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This article discusses a study that aimed to identify protein signatures associated with the response to poly(ADP-ribose) polymerase inhibitors (PARPi) in high-grade serous ovarian carcinoma (HGSOC). The researchers conducted a proteomic analysis of cancer tissues from HGSOC patients who received PARPi treatment and identified differentially expressed proteins between good and poor responders. They found that stearoyl-CoA desaturase 5 (SCD5) was upregulated in the poor response group and may serve as a potential predictive biomarker for PARPi response. The study provides insights into predicting PARPi responses and suggests potential strategies for personalized treatment in HGSOC patients. [Extracted from the article]

We investigated the efficacy and safety of durvalumab (D) with or without tremelimumab (T) in addition to single-agent chemotherapy (CT) in patients with platinum-resistant recurrent ovarian cancer (PROC) lacking homologous recombination repair (HRR) gene mutations. KGOG 3045 was an open-label, investigator-initiated phase II umbrella trial. Patients with PROC without HRR gene mutations who had received ≥2 prior lines of therapy were enrolled. Patients with high PD-L1 expression (TPS ≥25%) were assigned to arm A (D + CT), whereas those with low PD-L1 expression were assigned to arm B (D + T75 + CT). After completing arm B recruitment, patients were sequentially assigned to arms C (D + T300 + CT) and D (D + CT). Overall, 58 patients were enrolled (5, 18, 17, and 18 patients in arms A, B, C, and D, respectively). The objective response rates were 20.0, 33.3, 29.4, and 22.2%, respectively. Grade 3–4 treatment-related adverse events were observed in 20.0, 66.7, 47.1, and 66.7 of patients, respectively, but were effectively managed. Multivariable analysis demonstrated that adding T to D + CT improved progression-free survival (adjusted HR, 0.435; 95% CI, 0.229–0.824; P = 0.011). Favorable response to chemoimmunotherapy was associated with MUC16 mutation (P = 0.0214), high EPCAM expression (P = 0.020), high matrix remodeling gene signature score (P = 0.017), and low FOXP3 expression (P = 0.047). Patients showing favorable responses to D + T + CT exhibited significantly higher EPCAM expression levels (P = 0.008) and matrix remodeling gene signature scores (P = 0.031) than those receiving D + CT. Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non-mutated PROC, warranting continued clinical investigation. • Efficacy and safety of chemotherapy plus durvalumab with or without tremelimumab were studied in PROC without HRR mutation. • Addition of tremelimumab improved progression-free survival on multivariable Cox HR analysis. • Biomarkers were explored with immunohistochemistry and whole-exome and transcriptome sequencing. • Mutation in MUC16 and high EPCAM were associated with favorable response in the overall cohort. • Arm-specific biomarker in tremelimumab group were EPCAM expression and matrix remodeling score. [ABSTRACT FROM AUTHOR]

This multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between maintenance therapy with two poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and niraparib, in patients with BRCA -mutated, newly diagnosed advanced epithelial ovarian cancer (EOC) who responded to platinum-based chemotherapy. We enrolled stage III-IV EOC patients with germline and/or somatic BRCA1/2 mutations that had received maintenance therapy with olaparib or niraparib. A 3:1 propensity score matching was conducted using two variables: residual disease size and the presence of germline variants. The primary outcome was progression-free survival (PFS), and the secondary outcomes were time to first subsequent therapy (TFST), overall survival (OS), and treatment-emergent adverse events (TEAEs). In the propensity score-matched analysis, 80 patients who received olaparib and 31 patients who received niraparib were matched (3:1). In the propensity score-matched cohort, median PFS with olaparib vs. niraparib was not reached vs 31.5 months (HR, 1.08; 95% CI, 0.47–2.52; p = 0.854). The median TFST was not reached vs 31.8 months (HR, 1.20; 95% CI, 0.51–2.81; p = 0.682), and neither olaparib nor niraparib reached the median OS (HR, 0.42; 95% CI, 0.01–17.61; p = 0.649). In terms of the incidence rates of any-grade hematologic or non-hematologic TEAEs, higher rates of thrombocytopenia (p = 0.021) and neutropenia (p = 0.011) were observed in the niraparib group. Advanced EOC patients with BRCA1/2 mutations exhibited no significant difference in OS between olaparib and niraparib, indicating the need to consider individualized strategies for selecting PARP inhibitors based on adverse event profiles. • This multicenter study compared olaparib and niraparib in newly diagnosed BRCA-mutated ovarian cancer. • The study found no significant difference in PFS, TFST, or OS between two groups in the matched cohort. • Higher thrombocytopenia and neutropenia rates with niraparib suggest individualized PARP inhibitor selection. [ABSTRACT FROM AUTHOR]

Current treatment strategies for primary epithelial ovarian cancer (EOC) have significantly evolved, and the value of complete cytoreduction has not yet been reassessed. The study aimed to investigate the impact of residual disease after cytoreductive surgery for EOC on survival outcomes within the recent paradigm of frontline ovarian cancer treatment. We searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022. To evaluate the impact of postoperative residual tumors on progression-free survival (PFS) and OS, we constructed a linear regression model for log-transformed median PFS and OS. Patients who did or did not receive first-line maintenance therapy were examined. A total of 97 trials with 43,260 patients were included:2476 received poly(ADP-ribose) polymerase (PARP) inhibitors and 6587 received bevacizumab. Multivariable analysis of the linear regression model of all studies revealed that the median OS increased by 12.97% for every 10% increase in complete cytoreduction rates, independent of the use of systemic maintenance. In the subgroup analysis of patients receiving maintenance therapies, the effect of complete tumor clearance was potentiated, with a median OS increase of 19.13% for every 10% increase in complete cytoreduction rates. Total macroscopic tumor clearance at the initial presentation of EOC significantly prolongs OS. Our results establish the importance of complete surgical cytoreduction, even after the introduction of recent advances in frontline treatment for EOC. • Treatment strategies for primary EOC have evolved, but complete cytoreduction's value remains unassessed. • 97 trials, 43,260 patients, studied residual disease impact on EOC survival after surgery in this meta-analysis. • 10% rise in complete cytoreduction rate linked to a 12.97% increase in median log overall survival. [ABSTRACT FROM AUTHOR]

