From the Beginning of the Korean Gynecologic Oncology Group to the Present and Next Steps.

The Korean Gynecologic Oncology Group (KGOG) was established in 2002 and is the only organization in Korea conducting multi-center clinical trials for gynecologic cancers. Since its re-establishment as a non-profit organization in 2021, KGOG has grown significantly, now including 207 gynecologic oncology specialists from 76 hospitals. This growth is a testament to the dedication and hard work of all those involved in the organization. KGOG is committed to maximizing the activation of multi-center clinical research through policies that support patients with rare diseases and gynecologic cancer research, focusing on strengthening institutional capacity, equalizing participation opportunities, and enhancing information sharing. A significant milestone for KGOG was becoming a member of the US Gynecologic Oncology Group (GOG) in 2005, allowing participation in GOG clinical trials. KGOG later joined the Gynecologic Cancer InterGroup (GCIG) and strengthened its capabilities by hosting the first Endometrial Cancer Consensus Conference-Clinical Research (ECCC-CR) in 2023. KGOG holds biannual meetings and symposia, as well as 224 operating committee meetings annually to review the discussions of the Tumor Site Committee. KGOG has conducted 156 investigator-initiated trial (IIT) or sponsor-initiated trial (SIT) studies as KGOG-led or participated in research. Currently, 18 studies are registered, and 10 are in preparation. To date, 68 papers have been published. KGOG conducts six national projects and collaborates with external organizations such as the NRG Oncology Foundation, Gynecologic Oncology Group Partners (GOG-P), GCIG, East Asian Gynecologic Oncology Trial group (EAGOT), and the Japanese Gynecologic Oncology Group (JGOG). Through collaboration with renowned international research institutions, KGOG has significantly expanded the scope of its research, achieving noteworthy clinical outcomes. This report not only introduces the history and recent status of KGOG but also presents the exciting future direction of the organization, filled with potential breakthroughs and advancements in gynecologic oncology research.

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005.

PURPOSE: We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). PATIENTS AND METHODS: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes. RESULTS: Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib (v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725). CONCLUSION: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

Interfacial Engineering of Mn Porphyrin/Au Electrodes for Identifying MnOx as the Active Species under Oxygen Evolution Reactions.

Understanding the influence of surface structural features at a molecular level is beneficial in guiding an electrode's mechanistic proposals for electrocatalytic reactions. The relationship between structural stability and catalytic activity significantly impacts reaction performance, even though atomistic knowledge of active sites remains a topic of discussion. In this context, this work presents scanning tunneling microscopy (STM) results for the highly ordered arrangement of manganese porphyrin molecules on a Au(111) surface; STM allows us to monitor active sites at a molecular level to focus on long-standing issues with the electrocatalytic process, especially the exact nature of the real active sites at the interfaces. After water oxidation, manganese porphyrin rapidly decomposes into active catalytic species as bright protrusions. These newly formed active species drastically lost catalytic activity, up to 82%, through only acid treatment, one of the oxide removal methods, not by deionized water and acetone treatments. STM results of the obviated active species on the Au surface by an acidic solution support the forfeited catalytic activity. In addition, it shows a 67% decrement in catalytic activity by adsorption of phosphonic acid, one of the oxide's preferred adsorption materials, compared to the pristine one. Based on these observations, we confirm that the newly formed active species, as water oxidation catalysts, mostly consist of manganese oxides. Notable findings of our work provide molecular evidence for the active sites of Au and modified Au electrodes that spur the future development of water oxidation catalysts.

The Prognostic Value of Tumor Cell Clusters in the Fallopian Tube Lumen in Stage I Endometrioid Carcinoma.

