Lymphadenectomy in clinically early epithelial ovarian cancer and survival analysis (LILAC): a Gynecologic Oncology Research Investigators Collaboration (GORILLA-3002) retrospective study.

OBJECTIVE: This study aimed to evaluate the therapeutic role of lymphadenectomy in patients surgically treated for clinically early-stage epithelial ovarian cancer (EOC). METHODS: This retrospective, multicenter study included patients with clinically early-stage EOC based on preoperative abdominal-pelvic computed tomography or magnetic resonance imaging findings between 2007 and 2021. Oncologic outcomes and perioperative complications were compared between the lymphadenectomy and non-lymphadenectomy groups. Independent prognostic factors were determined using Cox regression analysis. Disease-free survival (DFS) was the primary outcome. Overall survival (OS) and perioperative outcomes were the secondary outcomes. RESULTS: In total, 586 patients (lymphadenectomy group, n=453 [77.3%]; non-lymphadenectomy groups, n=133 [22.7%]) were eligible. After surgical staging, upstaging was identified based on the presence of lymph node metastasis in 14 (3.1%) of 453 patients. No significant difference was found in the 5-year DFS (88.9% vs. 83.4%, p=0.203) and 5-year OS (97.2% vs. 97.7%, p=0.895) between the two groups. Using multivariable analysis, lymphadenectomy was not significantly associated with DFS or OS. However, using subgroup analysis, the lymphadenectomy group with serous histology had higher 5-year DFS rates than did the non-lymphadenectomy group (86.5% vs. 74.4%, p=0.048; adjusted hazard ratio=0.281; 95% confidence interval=0.107-0.735; p=0.010). The lymphadenectomy group had longer operating time (p<0.001), higher estimated blood loss (p<0.001), and higher perioperative complication rate (p=0.004) than did the non-lymphadenectomy group. CONCLUSION: In patients with clinically early-stage EOC with serous histology, lymphadenectomy was associated with survival benefits. Considering its potential harm, lymphadenectomy should be performed according to histologic subtype and subsequent chemotherapy in patients with clinically early-stage EOC. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0007309.

Effect of high-dose polymeric nanoparticle micellar paclitaxel on improved progression-free survival in patients with optimally resected stage III or IV high-grade carcinoma of the ovary: a prospective cohort study with historical controls.

Introduction: We evaluated the effect of high-dose polymeric nanoparticle micellar paclitaxel (PM-Pac) on survival in patients with stage III-IV high-grade serous ovarian cancer (HGSC) who underwent upfront surgery. Methods: We prospectively recruited the patients who received PM-Pac (280 mg/m2) and carboplatin at an area under the curve (AUC) of 5 (cohort 1) in two tertiary centers between October 2015 and June 2019. As historical controls, we retrospectively collected data on those who received paclitaxel (175 mg/m2) and carboplatin (AUC 5; cohort 2) or paclitaxel (175 mg/m2), carboplatin (AUC 5) and bevacizumab (15 mg/kg; cohort 3). Results: A total of 128 patients were divided into cohorts 1 (n=49, 38.3%), 2 (n=53, 41.4%), and 3 (n=26, 20.3%). Cohort 1 showed better progression-free survival (PFS) than cohort 2 in all patients and those treated with optimal debulking surgery (ODS; median, 35.5 vs. 28.1 and 35.5 vs. 28.9 months; p ≤ 0.01) despite no difference in PFS between cohorts 1 and 3 and between cohorts 2 and 3. In particular, stage III disease was a favorable factor for PFS, whereas cohort 2 was related to worse PFS (adjusted hazard ratios, 0.456 and 1.834; 95% confidence interval, 0.263 - 0.790 and 1.061 - 3.171), showing no difference in PFS between cohorts 1 and 3 in those treated with ODS. Conclusion: High-dose PM-Pac improved PFS compared to conventional chemotherapy, and the change of paclitaxel to PM-Pac had as much effect on PFS as the addition of bevacizumab in patients with stage III-IV HGSC who underwent ODS.

A predictive model for lymph node metastasis using tumor location in presumed early-stage endometrioid endometrial cancer patients.