To investigate the prognostic significance of L1 cell-adhesion molecule (L1CAM), β-catenin, and programmed death-ligand 1 (PD-L1) in endometrial cancer (EC) patients, with a focus on p53 wild-type subgroup, for additional risk stratification. This retrospective cohort study included EC patients classified according to Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) who underwent primary surgical treatment at the single center between January 2014 and December 2018. Immunohistochemical staining was performed for four mismatch repair (MMR) proteins, p53, L1CAM, β-catenin, and PD-L1. DNA polymerase epsilon (POLE) mutation was detected by hot spot sequencing via droplet digital polymerase chain reaction. Survival outcome of each subgroup of L1CAM, β-catenin, and PD-L1 was measured according to their expression. A total of 162 EC patients were included. Endometrioid histologic type and early-stage disease were 140 (86.4%) and 109 (67.3%), respectively. ProMisE classification assigned 48 (29.6%), 16 (9.9%), 72 (44.4%), and 26 (16.0%) patients to MMR-deficient, POLE -mutated, p53 wild-type, and p53 abnormal subgroups, respectively. L1CAM was identified as an independent poor prognostic factor for progression-free survival (PFS; adjusted hazard ratio [aHR], 3.207; 95% confidence interval (CI), 1.432–7.187; P = 0.005), whereas β-catenin and PD-L1 positivity were not associated with recurrence (P = 0.462 and P = 0.152, respectively). In p53 wild-type subgroup, L1CAM positivity was associated with worse PFS (aHR, 4.906; 95% CI, 1.685–14.287; P = 0.004). L1CAM positivity was associated with poor prognosis in EC and further stratified the risk of recurrence in p53 wild-type subgroup, whereas β-catenin and PD-L1 were not informative for risk stratification. • L1CAM was an independent poor prognostic factor for progression-free survival (PFS) in endometrial cancer (EC) patients. • L1CAM positivity was associated with worse PFS in p53 wild-type EC patients, whereas β-catenin and PD-L1 positivity were not. • L1CAM is a potential biomarker for identifying high-risk p53 wild-type EC patients and guiding clinical decision-making. [ABSTRACT FROM AUTHOR]

Previously, we suggested that patients with cervical cancer (CC) with tumors ≤2 cm on preoperative magnetic resonance imaging (MRI) are safe candidates for laparoscopic radical hysterectomy (LRH). Here, we aim to investigate whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors; lymph node metastasis (LNM) or parametrial invasion (PMI). We identified patients with 2009 FIGO stage IB1 CC who underwent Type C LRH or open radical hysterectomy (ORH) at three tertiary hospitals between 2000 and 2019. Those with a tumor ≤2 cm on preoperative MRI who were not suspicious of LNM or PMI preoperatively were included, while those who were indicated to receive adjuvant treatment but did not actually receive it were excluded. Survival outcomes were compared between the LRH and ORH groups in the overall population, then narrowed down to those with LNM, and then to those with PMI. In total, 498 patients were included: 299 in the LRH group and 199 in the ORH group. The LRH and ORH groups showed similar 3-year progression-free survival (PFS) (94.0% vs. 93.6%; P = 0.615) and 5-year overall survival (OS) rates (97.2% vs. 96.8%; P = 0.439). On pathologic examination, 49 (9.8%) and 16 (3.2%) patients had LNM and PMI, respectively, and 10 (2.0%) had both. In the LNM subgroup, 5-year PFS rate was not significantly different between the LRH and ORH groups (73.2% vs. 91.7%; P = 0.169). In the PMI subgroup, no difference in PFS was observed between the two groups (P = 0.893). LRH might not deteriorate recurrence and mortality rates in CC patients with tumors ≤2 cm when adjuvant treatment is appropriately administered, even if pathologic LNM and PMI are incidentally identified. • We investigated whether LRH deteriorates the prognosis of patients with incidentally identified high-risk factors. • In the LNM subgroup, the ORH group had a better PFS than the LRH group without statistical significance. • In the PMI subgroup, no difference in PFS was observed between the two groups. [ABSTRACT FROM AUTHOR]

To investigate the impact of conization on survival outcomes and to identify a specific population that might benefit from conization before radical hysterectomy (RH) in patients with early-stage cervical cancer. From six institutions in Korea, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who underwent primary type C RH between 2006 and 2021. The patients were divided into multiple groups based on tumor size, surgical approach, and histology. We performed a series of independent 1:1 propensity score matching and compared the survival outcomes between the conization and non-conization groups. In total, 1254 patients were included: conization (n = 355) and non-conization (n = 899). Among the matched patients with a tumor size of >2 cm, the conization group showed a significantly better 3-year disease-free survival (DFS) rate compared with the non-conization group when RH was conducted via minimally invasive surgery (MIS), in those with squamous cell carcinoma (96.3% vs. 87.4%, P = 0.007) and non-squamous cell carcinoma (97.0% vs. 74.8%, P = 0.021). However, no difference in DFS was observed between the two groups among the matched patients with a tumor size of ≤2 cm, regardless of surgical approach or histological type. In patients who underwent MIS RH, DFS significantly worsened as the residual tumor size increased (P < 0.001). Cervical conization was associated with a lower recurrence rate in patients with early-stage cervical cancer with a tumor size of >2 cm who underwent primary MIS RH. Cervical conization may be performed prior to MIS RH to minimize the uterine residual tumor. • We investigated survival impact of conization before RH on early cervical cancer. • A series of independent sample matching were performed in various patient groups. • Conization lowered relapse of MIS RH in patients with tumors >2 cm but not ≤2 cm. • Conization may be performed before MIS RH to minimize the uterine residual tumor. [ABSTRACT FROM AUTHOR]

The value of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery (CRS) for epithelial ovarian cancer (EOC) is controversial and its use remains experimental in most national and international guidelines. We wished to systematically evaluate all available evidence. A comprehensive review of data from MEDLINE, EMBASE, and Cochrane Library databases was conducted from the first report on HIPEC in EOC till April 3, 2022. Progression-free survival (PFS) and overall survival (OS) were compared between the HIPEC and control groups. This meta-analysis was registered with PROSPERO (CRD42021265810). Fifteen studies (10 case-control studies and 5 randomized controlled trials [RCTs]) were included in the present meta-analysis. Based on the time interval between the last systemic chemotherapy exposure and timing of CRS +/− HIPEC, all studies and patients' cohorts we classified into recent (<6 months; n = 9 studies/patients cohorts) and non-recent (≥6 months, n = 8 studies/patients cohorts) chemotherapy exposure groups. In the recent chemotherapy exposure group, HIPEC was associated with improvement of both PFS (HR, 0.585; 95% CI, 0.422–0.811) and OS (HR, 0.519; 95% CI, 0.346–0.777). On the contrary, in the non-recent chemotherapy exposure group, HIPEC failed to significantly affect PFS (HR, 1.037; 95% CI, 0.684–1.571) or OS (HR, 0.932; 95% CI, 0.607–1.430). Consistent results were observed in subsequent sensitivity analyses. Our present meta-analysis demonstrates that the value of HIPEC at CRS for EOC appears to depend on the timing of the last systemic chemotherapy exposure. Future trials are awaited to define the role of HIPEC in EOC. • The value of HIPEC at cytoreductive surgery for ovarian cancer remains controversial in most guidelines. • A total of 15 studies of 1861 patients contributed data for meta-analysis. • In the study, the value of HIPEC appears to depend on the timing of the last systemic chemotherapy exposure. [ABSTRACT FROM AUTHOR]

