Predictive value of SUVmax from initial 18F-FDG PET/CT scans for treatment outcomes in endometrial cancer patients undergoing fertility sparing management.

OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.

Laparo-endoscopic single-site versus conventional laparoscopic surgery for early-stage endometrial cancer: A randomized controlled non-inferiority trial.

OBJECTIVE: To evaluate the feasibility and safety of laparo-endoscopic single-site surgery (LESS) compared with conventional laparoscopic surgery (CLS) for early-stage endometrial cancer. METHODS: Patients with clinical stage IA, IB, grade 1-3 endometrial cancer were randomly assigned to undergo LESS or CLS. The primary endpoint was the non-inferiority of LESS to CLS in terms of operation time and the number of resected pelvic lymph nodes. We set the non-inferior margin of the operation time as within 15% (24 min) and the number of resected pelvic lymph nodes as within 20% (5.2 lymph nodes). RESULTS: There was no significant difference between the LESS group (n = 53) and the CLS group (n = 54) in terms of age, weight, body mass index, parity, menopausal status, history of abdominal surgery, and preoperative CA-125 levels. The total operation time was comparable between the two groups. On average, 4.6 fewer pelvic lymph nodes were retrieved in the LESS group, which was within the non-inferiority margin. There were no significant differences in the incidence of intra- and postoperative complications, estimated blood loss, and postoperative hospital stay between the two groups. After a median follow-up time of 34 months (range, 2-242), the progression-free survival rates were 96.2% and 98.1% (P = 0.55) in the LESS group and the CLS group, and the overall survival rates were 98.1% and 100.0% (P = 0.31), respectively. CONCLUSION: LESS surgical staging was non-inferior to CLS and had acceptable feasibility, safety, and efficacy for the surgical management of early-stage endometrial cancer. TRIAL REGISTRATION: Clinicaltrial.gov identifier number: NCT01679522.

Immune checkpoint inhibitors with chemotherapy for primary advanced mismatch repair-deficient endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.

A prospective randomized controlled trial evaluating the safety and efficacy of patient blood management program in patients with gynecologic cancer (KGOG 4011/PBM).

BACKGROUND: Gynecologic cancer has a high frequency of anemia, which is associated with increased morbidity and mortality. Blood transfusion is used to correct anemia, but carries its own side effects and problems in the blood supply have been emerging. As such, methods other than transfusion are needed to correct anemia in patients with cancer. PRIMARY OBJECTIVE: To determine whether intravenous administration of high-dose iron supplements before and after surgery as a patient blood management program is helpful in correcting anemia and reducing the frequency of transfusion in patients with gynecologic cancer. STUDY HYPOTHESIS: Patient blood management will reduce the transfusion rate by up to 25%. TRIAL DESIGN: This prospective, multicenter, interventional, randomized controlled study will consist of three steps. In step 1, the safety and effectiveness of patient blood management for surgical patients before, during, and after surgery will be evaluated. In steps 2 and 3, the safety and effectiveness of patient blood management in patients before, during, and after adjuvant radiation therapy and chemotherapy will be evaluated. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients who are diagnosed with gynecologic cancer (ie, endometrial cancer, cervical cancer, ovarian cancer) and scheduled for surgery will be included and their iron deficiency status will be assessed. Only those with a pre-operative hemoglobin level of 7 g/dL or higher will be included. Patients who underwent neoadjuvant chemotherapy or pre-operative radiation therapy will be excluded. Also, patients with serum ferritin >800 ng/mL or transferrin saturation >50% on serum iron panel tests will be excluded. PRIMARY ENDPOINT: Rate of transfusion within 3 weeks after surgery. SAMPLE SIZE: Eligible participants will be randomly assigned in a 1:1 ratio (167 patients each) into the patient blood management group and the conventional management group. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Patient recruitment will be completed by mid-2025, and management and follow-up will be completed by the end of 2025. TRIAL REGISTRATION NUMBER: NCT05669872.

Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.

Impact of bevacizumab and secondary cytoreductive surgery on survival outcomes in platinum-sensitive relapsed ovarian clear cell carcinoma: A multicenter study in Korea.

OBJECTIVE: This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method. METHODS: OCCC patients with platinum-sensitive recurrence that received secondary treatment at five institutions between July 2007 and June 2021 were included. Patient characteristics and survival outcomes were compared according to the use of bevacizumab (BEV) during second-line chemotherapy and secondary cytoreductive surgery (CRS). RESULTS: 138 patients were included. The BEV (n = 36) and non-BEV (n = 102) groups had similar initial FIGO stages and proportions of secondary CRS. The BEV group showed improved progression-free survival (PFS; median, 15.4 vs. 7.5 months; P = 0.042) and overall survival (OS; P = 0.043) compared to the non-BEV group. In multivariate analyses, BEV was identified as an independent prognostic factor for PFS (adjusted hazard ratio [aHR], 0.571; 95% confidence interval [CI], 0.354-0.921; P = 0.022) and OS (aHR, 0.435; 95%CI, 0.195-0.970; P = 0.042). The secondary CRS group (n = 42) had early-stage disease at diagnosis more frequently (P = 0.009) and multi-site metastasis (P < 0.001) at recurrence less frequently than the no surgery group (n = 96). The secondary CRS group showed significantly better PFS (median, 33.7 vs. 7.2 months; P < 0.001) and OS (P < 0.001). Secondary CRS was associated with a significantly improved PFS (aHR, 0.297; 95% CI, 0.183-0.481; P < 0.001) and OS (aHR, 0.276; 95% CI, 0.133-0.576; P = 0.001). The BEV and non-BEV groups showed similar PFS and OS among the patients who underwent secondary CRS. In contrast, the BEV group showed improved PFS and OS among patients who did not undergo surgery. CONCLUSIONS: The use of BEV during second-line chemotherapy and secondary CRS may improve PFS and OS in patients with platinum-sensitive relapsed OCCC. Further prospective studies are warranted.

The Clinical Significance and Utility of HPV-DNA Testing in Korean Women with Atypical Glandular Cells in Cervical Pap Tests: An Analysis of 311 Cases at a Single Institution.

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%, p < 0.001). In contrast, endometrial lesions were not associated with HPV infection (8.1 vs. 4.5%, p = 0.12). The HPV-DNA testing in women with AGC may be a useful tool for predicting clinically significant cervical lesions.

Continued medical treatment for persistent early endometrial cancer in young women.

OBJECTIVE: We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients. METHODS: We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed. RESULTS: Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p < 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001). CONCLUSIONS: Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.

Real-world experience of olaparib as maintenance therapy in BRCA-mutated recurrent ovarian cancer.

PURPOSE: The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. METHODS: We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. RESULTS: All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. CONCLUSION: Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.

Usefulness of sentinel lymph node mapping using indocyanine green and fluorescent imaging in the diagnosis of lymph node metastasis in endometrial cancer.

The lymph node status is the most important prognostic factor for endometrial cancer. This study aimed to assess whether sentinel lymph node mapping (SLNM) is applicable in endometrial cancer. A retrospective review of patients with endometrial cancer who were diagnosed and treated in Asan Medical Centre from September 2015 to December 2017 was conducted. One hundred patients underwent robotic (da Vinci®) or laparoscopic surgical treatment, including SLNM with indocyanine green (ICG) fluorescence detection using the Firefly® and NIR/ICG systems. At least one lymph node area was observed in 100% of SLNM cases. Sentinel node detection and frozen biopsy were performed in all cases, and all patients with metastasis were found on SLNM. The sensitivity and negative predictive value were both 100% in the patient-by-patient and station-by-station analyses. SLNM appears to be a feasible method to reduce the morbidity and increase the detection rate in early-stage endometrial carcinoma.What is already known on this subject? There are studies that it is safe to diagnose the possibility of lymph node metastasis through sentinel lymph node mapping in endometrial cancer.What do the results of this study add? In this study, it is shown that the accuracy of sentinel lymph node mapping is 100% accurate.What are the implications of these findings for clinical practise and/or further research? Therefore, total lymphadenectomy will not be necessary for the future.

