Incidence of postoperative thrombotic events in ovarian cancer patients with a de-escalated prophylactic strategy: A retrospective cohort study.

OBJECTIVE: This study aimed to determine the incidence of thrombotic events in ovarian cancer patients following a de-escalated prophylactic strategy and to stratify risk groups. METHODS: We reviewed the records of patients who underwent debulking surgery for ovarian cancer at a single institution between January 2007 and May 2019. We identified clinically diagnosed and radiologically confirmed cases of thrombotic events-classified as pulmonary thromboembolism (PE), deep vein thrombosis (DVT), and other thrombotic events-within 6 months of debulking surgery. RESULTS: After excluding 13 patients diagnosed with thromboembolism at the baseline or during neoadjuvant chemotherapy, 799 were analyzed. Since the introduction of medical prophylaxis at our institution in 2009, 482 patients (60%) received medical prophylaxis with subcutaneous injection of low molecular weight heparin for 5 days with mechanical prophylaxis, whereas 317 (40%) received mechanical prophylaxis only. After debulking surgery, thrombotic events occurred in 28 patients (3.5%) including PE (n = 11), DVT (n = 10), and other thrombotic events (n = 7). Multivariable analysis identified age, body mass index (BMI), and operative duration as independent risk factors associated with thrombotic events. A thrombotic event was an independent prognostic factor for overall survival (HR 2.17, 95% CI 1.16-4.1). A cut-off analysis for pre-operative identifiable risk factors showed age < 57 years and BMI < 21 could help define low-risk groups. One patient from 172 low-risk patients (0.58%) experienced a thrombotic event. CONCLUSIONS: The thrombotic event incidence was low in our cohort. A de-escalated prophylaxis strategy may be considered in young (age < 57 years) and lean (BMI < 21) patients.

Early Assessment of Response to Neoadjuvant Chemotherapy with 18F-FDG-PET/CT in Patients with Advanced-Stage Ovarian Cancer.

PURPOSE: The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients. MATERIALS AND METHODS: Forty consecutive patients underwent 18F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUVmax) with PET/CT. Decreases in SUVmax were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS. RESULTS: A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335). CONCLUSION: Early assessment with 18F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

Role of preoperative magnetic resonance imaging and histological assessment in identifying patients with a low risk of endometrial cancer: a Korean Gynecologic Oncology Group ancillary study.

Preoperative identification of individuals at low risk of lymph node metastasis is key to the proper management of endometrial cancer. This study evaluated the role of preoperative assessment based on magnetic resonance imaging (MRI) and histological analysis in identifying a group having a low risk of lymph node metastasis. Data of 529 patients with endometrial cancer were obtained from a prospective multicenter database, between January 2012 and December 2014. Clinical staging, based on MRI and histological analysis, was compared with final pathology results after the surgical staging procedure. The preoperative low-risk criteria, based on current guidelines from Korea, France, and Canada, and criteria used for fertility-sparing therapies, were applied to our multicenter cohort and the accuracy of each set of criteria for identifying group at low risk of lymph node metastasis was evaluated. When considering grades or MR stages separately, the overall agreement between preoperative and postoperative findings was poor (Kappa 0.45 for grades; 0.41 for stages). However, when combining these two parameters, the low-risk group, as defined by any of the guidelines, had an acceptable rate of lymph node metastasis (below 3%). The French guidelines identified 249 patients (47.1%) as being in the low-risk group. Criteria used to define fertility-sparing therapy candidates identified 48 patients (9.1%) among the study population, only one of whom had extra-uterine disease. This study shows that the current guidelines, using preoperative assessment based on MRI and histological analysis, can identify low-risk patients, who may be candidates for omitting lymphadenectomy.

External validation of chemotherapy response score system for histopathological assessment of tumor regression after neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma.