To compare survival outcomes of minimally invasive surgery (MIS) and open surgery for radical hysterectomy (RH) in early cervical cancer patients with histologic subtypes of usual-type adenocarcinoma and adenosquamous carcinoma. From two centers' cervical cancer cohorts, patients with 2009 FIGO stage IB1–IB2 who underwent RH between 2007 and 2020 were retrospectively identified. Patients with usual-type adenocarcinoma and adenosquamous carcinoma were included in the analysis after pathologic review according to the updated World Health Organization Classification of Tumors. Clinicopathologic characteristics and survival outcomes were compared in terms of open surgery or MIS. This study included 161 patients. No significant differences were noted in overall survival (OS; P = 0.241) and disease-free survival (DFS; P = 0.156) between patients with usual-type adenocarcinoma (n = 136) and those with adenosquamous carcinoma (n = 25). MIS RH group (n = 99) had a significantly smaller tumor size (P < 0.001), lesser pathologic parametrial invasion (P = 0.001), and lesser lymph node metastasis (P < 0.001) than open RH group (n = 62). MIS and open RH groups showed similar OS (P = 0.201) and 3-year DFS rate (87.9% vs. 75.1%; P = 0.184). In multivariate analysis, worse DFS was not associated with MIS (P = 0.589) but was associated with pathologic parametrial invasion (adjusted HR, 3.41; 95% CI, 1.25–9.29; P = 0.016). Consistent results were observed among patients with usual-type adenocarcinoma; MIS was not associated with worse DFS. Comparable survival outcomes were found for MIS and open RH in early-stage cervical usual-type adenocarcinoma and adenosquamous carcinoma. Although MIS RH was not a poor prognostic factor, pathologic parametrial invasion was significantly associated with worse DFS in cervical usual-type adenocarcinoma and adenosquamous carcinoma. • We examined survival after RH in early cervical cancer with usual-type adenocarcinoma and adenosquamous carcinoma. • We re-classified the cases pathologically according to the updated WHO Classification of Tumors. • Overall, minimally invasive RH was not associated with disease recurrence and mortality rates. • Consistent results were observed among patients with usual-type adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: To evaluate the impact of intraoperative hypotension and hemodynamic instability on survival outcomes in patients with high-grade serous ovarian carcinoma (HGSOC).Methods: We retrospectively identified patients with HGSOC, who underwent primary or interval debulking surgery between August 2013 and December 2019. We collected anesthesia-related variables, including the arterial blood pressure measurements (at 1-min intervals) during the surgery of patients. The cumulative duration of mean arterial blood pressure (MAP) readings under 65 mmHg and two performance measurements (median performance error [MDPE] and wobble) were calculated. We investigated associations between the factors indicating hemodynamic instability and prognosis.Results: In total, 338 patients were included. Based on the cumulative duration of MAP under 65 mmHg, we divided patients into two groups: ≥30 min and <30 min. The progression-free survival (PFS) was worse in the ≥30 min group (n = 107) than the <30 min group (n = 231) (median, 18.2 vs. 23.7 months; P = 0.014). In multivariate analysis adjusting for confounders, a duration of ≥30 min of MAP under 65 mmHg was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.376; 95% CI, 1.035-1.830; P = 0.028). Shorter PFS was observed in the group with a MDPE <-4.0% (adjusted HR, 1.351; 95% CI, 1.024-1.783; P = 0.033) and a wobble ≥7.5% (adjusted HR, 1.445; 95% CI, 1.100-1.899; P = 0.008). However, no differences were observed in overall survival.Conclusion: This study suggests that the three intraoperative variables for hemodynamic instability, cumulative duration of MAP <65 mmHg, MDPE, and wobble, might be novel prognostic biomarkers for disease recurrence in patients with HGSOC. [ABSTRACT FROM AUTHOR]

This study investigated survival outcomes for platinum-sensitive relapsed ovarian clear cell carcinoma (OCCC) by treatment method. 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). 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. 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. • Survival outcomes in platinum-sensitive recurrent ovarian clear cell carcinoma were investigated by treatment. • The use of bevacizumab (BEV) was associated with improvements in progression-free survival (PFS) and overall survival (OS). • An association between optimal secondary cytoreductive surgery and improved PFS and OS was observed. • BEV might increase PFS and OS in patients who did not receive secondary cytoreductive surgery. [ABSTRACT FROM AUTHOR]

With expanded use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi), there is a potential impact of PARPi resistance on platinum resistance. A post-hoc analysis of SOLO2 demonstrated a reduction in response to subsequent platinum-based therapy among patients who received prior olaparib but not placebo. The present multicentre, retrospective, observational study was conducted to determine the effects of olaparib on subsequent therapy for recurrent epithelial ovarian cancer (EOC). Data on EOC patients with BRCA1/2 -mutated tumours who received second-line platinum-based chemotherapy between January 2012 and June 2020, at three South Korean institutions (n = 197) were collected. Patients who received olaparib as maintenance therapy after second-line chemotherapy were assigned to the olaparib group (n = 105), and subjects who did not receive olaparib maintenance therapy were assigned to the control group (n = 92). The primary endpoint was time intervals from the date of second disease progression (PFS1) to the date of third disease progression (PFS2), expressed as PFS2 − PFS1. As expected, PFS1 in the olaparib group was longer than the control group. However, PFS2 – PFS1 in the olaparib group was significantly shorter than that of the control group (median 7.9 vs. 13.6 m; p = 0.0005). Even when the third-line PARPi maintenance (cross-over) patients were excluded from the control group, the response to subsequent therapy in the olaparib group remained poor (median 7.7 vs. 11.5; p = 0.0422). Patients with platinum-sensitive BRCA1/2 mutated tumours who progressed during olaparib maintenance after second-line chemotherapy were less likely to respond to third-line chemotherapy compared to controls who did not receive olaparib, suggesting that resistance to olaparib may contribute to chemotherapy resistance. • Although second-line olaparib significantly improved PFS1, olaparib did not prolong PFS2. • Relapsed patients despite 2 L-olaparib maintenance show poor response to subsequent chemotherapy. • The negative effects were more pronounced in patients with PFS1 > 12 months. [ABSTRACT FROM AUTHOR]

