Investigator
Ajou University
Clinical practice guidelines for ovarian cancer: an update to the Korean Society of Gynecologic Oncology guidelines
We updated the Korean Society of Gynecologic Oncology (KSGO) practice guideline for the management of ovarian cancer as version 5.1. The ovarian cancer guideline team of the KSGO published announced the fifth version (version 5.0) of its clinical practice guidelines for the management of ovarian cancer in December 2023. In version 5.0, the selection of the key questions and the systematic reviews were based on the data available up to December 2022. Therefore, we updated the guidelines version 5.0 with newly accumulated clinical data and added 5 new key questions reflecting the latest insights in the field of ovarian cancer between 2023 and 2024. For each question, recommendation was provided together with corresponding level of evidence and grade of recommendation, all established through expert consensus.
A predictive model for lymph node metastasis using tumor location in presumed early-stage endometrioid endometrial cancer patients
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. 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. 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). 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.
Extra-abdominal cytoreductive techniques in ovarian cancer: how far can (should) we go?
Complex surgery is an essential component in the management of advanced ovarian cancer. Furthermore, achieving complete gross resection in cytoreductive surgery appears to be associated with significant survival benefits in patients with advanced ovarian cancer. The goal of this review is to demonstrate the advancement of surgical techniques in gynecologic oncology surgery, including resection of disease within the intrathoracic and inguinal regions. This progress has expanded the option of surgery to more patients, especially those who would have previously been deemed inoperable. In this review we describe the most notable studies and reports of surgical resection of ovarian cancer involving cardiophrenic/supradiaphragmatic lymph nodes, mediastinum, lung pleura or parenchyma, and the inguinal region. We also describe the growing role that video-assisted thoracic surgery has played in advanced ovarian cancer diagnosis and management. The studies, series, and reports described demonstrate that comprehensive surgical procedures outside of the abdomen or pelvis can be both safe and feasible in properly selected patients. They also suggest that resection of disease outside of the abdomen or pelvis may benefit appropriately selected patients. Future studies are necessary to identify which patients may benefit most from upfront surgery versus neoadjuvant chemotherapy when ovarian cancer metastasis is present in the thoracic or inguinal regions.
Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines
Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.
Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis
Objectives This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients. Methods/Materials A systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis. Results The two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63). Conclusions In patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy.
Minimally invasive surgery versus open surgery in advanced stage endometrial cancer
AbstractAimStaging surgery in early stage endometrial cancer has been shown to be feasible and safe with minimally invasive surgery (MIS) in many previous studies. However, there is limited literature on MIS's safety in advanced stages. This study aims to identify factors associated with survival in stage III endometrial cancer and investigate survival differences based on surgical approach.MethodsPatients with stage III endometrial cancer who underwent staging surgery from March 2002 to March 2023 were included in this study. Various clinicopathological features, disease‐free survival (DFS), and overall survival (OS) were evaluated.ResultsAmong the 79 patients included in this study, 20 patients underwent MIS (25.3%) and 59 patients underwent open surgery (74.7%). The open surgery group had a higher prevalence of aggressive histology, a higher median pretreatment CA‐125 level, and a greater number of harvested lymph nodes compared to the MIS group. Five‐year OS and DFS was higher in the open surgery group than in the MIS group (DFS: 67.9% vs. 59.9%, p = 0.046; OS: 74.3 vs. 50.6%, p = 0.008). In multivariate analysis, younger than 55 years old (OR, 2.778; 95% CI, 1.078–7.156; p = 0.034), and open surgery (OR, 3.671; 95% CI, 1.581–8.522; p = 0.002) was related to improved OS.ConclusionsOpen staging surgery showed better survival outcomes when compared to MIS in stage III endometrial cancer patients in our study. For patients who are older than 55 years old and have aggressive histology in endometrial biopsy, considering open surgery may help improve their prognosis, even if preoperative MRI suggests early‐stage endometrial cancer.
Real world effectiveness and safety of pegylated liposomal doxorubicin in platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer: a Korean multicenter retrospective cohort study
To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea. We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013-2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR). Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923-1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group. The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice. ClinicalTrials.gov Identifier: NCT03562533.
Is restaging surgery quintessential in suspected early-stage epithelial ovarian cancer? An ancillary study of the Gynecologic Oncology Research Investigators coLLaborAtion study (GORILLA-3002)
To assess the necessity of restaging surgery for patients with suspected International Federation of Gynecology and Obstetrics (FIGO) stage I-II epithelial ovarian cancer (EOC) following incomplete surgical staging. This multicenter retrospective study evaluated patients with early-stage EOC referred for restaging. These patients were diagnosed with suspected FIGO stage I-II EOC between January 2007 and November 2022 after incomplete surgical staging, and no residual region was confirmed by radiological evaluation. Progression-free survival (PFS) and overall survival (OS) were examined. Among the 173 patients included in the study, 56 were assigned to the no restaging surgery group, and 117 to the restaging surgery group. After restaging, 23 were upstaged to other main stage. However, PFS and OS were not significantly different between the groups, also, dividing the groups into 4 groups who underwent chemotherapy and those who did not also did not show significant differences. In multivariate analysis, histologic grade independently influenced PFS outcomes. While restaging surgery resulted in upstaging in some patients, it was not associated with significant differences in PFS or OS in this retrospective analysis. However, the omission of any additional treatment warrants careful consideration and further discussion. Nevertheless, the observation that patients who did not undergo restaging surgery but received adjuvant chemotherapy did not show significantly different prognoses highlights the need for further research to establish appropriate treatment strategies tailored to diverse patient contexts.
A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11)
Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFI Progression-free survival. 124 patients. Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. NCT05704621.