The aim of this study was to investigate the pathologic prognostic factors such as tumor cell clusters (TCCs) in the fallopian tube lumen, myometrial invasion patterns, and positive peritoneal cytology (PPC) in women with Stage I endometrial endometrioid carcinoma (EEC). From 2009 to 2020, consecutive patients with Stage I EEC who underwent hysterectomy and bilateral salpingectomy were included. The primary outcome was the recurrence-free survival (RFS) rate, and the clinicopathological factors affecting RFS were analyzed. A total of 765 patients were enrolled. Seventeen patients (2.2%) had TCC in the fallopian tube lumen, and 58 patients showed a microcystic elongated and fragmented pattern (7.6%). PPC was found in 19 patients (2.5%). The median follow-up period was 61.0 months (range: 2.0-149.7). The majority (88.6%) of patients had Stage IA EEC. The 5-year RFS and overall survival rates were 97.5% and 98.5%, respectively. In multivariate analysis for RFS, the significant prognostic factors were lymphovascular invasion (hazard ratio = 4.604; 95% CI: 1.387-15.288; P = 0.013) and grade (grade 2; hazard ratio = 4.949; 95% CI: 1.035-23.654; P = 0.045, and grade 3; hazard ratio = 5.469; 95% CI: 1.435-20.848; P = 0.013). Other pathologic factors including TCC in the fallopian tube lumen, myometrial invasion patterns, PPC, and hormonal status had no prognostic significance. TCC in the fallopian tube lumen, myometrial invasion pattern, PPC, and estrogen and progesterone receptor positivity were not significant prognostic factors in Stage I EEC. In contrast, lymphovascular invasion and grade were significant prognostic factors.

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04).

OBJECTIVE: To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. METHODS: In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1-2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. RESULTS: Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1high (tumor area positivity ≥10%) than PD-L1low (tumor area positivity 5%-9%) subgroups with both regimens. At 8.5 months' median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months' median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings. CONCLUSION: The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

Nitrous oxide respiration in acidophilic methanotrophs.

Aerobic methanotrophic bacteria are considered strict aerobes but are often highly abundant in hypoxic and even anoxic environments. Despite possessing denitrification genes, it remains to be verified whether denitrification contributes to their growth. Here, we show that acidophilic methanotrophs can respire nitrous oxide (N2O) and grow anaerobically on diverse non-methane substrates, including methanol, C-C substrates, and hydrogen. We study two strains that possess N2O reductase genes: Methylocella tundrae T4 and Methylacidiphilum caldifontis IT6. We show that N2O respiration supports growth of Methylacidiphilum caldifontis at an extremely acidic pH of 2.0, exceeding the known physiological pH limits for microbial N2O consumption. Methylocella tundrae simultaneously consumes N2O and CH4 in suboxic conditions, indicating robustness of its N2O reductase activity in the presence of O2. Furthermore, in O2-limiting conditions, the amount of CH4 oxidized per O2 reduced increases when N2O is added, indicating that Methylocella tundrae can direct more O2 towards methane monooxygenase. Thus, our results demonstrate that some methanotrophs can respire N2O independently or simultaneously with O2, which may facilitate their growth and survival in dynamic environments. Such metabolic capability enables these bacteria to simultaneously reduce the release of the key greenhouse gases CO2, CH4, and N2O.

Transcriptome profiling and characterization of peritoneal metastasis ovarian cancer xenografts in humanized mice.

Although immunotherapy has not yet been as successful in ovarian cancer (OC), it remains a potential therapeutic strategy. Preclinical models of OC are necessary to evaluate the efficacy of immuno-oncology (IO) drugs targeting human immune components but have been underutilized. Developing mouse models with a humanized (Hu) immune system can help understand the human immune response to IO drugs which have demonstrated limited effectiveness in OC patients. We established OC xenograft Hu-mouse models by intraperitoneally injecting luciferase-expressing SKOV-3 Luc and OVCAR-3 Luc OC cells into CD34+ Hu-mice. Tumor growth was monitored through bioluminescence imaging (BLI). In the SKOV-3 Luc Hu-mouse model, we assessed the efficacy of PD-1 blockade with pembrolizumab. We observed the presence of human lymphocyte and myeloid cell subsets within the tumors, lymph nodes, blood, and spleens in these models. Notably, these tumors exhibited a high prevalence of tumor-infiltrating macrophages. Furthermore, we identified HDAC class I target genes, and genes associated with epithelial-mesenchymal transition (EMT) and fibroblasts in the tumors of Hu-mice treated with pembrolizumab. Our xenograft Hu-mouse model of OC provides a valuable tool for investigating the efficacy of IO drugs. The insights gained from this model offer useful information to explore potential mechanisms associated with unresponsive anti-PD-1 treatment in OC.

Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management.

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.

Efficacy and safety of BVAC-C in HPV type 16- or 18-positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study.

Background: BVAC-C, a B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV-positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16- or 18-positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy. Patients and methods: Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1-not reported), the median PFS was 5.8 months (95% CI 4.2-10.3), and the median OS was 17.7 months (95% CI 12.0-not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses. Conclusion: BVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response. Clinical trial registration: ClinicalTrials.gov, identifier NCT02866006.

In Situ Probing of CO2 Reduction on Cu-Phthalocyanine-Derived Cux O Complex.

An in situ measurement of a CO2 reduction reaction (CO2 RR) in Cu-phthalocyanine (CuPC) molecules adsorbed on an Au(111) surface is performed using electrochemical scanning tunneling microscopy. One intriguing phenomenon monitored in situ during CO2 RR is that a well-ordered CuPC adlayer is formed into an unsuspected nanocluster via molecular restructuring. At an electrode potential of -0.7 V versus Ag/AgCl, the Au surface is covered mainly with the clusters, showing restructuring-induced CO2 RR catalytic activity. Using a measurement of X-ray photoelectron spectroscopy, it is revealed that the nanocluster represents a Cu complex with its formation mechanism. This work provides an in situ observation of the restructuring of the electrocatalyst to understand the surface-reactive correlations and suggests the CO2 RR catalyst works at a relatively low potential using the CuPC-derived Cu nanoclusters as active species.

Immune checkpoint inhibitors with chemotherapy for primary advanced mismatch repair-deficient endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.

FDA Public Workshop Summary-Addressing Challenges in Inhaled Antifungal Drug Development.

Allergic bronchopulmonary aspergillosis and invasive fungal diseases represent distinct infectious entities that cause significant morbidity and mortality. Currently, administered inhaled antifungal therapies are unapproved, have suboptimal efficacy, and are associated with considerable adverse reactions. The emergence of resistant pathogens is also a growing concern. Inhaled antifungal development programs are challenged by inadequate nonclinical infection models, highly heterogenous patient populations, low prevalence rates of fungal diseases, difficulties defining clinical trial enrollment criteria, and lack of robust clinical trial endpoints. On September 25, 2020, the US Food and Drug Administration (FDA) convened a workshop with experts in pulmonary medicine and infectious diseases from academia, industry, and other governmental agencies. Key discussion topics included regulatory incentives to facilitate development of inhaled antifungal drugs and combination inhalational devices, limitations of existing nonclinical models and clinical trial designs, patient perspectives, and industry insights.

Methylococcus mesophilus sp. nov., the first non-thermotolerant methanotroph of the genus Methylococcus, from a rice field.

Strain 16-5T, a mesophilic methanotroph of the genus Methylococcus, was isolated from rice field soil sampled in Chungcheong Province, Republic of Korea. Strain 16-5T had both particulate and soluble methane monooxygenases and could only grow on methane and methanol as electron donors. Strain 16-5 T cells are Gram-negative, white to light tan in color, non-motile, non-flagellated, diplococcoid to cocci, and have the typical type I intracytoplasmic membrane system. Strain 16-5T grew at 18-38 °C (optimum, 27 °C) and at pH 5.0-8.0 (optimum, pH 6.5-7.0). C16 : 1 ω7c (38.8%), C16 : 1 ω5c (18.8%), C16 : 1 ω6c (16.8%) and C16 : 0 (16.9%) were the major fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified phospholipid were the major polar lipids. The main respiratory quinone was methylene-ubiquinone-8. Strain 16-5T displayed the highest 16S rRNA gene sequence similarities to other taxonomically recognized members of the genus Methylococcus, i.e. Methylococcus capsulatus TexasT (98.62%) and Methylococcus geothermalis IM1T (98.49 %), which were its closest relatives. It did, however, differ from all other taxonomically described Methylococcus species due to some phenotypic differences, most notably its inability to grow at temperatures above 38 °C, where other Methylococcus species thrive. Its 4.34 Mbp-sized genome has a DNA G+C content of 62.47 mol%, and multiple genome-based properties such as average nucleotide identity and digital DNA-DNA hybridization value distanced it from its closest relatives. Based on the data presented above, this strain represents the first non-thermotolerant species of the genus Methylococcus. The name Methylococcus mesophilus sp. nov. is proposed, and 16-5T (=JCM 35359T=KCTC 82050T) is the type strain.