To ascertain whether cervical conization before radical hysterectomy (RH) has a protective effect on survival outcomes in early cervical cancer, taking into account the surgical approach. From cervical cancer cohorts of two institutions, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH between July 2006 and June 2020. Patients were divided into conization group (n = 144) and control group (n = 434). We conducted three independent 1:1 propensity score matching processes for histology, lymphovascular space invasion, cervical tumor size, and surgical approach (all patients, those who underwent open surgery, and those who underwent minimally invasive surgery [MIS]). Survival outcomes were compared. Overall, the conization group had less cervical tumor size and received MIS more frequently (P = 0.010) and adjuvant treatment less often (P = 0.002) versus the controls. After matching, the conization group showed significantly better disease-free survival (DFS) versus control (3-year DFS rate, 94.2% vs. 86.3%; P = 0.012), but similar overall survival. Among the open RH matched patients (n = 96), no difference in DFS was observed between the conization and control groups (P = 0.984). In contrast, among the MIS RH matched patients (n = 192), the conization group showed significantly better DFS versus control (3-year DFS rate, 95.7% vs. 82.9%; P = 0.005). In multivariate analysis adjusting for cervical tumor size and adjuvant treatment, conization was identified as an independent favorable prognostic factor for DFS (adjusted HR, 0.318; 95% CI, 0.134–0.754; P = 0.009). Preoperative cervical conization might reduce the disease recurrence rate in early cervical cancer patients who undergo primary MIS RH. • We investigated survival impact of preoperative conization on IB1 cervical cancer. • Post-matching, the conization group had significantly better disease-free survival. • Conization lowered recurrence of minimally invasive radical hysterectomy patients. • Conization may improve minimally invasive radical hysterectomy results. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of computed tomography (CT)-based, artificial intelligence-driven waist skeletal muscle volume on survival outcomes in patients with endometrial cancer. Methods: We retrospectively identified endometrial cancer patients who received primary surgical treatment between 2014 and 2018 and whose pre-treatment CT scans were available (n = 385). Using an artificial intelligence-based tool, the skeletal muscle area (cm2) at the third lumbar vertebra (L3) and the skeletal muscle volume (cm3) at the waist level were measured. These values were converted to the L3 skeletal muscle index (SMI) and volumetric SMI by normalisation with body height. The relationships between L3, volumetric SMIs, and survival outcomes were evaluated. Results: Setting 39.0 cm2/m2 of L3 SMI as cut-off value for sarcopenia, sarcopenia (< 39.0 cm2/m2, n = 177) and non-sarcopenia (≥ 39.0 cm2/m2, n = 208) groups showed similar progression-free survival (PFS; p = 0.335) and overall survival (OS; p = 0.241). Using the median value, the low-volumetric SMI group (< 206.0 cm3/m3, n = 192) showed significantly worse PFS (3-year survival rate, 77.3% vs. 88.8%; p = 0.004) and OS (3-year survival rate, 92.8% vs. 99.4%; p = 0.003) than the high-volumetric SMI group (≥ 206.0 cm3/m3, n = 193). In multivariate analyses adjusted for baseline body mass index and other factors, low-volumetric SMI was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.762; 95% CI, 1.051–2.953; p = 0.032) and OS (adjusted HR, 5.964; 95% CI, 1.296–27.448; p = 0.022). Conclusions: Waist skeletal muscle volume might be a novel prognostic biomarker in patients with endometrial cancer. Assessing body composition before treatment can provide important prognostic information for such patients. [ABSTRACT FROM AUTHOR]

Background: To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH).Methods: We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB-IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group).Results: A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552-2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621-5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139).Conclusions: Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH. [ABSTRACT FROM AUTHOR]

To investigate the impact of changes in body composition during primary treatment on survival outcomes in patients with epithelial ovarian cancer (EOC). We retrospectively identified patients diagnosed with EOC between 2010 and 2019. Using an artificial intelligence-based tool, the volumes of skeletal muscle, visceral fat, and subcutaneous fat were measured automatically at the waist level from pre-treatment and post-treatment computed tomography scans. Associations between changes in body mass index (BMI) and volume of each body composition component and survival outcomes were evaluated. A total of 208 patients were included. A significant decrease in BMI and waist volumes of skeletal muscle and visceral fat was observed during the primary treatment. Patients with BMI loss ≥5% showed significantly worse progression-free survival (PFS) and overall survival (OS) than those with BMI loss <5%. In multivariate analyses adjusting for clinicopathologic factors, BMI loss ≥5% was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.565; 95% CI, 1.074–2.280; P = 0.020) and OS (adjusted HR, 2.754; 95% CI, 1.382–5.488; P = 0.004). Meanwhile, both muscle loss ≥10% and visceral fat loss ≥20% were associated with an increased mortality rate but did not affect disease recurrence. In multivariate analyses, muscle loss ≥10% (adjusted HR, 2.069; 95% CI, 1.055–4.058; P = 0.034) and visceral fat loss ≥20% (adjusted HR, 2.292; 95% CI, 1.023–5.133; P = 0.044) were poor prognostic factors for OS. Consistent results were observed in the advanced-stage disease subgroup (n = 173). Changes in BMI and waist volume of skeletal muscle and visceral fat were associated with survival outcomes in patients with EOC. • We investigated impact of changes in body composition during primary treatment on prognosis of epithelial ovarian cancer. • An artificial intelligence-based volumetric technique was applied on each patient's pre- and post-treatment CT scans. • Patients frequently experienced weight loss, preferentially originating from skeletal muscle and visceral fat depletion. • Changes in waist volume of skeletal muscle and visceral fat were associated with worse survival outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Prior research has identified various prognostic markers in epithelial ovarian cancer (EOC), including BRCA mutation status and a response to platinum-based chemotherapy, to predict outcomes in patients undergoing PARP inhibitor maintenance therapy. The role of CA-125 elimination rate constant K (KELIM), although recognized as a prognostic indicator, has not been fully investigated. This study underscores the prognostic significance of KELIM, revealing that a favorable KELIM score significantly correlates with better PFS in patients treated with primary cytoreductive surgery (PCS) followed by PARP inhibitor therapy. It also shows that KELIM's predictive value varies with the timing of surgery, extending a different view of its utility in real-world practice. KELIM could be integrated into clinical decision-making processes, potentially informing future clinical guidelines and research into optimal treatment strategies for targeted use of PARP inhibitors in advanced EOC patients. Background: This multicenter retrospective study aimed to investigate the prognostic value of the CA-125 elimination rate constant K (KELIM) in EOC patients who received platinum-based chemotherapy followed by PARP inhibitors, in either upfront or interval treatment settings. Methods: Between July 2019 and November 2022, we identified stage III–IV EOC patients who underwent primary or interval cytoreductive surgery and received olaparib or niraparib. Individual KELIM values were assessed based on validated kinetics and classified into favorable and unfavorable cohorts. Results: In a study of 252 patients undergoing frontline maintenance therapy with olaparib or niraparib, favorable KELIM (≥1) scores were associated with a higher PFS benefit in the primary cytoreductive surgery (PCS) cohort (hazard ratio (HR) for disease progression or death 3.51, 95% confidence interval (CI); 1.37–8.97, p = 0.009). Additionally, within the interval cytoreductive surgery (ICS) cohort, a favorable KELIM score (≥1) significantly increased the likelihood of achieving complete resection following cytoreductive surgery, with 59.4% in the favorable KELIM group compared to 37.8% in those with unfavorable KELIM. Conclusions: A favorable KELIM score was associated with improved PFS in patients with advanced EOC undergoing PCS. Furthermore, in the ICS cohort, a favorable KELIM score increased the probability of complete cytoreduction. [ABSTRACT FROM AUTHOR]

