Kidong Kim

Impact of time elapsed since diagnosis on neuropathic symptoms, sexual function, lymphedema, and overall quality of life in ovarian cancer survivors (KGOG 3068)

ObjectiveTo assess the impact of time since treatment on the quality of life (QOL), neurotoxicity, sexual function, lymphedema, and utility in ovarian cancer survivors.MethodsThis secondary analysis of a cross-sectional study examined the QOL, neurotoxicity, sexual function, lymphedema, and utility in 172 epithelial ovarian cancer survivors treated with first-line platinum-based chemotherapy without recurrence. Associations between time since treatment and overall QOL (National Comprehensive Cancer Network/functional assessment of cancer therapy ovarian symptom index-18 [NFOSI-18]), neurotoxicity (neurotoxicity subscale, version-4 [NTX-4]), sexual function (female sexual function index, 6-item Korean version [FSFI-6K]), lymphedema (gynecologic cancer lymphedema questionnaire [GCLQ]), and utility (EuroQol 5-dimension [EQ-5D]) were visualized using jittered box plots.ResultsOverall QOL (NFOSI-18) improved up to 3 years post-treatment (scores: 29.3 at 1 year, 28.6 at 2 years, and 26.6 at 3 years), followed by minor fluctuations over time. NTX-4 scores improved until 5 years (8.2, 7.7, 6.2, and 5.8), but remained above normal (score 0). Sexual function (FSFI-6K) increased until 3 years of age (4.6, 6.9, and 10.4 years), stabilizing at a level indicative of dysfunction (score <21). The lymphedema (GCLQ) scores fluctuated over time (4.9, 5.6, 3.3, 4.3, 5.2, and 3.8). Utility (EQ-5D index) improved up to 3 years (0.8250, 0.885, and 0.925), whereas the EQ-5D visual analog scale score increased gradually up to 5 years (71.5, 72, 73, 76, and 74), indicating ongoing recovery.ConclusionIn ovarian cancer survivors, QOL, symptom burden, and utility gradually improved over time post-treatment but did not fully return to pre-treatment levels.

Association of cul-de-sac seeding with intraperitoneal tumor burden in advanced ovarian cancer (CIEL, KGOG 4003)

To evaluate the relationship between tumor seeding in the cul-de-sac, assessed by transvaginal or transrectal ultrasound, and intraperitoneal tumor burden in advanced ovarian cancer. We prospectively enrolled 101 patients scheduled for surgery due to suspected or newly diagnosed ovarian, fallopian tube, or peritoneal cancer at three hospitals in Korea (Feb 2022-Dec 2023). Five were excluded for missing ultrasound or surgery, and eleven for benign or other malignancies. Preoperative ultrasound was used to assess cul-de-sac tumor seeding, categorized as no seeding, reticulonodular, serosal, or mass seeding. Intraperitoneal tumor burden was evaluated using the Peritoneal Cancer Index (PCI) and Fagotti score. Associations with bowel surgery and residual tumors >1 cm were also analyzed. Eighty-five patients were included; 28 received neoadjuvant chemotherapy. Cul-de-sac seeding was classified as no seeding (42 %), reticulonodular (14 %), serosal (18 %), or mass (26 %). Higher PCI and Fagotti scores correlated with more severe seeding. Intraoperative confirmation of seeding was seen in 69 % of cases. Bowel surgery was less frequent in patients without seeding. No significant differences were found in residual tumors >1 cm between groups. Cul-de-sac tumor seeding identified by transvaginal or transrectal ultrasound may reflect intraperitoneal tumor burden and could help predict surgical complexity in advanced ovarian cancer.