OBJECTIVE: The chemotherapy response score (CRS) system based on histopathological examination has been recently proposed for tubo-ovarian high-grade serous carcinoma (HGSC) to assess response to neoadjuvant chemotherapy (NAC). This study was aimed at validating the CRS system in an external cohort of tubo-ovarian HGSC patients. METHODS: This study included 110 tubo-ovarian HGSC patients who underwent NAC followed by interval debulking surgery. The 3-tiered CRS of the omental and adnexal tissue sections was determined by 3 independent pathologists. Differences in patient outcomes according to CRS were analyzed. RESULTS: The CRS system was highly reproducible among the 3 pathologists. Fleiss' kappa value and Kendall's coefficient of concordance for the omental CRS were 0.656 and 0.669, respectively. The omental CRS significantly predicted progression-free survival (PFS). The median PFS of patients whose tumors exhibited the omental CRS 1-2 (15 months) was significantly shorter than that of patients with an omental CRS of 3 (19 months; p=0.016). In addition, after adjusting for age, stage, and debulking status, the omental CRS was an independent prognostic factor for PFS of tubo-ovarian HGSC patients who were treated with NAC (adjusted hazard ratio [HR]=1.74; 95% confidence interval [CI]=1.05-2.87). CONCLUSION: The CRS system for assessing NAC response was a reproducible prognostic tool in our cohort. The application of the CRS system after NAC can improve survival estimation in HGSC patients.

A novel algorithm for the treatment strategy for advanced epithelial ovarian cancer: consecutive imaging, frailty assessment, and diagnostic laparoscopy.

BACKGROUND: This study aimed to evaluate the perioperative outcomes and prognostic impact of the consecutive steps of imaging, frailty assessment, and diagnostic laparoscopy (DLS) in patients with advanced epithelial ovarian cancer (EOC). METHODS: Patients diagnosed with EOC during 2012-2015 were analyzed retrospectively. Surgical and survival outcomes were compared between three treatment groups: patients without high tumor dissemination (HTD) who underwent primary debulking surgery (PDS group); patients with HTD who underwent DLS (DLS group); and patients with HTD diagnosed by cytological confirmation of malignancy followed by neoadjuvant chemotherapy (NACT group). RESULTS: Of 181 patients, 85, 38, and 58 underwent PDS, DLS, and NACT, respectively. Among the 38 consecutive patients who initially underwent DLS, 6 were considered suitable for PDS; the remaining 32 were eligible for NACT followed by interval debulking surgery. The median operative times of debulking surgery in the PDS, DLS, and NACT groups were 365 min (interquartile range [IQR]: 216.5-476.5 min), 266.2 min (IQR: 160.3-193.5 min), and 339.0 min (IQR: 205-425 min; P = 0.042), respectively, with respective median estimated blood loss volumes of 962.2 mL (IQR: 300-1037.5 mL), 267.1 mL (IQR: 150-450 mL), and 861.7 mL (IQR: 150-1200 mL; P = 0.023). The DLS group had significantly reduced transfusion requirements and intensive care unit admission rates (P = 0.006). The Kaplan-Meier survival analysis indicated significantly poor PFS in the NACT group. However, there was no significant difference in OS among the three groups. CONCLUSIONS: The consecutive steps of imaging, frailty assessment, and DLS might facilitate rapid assessments of peritoneal disease extent and resectability; this novel algorithm might also be used to individualize treatment.

Preoperative assessment of lymph node metastasis in endometrial cancer: A Korean Gynecologic Oncology Group study.

BACKGROUND: Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed. METHODS: Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV). RESULTS: From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%. CONCLUSIONS: The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263-272. © 2016 American Cancer Society.

Treatment preferences of advanced ovarian cancer patients for adding bevacizumab to first-line therapy.

BACKGROUND: The GOG-218 and ICON-7 studies recently showed that adding bevacizumab to first-line therapy for patients with advanced ovarian cancer increased progression-free survival. However, the high cost and long treatment duration prevents the incorporation of bevacizumab in practice. The aim of this study was to explore and quantify patients' preferences for adding bevacizumab to first-line therapy. METHODS: A discrete choice experiment (DCE) and trade-off question were designed and distributed to 102 ovarian cancer patients. Participants were asked to choose between two hypothetical first-line therapies that differed in terms of effectiveness, safety, and the financial burden. A trade-off technique varying the cost of bevacizumab was used to quantify a willingness-to-pay threshold for selecting bevacizumab. RESULTS: All attributes of the DCE had a statistically significant impact on respondents' preferences and the financial burden was the most important attribute. The results of the trade-off question showed that more than half of patients would prefer to add bevacizumab to standard chemotherapy when the cost of the drug was reduced to 17% (1/6) of the baseline cost. CONCLUSION: Patients' preferences for bevacizumab in the adjuvant treatment of ovarian cancer depend primarily on drug costs. Our results suggest that the current cost of bevacizumab is sufficiently high that the majority of ovarian cancer patients are not willing to pay to accept a small increase in progression-free survival.

