Sang-Yoon Park

Pattern of first recurrence in advanced epithelial ovarian, fallopian tube and peritoneal cancers treated with cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy

Developing standardized informed consent for hysterectomy and vulva cancer surgery

Informed consent is a fundamental aspect of surgical care, designed to reinforce patient autonomy, promote shared decision-making, and potentially mitigate legal conflicts by ensuring the provision of comprehensive and consistent information in clinical practice. The Korean Society of Gynecologic Oncology (KSGO) previously published detailed informed consent documents for cervical, endometrial, and ovarian cancer surgery. However, standardized consent forms remain relatively lacking for laparoscopic-robotic hysterectomy performed for non-malignant indications, as well as for vulvar cancer surgery. Hence, the KSGO subcommittee collected, reviewed, and discussed consent forms from domestic medical institutions and subsequently developed informed consent for laparoscopic-robotic hysterectomy and vulvar cancer surgery, aiming to build patient trust and understanding.

Neoadjuvant Chemotherapy with Dual Immune Checkpoint Inhibitors for Advanced-Stage Ovarian Cancer: Final Analysis of TRU-D Phase II Nonrandomized Clinical Trial

Abstract Purpose: This open-label, investigator-initiated, phase II study was conducted to evaluate the safety, survival, and neoadjuvant outcomes of neoadjuvant chemotherapy (NAC) combined with dual immune checkpoint inhibitors in advanced-stage epithelial ovarian cancer (EOC). Patients and Methods: Between June 2019 and July 2021, 45 patients with unresectable stage III to IV EOC were enrolled. The patients received three cycles of NAC combined with durvalumab and tremelimumab. All patients underwent interval debulking surgery and received three cycles of durvalumab and adjuvant chemotherapy, followed by 12 cycles of durvalumab as maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate; the secondary endpoints were the objective response rate after NAC, a chemotherapy response score, pathologic complete response, overall survival, and safety. The preplanned exploratory analyses assessed the lymphocyte infiltration, PD-L1 expression, and genomic profiles of pretreatment tumors. Results: The 12-month PFS rate was 65.9% [95% confidence interval (CI), 52.8–not estimated (NE)], whereas the 24- and 30-month PFS rates were 38.6% (95% CI, 26.7–NE) and 36.4% (95% CI, 24.7–NE), respectively. After NAC, the objective response rate was 86.7%, whereas 14 patients (31.1%) had a chemotherapy response score of three, and five (11.1%) achieved pathologic complete response. The 30-month overall survival rate was 87.7%. The most common grade ≥3 adverse event was neutropenia (26.7%). In an exploratory analysis, patients with pre-NAC tumors showing PD-L1 (combined positive score) ≥1, high Mutation Signature 3, and a high extracellular matrix signature demonstrated improved PFS outcomes. Conclusions: NAC combined with dual immune checkpoint inhibitors is feasible for advanced-stage EOC and shows promising activity with a durable clinical response.

The pathologic and clinical outcomes of risk-reducing salpingo-oophorectomy in asymptomatic carriers of homologous recombination repair gene mutation

To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

Prospective analysis of pre and postoperative laboratory parameters associated with thrombosis in patients with ovarian cancer

Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including deep vein thrombosis and pulmonary thromboembolism in patients treated for ovarian cancer. We collected pre and post operative blood samples from 133 patients undergoing surgery for ovarian cancer between December 2021 and August 2022. The measured parameters were white blood cell count, hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, antithrombin III, protein C, protein S, plasminogen, plasminogen activator inhibitor 1, homocysteine, N-terminal pro-brain natriuretic peptide, interleukin 6, thrombopoietin, soluble P-selectin and granulocyte stimulating factor. Body mass index of patients were collected. Differences between patients who developed thrombosis and those without were compared with Wilcoxon rank-sum test and we analyzed the continuous variables using logistic regression. Twenty-one (15.8%) patients developed thrombosis ranging from 6 to 146 days (median 15 days) after surgery. Pre operative values of homocysteine (p = 0.033) and IL-6 (p = 0.043) were significantly increased and post operative aPTT (p = 0.022) was prolonged and plasminogen (p = 0.041) was decreased in patients with thrombosis. It is important to find novel biomarkers for thrombosis to carefully manage patients who are prone to develop thrombosis despite preventive measures were applied.