Durvalumab versus Physician’s Choice Chemotherapy in Recurrent Ovarian Clear Cell Adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3): A Multicenter, Randomized, Phase 2 Trial

Abstract Purpose: The optimal treatment of recurrent ovarian clear cell carcinoma (rOCCC) remains unknown. This is the first randomized trial to compare durvalumab with chemotherapy in rOCCC. Patients and Methods: MOCCA is a randomized, phase 2 trial conducted in Singapore, Korea, and Australia. Eligible patients had rOCCC with recurrence after platinum-based chemotherapy, Eastern Cooperative Oncology Group performance status ≤2, and no prior immune checkpoint blockade. Patients were randomly assigned (2:1) to durvalumab (1,500 mg every 4 weeks) or chemotherapy. Patients progressing on chemotherapy were allowed to cross over to durvalumab. The primary outcome was progression-free survival. Secondary outcomes included overall survival, objective response rates, and safety. Results: Forty-eight eligible women were assigned to durvalumab (N = 31) or chemotherapy (N = 17). The median progression-free survival was 7.6 [95% confidence interval (CI), 7.0–16.0] and 14.0 (95% CI, 7.0–32.9) weeks with durvalumab and chemotherapy, respectively (HR = 1.6; 95% CI, 0.8–3.0; P = 0.92). The median overall survival was 37.9 (95% CI, 21.7–143.0) and 40.6 (95% CI, 25.0–not reached) weeks, respectively (HR = 1.5; 95% CI, 0.7–3.3; P = 0.85). The difference in objective response rates between the groups was not statistically significant (durvalumab 9.7% vs. physician’s choice chemotherapy 18.8%; difference −9.1%; 95% CI, −31.3% to 12.9%; P = 0.83). Fewer all-grade (35.5% vs. 68.8%) and high-grade (9.7% vs. 31.3%) treatment-related adverse events were observed for durvalumab. PD-L1 combined positive score (CPS)+ was observed in 28.9% (CPS ≥1%) and 10.5% (CPS ≥10%) of patients. PIK3CA mutations were associated with time to progression on durvalumab ≥12 weeks [relative risk (mutated vs. wild-type) 2.83; 95% CI, 1.16–14.17]. Conclusions: Durvalumab was well-tolerated but did not improve efficacy outcomes compared with chemotherapy in rOCCC.

Rate of occult atypical hyperplasia or endometrial cancer in women of older age groups with nonatypical endometrial hyperplasia (KGOG 2026)

Enrichment for the POLE mutated against p53 wild subtype using clinicopathologic factors and cyclin B1 immunohistochemistry in endometrial cancer

Clinicopathologic and protein markers distinguishing the “polymerase epsilon exonuclease” from the “copy number low” subtype of endometrial cancer

The need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease ( Ninety-one samples (15 Body mass index (BMI) and tumor grade were significantly associated with the BMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the

Clinical evaluation of a droplet digital PCR assay for detecting POLE mutations and molecular classification of endometrial cancer

We evaluated droplet digital polymerase chain reaction (ddPCR) method for detecting We reviewed 240 EC specimens from our hospital database. A ddPCR assay was used to identify The ddPCR assay identified Hotspot

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.

A multicenter phase II randomized trial of durvalumab (MEDI-4736) versus physician’s choice chemotherapy in recurrent ovarian clear cell adenocarcinoma (MOCCA)

The optimal treatment of recurrent ovarian clear cell carcinoma remains unknown. There is increasing rationale to support the role of immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD To evaluate the efficacy of durvalumab (MEDI-4736) compared with standard chemotherapy in patients with recurrent ovarian clear cell carcinoma. Patients with recurrent ovarian clear cell carcinoma treated with durvalumab will have improved progression-free survival compared with those treated with chemotherapy of physician's choice. The MOCCA study is a multicenter, open-label, randomized phase II trial in patients with recurrent ovarian clear cell carcinoma, which recruited from eight sites across Gynecologic Cancer Group Singapore (GCGS), Korean Gynecologic-Oncology Group (KGOG), and Australia New Zealand Gynecological Oncology Group (ANZGOG). Enrolled patients were randomized in a 2:1 ratio to receive durvalumab or physician's choice of chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. Eligible patients required histologically documented diagnosis of recurrent ovarian clear cell carcinoma, as evidenced by WT1 negativity. All patients must have been of Eastern Cooperative Oncology Group (ECOG) performance status 2 or better, and have had previous treatment with, and progressed or recurred after prior platinum-based chemotherapy. No more than four prior lines of treatment were allowed and prior immune checkpoint inhibitor treatment was not permitted. The primary endpoint was the median progression-free survival following treatment with durvalumab, compared with physician's choice of chemotherapy. Progression-free survival was defined as the time from the first day of treatment to the first observation of disease progression, or death due to any cause, or last follow-up. The target sample size was 46 patients. Accrual has been completed and results are expected to be presented by mid-2021. Clinicaltrials.gov: NCT03405454.