Treatment strategies for stage IB cervical cancer: A cost-effectiveness analysis from Korean, Canadian and U.S. perspectives.

OBJECTIVES: To assess the cost-effectiveness of two commonly used strategies and an alternative triage strategy for patients with Stage IB cervical cancer in the U.S., Canada, and Korea. METHODS: A Markov state-transition model was constructed to compare three strategies: (1) radical hysterectomy followed by tailored adjuvant therapy (primary surgery), (2) primary chemoradiation, and (3) an MRI-based triage strategy, in which patients without risk factors in preoperative MRI undergo primary surgery and those with risk factors undergo primary chemoradiation. All relevant literature was identified to extract the probability data. Cost data were calculated from the perspective of U.S., Canadian, and Korean payers. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Cost-effectiveness ratios were analyzed separately using data from each country. RESULTS: Base case analysis showed that the triage strategy was the most cost-effective of the three strategies in all countries at usual willingness-to-pay threshold (Korea: $30,000 per quality-adjusted life year (QALY), Canada and US: $100,000 per QALY). Monte Carlo simulation acceptability curves from Korea indicated that at a willingness-to-pay threshold of $30,000/QALY, triage strategy was the treatment of choice in 71% of simulations. Monte Carlo simulation acceptability curves from US and Canada indicated that at a willingness-to-pay threshold of $100,000/QALY, triage strategy was the treatment of choice in more than half of simulations. CONCLUSIONS: An MRI-based triage strategy was shown to be more cost-effective than primary surgery or primary chemoradiation in the US, Canada, and Korea.

Cost-effectiveness of para-aortic lymphadenectomy before chemoradiotherapy in locally advanced cervical cancer.

OBJECTIVE: To evaluate the cost-effectiveness of nodal staging surgery before chemoradiotherapy (CRT) for locally advanced cervical cancer in the era of positron emission tomography/computed tomography (PET/CT). METHODS: A modified Markov model was constructed to evaluate the cost-effectiveness of para-aortic staging surgery before definite CRT when no uptake is recorded in the para-aortic lymph nodes (PALN) on PET/CT. Survival and complication rates were estimated based on the published literature. Cost data were obtained from the Korean Health Insurance Review and Assessment Service. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed, including estimates for the performance of PET/CT, postoperative complication rate, and varying survival rates according to the radiation field. RESULTS: We compared two strategies: strategy 1, pelvic CRT for all patients; and strategy 2, nodal staging surgery followed by extended-field CRT when PALN metastasis was found and pelvic CRT otherwise. The ICER for strategy 2 compared to strategy 1 was $19,505 per quality-adjusted life year (QALY). Under deterministic sensitivity analyses, the model was relatively sensitive to survival reduction in patients who undergo pelvic CRT alone despite having occult PALN metastasis. A probabilistic sensitivity analysis demonstrated the robustness of the case results, with a 91% probability of cost-effectiveness at the willingness-to-pay thresholds of $60,000/QALY. CONCLUSION: Nodal staging surgery before definite CRT may be cost-effective when PET/CT imaging shows no evidence of PALN metastasis. Prospective trials are warranted to transfer these results to guidelines.

Life after the pan and the fire: Depression, order, attachment, and the legacy of abuse among North Korean refugee youth and adolescent children of North Korean refugees.

Given previous research on depression, history of physical abuse, family order, attachment, and parenting, we hypothesized that the physical abuse-depression relationship would be moderated by (a) family order and (b) attachment, and that (c) attachment and family order would interact significantly in predicting depression. Hypotheses were tested in South Korea in a random cluster sample of 82 youth aged 15-25 who were either themselves North Korean refugees (n=39) or who were born to North Korean refugee mothers in China (n=43). A qualitative interview was used to shed further light on the findings. Family order appears to be a protective factor against depression in that more order is associated with a weakened past abuse-depression relationship.

The cost-effectiveness of selective lymphadenectomy based on a preoperative prediction model in patients with endometrial cancer: insights from the US and Korean healthcare systems.