OBJECTIVE: The aim of this study was to identify high- and low-risk subgroups of patients with lymph node (LN) metastasis in presumed early-stage endometrioid endometrial cancer (EC) patients. METHODS: Clinicopathologic data of presumed early-stage endometrioid EC patients (n=361) treated with lymphadenectomy between March 2000 and July 2022 were analyzed. None of the patient had definite evidence of LN metastasis in a preoperative magnetic resonance imaging (MRI). A received operating characteristic curve analysis was conducted to define the sensitivity and specificity for the combined preoperative risk factors for LN metastasis, which was determined by multivariate analysis. RESULTS: Nineteen patients (5.3%) had LN metastasis. Multivariate analysis identified cervical stromal invasion on MRI (odds ratio [OR]=4.386; 95% confidence interval [CI]=1.020-18.852; p=0.047), cornual location of tumor on MRI (OR=36.208; 95% CI=7.902-165.913; p<0.001), and lower uterine segment/isthmic location of tumor on MRI (OR=8.454; 95% CI=1.567-45.610; p=0.013) as independent prognostic factors associated with LN metastasis. Patients were categorized into low- and high-risk groups according to risk criteria. Significant differences in the rates of LN metastasis were observed between the two groups (0.4% vs. 22.2%, p<0.001). CONCLUSION: Approximately 95% of presumed early-stage endometrioid EC patients did not have LN metastasis. A model using tumor location was significantly correlated with the risk of LN metastasis. Even in presumed early-stage endometrioid EC patients, therefore, tumor location should be investigated to determine whether to perform LN assessment.

Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

Risk factors for the failure of first-line PARP inhibitor maintenance therapy in patients with advanced ovarian cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3004).

OBJECTIVE: To identify the risk factors for failure of first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy in patients with advanced ovarian cancer. METHOD: Patients with stage III-IV epithelial ovarian cancer who received first-line PARPi maintenance therapy were retrospectively reviewed. Clinicopathologic factors were compared between two groups-recur/progression of disease (PD) and non-recur/PD. RESULTS: In total, 191 patients were included. Median follow-up was 9.9 months, and recurrence rate was 20.9%. BRCA mutations were found in 63.4% patients. Postoperative residual tumor (60.5% vs. 37.8%), non-high grade serous carcinoma (HGSC) (15.0% vs. 6.0%), neoadjuvant chemotherapy (NAC) (55.0% vs. 35.8%), and pre-PARPi serum CA-125 levels ≥23.5 U/mL (35.9% vs. 15.2%) were more frequently observed in the recur/PD group. Multivariate Cox-regression analysis revealed pre-PARPi serum CA-125 levels ≥23.5 U/mL (HR, 2.17; 95%CI, 1.03-4.57; p = 0.042), non-HGSC (3.28; 1.20-8.97; p = 0.021), NAC (2.11; 1.04-4.26; p = 0.037), and no BRCA mutation (2.23; 1.12-4.44; p = 0.023) as independent risk factors associated with poor progression-free survival (PFS). A subgroup analysis according to BRCA mutation status showed that pre-PARPi serum CA-125 levels ≥26.4 U/mL were the only independent risk factor for poor PFS in women with BRCA mutations (2.75; 1.03-7.39; p = 0.044). Non-HGSC (5.05; 1.80-14.18; p = 0.002) and NAC (3.36; 1.25-9.04; p = 0.016) were independent risk factors in women without BRCA mutations. CONCLUSION: High pre-PARPi serum CA-125 levels, non-HGSC histology, NAC, and no BRCA mutation might be risk factors for early failure of first-line PARPi maintenance therapy. In women with BRCA mutations, high pre-PARPi serum CA-125 levels, which represent a large tumor burden before PARPi, were the only independent risk factor for poor PFS.

Is minimally invasive radical surgery safe for patients with cervical cancer ≤2 cm in size? (MISAFE): Gynecologic Oncology Research Investigators coLLborAtion study (GORILLA-1003).