Difluoromethylornithine Induces Apoptosis through Regulation of AP-1 Signaling via JNK Phosphorylation in Epithelial Ovarian Cancer

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.

Comparisons of survival outcomes between bevacizumab and olaparib inBRCA-mutated, platinum-sensitive relapsed ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG 3052)

To compare survival outcomes between bevacizumab (BEV) and olaparib (OLA) maintenance therapy in From 10 institutions, we identified HGSOC patients with germline and/or somatic Overall, OLA users showed significantly better progression-free survival (PFS) than BEV users (median, 23.8 vs. 17.4 months; p=0.004). Before matching, PFS improved in the OLA intent group but marginal statistical significance (p=0.057). After matching, multivariate analyses adjusting confounders identified intention-to-treat OLA as an independent favorable prognostic factor for PFS in the OLA 65P (adjusted hazard ratio [aHR]=0.505; 95% confidence interval [CI]=0.280-0.911; p=0.023) to OLA 100P (aHR=0.348; 95% CI=0.184-0.658; p=0.001) datasets. The aHR of intention-to-treat OLA for recurrence decreased with increasing proportions of OLA users. No differences in overall survival were observed between the BEV and OLA intent groups, and between the BEV and OLA users. Compared to BEV, intention-to-treat OLA and actual use of OLA maintenance therapy were significantly associated with decreased disease recurrence risk in patients with

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study

Objective This study aimed to investigate incidence and risk for venous thromboembolism (VTE) according to primary treatment in women with ovarian cancer. Methods We selected 26,863 women newly diagnosed with ovarian cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and the first six months after initiation of primary treatments, incidence and risk of VTE were evaluated according to primary treatment as no treatment, surgery, radiotherapy, or chemotherapy. Results The mean follow-up period was 1285.5±6 days. The VTE incidence was highest in women who underwent chemotherapy (306 per 10,000 women). Among women who underwent surgery, VTE was highest in surgery with neoadjuvant chemotherapy (536 per 10,000 women), followed by surgery with adjuvant chemotherapy (360 per 10,000 women) and surgery alone (132 per 10,000 women). During the first 12 months, monthly incidence of VTE decreased. Compared with women with no treatment, risk of VTE significantly increased in women undergoing chemotherapy (HR 1.297; 95% CI, 1.08–1.557; P = 0.005) during the total follow-up period and decreased in women undergoing surgery (HR 0.557; 95% CI, 0.401–0.775; P<0.001) and radiotherapy (HR 0.289; 95% CI, 0.119–0.701; P = 0.006) during the first six months. Among women who underwent surgery, VTE risk significantly increased in surgery with neoadjuvant chemotherapy (HR 4.848; 95% CI, 1.86–12.632; P = 0.001) followed by surgery with adjuvant chemotherapy (HR 2.807; 95% CI, 1.757–4.485; P<0.001) compared with surgery alone during the total follow-up period and in surgery with neoadjuvant chemotherapy (HR 4.223; 95% CI, 1.37–13.022; P = 0.012) during the first six months. Conclusions In this large Korean cohort study, incidence and risk of VTE were highest in women with ovarian cancer who underwent chemotherapy and surgery with neoadjuvant chemotherapy as a primary cancer treatment. Incidence of VTE decreased over time.

