An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2.

Recent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic heterozygous missense mutation (c.402C>G; p.C134W) in FOXL2, a feature shared by virtually all adult-type granulosa cell tumors (AGCTs), introduces a target site for miR-1236, which causes haploinsufficiency of the tumor-suppressor FOXL2. This miR-1236-mediated selective degradation of the variant FOXL2 mRNA is preferentially conducted by a distinct miRNA-loaded RNA-induced silencing complex (miRISC) directed by the Argonaute3 (AGO3) and DHX9 proteins. In both patients and a mouse model of AGCT, abundance of the inversely regulated variant FOXL2 with miR-1236 levels is highly correlated with malignant features of AGCT. Our study provides a molecular basis for understanding the conserved FOXL2 CDS mutation-mediated etiology of AGCT, revealing the existence of a previously unidentified mechanism of miRNA-targeting disease-associated mutations in the CDS by forming a non-canonical miRISC.

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.

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.

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.

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.

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.

BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells.

The adaptor-related protein complex 5 subunit mu 1 (AP5M1) is an evolutionally conserved protein with ubiquitous expression in human tissues. However, the major function of AP5M1 in living organisms is unclear owing to few published studies. Here, we demonstrate that AP5M1 is a potent apoptosis-inducing molecule in cervical cancer cells. We also found that AP5M1 upregulated the level of BAX protein, a key pro-apoptotic B cell lymphoma (BCL)-2 family member regulating mitochondrial apoptotic cell death pathway. Moreover, AP5M1 completely lost its apoptotic activity in BAX-knockout or -knockdown cells, indicative of its functional dependence on BAX. Comparative analysis of cervical tissues from patients with cervical carcinoma and non-cancer control revealed a prominent downregulation in AP5M1 expression with a concomitant downregulation in BAX expression; AP5M1 and BAX mRNA expression levels in cervical tissues exhibited a strong positive correlation (r = 0.97). Thus, we identified AP5M1 as a previously unrecognized apoptotic protein that governs BAX expression and revealed the association between AP5M1 and malignancy.

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.

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.

Comparison of Laparoscopic and Open Surgery for Patients With Borderline Ovarian Tumors.

OBJECTIVES: The aim of this study was to compare surgical and oncologic outcomes of open and laparoscopic surgery in patients with borderline ovarian tumors (BOTs). MATERIALS AND METHODS: This study included patients with BOTs who underwent open (n = 433) or laparoscopic (n = 210) surgery between 1990 and 2015. Surgical outcomes, perioperative morbidity, and disease-free survival and overall survival were compared. RESULTS: There was no significant difference in age, histologic type of tumor, and laterality of tumor. However, body mass index was slightly higher for the open surgery group (P = 0.046). The open surgery group had a higher serum cancer antigen 125 level (P < 0.001), larger tumor size (P < 0.001), more frequent radical surgery (P = 0.001), higher stage (P = 0.034), and higher incidence of invasive implants (P = 0.035). The operative time (P < 0.001), time interval to return of bowel movement (P < 0.001), and length of postoperative hospital stay (P < 0.001) were significantly shorter and estimated blood loss was significantly less (P < 0.001) in the laparoscopic group. Perioperative complications were documented in 5 (2.4%) patients in the laparoscopic surgery group and 17 (3.9%) in the open surgery group (P = 0.064). Twenty-three (5.3%) patients in the open surgery group and 9 (4.3%) in the laparoscopic surgery group had recurrence (P = 0.902) at a median follow-up of 57 months. The 10-year disease-free survival was 96% and 97% for the open and laparoscopic groups, respectively (P = 0.851), with no significant difference between the groups after adjusting for independent factors (odds ratio, 1.0; 95% confidence interval, 0.4-2.4; P = 0.999). The 10-year overall survival was 99% for both groups, respectively (P = 0.441). CONCLUSIONS: Laparoscopic surgery and open surgery showed similar survival outcomes in BOTs. The surgical outcomes of laparoscopic surgery were more favorable.