Background: To determine if extended chemotherapy improves survival outcomes in patients with platinum-sensitive relapsed epithelial ovarian cancer (EOC) who have residual disease after six cycles of second-line chemotherapy.Methods: In this study, 135 EOC patients who experienced platinum-sensitive recurrence after primary treatment between 2008 and 2018, and had a residual tumor ≥0.5 cm (detected on CT scans) after completing six cycles of second-line, platinum-based chemotherapy, were retrospectively reviewed. Based on the number of main therapy cycles (second-line chemotherapy), we divided patients into an extended group (>6 cycles, n = 52) or a standard group (6 cycles, n = 83) and compared patient characteristics and survival outcomes between these groups.Results: The extended group had a shorter platinum-free interval after primary treatment than the standard group (median, 11.0 vs. 13.1 months; P = 0.018). Secondary debulking surgery was less frequently performed in the standard group (1.9% vs. 19.3%; P = 0.003). After six chemotherapy cycles, the extended and standard groups showed similar serum CA-125 levels (P = 0.122) and residual tumor sizes (P = 0.232). There was no difference in overall survival (OS) between the groups (P = 0.382), although the extended group had significantly worse progression-free survival (PFS) than the standard group (median, 13.9 vs. 15.1 months; P = 0.012). Multivariate analyses revealed that platinum-free interval was an independent prognostic factor for PFS and OS, but extended chemotherapy was not (PFS: HR, 1.25; 95% CI, 0.84-1.85; P = 0.279; and OS: HR, 1.36; 95% CI, 0.72-2.56; P = 0.342). We observed consistent results in the subset of patients who did not undergo secondary debulking surgery.Conclusions: More than six cycles of platinum-based chemotherapy might not improve survival outcomes in patients with platinum-sensitive recurrent EOC who had a residual tumor ≥0.5 cm after six cycles of second-line chemotherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To compare survival outcomes of primary laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in patients with FIGO stage IB cervical cancer. We retrospectively identified stage IB1–IB2 cervical cancer patients who received either LRH (n = 343) or ORH (n = 222) at two tertiary institutional hospitals between 2000 and 2018. To adjust for confounders, we conducted Mahalanobis distance-based sample matching for stage, histology, cervical mass size, parametrial invasion, and lymph node metastasis. Then, survival outcomes were compared between the matched groups. Through the independent matching processes, we narrowed the study population to stage IB1 patients and stage IB1 patients with tumor size ≤2 cm on pre-operative MRI. After matching, LRH group showed poorer progression-free survival (PFS) than ORH group (3-year: 85.4% vs. 91.8%; P = 0.036), whereas no significant difference in overall survival (OS) was found. Regarding recurrence patterns, no significant differences in the incidences of pelvic, retroperitoneal lymph node and abdominal recurrences, or distant metastasis were observed between the two groups. Among the matched patients with stage IB1 who had cervical mass size ≤2 cm, the LRH and ORH groups showed similar PFS (3-year: 90.0% vs. 93.1%; P = 0.8) and OS (5-year: 98.6% vs. 96.4%; P = 0.6). Despite the retrospective design, our matched cohort study suggests that ORH might be preferable for the surgical treatment of FIGO stage IB cervical cancer. However, in stage IB1 patients with tumor size ≤2 cm, LRH might be applicable, as equivalent outcomes were found regardless of the surgical approach. Further prospective studies are warranted. • We conducted a matching study to investigate survival of laparoscopic radical hysterectomy (LRH) in stage IB cervical cancer. • After matching, LRH group showed a higher recurrence rate compared to open group, whereas overall survival was not different. • In stage IB1 patients with tumor size ≤2 cm, equivalent survival outcomes were observed regardless of the surgical approach. [ABSTRACT FROM AUTHOR]

Abstract Objective To compare survival outcomes of minimally invasive surgery (MIS) and conventional open surgery for radical hysterectomy (RH) among patients with early-stage cervical cancer (CC). Methods We retrospectively identified stage IB1-IIA2 CC patients who underwent either laparoscopic or open Type C RH between 2000 and 2018. Patients' clinicopathologic characteristics and survival outcomes were compared according to the surgical approach. For a more robust statistical analysis, we narrowed the study population down to the patients with stage IB1 who underwent pre-operative MRI. Results In total, 435 and 158 patients were assigned to open surgery and MIS groups, respectively. MIS group had significantly less parametrial invasion (6.3% vs. 15.4%; P = 0.004). Despite similar proportions of patients received adjuvant treatment, concurrent chemoradiation therapy was performed less frequently in MIS group. After a median follow up of 114.8 months, the groups showed similar overall survival; however, MIS group displayed poorer progression-free survival (PFS; 5-year rate, 78.5% vs. 89.7%; P < 0.001). Multivariate analyses identified MIS as an independent poor prognostic factor for PFS (adjusted HR, 2.883; 95% CI, 1.711–4.859; P < 0.001). Consistent results were observed among 349 patients with stage IB1: MIS was associated with higher recurrence rates (adjusted HR, 2.276; 95% CI, 1.039–4.986; P = 0.040). However, MIS did not influence PFS of stage IB1 patients with cervical mass size ≤2 cm on pre-operative MRI (adjusted HR, 1.146; 95% CI, 0.278–4.724; P = 0.850). Conclusions Overall, MIS RH was associated with higher recurrence rates than open RH in patients with early-stage CC. However, MIS was not a poor prognostic factor among those with stage IB1 and cervical mass size ≤2 cm on pre-operative MRI. Highlights • We investigated survival outcome of radical hysterectomy (RH) by laparoscopic surgery in early-stage cervical cancer. • Compared to open RH, minimally invasive surgery (MIS) was associated with higher recurrence rates. • MIS RH was not a poor prognostic factor in patients with stage IB1 and cervical mass size ≤2 cm on pre-operative MRI. [ABSTRACT FROM AUTHOR]