Effect of risk-reducing salpingo-oophorectomy on the quality of life in Korean BRCA mutation carriers

This study aimed to compare the quality of life (QOL), psychosocial status, sexual function, and menopausal symptoms between the risk-reducing salpingo-oophorectomy (RRSO) and non-RRSO groups comprising BRCA mutation carriers and to evaluate the effect of timing of RRSO on those aspects. This cross-sectional study recruited BRCA mutation carriers aged ≥35 years between September 2015 and September 2016. Demographic data of carriers were collected. Outcomes were measured using the questionnaires addressing QOL, anxiety, depression, optimism, sexual function, and menopausal symptoms. Of 52 participants, 30 (57.7%) underwent RRSO, whereas 22 (42.3%) did not. In the RRSO group, 16 (53.3%) and 14 (46.7%) women underwent RRSO before and after menopause, respectively. The mean age in the RRSO group was higher than that in the non-RRSO group (49.8 vs. 42.1 years, respectively, p = 0.002). The scores for QOL, anxiety, depression, optimism, sexual function, and menopausal symptoms were similar between both groups. In the multivariate analysis, RRSO uptake was associated with worse physical QOL (coefficient, -5.350; 95% confidence interval, -10.593 to -0.108). With respect to the timing of RRSO, only the mental QOL was significantly lower in the postmenopausal RRSO group than in the premenopausal RRSO group (39.2 vs. 43.7, respectively, p = 0.043). We could not find any difference in mental QOL, psychosocial status, sexual function, and menopausal symptoms between the RRSO and non-RRSO groups. RRSO uptake only affected worse physical QOL. These results will help physicians counsel BRCA mutation carriers about the effect of RRSO on QOL.

The upper limit of optimal tumor size in patients with FIGO 2018 stage IB2 cervical cancer undergoing radical hysterectomy

Patients who undergo radical hysterectomy may require postoperative adjuvant radiotherapy, and all efforts should be made to reduce dual therapy in such patients. The aim of this study was to determine the optimal upper limit of tumor size in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB2 cervical cancer who undergo radical hysterectomy. We retrospectively reviewed the records of 114 patients with FIGO 2018 stage IB2 cervical cancer who underwent primary surgery either with (n=55) or without (n=59) adjuvant radiotherapy from June 2004 to December 2018. The inclusion criteria were as follows: women diagnosed with stage IB2 cervical cancer; primary radical surgery with pelvic lymph node dissection with or without para-aortic lymph node dissection; and patients treated with or without postoperative adjuvant radiation therapy, concurrent chemoradiation therapy, or chemotherapy. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal tumor size cut-off value. The optimal tumor size cut-off value was determined by the maximum sum of sensitivity and specificity. There were 55 and 59 patients treated with or without adjuvant therapy, respectively, after radical hysterectomy. Age, histologic type, and pelvic and para-aortic lymph node sampling/dissection status were similar between each group. The number of patients with a tumor size <2.7 cm and ≥2.7 cm was 39 and 75, respectively. The decision for adjuvant treatment after radical hysterectomy in patients with stage IB2 cervical cancer was influenced by intermediate risk factors (lymphovascular space invasion, 23.7% vs 76.4%, p<0.001; deep 1/3 of invasion, 16.9% vs 61.8%, p<0.001) and high risk factors (lymph node metastasis, 0% vs 40.0%, p<0.001; involvement of parametrium, 1.7% vs 16.4%, p=0.007). According to the ROC curve results considering the best sensitivity and specificity, the optimal cut-off value of tumor size for predicting adjuvant treatment was 2.7 cm (sensitivity 0.85, specificity 0.52). The number of patients with a tumor size <2.7 cm and ≥2.7 cm was 39 (34.2%) and 75 (65.8%), respectively. No significant differences were observed in the progression-free survival (p=0.22) and overall survival (p=0.28) rates between tumor size smaller than 2.7 cm and larger than 2.7 cm. A cervical tumor larger than 2.7 cm before radical surgery in stage IB2 may predispose to potential complications from combining radical hysterectomy and concurrent chemoradiation,. We consider that concurrent chemoradiation therapy is a more appropriate choice for tumor size over 2.7 cm per the revised FIGO 2018 criteria for stage IB2 cervical cancer.