Methylacidiphilum caldifontis gen. nov., sp. nov., a thermoacidophilic methane-oxidizing bacterium from an acidic geothermal environment, and descriptions of the family Methylacidiphilaceae fam. nov. and order Methylacidiphilales ord. nov.

Strain IT6T, a thermoacidophilic and facultative methane-oxidizing bacterium, was isolated from a mud-water mixture collected from Pisciarelli hot spring in Pozzuoli, Italy. The novel strain is white when grown in liquid or solid media and forms Gram-negative rod-shaped, non-flagellated, non-motile cells. It conserves energy by aerobically oxidizing methane and hydrogen while deriving carbon from carbon dioxide fixation. Strain IT6T had three complete pmoCAB operons encoding particulate methane monooxygenase and genes encoding group 1d and 3b [NiFe] hydrogenases. Simple carbon-carbon substrates such as ethanol, 2-propanol, acetone, acetol and propane-1,2-diol were used as alternative electron donors and carbon sources. Optimal growth occurred at 50-55°C and between pH 2.0-3.0. The major fatty acids were C18 : 0, C15 : 0 anteiso, C14 : 0 iso, C16 : 0 and C14 : 0, and the main polar lipids were phosphatidylethanolamine, aminophospholipid, phosphatidylglycerol, diphosphatidylglycerol, some unidentified phospholipids and glycolipids, and other unknown polar lipids. Strain IT6T has a genome size of 2.19 Mbp and a G+C content of 40.70 mol%. Relative evolutionary divergence using 120 conserved single-copy marker genes (bac120) and phylogenetic analyses based on bac120 and 16S rRNA gene sequences showed that strain IT6T is affiliated with members of the proposed order 'Methylacidiphilales' of the class Verrucomicrobiia in the phylum Verrucomicrobiota. It shared a 16S rRNA gene sequence identity of >96 % with cultivated isolates in the genus 'Methylacidiphilum' of the family 'Methylacidiphilaceae', which are thermoacidophilic methane-oxidizing bacteria. 'Methylacidiphilum sp.' Phi (100 %), 'Methylacidiphilum infernorum' V4 (99.02 %) and 'Methylacidiphilum sp.' RTK17.1 (99.02 %) were its closest relatives. Its physiological and genomic properties were consistent with those of other isolated 'Methylacidiphilum' species. Based on these results, we propose the name Methylacidiphilum caldifontis gen. nov., sp. nov. to accommodate strain IT6T (=KCTC 92103T=JCM 39288T). We also formally propose that the names Methylacidiphilaceae fam. nov. and Methylacidiphilales ord. nov. to accommodate the genus Methylacidiphilum gen. nov.

Application of preoperative fluorodeoxyglucose-PET/CT parameters for predicting prognosis of high-grade neuroendocrine cervical cancer.