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

AbstractIntroductionThis study aimed to verify the association between ovarian cancer (OC) and reproductive‐ and lifestyle‐related risk factors stratified by the subtype of OC.MethodsIn 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.ResultsAs 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).ConclusionA 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.

How to manage synchronous endometrial and ovarian cancer patients?

Abstract Backgrounds We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC). Methods The medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses. Results The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis. Conclusions Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC.

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.

Preoperative laboratory parameters associated with deep vein thrombosis in patients with ovarian cancer: retrospective analysis of 3,147 patients in a single institute

Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate laboratory parameters associated with deep vein thrombosis (DVT) in patients treated for ovarian cancer. We retrospectively analyzed pre-operation laboratory data of patients with ovarian cancer for DVT at the National Cancer Center, Korea, between January 2000 and February 2021. The test items were white blood cell count, absolute neutrophil count (ANC), hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), and body mass index (BMI). Differences between patients with and without DVT were compared with Wilcoxon rank-sum test. We analyzed the variables using logistic regression. Items with significant odds ratios were included in multivariate logistic regression. Significant variables were selected using backward elimination. Items were further categorized based on reference ranges. Univariate and multivariate analyses were performed to identify items with abnormal values associated with DVT. From 3,147 patient samples analyzed, 286 (9.1%) patients with DVT were selected. Differences between patients with vs without DVT were statistically significant for hemoglobin, monocyte, serum glucose, CA125, PT, aPTT, fibrinogen, D-dimer, and BMI. After univariate and multivariate analysis, monocyte, glucose, and PT remained significant. Among the categorical variables, low hemoglobin, high monocyte, high CA125, prolonged PT, and high BMI remained significant after univariate and multivariate analysis. Pre-operation laboratory data of low hemoglobin, high monocyte percentage, high serum glucose, high CA125, prolonged PT, and high BMI were associated with DVT.

Adherence of PARP inhibitor for frontline maintenance therapy in primary epithelial ovarian cancer: a cross-sectional survey

To identify the adherence rate to poly (ADP-ribose) polymerase (PARP) inhibitors and identify factors contributing to the deterioration of adherence at our institution. The adherence rate to PARP inhibitors was calculated using self-reported Adherence to Refills and Medications Scale questionnaires from a cross-sectional survey. Multivariable logistic regression analysis was performed to identify the factors that affected adherence. Of the 131 respondents, 32 (24.4%) showed non-adherence to PARP inhibitors. In the multivariable logistic regression analysis, unemployed or retired status (odds ratio [OR]=4.878; 95% confidence interval [CI]=1.528-15.572; p=0.008), patients receiving niraparib (OR=3.387; 95% CI=1.283-8.940; p=0.014), and a lower score on the quality-of-life assessment (EORTC-QLQ-OV28), which reflects a better quality of life (QOC) with a lower symptom burden (OR=1.056; 95% CI=1.027-1.086; p<0.001) were associated with high adherence to PARP inhibitors. Approximately one-fourth of patients with ovarian cancer are non-adherent to PARP inhibitors as maintenance treatment for newly diagnosed advanced ovarian cancer. The occupational status, type of PARP inhibitor, and QOC may affect adherence to PARP inhibitors.

Survival Effects of Cytoreductive Surgery for Refractory Patients after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer

Salvage second-line chemotherapy is usually recommended for patients with advanced epithelial ovarian cancer (AEOC) who develop progressive disease (PD) after neoadjuvant chemotherapy (NAC). Herein, we investigated the role of cytoreductive surgery (CRS) for such patients. We retrospectively reviewed the medical records of 36 patients with AEOC who developed PD after receiving NAC at two tertiary academic centers with different treatment strategies between 2001 and 2016. Patients who developed PD after NAC were consistently treated with CRS at one hospital (group A; n=13) and second-line chemotherapy at another (group B; n=23). The clinical characteristics and treatment outcomes were compared between the groups. Overall survival (OS) was longer in group A than in group B (19.4 months vs. 7.9 months; CRS may result in a survival benefit even in patients with AEOC who develop PD after NAC.

