Ji Hyun Kim

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

Impact of Clostridium difficile Infection on Chemotherapy in Patients With Primary Ovarian Cancer

To investigate the impact of This retrospective study included patients with primary ovarian cancer diagnosed with CDI at the National Cancer Center, Korea, between January 2014 and December 2023. Patients with gastrointestinal symptoms and positive A total of 111 CDI episodes were identified in 90 patients, with 17 patients experiencing recurrent CDI. Among initial CDI episodes, 51.1% occurred during the first or second cycle of adjuvant chemotherapy after cytoreductive surgery. Adjuvant chemotherapy cycles were delayed in 81.1% of cases, with a median delay of 13 days. Additionally, 7.8% of patients discontinued chemotherapy, and CDI-related mortality was 2.2%. Severe or fulminant CDI was associated with higher rates of intensive care unit admission, bowel surgery, or death (38.9% vs. 4.2%; CDI can cause chemotherapy delays and severe adverse outcomes, such as septic shock or death. Early identification of CDI and a multidisciplinary approach are essential to minimize CDI-related complications in patients with ovarian cancer. Further research is needed to develop preventive strategies and evaluate the long-term impact of CDI on cancer prognosis.

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.

Comparison of survival outcomes and safety between early and late initiation of niraparib maintenance in newly diagnosed advanced epithelial ovarian cancer

This multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between early and late initiation of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer. We included patients with stage III-IV ovarian cancer who showed a complete or partial response to frontline platinum-based chemotherapy and received niraparib maintenance therapy between October 2019 and December 2022. The primary endpoint was the HR for progression-free survival based on the median initiation interval, which was defined as the duration between the completion of chemotherapy and commencement of maintenance therapy. The secondary endpoint was the comparison of progression-free survival at another time point that determined the interval that maximized the difference between the survival curves of the two groups using the Contal and O'Quigley method. This analysis included 146 patients who received niraparib maintenance therapy. The median age was 58 years (IQR 50-63.3). The median initiation interval was 8.4 (IQR 5.7-8.9) weeks. After adjusting for prognostic factors for progression-free survival identified through multivariable analysis, early initiation (≤8 weeks) of niraparib was associated with significantly better progression-free survival (HR=0.57; 95% CI 0.33 to 0.99; p=0.047). Furthermore, the initiation interval that maximized the difference in progression-free survival was 6 weeks. Multivariable analysis revealed that early initiation (≤6 weeks) of niraparib significantly increased progression-free survival (HR=0.37; 95% CI 0.18 to 0.76; p=0.007). The rate of treatment discontinuation due to treatment-emergent adverse events was higher (12.5% versus. 2.8%; p=0.036) in patients receiving niraparib within 6 weeks than those treated later, with no significant effect in those initiating treatment within 8 weeks. Early initiation of niraparib maintenance therapy within 8 weeks of chemotherapy completion improved progression-free survival, with further benefits observed with treatment within 6 weeks in patients with newly diagnosed advanced ovarian cancer.

Deep Learning-Based Dynamic Risk Prediction of Venous Thromboembolism for Patients With Ovarian Cancer in Real-World Settings From Electronic Health Records