Background: Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC.Methods: In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification. Heightened levels of cancer-related genes expressed in concert with LYL1 amplification were similarly investigated through differentially expressed gene and gene set enrichment analyses. Factors associated with survival outcomes were also identified.Results: Somatic LYL1 gene amplification was observed in 22 patients (5.9%) with UCEC. Patients displaying amplification (vs. non-amplification) were significantly older at the time of diagnosis and more often were marked by non-endometrioid, high-grade, or advanced disease. In survival analysis, the amplification subset showed poorer progression-free survival (PFS) and overall survival (OS) rates (3-year PFS: 34.4% vs. 79.9%, P = 0.031; 5-year OS: 25.1% vs. 84.9%, P = 0.014). However, multivariate analyses adjusted for tumor histologic type, grade, and stage did not confirm LYL1 gene amplification as an independent prognostic factor for either PFS or OS. Nevertheless, MAPK, WNT, and cell cycle pathways were significantly enriched by LYL1 gene amplification (P < 0.001, P = 0.002, and P = 0.004, respectively).Conclusions: Despite not being identified as an independent prognostic factor in UCEC, LYL1 gene amplification is associated with other poor prognostic factors and correlated with upregulation of cancer-related pathways. [ABSTRACT FROM AUTHOR]

Objective To analyze whole exome sequencing (WES) data on ovarian clear cell carcinoma (OCCC) in Korean patients via the technique of next generation sequencing (NGS). Genomic profiles were compared between endometriosis-associated OCCC (EMS-OCCC) and Non-EMS-OCCC. Methods We used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were initially collected from women diagnosed with OCCC between 2012 and 2016. In total, 15 patients were enrolled: 5 with pathologically confirmed EMS-OCCC and 10 with Non-EMS-OCCC. We performed NGS WES on 15 fresh frozen OCCC tissues and matched serum samples, enabling comprehensive genomic characterization of OCCC. Results OCCC was characterized by complex genomic alterations, with a median of 178 exonic mutations (range, 111-25,798) and a median of 343 somatic copy number variations (range, 43-1,820) per tumor sample. In all, 54 somatic mutations were discovered across 14 genes, including PIK3CA (40%), ARID1A (40%), and KRAS (20%) in the 15 Korean OCCCs. Copy number gains in NTRK1 (33%), MYC (40%), and GNAS (47%) and copy number losses in TET2 (73%), TSC1 (67%), BRCA2 (60%), and SMAD4 (47%) were frequent. The significantly altered pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 87% of OCCCs and with chromatin remodeling in 47% of OCCCs. No significant differences in frequencies of genetic alterations were detected between EMS-OCCC and Non-EMS-OCCC groups. Conclusion We successfully characterized the genomic landscape of 15 Korean patients with OCCC. We identified potential therapeutic targets for the treatment of this malignancy. [ABSTRACT FROM AUTHOR]

Objectives: Preoperative cervical conization, while reducing the cervical mass size, might decrease the chance of tumor spillage during surgery. This study aimed to ascertain whether cervical conization before primary radical hysterectomy (RH) has a protective effect in patients with early cervical cancer. Methods: We retrospectively identified node-negative, marginnegative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH at two tertiary institutional hospitals between July 2006 and June 2020. Whether they received preoperative cervical conization or not, patients were divided into conization group (n =144) and control group (n =434). To adjust for confounders, we conducted a 1:1 propensity score matching for histology, surgical approach, lymphovascular space invasion, and cervical mass size (calculated by summing pathologic tumor size on conization and uterine specimens). Then, survival outcomes were compared between the matched groups. Results: Overall, the conization group had less cervical mass size and received minimally invasive surgery (MIS) more frequently (p =0.010) and adjuvant treatment less often (p =0.002) compared to the control group. Of 37 patients who received preoperative conization and had no residual tumor in the uterine specimen, only one (2.7%) recurred during 56.5 months of a median observation period. After matching, the conization group showed significantly better progression-free survival (PFS) than the control group (3-year: 94.2% vs 86.3%; p =0.012), whereas no significant difference in overall survival (OS) was found. Subgroup analysis in the open RH (n =91) revealed that PFS did not differ by preoperative conization (p =0.799). In contrast, in the MIS RH subgroup (n =197), preoperative conization was associated with significantly better PFS (p =0.005). Conclusions: Despite the retrospective design, our matched cohort study suggests that preoperative cervical conization might have a protective effect on disease recurrence in early cervical cancer, especially for those who are planning to undergo MIS RH. Further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

In 2014, the World Health Organization introduced a new histologic classification by dividing primary mucinous ovarian carcinoma (PMOC) into two: expansile (ES) or infiltrative subtypes (IS). This study investigated the clinical implications of these histological subtypes on survival outcomes. Data from 131 patients with PMOC who underwent primary surgery between 2003 and 2021 were analyzed. The patients baseline characteristics, surgical and pathological information were collected. Survival outcomes were calculated, while factors affecting them were also investigated. During 55.9 months of median follow-up, 27 (20.6%) patients experienced recurrence and 20 (15.3%) died. Among 131 patients, 113 patients were classified into 87 (77%) ES and 26 (23%) IS after a slide review. Advanced stage, lymph node involvement, and residual tumors after surgery were more common in the IS, showing poorer prognosis. In multivariate analyses, advanced stage and residual tumors after surgery were associated with worse survival, while the IS showed no statistical significance. In subgroup analysis for stage I disease, survival did not vary between subtypes. Nevertheless, patients in the IS group who underwent fertility-sparing surgeries demonstrated a 5-year progression-free survival (PFS) rate of 83.3%, significantly lower than patients without fertility preservation, irrespective of histologic subtypes (5-year PFS rate: 97.9%; P = 0.002 for the ES, 5-year PFS rate: 100%; P = 0.001 for the IS). The IS of PMOC had poorer survival outcomes and a higher proportion of advanced-stage tumors. Although its independent prognostic significance remains uncertain, adjuvant chemotherapy should be considered for patients with fertility preservation in the IS group. • The infiltrative subtype is known to be more aggressive than the expansile subtype in primary mucinous ovarian carcinoma. • The infiltrative subtype showed worse survival than the expansile subtype, with a higher proportion of advanced stage tumors. • In stage I disease, there was no difference in survival between the two histologic subtypes due to its excellent survival. • Fertility sparing surgery appears to be an important prognostic factor for progression-free survival in stage I disease. • It remains uncertain if the infiltrative subtype is an independent prognostic factor. [ABSTRACT FROM AUTHOR]