OBJECTIVE: To identify clinicopathological factors associated with disease recurrence for patients with 2018 FIGO stage IA with lymphovascular invasion to IB1 cervical cancer treated with minimally invasive surgery (MIS). METHODS: A total of 722 patients with cervical cancer between January 2010 and February 2021 were identified. Clinicopathological factors related to disease recurrence were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. To determine prognostic factors for DFS, a Cox proportional hazard regression model was used. RESULTS: Of 722 patients, 49 (6.8%) experienced disease recurrence (37 pelvis, 1 para-aortic lymph node, and 11 peritoneum). Five-year DFS and OS rates were 90.7% and 98.1%, respectively. In multivariate analysis, risk factors associated with disease recurrence were residual disease in the remaining cervix (OR, 3.122; 95% CI, 1.152-8.461; p = 0.025), intracorporeal colpotomy (OR, 3.252; 95% CI, 1.507-7.017; p = 0.003), and positive resection margin (OR, 3.078; 95% CI, 1.031-9.193; p = 0.044). The non-conization group had a higher percentage of stage IB1 (77.4% vs. 64.6%; p = 0.004) and larger tumor (10 mm vs. 7 mm; p < 0.001) than the conization group. Intracorporeal colpotomy and residual disease in the remaining cervix were independent variables associated with disease recurrence in patients undergoing MIS following conization. CONCLUSION: During MIS, patients with cervical cancer ≤2 cm in size can be vulnerable to peritoneal recurrences. Patients diagnosed with invasive cancer through conization often have low-risk pathological features, which may affect their survival outcomes.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

BACKGROUND: To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. RESULTS: Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). CONCLUSIONS: The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

Fertility-sparing hormonal treatment in patients with stage I endometrial cancer of grade 2 without myometrial invasion and grade 1-2 with superficial myometrial invasion: Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-2001).

OBJECTIVES: To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC) without myometrial invasion (MI) or grade 1-2 with superficial MI. METHODS: Multicenter data of patients with stage I grade 2 EC without MI or grade 1-2 EC with superficial MI, who received FST between 2005 and 2021, were analyzed. Cox regression analysis identified independent factors for progressive disease (PD) during the FST. RESULTS: Altogether, 54 patients received FST [medroxyprogesterone acetate (500-1000 mg) in 44, megestrol acetate (40-800 mg) in 10] with concurrent levonorgestrel-releasing intrauterine devices use in 31. With median time to achieve a complete response (CR) of 10 (3-24) months, 39 patients (72.2%) achieved CR. Of the 15 patients who attempted to conceive after achieving CR, 7 (46.7%) became pregnant (2 abortions, 5 live births). During a median FST duration of 6 (3-12) months, nine patients (16.6%) were diagnosed with PD. Fifteen (38.5%) experienced recurrence with a median recurrence-free survival of 23 (3-101) months. In the multivariable analysis, tumor size before FST ≥2 cm (HR 5.456, 95% CI 1.34 to 22.14; p = 0.018) was significantly associated with a high PD rate during FST. CONCLUSION: The overall response rate to FST was promising, however, the PD rate was significant during the first 12 months of FST. Therefore, performing thorough endometrial biopsy and imaging studies is essential to strictly evaluate the extent of the disease every 3 months from FST initiation.

Significance of cholecystectomy in cytoreductive surgery for advanced ovarian cancer.

BACKGROUND: There have been no studies concerning the complications or benefits of cholecystectomy in ovarian cancer. In this study, we aimed to evaluate the outcomes of cholecystectomy performed during various time periods of the disease course and suggest a management strategy for cholecystectomy in ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with advanced ovarian cancer who underwent cholecystectomy during the cytoreductive surgery from 2009 to 2020. Cholecystectomy was primarily indicated when the gallbladder and surrounding structures were considered to have metastatic tumor invasion. If the final pathologic results showed free of malignant tumor, patients were placed into the no-infiltration group. Clinical outcomes including the recurrence rate and complications were analyzed. RESULTS: A total of 62 patients underwent cholecystectomy, 48 of whom (77.4%) underwent cholecystectomy during primary or interval debulking surgery, whereas 14 (22.6%) underwent cholecystectomy during the follow-up period (five with benign disease and 9 with disease recurrence). Among the patients, 32 (51.6%) patients were included in the no-infiltration group in the final pathology. There were no complications observed in the no-infiltration group (n = 32). Seven (78%) of the nine patients who received cholecystectomy for disease recurrence had metastatic disease in the porta-hepatis or lesser sac at the time of primary surgery. However, no recurrent lesions were observed around the porta-hepatis in patients who received cholecystectomy during primary treatment. CONCLUSION: Considering the safety of the procedure, as well as the risk of disease recurrence or cholecystitis, a cholecystectomy can be offered to patients with ovarian cancer who have metastatic lesions around the gallbladder and porta-hepatis at the time of primary surgery.