OBJECTIVE: The aim of this study was to determine the cost-effectiveness of selective lymphadenectomy using a preoperative prediction model compared to routine lymphadenectomy for patients undergoing surgery for endometrial cancer in the US and Korea. METHODS: We used a modified Markov model to estimate clinical and economic outcomes for newly diagnosed, apparent early-stage endometrial cancer patients under two different strategies: (1) selective lymphadenectomy, where patients classified as low risk based on the preoperative prediction model did not undergo complete surgical staging, and (2) routine lymphadenectomy, where all patients underwent complete surgical staging. Published data were used to estimate the rates of adjuvant therapy and survival. Costs were calculated from the perspective of US or Korean payers. Cost-effectiveness ratios were analyzed separately using data from each country. RESULTS: Base-case analysis indicated that selective lymphadenectomy was less costly ($6454 vs. $7079 in Korea; $23,995 vs. $26,318 in the US) and more effective (6.91 quality-adjusted life years (QALYs) vs. 6.85 QALYs in Korea; 6.87 QALYs vs. 6.81 QALYs in the US) than routine lymphadenectomy in both countries. This result was robust in a deterministic sensitivity analysis, with the exception of when the utility scores for patients with lymphedema were varied. So long as a modest preference for avoiding lymphedema (disutility of 0.04) was obtained, selective lymphadenectomy remained the dominant strategy. CONCLUSIONS: A selective lymphadenectomy strategy based on a preoperative prediction model was shown to be more cost-effective than routine lymphadenectomy for endometrial cancer patients in the US and Korea.

The associations between bridal pregnancy and obstetric outcomes among live births in Korea: population-based study.

OBJECTIVE: In East Asia the recently increased number of marriages in response to pregnancy is an important social issue. This study evaluated the association of marriage preceded by pregnancy (bridal pregnancy) with obstetric outcomes among live births in Korea. METHODS: In this population-based study, 1,152,593 first singleton births were evaluated from data registered in the national birth registration database from 2004 to 2008 in Korea. In the study population, the pregnancy outcomes among live births from the bridal pregnancy group (N = 62,590) were compared with the outcomes of the post-marital pregnancy group (N = 564,749), composed of women who gave birth after 10 months but before 24 months of marriage. The variables preterm birth (PTB; <37 weeks gestation) and low birth weight (LBW; <2.5 kg) were used to determine the primary outcome. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated after controlling for socio-demographic factors. RESULTS: The socio-demographic factors among the bridal pregnancy group were associated with a social disadvantage and particular risk factors. In the subgroup analyses of maternal age, differences in adverse pregnancy outcomes from bridal pregnancy were identified between women in the following age group: (i) ≤19, (ii) 20-39, and (iii) ≥40 years. After the multivariate analysis, the aORs for each age group were 1.47 (95% CI: 1.15-1.89), 1.76 (1.70-1.83), and 1.13 (0.77-1.66), respectively, for PTB and 0.92 (0.70-1.21), 1.60 (1.53-1.66), and 1.11 (0.71-1.74), respectively, for LBW. In the adjusted logistic regression models, bridal pregnancy was associated with PTB (1.76, 1.69-1.82) and LBW (1.53, 1.48-1.59). CONCLUSION: Pregnancy outcomes among live births from bridal pregnancies are associated with higher risks for PTB and LBW in Korea.

Necessity of education for oral contraceptive use in Korea: results from the fourth Korean national health and nutrition examination survey 2007-2009.

BACKGROUND/AIMS: To compare the prevalence of contraindications to oral contraceptive (OC) use between OC users and nonusers and to identify high-risk groups related to contraindications to OC use among OC users. METHODS: This health-interview survey is part of the Fourth Korean National Health and Nutrition Examination Survey 2007-2009. Of 13,561 women who participated in the survey, 672 were OC users and 3,720 were OC nonusers. The adjusted proportions of contraindications to OC use were measured according to the current OC use status. Factors associated with contraindications to OC use among OC users were identified using multivariate analysis. RESULTS: The prevalence of contraindications to OC use was higher in OC users than in OC nonusers (12.6 vs. 7.8%, p < 0.001). The adjusted proportion of women who were smokers and aged ≥ 35 years was greater in OC users than in OC nonusers (5.8 vs. 1.9%, p < 0.001). Among OC users, the 40-50 age group, lower education level, and a BMI ≥ 25 had higher odds of having contraindications. CONCLUSION: Education programs for OC use are urgently required to improve knowledge about correct use of and contraindications to OC use.