An examination of restaurant employees' work-life outlook: The influence of support systems during COVID-19.

The main objective of this research paper is to examine the influence of perceived support (i.e., organizational support and social support) on life satisfaction (i.e., current and anticipated life satisfaction), which is hypothesized to increase restaurant employees' loyalty organizational citizenship behavior (OCB) and decrease their intentions to leave the restaurant industry during the COVID-19 pandemic. Moreover, the moderating effects of employees' resilience and employment status are also examined. Analyzing the responses of 609 restaurant employees using structural equation modeling (SEM), findings revealed that all direct effects were supported, except for the effect of anticipated life satisfaction on intention to leave the restaurant industry. Lastly, the moderating role of resilience in the relationships between current life satisfaction and restaurant employees' loyalty OCB and intentions to leave the industry was confirmed. Theoretical and practical implications are discussed in detail.

Employee work status, mental health, substance use, and career turnover intentions: An examination of restaurant employees during COVID-19.

The COVID-19 pandemic has negatively impacted the restaurant industry and employees in the worst possible way. This empirical study aims to examine the relationships between employees' work status (working, furloughed, or laid-off), mental health (psychological well-being and psychological distress), substance use (drug and alcohol use), and career turnover intentions during the pandemic. Analyzing the responses of 585 restaurant employees using structural equation modelling (SEM), findings revealed that working employees experienced higher levels of psychological distress, drug and alcohol use than furloughed employees. Moreover, psychological distress increased drug and alcohol use, as well as career turnover intentions. Lastly, all employees, regardless of their mental health, increased their substance use and indicated a desire to seek future employment in alternate industries during the pandemic. Practical and theoretical implications are discussed in detail.

Low value of staging in detecting extraovarian occult metastasis in mucinous borderline ovarian tumors.

OBJECTIVES: Staging procedure in borderline ovarian tumors is a topic of controversy. Upstaging in non-serous borderline ovarian tumors that are confined to the ovary is rare. The aim of this study was to assess the impact of surgical staging on clinical outcomes in mucinous borderline ovarian tumors. METHODS: This was a retrospective study conducted at the Asan Medical Center, Seoul, Korea between January 1990 and December 2015, that included 432 patients with mucinous borderline ovarian tumors and at least 6 months follow-up. These patients were divided into a 'staging group' and 'unstaged group'. The staging group referred to patients who, in addition to hysterectomy and/or adnexal surgery, underwent at least one of the following: cytology, omental biopsy/omentectomy, peritoneal biopsy, lymph node biopsy/lymphadenectomy, or appendectomy. The unstaged group referred to patients who did not undergo any staging procedure but underwent adnexal surgery (cystectomy or oophorectomy). RESULTS: Median patient age was 40 (range 9-87) years. A total of 367 patients (85%) underwent a staging procedure (staging group) and 65 (15.0%) patients did not (unstaged group). Among the staging group, 258, 4, 100, and 5 patients were FIGO stage IA, IB, IC, or II-III, respectively. Overall recurrence was confirmed in 15 patients and median time to recurrence was 13.4 (range 0.4-127.3) months. One patient was in the unstaged group and had borderline recurrence. Fourteen were in the staging group, and 11 of them had borderline and three had invasive recurrence. Extraovarian disease was found at recurrence only in two patients. There was no significant difference in recurrence-free survival (p=0.39) and in overall survival between the staging group and the unstaged group (p=0.40). In total, 16 (4.4%) of 367 patients who underwent a staging procedure were upstaged. CONCLUSION: Staging in mucinous borderline ovarian tumors may be omitted if there is no obvious evidence of gross extraovarian disease.

Prognostic Factors and Impact of Minimally Invasive Surgery in Early-stage Neuroendocrine Carcinoma of the Cervix.

STUDY OBJECTIVE: To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). DESIGN: Retrospective cohort study. SETTING: Asan Medical Center, Seoul, Korea. PATIENTS: Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. INTERVENTIONS: All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. MEASUREMENTS AND MAIN RESULTS: Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1-42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018-4.871; p =.045 and HR, 6.494; 95% CI, 1.415-29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188-8.815; p =.022 and HR, 12.710; 95% CI, 1.128-143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). CONCLUSION: Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.

Effectiveness of adjuvant treatment for morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma: A Korean multicenter study.

AIM: To evaluate the effectiveness of adjuvant treatment for morcellated, uterus-confined leiomyosarcoma in a multicenter setting. METHODS: We identified patients with International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma primarily treated with surgery between 2003 and 2016. Among them, patients who underwent one of the following morcellation methods were included: (i) power morcellation; (ii) intracorporeal morcellation using scalpels or electrocautery; and (iii) vaginal morcellation. Patients' survival outcomes were compared according to the implementation of adjuvant treatment. RESULTS: From 13 institutions, 55 patients were included; 31 for adjuvant treatment group and 24 for surgery only group. The clinicopathological characteristics including the mass size, morcellation methods, extent of surgery, and mitotic count were similar between the groups. In the adjuvant treatment group, 67.7%, 19.4% and 12.9% of patients received chemotherapy, chemoradiation and radiation, respectively. After a median follow-up of 50.5 months, the adjuvant treatment and surgery only groups showed similar overall survival (5-year rate, 92.0% vs 90.4%; P = 0.959). No significant difference in progression-free survival was observed between the two groups (3-year rate, 46.1% vs 78.2%; P = 0.069). On multivariate analyses, adjuvant treatment did not affect progression-free survival (adjusted HR, 2.138; 95% CI, 0.550-8.305; P = 0.273). The adjuvant treatment group showed a trend towards more common distant metastasis, compared to the surgery only group (25.8% vs 4.2%; P = 0.062). The incidences of pelvic, retroperitoneal, and abdominal recurrences were not different between the groups. CONCLUSION: Despite its frequent use in clinical practice, adjuvant treatment did not improve the survival outcomes of patients with morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma.

Histologic Correlation and Clinical Significance of Atypical Glandular Cells on Cervical Pap Tests: Analysis of 540 Cases at a Single Institution.

The aim of this study is to determine the rate of clinically significant histopathologic lesions in women identified with atypical glandular cells (AGC). Five-hundered and forty patients with AGC, from a cohort of 1013 with AGC, met inclusion criteria for this study by having a proper histologic evaluation. Clinically significant histologic results were obtained in 170 cases with AGC (31.5%). Of the 170 clinically significant cases, 86 of 540 (15.9%) were diagnosed with malignant lesions. The findings of clinically significant lesions in more than 30% of patients support the recommendation that women identified with AGC require extensive histologic examination.

Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Real-world effectiveness of bevacizumab based on AURELIA in platinum-resistant recurrent ovarian cancer (REBECA): A Korean Gynecologic Oncology Group study (KGOG 3041).