OBJECTIVE: High-grade neuroendocrine cervical cancer (HGNECC) is a rare and aggressive cervical cancer subtype. In this study, we aimed to evaluate the prognostic value of fluorodeoxyglucose-PET/computed tomography (CT) parameters for HGNECC. MATERIALS AND METHODS: This single-center retrospective study included 29 patients with HGNECC who underwent fluorodeoxyglucose-PET/CT scan followed by surgery between 2006 and 2016. RESULTS: The median follow-up period was 40 (range, 4-184) months. After surgery, the resection margins were tumor-negative in 28 patients (96.6%), 8 (27.6%) patients had parametrial tumor invasion, and 7 patients (24.1%) tested positive for lymph node metastasis. The tumor recurred in 20 patients (69%) and 18 patients (62.1%) died during the observation period. In the univariate analyses, age and total lesion glycolysis (TLG) were associated with worse disease-free survival (DFS) (age, hazard ratio 1.056, 95% CI 1.014-1.100, P  = 0.009; TLG2.5, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.033; and TLG3.0, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.034). In the multivariate analyses, older age and higher TLG3.0 were identified as independent poor prognostic factors for DFS (age, hazard ratio 1.058, 95% CI 1.014-1.104, P  = 0.009; TLG3.0, hazard ratio 1.004, 95% CI 1-1.007, P  = 0.033), while resection margin involvement was identified as an independent factor to predict poor overall survival (hazard ratio 20.717, 95% CI 1.289-332.964, P  = 0.032). CONCLUSION: Among the preoperative fluorodeoxyglucose-PET/CT parameters, TLG3.0 may be useful for predicting DFS in patients with HGNECC.

Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.

East Asian Gynecologic Oncology Trial Group (EAGOT): founding history and future perspective.

Racial and regional differences exist in morbidity, histology, drug response, toxicity, and prognosis of gynecologic cancer. However, most large-scale phase III studies have been conducted in Western countries, and these data on Asians, who account for more than half of the world's population, are limited. To build a global clinical trial network in Asia, four clinical trial groups with high expertise and international competitiveness in East Asia, namely the Japanese Gynecologic Oncology Group in Japan, the Korean Gynecologic Oncology Group in Korea, the Taiwanese Gynecologic Oncology Group in Taiwan, and the Chinese Gynecologic Cancer Society in the People's Republic of China, established a new group called the East Asia Gynecologic Oncology Trial Group (EAGOT) on November 19, 2021. It includes four committees: the Cervical Cancer Committee, Uterine Corpus Cancer Committee, Ovarian Cancer Committee, and Translational Research Committee. The purpose of EAGOT is to conduct international clinical trials in an effort to provide the best treatments for Asian women affected by gynecologic cancer. Discussions on new collaborative clinical trials have already begun. The first Annual EAGOT Meeting was held on May 25-27, 2023 in Niigata, Japan. EAGOT, the largest healthcare/investigational innovation network in Asia in the area of gynecologic cancers, will become a platform for establishing standards of care and lead to guidelines for Asian women suffering from gynecologic cancer. The harmonization of regulatory/investigator-initiated clinical trials, simultaneous approval of unapproved drugs in the four countries under a common protocol, and expansion of indications will improve the prognosis of gynecologic cancers in Asia in the near future.

Outcomes and prognostic factors of surgically treated extramammary Paget's disease of the vulva.

OBJECTIVE: Extramammary Paget's disease (EMPD) of the vulva is a rare disease which predominantly presents in postmenopausal Caucasian women. As yet, no studies on Asian female patients with EMPD have been performed. This study aimed to identify the clinical features of patients with vulvar EMPD in Korea, and to evaluate the risk factors of recurrence and postoperative complications in surgically treated EMPD. METHODS: We retrospectively reviewed 47 patients with vulvar EMPD who underwent wide local excision or radical vulvectomy. The clinical data and surgical and oncological outcomes following surgery were extracted from medical records and analyzed. Univariate and multivariate analyses for predicting recurrence and postoperative complications were performed. RESULTS: 21.3% of patients had complications after surgery, and wound dehiscence was the most common. 14.9% of patients experienced recurrence, and the median interval to recurrence from initial treatment was 69 (range 33-169) months. Vulvar lesions larger than 40 mm was the independent risk factor of postoperative complications (odds ratio [OR]=7.259; 95% confidence interval [CI]=1.545-34.100; p=0.012). Surgical margin status was not associated with recurrence in surgically treated vulvar EMPD patients (OR=0.83; 95% CI=0.16-4.19; p=1.000). CONCLUSION: Positive surgical margin is a frequent finding in the patients with vulvar EMPD, but disease recurrence is not related with surgical margin status. Since EMPD is a slow growing tumor, a surveillance period longer than 5 years is required.