Major clinical research advances in gynecologic cancer in 2022: highlight on late-line PARP inhibitor withdrawal in ovarian cancer, the impact of ARIEL-4, and SOLO-3.

In the 2022 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Ovarian cancer: long-term follow-up data, new poly (ADP-ribose) polymerase (PARP) inhibitors, overall survival (OS) issues with PARP inhibitor monotherapy, hyperthermic intraperitoneal chemotherapy, immunotherapy, and antibody-drug conjugate; 2) Cervical cancer: surgery in early stage disease, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Corpus cancer: follow-up regimen, immune checkpoint inhibitor, WEE1 inhibitor, selective inhibitor of nuclear export. A special note was made on the withdrawal of PARP inhibitor from the market for heavily pretreated ovarian cancer patients based on the final OS results of ARIEL-4 and SOLO-3 due to concerns of increased risk of death.

Spillage and displacement of indocyanine green-stained tissues from uterine cervix to pelvic peritoneum: A proof of concept study for colpotomy approach in minimally invasive surgery.

OBJECTIVE: To analyze peritoneal spillage and displacement of indocyanine green (ICG)-stained tissues from uterine cervix to pelvis during intracorporeal/vaginal colpotomy in laparoscopic-assisted hysterectomy. MATERIALS AND METHODS: Eleven patients undergoing laparoscopic-assisted hysterectomy were included. One patient with an incidental diagnosis of endometrial cancer was excluded. Of the 10 patients, five underwent intracorporeal colpotomy (IC) and five received vaginal colpotomy (VC) during laparoscopic-assisted hysterectomy. Approximately 5 cm of resected round ligament from each patient was stained with ICG and cut to 1.0 × 1.0 cm in size. Four to five fragments of ICG-stained tissues were placed and sutured on the uterine cervix before colpotomy. During and after colpotomy, serial pictures under white and fluorescence light were taken to document peritoneal spillage and displacement of ICG-stained tissues to the pelvic peritoneum. RESULTS: Peritoneal spillage of ICG occurred in the entire IC group. Displacement of ICG-stained tissues from uterine cervix to pelvic peritoneum were visualized in three (60%) patients undergoing IC. In the five patients who received VC, peritoneal spillage of ICG and displacement of ICG-stained tissue to pelvic peritoneum did not occur. There were no perioperative complications. CONCLUSIONS: IC in minimally invasive radical hysterectomy should not be performed because peritoneal spillage of ICG and displacement of ICG-stained tissues from uterine cervix to pelvis frequently occurs during IC. Therefore, specific measures to prevent tumor exposure during colpotomy should be implemented in cervical cancer patients.

Simplified Selection Criteria for Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer.

(1) Background: Multiple confounding factors influence the indications for secondary cytoreductive surgery (SCS) in patients with ovarian cancer (OC). We aimed to identify the factors associated with patients most likely to benefit from SCS. (2) Methods: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer from 2003 to 2021. The potential factors influencing treatment outcomes and survival between patients who received chemotherapy alone and those who received SCS after recurrence were evaluated. (3) Results: Recurrent OC was identified in 262 patients, with a median age of 53 (20-80) years. Of these patients, 87.4% had an initial stage III/IV disease. Eighty-nine (34%) patients received SCS. The median survival was 41.0 (95% confidence interval [CI], 37.4-44.5) months and 88.0 (95% CI, 64.2-111.7) months in the chemotherapy and surgery groups, respectively. A multivariate analysis showed limited regional carcinomatosis (single region or up to three regions with limited carcinomatosis) (p = 0.045) as the only significant factor for predicting no residual disease after SCS. In platinum-sensitive recurrent patients with limited regional recurrence, the complete resection rate was 87.6%. (4) Conclusions: SCS had a significant impact on survival in the selected patient population. Limited regional recurrence (single region or up to three regions with limited carcinomatosis) may be a simple criterion for SCS in platinum-sensitive recurrent OC patients.