Lymphadenectomy in clinically early epithelial ovarian cancer and survival analysis (LILAC): a Gynecologic Oncology Research Investigators Collaboration (GORILLA-3002) retrospective study
This study aimed to evaluate the therapeutic role of lymphadenectomy in patients surgically treated for clinically early-stage epithelial ovarian cancer (EOC). 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. 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. 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. Clinical Research Information Service Identifier: KCT0007309.
A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2
This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. ClinicalTrials.gov Identifier: NCT02139267.
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)
AbstractBackgroundTo 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.MethodsWe 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.ResultsAmong 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).ConclusionsThe 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.
Quality of life outcomes from the randomized trial of hyperthermic intraperitoneal chemotherapy following cytoreductive surgery for primary ovarian cancer (KOV-HIPEC-01)
To investigate the health-related quality of life (HRQOL) related to hyperthermic intraperitoneal chemotherapy (HIPEC) following primary or interval cytoreductive surgery for primary ovarian cancer. Between 2010 and 2016, a total of 184 patients were randomly assigned to receive cytoreductive surgery with HIPEC (n=92) or without HIPEC (n=92). Quality of life (QOL) assessment was evaluated at baseline (before surgery); on postoperative day 7; after the 3rd and 6th cycle of adjuvant chemotherapy; and at 3, 6, 9, and 12 months after randomization. Patient-reported QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC-QLQ-C30), ovarian cancer questionnaire modules (QLQ-OV28), and the MD Anderson Symptoms Inventory (MDASI). Of the 184 patients enrolled, 165 (83/92 in the HIPEC group and 82/92 in the control group) participated in the baseline QOL assessment. There were no statistically significant differences in functional scales and symptom scales in QLQ-C30; symptom scales, including gastrointestinal symptoms QLQ-OV28; and severity and impact score in MDASI between the 2 treatment groups until 12 months after randomization. HIPEC with cytoreductive surgery showed no statistically significant difference in HRQOL outcomes. Thus, implementation of HIPEC during either primary or interval cytoreductive surgery does not impair HRQOL. ClinicalTrials.gov Identifier: NCT01091636.
Selection criteria and colpotomic approach for safe minimally invasive radical hysterectomy in early-stage cervical cancer
To evaluate oncologic outcomes of minimally invasive radical hysterectomy (RH) in early cervical cancer before and after the application of parametrial invasion (PMI) criterion on magnetic resonance imaging (MRI) and vaginal colpotomy (VC). A total of 216 International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer patients who underwent minimally invasive RH was identified between April 2006 and October 2018. Patients were classified into the pre-PMI intracorporeal or VC (IVC) (n=117) and post-PMI VC groups (n=99). In the pre-PMI IVC group, PMI criterion (intact stromal ring) on MRI was not applied and the patients received IVC. In the post-PMI VC group, surgical candidates were selected using the PMI criterion on MRI and all patients received VC only. Oncologic outcomes and prognostic factors associated with disease recurrence were analyzed. The rate of positive vaginal cuff margins in the pre-PMI IVC group was higher than that in the post-PMI VC group (11.1% vs. 1.0%, p=0.003). Two-year disease-free survival was different between the 2 groups (84.5% in pre-PMI IVC vs. 98.0% in post-PMI VC groups, p=0.005). Disrupted stromal ring on MRI (hazard ratio [HR]=20.321; 95% confidence interval [CI]=4.903-84.218; p<0.001) and intracorporeal colpotomy (HR=3.059; 95% CI=1.176-7.958; p=0.022) were associated with recurrence. The intact cervical stromal ring on MRI might identify the low-risk group of patients in terms of PMI and lymphovascular/stromal invasion in early cervical cancer. Minimally invasive RH should be performed in optimal candidates with an intact stromal ring on MRI, using VC.
Secondary Cytoreductive Surgery (CRS) in Patients With Relapsed Ovarian Cancer Who Have Progressed on PARP Inhibitor Maintenance
This is a randomized phase II study of secondary cytoreductive surgery (CRS) in patients with relapsed ovarian cancer who have progressed on PARP inhibitor maintenance.
Real-World Effectiveness of PLD in Platinum- Sensitive Recurrent Ovarian Cancer
This retrospective multicenter study aimed to evaluate the effectiveness of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with carboplatin and paclitaxel (CP) in patients who had disease progression longer than 6 months after first-line platinum+taxane chemotherapy for ovarian cancer in real world clinical practice.
Intraoperative Hyperthermic Intraperitoneal Chemotherapy With Ovarian Cancer
The current standard treatment for ovarian cancer, tubal cancer, and primary peritoneal cancer is maximal cytoreductive surgery followed by chemotherapy. Recent randomized trials of Gynecologic Oncology Group (GOG) revealed the survival gain in intraperitoneal chemotherapy compared to the intravenous chemotherapy after the optimal cytoreduction in ovarian cancer (GOG#104, GOG#114, GOG#172). Experts attributed such survival gain to the earlier cycles of intraperitoneal chemotherapy when adhesion was minimal from extensive cytoreductive procedures. Hyperthermia has an anti-cancer activity itself. Especially, hyperthermia promotes chemotherapy to penetrate deeper into the cancer tissue. Therefore, the combination of intraperitoneal chemotherapy with hyperthermia theoretically could lead to higher response rate and better survival outcomes. \*HIPEC: hyperthermic intraperitoneal chemotherapy There will be an interim analysis when 50% of patients are enrolled. At the interim analysis, a statistical test will be performed. The nominal significance levels will be determined later. The exact nominal significance level will be determined based on the exact number of events at the time of the interim analysis. The Stopping boundaries will be calculated using an O'Brien-Fleming error spending function