Transabdominal cardiophrenic lymph node dissection for cytoreductive surgery in advanced ovarian cancer

Minimizing residual tumors is one of the most important prognostic factors in the management of advanced ovarian cancer [1]. In ovarian cancer patients with cardiophrenic lymph node (LN) metastases, transabdominal cardiophrenic lymph node dissection (CPLND) has been performed along with the surgery on the primary site [2]. However, CPLND for the complicated locations in the thoracic cavity is still technically challenging. This video aims to share our surgical technique for the transabdominal CPLND. A 60-year-old woman who presented with suspicious bilateral ovarian cancer was hospitalized for cytoreductive surgery. Preoperative CT demonstrated peritoneal seeding and multiple LN metastases including right anterior, lateral, posterior, and left anterior cardiophrenic LNs. The gynecology and general surgery team underwent hysterectomy, bilateral salpingo-oophorectomy, supracolic omentectomy, lower anterior resection, right diaphragmatic and bladder peritonectomy, pelvic and paraaortic LN dissection, and appendectomy. The thoracic surgeon took over the operation because the pelvic cavity was regarded as R0. CPLND was performed by transabdominal, subxiphoid approach. The procedure is narrated in the video. Complete clearance of CPLN leaving no gross residual disease was possible without complication. A long, transverse incision of the anterior diaphragm was closed with a 1-0 polypropylene in the way of double layered continuous running suture and 8 times ties for the final knot. Transabdominal CPLND can be used safely and effectively without change of patient's position and with minimal diaphragmatic injury. However, this approach may be unfeasible for metastatic internal mammary LN dissection and still needs meticulous surgical skills to avoid complications.

A single-arm phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer (OPEB-01)

The optimal treatment of ClinicalTrials.gov Identifier: NCT04361370, Clinical Research Information Service Identifier: KCT0005144.

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.

Reducing distal pancreatectomy by posterolateral approach for splenectomy in the surgical management of ovarian cancer

Efficacy and toxicity of PARP inhibitor in elderly patients with homologous recombination-deficient newly diagnosed advanced ovarian cancer: the role of dose modification

To investigate the impact of age on the progression-free survival (PFS) and dose modification, discontinuation and adverse events of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in homologous recombination-deficient (HRD) ovarian cancer patients. We analyzed 324 patients with advanced stage III-IV epithelial ovarian cancer who had either BRCA mutation or HRD between July 2019 and November 2022. The primary objective was to evaluate the efficacy of PARPis by comparing PFS between patients who received PARPis and those who did not, specifically within 2 age groups: patients aged <60 years and those aged ≥60 years. The secondary objective included evaluating the rates of dose modification, discontinuation, and occurrence of treatment-emergent adverse events in patients who used PARPis. Of the 324 patients, 139 patients (42.9%) were diagnosed at ≥60 years. The use of PARPis resulted in a significant improvement in PFS in both age groups (hazard ratio [HR]=0.37; p<0.01) for patients aged <60 years (HR=0.41; p<0.01) for those aged ≥60 years. The multivariable Cox proportional hazards analysis revealed no significant difference in the PFS benefit between the 2 age groups (HR=0.95; 95% confidence interval [CI]=0.65-1.37; p=0.76). Dose modifications were more frequent in the elderly cohort (63.9% vs. 46.5%; p=0.04). PARPis significantly improved PFS in elderly ovarian cancer patients with BRCA mutations and HRD, with a toxicity profile similar to that of younger patients. Elderly patients benefited from frequent dose modifications without any negative impact on PFS outcomes.

Olaparib Maintenance With Pembrolizumab & Bevacizumab in BRCA Non-mutated Patients With Platinum-sensitive Recurrent Ovarian Cancer

This study is phase II, open label, clinical trial to determine the efficacy of Olaparib maintenance with Bevacizumab and Pembrolizumab by assessment progression-free survival(6 months PFS rate) in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer.

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