PURPOSE Patients with epithelial ovarian cancer (EOC) have an elevated risk for venous thromboembolism (VTE). To assess the risk of VTE, models were developed by statistical or machine learning algorithms. However, few models have accommodated deep learning (DL) algorithms in realistic clinical settings. We aimed to develop a predictive DL model, exploiting rich information from electronic health records (EHRs), including dynamic clinical features and the presence of competing risks. METHODS We extracted EHRs of 1,268 patients diagnosed with EOC from January 2007 through December 2017 at the National Cancer Center, Korea. DL survival networks using fully connected layers, temporal attention, and recurrent neural networks were adopted and compared with multi-perceptron–based classification models. Prediction accuracy was independently validated in the data set of 423 patients newly diagnosed with EOC from January 2018 to December 2019. Personalized risk plots displaying the individual interval risk were developed. RESULTS DL-based survival networks achieved a superior area under the receiver operating characteristic curve (AUROC) between 0.95 and 0.98 while the AUROC of classification models was between 0.85 and 0.90. As clinical information benefits the prediction accuracy, the proposed dynamic survival network outperformed other survival networks for the test and validation data set with the highest time-dependent concordance index (0.974, 0.975) and lowest Brier score (0.051, 0.049) at 6 months after a cancer diagnosis. Our visualization showed that the interval risk fluctuating along with the changes in longitudinal clinical features. CONCLUSION Adaption of dynamic patient clinical features and accounting for competing risks from EHRs into the DL algorithms demonstrated VTE risk prediction with high accuracy. Our results show that this novel dynamic survival network can provide personalized risk prediction with the potential to assist risk-based clinical intervention to prevent VTE among patients with EOC.

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.

Development of an Automatic Rule-Based Algorithm for the Detection of Ovarian Cancer Recurrence From Electronic Health Records

PURPOSE As the onset of cancer recurrence is not explicitly recorded in the electronic health record (EHR), a high volume of manual chart review is required to detect the cancer recurrence. This study aims to develop an automatic rule-based algorithm for detecting ovarian cancer (OC) recurrence on the basis of minimally preprocessed EHR data. METHODS The automatic rule-based recurrence detection algorithm (Auto-Recur), using notes on image reading (positron emission tomography-computed tomography [PET-CT], CT, magnetic resonance imaging [MRI]), biomarker (CA125), and treatment information (surgery, chemotherapy, radiotherapy), was developed to detect the first OC recurrence. Auto-Recur contains three single algorithms (images, biomarkers, treatments) and hybrid algorithms (combinations of the single algorithms). The performance of Auto-Recur was assessed using sensitivity, specificity, and accuracy of the recurrence time detected. The recurrence-free survival probabilities were estimated and compared with the retrospective chart review results. RESULTS The proposed Auto-Recur considerably reduced human resources and time; it saved approximately 1,340 days when scaled to 100,000 patients compared with the conventional retrospective chart review. The hybrid algorithm on the basis of a combination of image, biomarker, and treatment information was the most efficient (sensitivity: 93.4%, specificity: 97.4%) and precisely captured recurrence time (average time error: 8.5 days). The estimated 3-year recurrence-free survival probability (44%) was close to the estimates by the retrospective chart review (45%, log-rank P value = .894). CONCLUSION Our rule-based algorithm effectively captured the first OC recurrence from large-scale EHR while closely approximating the recurrence-free survival estimates obtained by conventional retrospective chart reviews. The study findings facilitate large-scale EHR analysis, enhancing clinical research opportunities.

Incidence and treatment outcomes of ovarian carcinosarcoma from the national cancer registry of Korea

To investigate the incidence and survival outcomes of ovarian carcinosarcoma in Korea between 1999 and 2018. Patients diagnosed with ovarian carcinosarcoma between 1999 and 2018 were identified from the Korea Central Cancer Registry (KCCR) and their information was collected. Age-standardized incidence rates (ASRs), annual percent changes (APC), and relative survival rates of ovarian carcinosarcoma were calculated and compared to those of epithelial ovarian cancer. According to the KCCR, 458 cases of ovarian carcinosarcoma were detected, and accounted for 1.5% (458/30,679) of all epithelial ovarian cancers in Korea between 1999 and 2018. The ASR of ovarian carcinosarcoma between 1999 and 2018 was 0.064 per 100,000 women. The incidence rate of ovarian carcinosarcoma increased during the study period, with an ASR of 0.029 per 100,000 in 1999 and 0.073 per 100,000 in 2018. The APC of ovarian carcinosarcoma during 1999-2018 was 5.86 (p<0.001). The median overall survival (OS) of patients with ovarian carcinosarcoma was 39 months, and the 5-year OS rate was 42.5%. Among ovarian carcinosarcomas, patients with localized stages showed better clinical outcomes than those with regional or distant stages (5-year OS, 60.8%, 57.9%, and 32.8%, respectively; p<0.001). In addition, younger (<50 years) patients showed better OS than older (≥50 years) patients (5-year OS, 52.6% vs. 40.2%; p<0.001). Our nationwide registry-based study demonstrated that the incidence of ovarian carcinosarcoma increased from 1999 to 2018 in Korea. Patients with advanced-stage disease and older age (≥50 years) had poorer survival outcomes.

Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis

To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Trends in the incidence and survival outcomes of endometrial cancer in Korea: a nationwide population-based cohort study

To evaluate trends in the incidence and survival outcomes of endometrial cancer (EC) based on the year of diagnosis, stage, age, and histologic types. Women with primary EC diagnosed between 1999 and 2018, and who were followed up with until 2019, were identified from the Korea Central Cancer Registry using the International Classification of Diseases, 10th revision. The age-standardized rates (ASRs) of incidence, annual percent changes (APCs), and survival were estimated according to age, stage, histology, and year of diagnosis. The ASR for EC increased from 2.38 per 100,000 in 1999 to 7.29 per 100,000 in 2018 across all histologic types (APCs of 9.82, 15.97, and 7.73 for endometrioid, serous, and clear cell, respectively, p<0.001). There were significant differences in the 5-year survival rates based on histology (90.9%, 55.0%, and 68.5% for endometrioid, serous, and clear cell, respectively, p<0.001), stage (93.4%, 77.0%, and 31.0% for localized, regional, and distant, respectively, p<0.001), and age (93.0% for <50 years and 80.6% for ≥50 years, p<0.001). The 5-year survival was significantly better in the group diagnosed between 2000 and 2018 (85.9%) than that in the 1999-2008 group (83.3%) (p<0.001). This trend was only observed for endometrioid cancer (p<0.001). The incidence of EC increased across the all 3 subtypes. Survival of patients with endometrioid histology improved over the past two decades, but remained static for serous or clear cell histology. Healthcare strategies to prevent EC incidence in at-risk populations and apply effective treatments for high-risk histology are needed.

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.

Ten-year treatment outcomes of consolidation hyperthermic intraperitoneal chemotherapy for ovarian cancer (HIPEC-KOV-03R)

We aimed to evaluate the long-term efficacy of consolidation hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with primary epithelial ovarian cancer. This retrospective cohort study included patients who underwent second-look surgery either with or without HIPEC after having complete or partial response to primary cytoreductive surgery and adjuvant platinum-based chemotherapy between January 1991 and December 2003 at Seoul St. Mary's Hospital. The 10-year progression-free survival (PFS), overall survival (OS), and toxicity within postoperative 28 days were investigated. A total of 87 patients were identified, 44 (50.6%) received second-look surgery with HIPEC whereas 43 (49.4%) received only second-look surgery. The 10-year PFS and OS were significantly longer in the HIPEC group compared with the control group (PFS, 53.6% vs. 34.9%, log-rank p=0.009; OS, 57.0% vs. 34.5%, log-rank p=0.025). Multivariable analysis identified HIPEC as an independent favorable prognostic factor for PFS (adjusted hazard ratio [HR]=0.42; 95% confidence interval [CI]=0.23-0.77; p=0.005) but not for OS (adjusted HR=0.58; 95% CI=0.32-1.07; p=0.079). The more common adverse events in the HIPEC group were thrombocytopenia (90.9% vs. 68.3%, p=0.005), elevated liver enzymes (65.9% vs. 29.3%, p=0.002), and wound complications (18.2% vs. 2.4%, p=0.032). However, these adverse events were reversible and did not delay subsequent consolidation chemotherapy. The consolidation HIPEC demonstrated a significant improvement in 10-year PFS but not OS, with acceptable toxicity in patients with primary epithelial ovarian cancer. Further randomized controlled trials are warranted to confirm these results.

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.

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.

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