Pathologic discrepancies between colposcopy-directed biopsy and loop electrosurgical excision procedure of the uterine cervix in women with cytologic high-grade squamous intraepithelial lesions

To investigate pathologic discrepancies between colposcopy-directed biopsy (CDB) of the cervix and loop electrosurgical excision procedure (LEEP) in women with cytologic high-grade squamous intraepithelial lesions (HSILs). We retrospectively identified 297 patients who underwent both CDB and LEEP for HSILs in cervical cytology between 2015 and 2018, and compared their pathologic results. Considering the LEEP to be the gold standard, we evaluated the diagnostic performance of CDB for identifying cervical intraepithelial neoplasia (CIN) grades 2 and 3, adenocarcinoma in situ, and cancer (HSIL+). We also performed age subgroup analyses. Among the study population, 90.9% (270/297) had pathologic HSIL+ using the LEEP. The diagnostic performance of CDB for identifying HSIL+ was as follows: sensitivity, 87.8%; specificity, 59.3%; balanced accuracy, 73.6%; positive predictive value, 95.6%; and negative predictive value, 32.7%. Thirty-three false negative cases of CDB included CIN2,3 (n=29) and cervical cancer (n=4). The pathologic HSIL+ rate in patients with HSIL- by CDB was 67.3% (33/49). CDB exhibited a significant difference in the diagnosis of HSIL+ compared to LEEP in all patients (p<0.001). In age subgroup analyses, age groups <35 years and 35-50 years showed good agreement with the entire data set (p=0.496 and p=0.406, respectively), while age group ≥50 years did not (p=0.036). A significant pathologic discrepancy was observed between CDB and LEEP results in women with cytologic HSILs. The diagnostic inaccuracy of CDB increased in those ≥50 years of age.

Perioperative outcomes in patients with very low‐risk endometrial cancer undergoing surgery without lymph node dissection: Results from KGOG 2021

AbstractAimTo evaluate the perioperative outcomes of patients with endometrial cancer meeting the Korean Gynecologic Oncology Group (KGOG) criteria who underwent surgery without lymph node dissection.MethodsThis study included 153 patients who met the KGOG criteria: (1) endometrioid histology, (2) myometrial invasion &lt;50%, (3) tumor confined to the corpus, (4) no lymph node &gt;1 cm, and (5) serum CA125 ≤ 35 U/mL. The patients underwent surgery without lymph node dissection at 11 hospitals in Korea between February 2020 and May 2024. Perioperative outcomes were collected prospectively.ResultsAmong the 153 patients, 89 (58%) underwent surgery without lymph node removal, while 64 (42%) underwent surgery with lymph node removal. Minimally invasive surgery was performed in &gt;90% of cases, with a conversion rate to laparotomy of 1%. The mean surgery time was 109.37 ± 37.67 min. Estimated blood loss was minimal (93.74 ± 93.13 mL), with a mean hemoglobin drop of 1.32 ± 1.01 g/dL. Transfusions were required in only three patients (2%). Postoperative hospital stays exceeded 2 days in 51% of cases. Lymph node metastasis was observed in just one case (1%). Adverse events included 52 grade 1 and 2 grade 2 events (e.g., headache, paresthesia). Patients undergoing lymph node removal (primarily sentinel lymph node biopsy) had significantly longer surgery times and postoperative hospital stays compared to those without lymph node removal.ConclusionSurgery without lymph node dissection demonstrated excellent perioperative outcomes and minimal adverse events in patients meeting KGOG criteria.