Shin-Wha Lee

Oncogenic pathway landscape of ovarian cancer and correlation with clinical prognosis

We aimed to identify the main oncogenic pathway by histological type of ovarian cancer based on Next-generation sequencing (NGS) test and to determine the correlation with clinical prognosis. We conducted a retrospective review of 420 patients with ovarian cancer who underwent NGS testing at Asan Medical Center from June 1, 2017, to May 31, 2021. Identified mutations were categorized into seven oncogenic pathways that are most frequently associated with ovarian cancer. The average number of oncogenic pathways involved in each cancer patient was 1.76 (range, 0-6). TP53 mutation was the primary oncogenic pathway in patients with high-grade serous carcinoma (HGSC) (92.8%) and carcinosarcoma (87.5%). MAP kinase signaling was the primary oncogenic pathway in low-grade serous carcinoma (58.3%) and mucinous carcinoma (54.5%). The involvement of more diverse oncogenic pathways has been identified in patients with endometrioid carcinoma and clear cell carcinoma and PI3K-AKT-mTOR signaling and SWI/SNF family pathways were the most common in both groups. The involvement of the DNA damage response pathway showed an association with better progression free survival (PFS), but not with overall survival (OS) in patients with HGSC. On the other hand, the involvement of the RTK signaling family pathway showed an association with better OS despite no association with PFS in patients with HGSC. The clinical prognosis may be improved by implementing targeted treatment tailored to the patient's genetic profile through NGS. Additional research is needed to determine whether the involvement of the RTK signaling family pathway is indeed associated with better OS and to identify the underlying reasons for this association.

Clinical outcome and pattern of care for isolated or incidental serous tubal intraepithelial carcinoma: a multicenter retrospective cohort study

Serous tubal intraepithelial carcinoma (STIC), a potential precursor of high-grade serous carcinoma, is associated with subsequent carcinomas development. This study aimed to identify cases of STIC and serous tubal intraepithelial lesions (STIL) and examine clinical outcomes and patterns of care in This retrospective study was conducted at six institutions to examine patients with isolated STIC/STIL. Demographic, adjuvant treatment, and follow-up data were collected from the date of implementation of Sectioning and Extensively Examining the Fimbriated end protocol, which varied from 2006 to 2015, until December 2022. We analyzed the data of 1,119 women who underwent RRSO and were carriers of While patient monitoring after STIC/STIL detection may be considered due to the minimal risk of carcinoma, excessive concern may not be necessary. Furthermore, adjuvant chemotherapy should be considered only with caution.

Clinical practice guidelines for ovarian cancer: an update to the Korean Society of Gynecologic Oncology guidelines

We updated the Korean Society of Gynecologic Oncology (KSGO) practice guideline for the management of ovarian cancer as version 5.1. The ovarian cancer guideline team of the KSGO published announced the fifth version (version 5.0) of its clinical practice guidelines for the management of ovarian cancer in December 2023. In version 5.0, the selection of the key questions and the systematic reviews were based on the data available up to December 2022. Therefore, we updated the guidelines version 5.0 with newly accumulated clinical data and added 5 new key questions reflecting the latest insights in the field of ovarian cancer between 2023 and 2024. For each question, recommendation was provided together with corresponding level of evidence and grade of recommendation, all established through expert consensus.

Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines

Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.

Clinical practice guideline for high-risk human papillomavirus testing in cervical cancer screening: a consensus statement from the Korean Society of Gynecologic Oncology

High-risk human papillomavirus (hrHPV) is a necessary cause of cervical cancer, and hrHPV testing has increasingly been recognized as an effective screening tool that overcomes the limitations of cytology-based screening. However, standardized clinical guidance for the use of hrHPV testing in cervical cancer screening has been limited in Korea, resulting in variability in clinical practice. This consensus-based clinical practice guideline was developed under the auspices of the Korean Society of Gynecologic Oncology through multidisciplinary collaboration involving experts in gynecology, pathology, laboratory medicine, and public health. Relevant domestic and international evidence was systematically reviewed, and input from diverse clinical settings was incorporated through four public hearings. Final recommendations were established through expert consensus. The guideline presents four key recommendations: hrHPV testing may be considered for women aged 25 years or older, with a recommended screening interval of 3 to <5 years; screening assays should differentiate HPV genotypes 16 and 18 and detect other high-risk types, with preference given to clinically validated tests; testing should be performed in appropriately equipped settings with standardized specimen handling and reporting, including documentation of HPV 16/18 status in positive cases; and hrHPV testing should be conducted under rigorous internal and external quality control systems. This guideline aims to support consistent and rational implementation of hrHPV testing in cervical cancer screening in Korea.

Evaluation of the anti-cancer efficacy of lipid nanoparticles containing siRNA against HPV16 E6/E7 combined with cisplatin in a xenograft model of cervical cancer

Objective To investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo. Methods CaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot. Results ENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined. Conclusion The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.

Application of Immunoprofiling Using Multiplexed Immunofluorescence Staining Identifies the Prognosis of Patients with High-Grade Serous Ovarian Cancer

Immunoprofiling has an established impact on the prognosis of several cancers; however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420–0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.

Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer

The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.