PURPOSE: To evaluate the effectiveness of bevacizumab with single-agent chemotherapy for platinum-resistant ovarian cancer in a real-world setting. PATIENTS AND METHODS: We enrolled recurrent platinum-resistant ovarian cancer patients from 27 institutions. All had received bevacizumab with single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan) between 2015 and 2017 for second- or third-line chemotherapy in routine clinical practice. The primary endpoint was progression-free survival (PFS) and safety. Secondary endpoints included the objective response rate (ORR), PFS2, overall survival, duration of chemotherapy, and reasons for discontinuing chemotherapy. RESULTS: Of 391 patients, 259 (66.2%) received bevacizumab with PLD, 94 (24.0%) with topotecan, and 38 (9.7%) with weekly paclitaxel. The median PFS was 6.1 months with all forms of bevacizumab-containing therapy. Although the cohort with weekly paclitaxel had a better PFS than the PLD cohort (P = 0.028), this finding was not found in patients with a previous platinum-free interval of less than three months. The median duration of therapy was five cycles (range, one to 20 cycles), and 29 patients (7.4%) discontinued treatment because of adverse events from bevacizumab-containing regimens. The PLD cohort had fewer grade ≥ 3 adverse events than the other regimens (PLD, 35.8%; weekly paclitaxel, 52.6%; topotecan, 51.1%; P = 0.012), especially events of hematologic toxicities. CONCLUSION: In Korean ovarian cancer patients, the safety and effectiveness of chemotherapy with bevacizumab in a real-world setting was consistent with the results from a randomized controlled study. The effectiveness and toxicity profiles varied among the chemotherapy regimens, and this finding should be considered in practice. CLINICAL TRIALS REGISTRATION: NCT03367182.

Complete Histologic Regression of Endometrioid Adenocarcinoma on Endometrial Biopsy After Progestin Treatment Does Not Guarantee the Regression of an Invasive Carcinoma Within the Myometrium.

Currently, the indications for progestin therapy are limited to endometrioid adenocarcinoma that are International Federation of Gynecology and Obstetrics (FIGO) grade 1, FIGO stage IA, and confined to the endometrium. However, there have been attempts to broaden the indications of progestin therapy to patients with higher FIGO grades and/or with superficial myometrial invasion. We experienced a case with myoinvasive endometrioid adenocarcinoma treated with oral progestin, whose follow-up endometrial curettage specimen showed an apparent complete histologic regression; however, the final hysterectomy specimen disclosed myoinvasive endometrioid adenocarcinoma within the superficial myometrium, with absence of residual tumor in the endometrium. We describe this case to demonstrate that complete histologic regression of the endometrial lesion in a follow-up curettage specimen after progestin treatment does not guarantee histologic regression of the carcinoma within the myometrium. Our case indicates that current indications for progestin treatment should not be broadened to patients with superficial myometrial invasion.

The combination of histone deacetylase and p53 expressions and histological subtype has prognostic implication in uterine leiomyosarcoma.

OBJECTIVE: To investigate the expression of different histone deacetylases and their association with disease characteristics and survival outcomes in uterine leiomyosarcoma patients. METHODS: The immunohistochemical expression of different histone deacetylases and p53 by tissue microarray and histological subtypes were assessed in tumor tissue samples of 42 eligible patients. RESULTS: Histone deacetylases 1-4, 6 and 8 showed prevalent and strong (3+) expression (88.1, 90.5, 95.2, 92.9, 83.3 and 100%, respectively). Histone deacetylases 5, 7 and 9 showed infrequent strong expression (33.3, 50 and 38.1%, respectively). There were trends of higher disease-free survival rates according to the combination of weaker expression of histone deacetylase 5, 7 or 9 with positive p53 expression or with non-epithelial subtype. The patients with triple-positive favorable prognostic factors (any of weaker histone deacetylase 5, 7 and 9 expression, p53 positive, and non-epithelioid subtype) had the better survival outcomes while the patients with other combinations had the worse survival outcomes. In multivariate analysis, histone deacetylase 5 in combination with epithelioid subtype was an independent predictor for disease-free survival. CONCLUSIONS: Expression of histone deacetylase 5, 7 and 9 is a potential prognostic marker in uterine leiomyosarcoma when combined with pathologically relevant prognostic factors (p53 and histological subtype). This prevalent and strong histone deacetylase expression warrants further study in well-designed investigations of histone deacetylases as therapeutic targets in uterine leiomyosarcoma.