Gastrointestinal/genitourinary perforation and fistula formation with or without bevacizumab in patients with previously irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators Collaboration (GORILLA) group (GORILLA-1001).

BACKGROUND: This study aims to evaluate the incidence of and identify risk factors for gastrointestinal (GI) and genitourinary (GU) fistula or perforation formation with or without bevacizumab in patients with recurrent cervical cancer who underwent pelvic radiation therapy (RT). METHODS: Medical records of patients with recurrent cervical cancer who previously underwent pelvic RT between 2007 and 2020 were retrospectively reviewed. Clinicopathological factors were compared between groups that are stratified according to: 1) fistula/perforation (+) versus (-); and 2) bevacizumab plus conventional chemotherapy (BC) versus chemotherapy alone (C). Univariate and multivariate regression analyses were performed to identify risk factors for fistula/perforation. Overall survival (OS) was compared between the different groups. RESULTS: Of 219 participants, fistula/perforation of any grade occurred in 36 patients (16.4%); 27 fistulas and 9 perforations. Bevacizumab was more frequently used in Bevacizumab was more frequently used ( +) group than fistula/perforation (-) group (p = 0.015). Multivariate analysis showed that bevacizumab administration was the only independent risk factor for fistula or perforation (HR, 3.27; 95% CI, 1.18-9.10; P = 0.023). F/P was observed more frequently in women receiving BC (n = 144) than those receiving C (n = 75) (20.8% vs. 8.0%; P = 0.019). During median follow-up of 33.7 months (1.2-185.6 months), no significant OS difference was observed between fistula/perforation ( +) vs. (-) (hazards ratio [HR], 1.78; median 84.2 months [95% CI, 59.3-109.0] vs. 129.5 months [95% CI, 114.1-144.9]; P = 0.065) or BC vs. C (HR, 1.03; median 119.8 months [95% CI, 97.3-142.3] vs. 115.7 months [95% CI, 96.0-135.4]; P = 0.928). CONCLUSIONS: This study suggests that incorporation of bevacizumab in chemotherapy regimens for treating recurrent cervical cancer in patients who underwent pelvic RT incurs considerable risk for GI/GU fistula or perforation. There were no other independent risk factors for developing GI/GU fistula or perforation in this study population.

Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol.

BACKGROUND: The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. METHODS: This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. DISCUSSION: We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT04370496 ; registration date, May 2020.

A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer.

BACKGROUND: PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. METHODS: Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101. DISCUSSION: PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04678102 .

Treatment outcomes and complications in FIGO stage IIIC and IVB endometrioid endometrial cancer patients presenting as nodal spreads following systematic lymphadenectomy and adjuvant therapy.