Significance of Ovarian Endometriosis on the Prognosis of Ovarian Clear Cell Carcinoma.

INTRODUCTION: The aim of this study was to evaluate the significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma (OCCC). METHODS: Patients with OCCC were divided into 2 groups according to the presence of ovarian endometriosis: group 1, no coexisting ovarian endometriosis; group 2, clear cell carcinoma arising from ovarian endometriosis or the presence of ovarian endometriosis elsewhere in the ovary. Clinicopathologic characteristics, disease-free survival (DFS), and overall survival (OS) were compared between the 2 groups. RESULTS: Of 155 patients with OCCC, 77 were categorized into group 1 and 78 into group 2. Group 2 patients were younger than group 1 (median age, 48 vs 51 years; P = 0.005) and had higher incidence of early-stage disease (stage I, 77% vs 58%; P = 0.001) and lower incidence of lymph node metastasis (4% vs 17%; P = 0.008). Group 2 patients were observed to have a significantly higher 5-year DFS (P < 0.001) and OS (P = 0.001) compared with group 1. In stage I disease, group 2 had a significantly higher 5-year DFS (P = 0.004) and OS (P = 0.016) than did group 1. In the multivariate analysis, coexisting endometriosis and advanced International Federation of Obstetrics and Gynecology stage were significant factors for both DFS and OS rates. CONCLUSIONS: Ovarian clear cell carcinoma with endometriosis was found more frequently in younger women and had a higher incidence of early-stage disease and a lower incidence of lymph node metastasis compared with OCCC without endometriosis. Ovarian endometriosis was associated with improved prognostic factors and a better DFS and OS even in stage I disease. Ovarian endometriosis was an independent prognostic factor for OCCC.

The efficacy of sentinel lymph node mapping with indocyanine green in cervical cancer.

BACKGROUND: Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients. Given the importance of lymph node metastasis, it is imperative that patients harboring metastasis are identified and can undergo appropriate treatment. Sentinel lymph node (SLN) mapping has drawn attention as a lymph node mapping technique. We evaluated the feasibility and efficacy of (SLN) mapping using indocyanine green (ICG) in cervical cancer. METHODS: We performed a single-center, retrospective study of 103 surgically treated cervical cancer patients who underwent SLN mapping. After using ICG to detect SLN during surgery, we removed the SLNs followed by laparoscopic or robotic-assisted radical surgery and bilateral pelvic lymphadenectomy. RESULTS: Stage IB1 was the most common (61.17%). At least one SLN was detected in all cases. Eighty-eight patients (85.44%) had bilateral pelvic SLNs. The mean number of SLN per patient was 2.34. The side-specific sensitivity was 71.43%, the specificity was 100%, the negative predictive value (NPV) was 93.98%, and the false negative rate (FNR) was 28.57%. In cases of tumors smaller than 2 cm with negative lymph node metastasis on imaging, the study revealed a side-specific sensitivity of 100%, a specificity of 100%, a NPV of 100%, and a FNR of 0%. Large tumor size (≥ 4 cm), a previous history of a loop electrosurgical excision procedure (LEEP), depth of invasion (≥ 50%), the microscopic parametrial (PM) invasion, and vaginal extension were significantly associated with the false-negative detection of SLN. Moreover, the microscopic PM invasion was the only risk factor of the false-negative detection of SLN in multivariate analysis. CONCLUSION: SLN mapping with ICG in cervical cancer is feasible and has high detection rate. The sensitivity of 100% was high enough to perform SLN biopsy alone in an early stage in which the tumor is less than 2 cm, with no lymphadenopathy on image examination. However, for large or invasive tumors, we would have to be cautious about performing SLN biopsy alone. TRIAL REGISTRATION: Retrospectively registered 2017-0600.