Stratifying the risk of ovarian cancer incidence by histologic subtypes in the Korean Epithelial Ovarian Cancer Study (Ko-EVE).

INTRODUCTION: This study aimed to verify the association between ovarian cancer (OC) and reproductive- and lifestyle-related risk factors stratified by the subtype of OC. METHODS: In this matched case-control study derived from the Korean epithelial ovarian cancer study (Ko-EVE), we calculated the risk of OC subtypes using odds ratios (ORs) and 95% confidence intervals (95% CIs) in a logistic regression model. RESULTS: As a result of matching, 531 cases and 2,124 controls were selected. Smoking had positive association with high-grade serous (HGS) OC (OR = 2.69, 95% CI = 1.15-6.30), whereas alcohol consumption had positive association with mucinous type (MUC) (OR = 3.63, 95% CI = 1.39-9.49). Obesity (≥30 kg/m2 ) was associated with clear cell type (CLC) (OR = 4.57, 95% CI = 1.06-19.77). Spontaneous abortion was negatively associated with CLC (OR = 0.34, 95% CI = 0.13-0.90), in contrast to HGS (OR = 1.43, 95% CI = 0.96-2.15). Tubal ligation, hysterectomy, and oophorectomy were associated with decreased risk of HGS (OR = 0.14, 95% CI = 0.05-0.39; OR = 0.23, 95% CI = 0.07-0.73; OR = 0.28, 95% CI = 0.08-0.97, respectively). Early menarche was strongly associated with increased risk of CLC, but not MUC (OR = 6.11, 95% CI = 1.53-24.42; OR = 3.23, 95% CI = 0.98-10.86). Further, childbirth (≥2 times) was negatively associated with endometrioid type OC and CLC (OR = 0.11, 95% CI = 0.04-0.35; OR = 0.12, 95% CI = 0.02-0.37, respectively). Oral contraceptives and hormone replacement therapy were negatively associated with OC (OR = 0.61, 95% CI = 0.40-0.93; OR = 0.51, 95% CI = 0.32-0.80, respectively), and similar negative associations were also observed in HGS (OR = 0.69; OR = 0.60, respectively). Associations between family history of breast cancer and OC, regular exercise (≥5/week), and artificial abortion and OC were similar across all subtypes (OR = 3.92; OR = 0.41; OR = 0.72, respectively). CONCLUSION: A heterogeneous association between some risk factors and the incidence of each subtype of epithelial OC was observed, suggesting that the carcinogenic mechanisms of each subtype may be partly different.

CD8α+ dendritic cells potentiate antitumor and immune activities against murine ovarian cancers.

Dendritic cell (DC)-based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. Here, we report the effectiveness of mouse CD8α+ DCs derived from bone marrow hematopoietic stem cells (BM-HSCs), equivalent to human CD141+ DCs, which have proven to be a highly superior subset. Mono-DCs from monocytes and stem-DCs from HSCs were characterized by CD11c+ CD80+ CD86+ and CD8α+ Clec9a+ expression, respectively. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle-treated mice. These mice treated with pulsed stem-DCs appeared to have fewer tumor implants, which were usually confined in the epithelium of tumor-invaded organs. All mice treated with DCs showed longer survival than the vehicle group, especially in the medium/high dose pulsed Stem-DC treatment groups. Moreover, the stem-DC-treated group demonstrated a low proportion of myeloid-derived suppressor cells and regulatory T cells, high interleukin-12 and interferon-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Together, these results indicate that mouse CD8α+ DCs derived from BM-HSCs decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer, suggesting that better DC vaccines can be used as an effective immunotherapy in EOC treatment. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs.