initial version of the system was conducted. Results: The following three steps of CHSNA were embedded in the system, which had a user-friendly screen and images: basic health assessment, life and activity assessment, and in-depth health assessment. The assessment results for the community residents were presented with visualized health profiles, including images, graphs, and an ICF model. Conclusions: The developed CHSNA system can be used by healthcare professionals, social workers, and community residents to evaluate the reasoning underlying health and social needs, to facilitate the identification of more appropriate healthcare plans, and to guide community residents to receive the best healthcare services. A CHSNA system can improve the implementation of standardized terminology utilizing the ICF and the accuracy of needs assessments of community residents.