Trends in treatment during the last stages of life in end-stage gynecologic cancer patients who received active palliative chemotherapy: a comparative analysis of 10-year data in a single institution.

BACKGROUND: Palliative chemotherapy should be used with caution when attempting to alleviate symptoms in patients with end-stage cancer. However, palliative chemotherapy continues to be utilized in cancer patients during their last stages of life. In this study, we analyzed the pattern of chemotherapy administered during the last 6 months of life in patients with end-stage gynecologic cancer who were treated with active palliative chemotherapy for the past 10 years. METHOD: We retrospectively analyzed the data for patients with gynecologic cancer who died after undergoing active palliative chemotherapy without receiving hospice management at Asan Medical Center from 2006 to 2015. Patients were divided into two groups: those who died between 2006 and 2010, and those who died between 2011 and 2015. Based on the electronic medical records, the demographic and baseline characteristics of the patients, hospital admission during the last 6 months, invasive procedures, palliative chemotherapy patterns, and the time of the last chemotherapy session were confirmed. RESULTS: A total of 193 patients with gynecologic cancer were eligible for this study. 92 patients died during 2006 to 2010, and 101 patients died during 2011 to 2015. The mean frequency of admission during the last 6 months was 5.12 for those who died in 2006-2010 and 6.06 for those who died during 2011-2015 (p = 0.003); similarly, the mean frequency of palliative chemotherapy during the last 6 months was 3.84 (2006-2010) vs. 4.93 times (2011-2015; p < 0.001). The proportion of patients undergoing invasive procedures during the last 3 months was 41.3% (2005-2010) vs. 56.4% (2011-2015; p = 0.044). CONCLUSIONS: The frequency of palliative chemotherapy and the rate of invasive procedures have increased in patients with end-stage gynecologic cancer who were treated aggressively without hospice management over 2011-2015 when compared to 2006-2010, along with an increase in the mean frequency of admission during the last 6 months at our institution. Gynecologic oncologists need to evaluate whether active palliative chemotherapy is beneficial to patients at the end-of-life stage, and if not helpful, should communicate with the patients and caregivers about when the palliative chemotherapy should be discontinued.

Analysis of outcomes and prognostic factors after fertility-sparing surgery in malignant ovarian germ cell tumors.

OBJECTIVE: To evaluate the oncologic and reproductive outcomes and to analyze prognostic factors after fertility-sparing surgery in patients with early and advanced malignant ovarian germ cell tumors (MOGCTs). METHODS: This study included 171 patients who underwent fertility-sparing surgery. Data were gathered from patients' medical records. Survival analysis was performed using the log-rank test and Cox's proportional hazards model. Reproductive outcomes were analyzed. RESULTS: Twenty-five patients (14.6%) had recurrent disease, and five patients (2.9%) died of disease during the median follow-up time of 86months (range, 9-294months). The 5-year disease-free survival (DFS) was 86%, and the 5-year overall survival (OS) was 97%. The 5-year DFS was 84% for stage I and 89% for stage II-IV. The 5-year OS was 99% for stage I and 91% for stage II-IV. In multivariate analysis, yolk sac tumor, incomplete staging surgery, and residual tumor were independent risk factors for reduced DFS, and yolk sac tumor and residual tumor were independent risk factors for reduced OS. Reproductive and obstetric outcomes were evaluable in 124 patients, and 106 patients (85.5%) had regular menstruation, 12 patients (9.7%) had irregular menstruation, and six patients (4.8%) had premature menopause. Twenty patients tried to conceive, 15 patients (75%) succeeded in achieving 21 pregnancies, and 13 of the patients (65%) gave birth to 20 healthy babies. CONCLUSION: Fertility-sparing surgery has excellent survival outcomes in young women with MOGCTs, even in advanced stages. Reproductive and obstetric outcomes were promising. Yolk sac tumor, incomplete surgical staging, and residual tumor were independent prognostic factors.