OBJECTIVE: To evaluate the treatment outcomes and complications of patients with FIGO stage IIIC and IVB endometrioid endometrial cancer (EC) presenting primarily as nodal spreads following systematic lymphadenectomy and adjuvant therapy. MATERIAL AND METHODS: Forty-four FIGO stage IIIC and IVB endometrioid EC patients between July 2003 and March 2020 received staging procedures including systematic lymphadenectomy. The survival outcomes and late treatment-related complications were compared between adjuvant chemoradiation-based group and chemotherapy-based group. RESULTS: Of the 44 patients, 16 (36.4%) had stage IIIC1, 26 (59.1%) had stage IIIC2, and 2 (4.5%) had stage IVB disease. The median follow-up time was 54 months (range, 10-185 months). There was no statistical difference in mortality between the microscopic and macroscopic nodal groups (6.2% vs 4.3%, p > 0.999). Eleven patients (25.0%) and 33 patients (75.0%) received adjuvant chemoradiation and chemotherapy, respectively. The 5-year disease-free and overall survival rates were not different between the two groups (disease-free survival, 81.8% vs 82.1%, p = 0.743; overall survival, 90.9% vs 95.8%, p = 0.537). The incidence rates of grade 2 lymphedema (36.4% vs 9.1%, p = 0.032) and grade 2/3 gastrointestinal complications (36.4% vs 0.0%, p < 0.001) were higher in the chemoradiation-based group than those in the chemotherapy-based group. CONCLUSIONS: Systematic lymphadenectomy and adjuvant chemotherapy might be the preferred treatment for FIGO stage IIIC and IVB endometrioid EC patients presenting as nodal spreads given that no difference in patient survival was found, but a higher incidence of treatment-related complications was observed in the chemoradiation-based group.

Anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma in Korea: three case reports.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune paraneoplastic syndrome associated with ovarian teratomas. Most patients develop neurologic symptoms, including psychosis, memory deficits, seizures, or abnormal movements, and experience abdominal pain related to ovarian neoplasm. We present a case report of three patients diagnosed with anti-NMDAR encephalitis accompanied by ovarian teratomas at Ajou University Hospital in Korea. The patients demonstrated a different clinical course of the disease. However, upon diagnosis, all patients underwent surgical removal of the ovarian teratoma followed by intensive immunotherapy. The symptoms progressively improved following treatment. This is a case report of a rare autoimmune anti-NMDAR encephalitis associated with ovarian neoplasms, including immature teratoma.

Prognostic factors influencing pelvic, extra-pelvic, and intraperitoneal recurrences in lymph node-negative early-stage cervical cancer patients following radical hysterectomy.

OBJECTIVE: The aim of this study was to evaluate the clinicopathologic factors influencing pelvic, extra-pelvic, and intraperitonal recurrences and survival in patients with lymph node-negative early-stage cervical cancer treated with abdominal/laparoscopic/robotic radical hysterectomy (ARH/LRH/RRH). STUDY DESIGN: We retrospectively reviewed clinicopathologic data of 342 patients with FIGO stage IB-IIA cervical cancer (2018 FIGO staging) treated with RH and retroperitonal lymphadenectomy between February 2000 and November 2018. Several clinicopathologic factors such as surgical methods including LRH/RRH-vaginal colpotomy (VC) and LRH/RRH-intracorporeal colpotomy (IC), surgical resection margin, and parametrial/endomyometrial infiltration were selected. Univariate and multivariate Cox proportional hazard regression and logistic regression models were used to determine prognostic factors. RESULTS: The median follow-up time was 54 months (range, 6-202 months). In multivariate analysis, positive endomyometrial infiltration (HR, 13.576; 95 % CI, 2.917-63.179; P = 0.001), positive parametrial resection margin (HR, 32.648; 95 % CI, 2.774-384.181; P = 0.006), and LRH/RRH-IC (HR, 4.752; 95 % CI, 1.154-19.578; P = 0.031) were significantly related to overall survival. Six (26.3 %) out of 21 patients with endomyometrial infiltration showed extra-pelvic recurrences associated with lung, liver, and brain. Three (50.0 %) out of 6 patients with positive parametrial margin showed both pelvic and extra-pelvic metastases, such as pelvis and supraclavicular/paratracheal lymph nodes. Five (62.5 %) out of the eight relapsed patients who received LRH/RRH-IC showed intraperitoneal recurrences including omentum, liver surface, colon serosa, and splenic hilum. CONCLUSIONS: Three risk factors including parametrial margin, endomyometrial infiltration, and laparoscopic IC appear to be involved in pelvic, extra-pelvic, and intraperitoneal recurrences in node-negative early-stage cervical cancer patients following RH. In particular, endomyometrial infiltration may be one of the strongest independent prognostic factors for extra-pelvic recurrence. Adjuvant systemic therapy may be indicated for lymph node-negative early-stage cervical cancer patients with endomyometrial infiltration.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology.

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.