We explored the prevalence of smoking, alcohol consumption, physical activity, and obesity in cervical cancer survivors and examined associations between sociodemographic factors and each health behavior. We studied 448 cervical cancer survivors ≥2 years after their initial diagnosis who had completed treatment. The total sample consisted of these survivors, and 4,480 cancer-free controls who were grouped into 5-year age cohorts and matched to the survivors in terms of both education and monthly household income. The prevalence of current smoking, current alcohol consumption, physical inactivity, and obesity in cervical cancer survivors (2.68, 23.88, 62.02, and 32.81%, respectively) did not differ significantly from those of matched non-cancer controls. Age (younger), marital status (married), and education (≥college) were associated with lower probabilities of current alcohol consumption (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.88–0.95; OR = 0.42, 95% CI = 0.23–0.78; OR = 0.49, 95% CI = 0.25–0.97, respectively). A monthly household income ≥$2,000, being employed, and self–rated health status (less healthy) were associated with physical inactivity (OR = 0.61, 95% CI = 0.37–0.99; OR = 2.16, 95% CI = 1.36–3.42; OR = 1.94, 95% CI = 1.23–3.05, respectively). Both age and number of years since diagnosis were associated with obesity (OR = 1.04, 95% CI = 1.01–1.08; OR = 0.38; 95% CI = 0.20–0.72, respectively). The health behaviors of cervical cancer survivors did not differ from those of matched cancer-free controls. As health behaviors are modifiable, identification of cervical cancer survivors who are at risk of an unhealthy lifestyle would allow individual- and population-based intervention programs to more effectively use their limited resources. [ABSTRACT FROM AUTHOR]

Objectives: AMBITION is a multi-center, open-label, five-arm, uncontrolled, umbrella trial in platinum-resistant ovarian cancer patients (NCT03699449). Here, we present an exploratory analysis of clinical and molecular characteristics associated with the benefit of two olaparib-based regimens in the homologous recombination repair (HRR) gene mutation cohort. Methods: Between December 2018 and October 2020, 30 patients who had mutations in HRR genes were randomized, and received either olaparib 200mg bid + cediranib 30mg QD (arm 1; n =16) or olaparib 300mg bid + durvalumab 1500mg q4w (arm 2; n =14). From the pre-treatment biopsy (n =22) and archival (n =8) tumor samples, next-generation whole-exome and whole-transcriptomic sequencing were conducted. We also evaluated tumor immunologic signatures, including the PD-L1 (SP263) assay and tumor-infiltrating lymphocytes (TILs). Clinical and molecular features were compared between responders and non-responders. Results: Arms 1 and 2 showed an acceptable objective response rate at 50.0% and 42.9%, respectively. The responders (n =14) had 12.4 months of a median duration of response. Overall, no differences in serum CA-125 levels, ECOG performance status, histologic subtype, prior lines of therapy, and last treatment-free interval were observed between the responders and non-responders. Intratumoral TILs and stromal TILs were also similar between the responders and non-responders. While all responders had BRCA1/2 mutations, 54.5% of non-responders had BRCA1/2 mutations. DNA damage repair pathways were enriched in the responders. Especially, enrichment of DNA mismatch repair and nucleotide excision repair pathways were associated with prolonged progression-free survival (PFS). In arm 1, cell cycle pathway enrichment significantly improved PFS (p =0.006), but PD-L1 expression did not. In arm 2, patients with PD-L1 ≥1% of tumor cells showed significantly better PFS than those with PD-L1 <1% (p =0.027), and the responders had a significantly higher level of myeloid-derived suppressor cell recruiting score than the non-responders (p =0.041). Conclusions: Responders in the randomly assigned arms 1 and 2 of AMBITION showed distinct molecular features. Based on integrative molecular analyses, pre-treatment identification of responders to the olaparib doublet treatment for platinum-resistant ovarian cancer might be possible. [Display omitted] [ABSTRACT FROM AUTHOR]

To determine whether prognostic impact of lymph node ratio (LNR), defined as the ratio between the number of positive lymph nodes and removed lymph nodes, is different by the surgical approach of radical hysterectomy (RH) in node-positive, early-stage cervical cancer. We retrospectively identified 2009 FIGO stage IB1-IIA2 patients who underwent primary Type C RH between 2010 and 2018 at two tertiary hospitals. Among them, only those with pathologically proven lymph node metastases and received adjuvant radiation therapy were included. Each patient's LNR was calculated, and its prognostic significance was investigated according to the two surgical approaches, open surgery, and minimally invasive surgery (MIS). In total, 55 patients were included in this analysis. All patients received concurrent chemoradiation therapy after surgery, and the median LNR (%) was 9.524 (range, 2.083-62.500). Based on receiver operating characteristic-curve analysis, the cut-off value for LNR (%) was determined as 8.831. Overall, patients with high LNR (≥8.831%; n=29) showed worse disease-free survival (DFS) than those with low LNR (<8.831%, n=26) (P=0.027), whereas no difference in overall survival was observed. Multivariate analyses adjusting clinicopathologic factors revealed that DFS was adversely affected by both MIS (HR, 8.132; P=0.038) and high LNR (HR, 10.837; P=0.045). In a subgroup of open RH, LNR was not associated with disease recurrence. However, in a subgroup of MIS, high LNR was identified as an independent poor prognostic factor for DFS (adjusted HR, 14.578; P=0.034). In patients with node-positive, early-stage cervical cancer, high LNR was associated with a significantly higher disease recurrence rate. This relationship was further consolidated among patients who received MIS RH. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of adjuvant radiotherapy (RT) on survival outcomes in patients with intermediate-risk, early-stage cervical cancer who underwent radical hysterectomy (RH). From the cervical cancer cohorts of two tertiary hospitals, patients with 2009 FIGO stage IB-IIA who underwent primary RH between 2010 and 2018 were identified. Patients with intermediate-risk factors that met the Sedlis criteria were included. Survival outcomes were compared between the patients who received adjuvant RT (study group; n=53) and those who did not receive adjuvant treatment (control group; n=30). Compared to the control group, the study group showed significantly better recurrence-free survival (RFS; 5-year survival rate, 85.6% vs. 61.0%; p=0.009). In multivariate analysis, adjuvant RT was associated with a significantly lower risk of disease recurrence (adjusted HR, 0.241; 95% CI, 0.082-0.709; p=0.010). In a subgroup that underwent open RH (n=33), adjuvant RT showed a trend toward improved RFS with borderline statistical significance (adjusted HR, 0.098; 95% CI, 0.009-1.027; p=0.053). However, in a subgroup of minimally invasive surgery (n=50), adjuvant RT did not improve RFS. In conclusion, the implementation of adjuvant RT significantly reduced the disease recurrence rate in patients with intermediate-risk, stage IB-IIA cervical cancer treated primarily with surgery. A survival benefit from adjuvant RT differed according to the surgical approach. [ABSTRACT FROM AUTHOR]

To investigate the molecular characteristics of high-grade serous ovarian cancer (HGSOC) through integrative analysis of whole exome sequencing (WES) and RNA sequencing (RNA-seq) data. We used blood samples and primary ovarian cancer tissues that were initially collected from HGSOC patients. Ten patients had germline mutations in either BRCA1 or BRCA2 gene, while 10 patients had wild-type BRCA1/2 genes. We performed WES and RNA-seq on fresh frozen, chemotherapy naïve cancer tissues, and matched blood samples. Genomic and transcriptomic profiles were comprehensively compared between patients with germline BRCA1/2 mutation and those with wild type BRCA1/2. HGSOC samples initially divided into two groups by the presence of germline BRCA1/2 mutations showed mutually exclusive mutational patterns. Implementation of RNA-seq and application of epithelial-to-mesenchymal transition index (EMT index) onto the HGSOC samples revealed that they can be divided into two subtypes; homologous recombination repair (HRR)-activated and mesenchymal. Patients with mesenchymal HGSOC, characterized by the activation of EMT transcriptional program, low genomic alteration, and diverse cell-type compositions, exhibited significantly worse overall survival than did those with HRR-activated HGSOC (P =0.002). By applying the EMT index to TCGA HGSOC data, patients with high EMT index (≥ the median) showed significantly worse overall survival than did those with low EMT index (< the median) (P =0.030). We identified the EMT index as a potential prognostic biomarker for HGSOC. Genes related to this index can be therapeutic targets for the treatment of HGSOC. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of lower limb lymphedema (LLL) on quality of life (QOL) in cervical, ovarian, and endometrial cancer survivors after pelvic lymph node dissection. Study design A cross-sectional case-control study was performed using the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). In total, 25 women with LLL and 28 women without LLL completed both questionnaires. Results The GCLQ-K total symptom score and scores for swelling-general, swelling-limb, and heaviness were significantly higher in the LLL group than in the control group. In the EORTC QLQ-C30, the LLL group reported more financial difficulties compared to the control group (mean score, 16.0 vs. 6.0; P = 0.035). Global health status was poorer in the LLL group with borderline statistical significance (mean score, 62.7 vs. 71.4; P = 0.069). Spearman's correlations suggested that global health status in the EORTC QLQ-C30 correlated with the GCLQ-K total symptom score (in the LLL group, R = −0.64, P = 0.001; in the control group, R = −0.42, P = 0.027). Conclusions QOL decreases due to LLL-related symptoms and financial difficulty in women with LLL. Well-designed prospective studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the surgical outcome of a subcutaneous negative pressure drain without subcutaneous suture on wound healing in women undergoing abdominal gynecologic surgery. Study design: The medical records of total 322 patients who underwent abdominal surgery, including cytoreductive surgery for ovarian cancer, between March 2010 and January 2013 were reviewed retrospectively. Patients were divided into two groups by the presence of subcutaneous negative pressure drains without subcutaneous suture, or suture without drainage. Results: Patient's characteristics in the two groups were not statistically different. Among all patients, the 71 patients who had a subcutaneous wound drain achieved a higher rate of clear healing (97.2% vs. 88.8%; p =0.033): 100% vs. 98.0% (not significant) in 126 benign and 95.6% vs. 82.8% (p =0.032) in 196 malignant disease patients. In a multivariate analysis, wound drain placement was an independent prognostic factor affecting the surgical wound outcome; the disruption (OR, 0.100; 95% CI, 0.021–0.485; p =0.004) rate was significantly lower with subcutaneous negative pressure drain. Placement of a subcutaneous negative pressure drain without subcutaneous suture resulted in clinical benefit, such as shorter admission duration (median, 8 vs. 11 days; p =0.021). Conclusions: Application of subcutaneous negative pressure drain is one of the effective and easy ways for clearer wound healing after major gynecologic surgery for malignant disease. [Copyright &y& Elsevier]

Simple Summary: Despite the importance of vaccination against Coronavirus disease 2019 (COVID-19) in cancer patients, general vaccine uptake rates among cancer patients are known to be low. Here, we tried to investigate the attitude and acceptance rates for COVID-19 vaccine in cancer patients and identify predictive factors for vaccination that could be modified to promote vaccine uptake rates. Between February and April 2021, a total of 1001 cancer patients from five institutions participated in a paper-based survey, consisting of 58 items over six domains. Among the respondents, 61.8% were willing to receive the COVID-19 vaccine. Along with the previously reported predictors for COVID-19 vaccination, including male gender, older age, and influenza vaccination history, we distinctively found that patient's disease status and health status (absence of cancer recurrence, time since cancer diagnosis over 5 years, and higher EuroQol Visual Analogue Scale scores) were associated with higher acceptance rates of vaccination. Furthermore, physician's recommendations effectively reduced patient's vaccine hesitancy. Considering the high morbidity and mortality of Coronavirus disease 2019 (COVID-19) in patients with malignancy, they are regarded as a priority for COVID-19 vaccination. However, general vaccine uptake rates among cancer patients are known to be lower than in their healthy counterparts. Thus, we aimed to investigate the attitude and acceptance rates for the COVID-19 vaccine in cancer patients and identify predictive factors for vaccination that could be modified to increase vaccine uptake rates, via a paper-based survey (58 items over six domains). A total of 1001 cancer patients participated in this nationwide, multicenter survey between February and April 2021. We observed that 61.8% of respondents were willing to receive the COVID-19 vaccine. Positive predictive factors found to be independently associated with vaccination were male gender, older age, obesity, previous influenza vaccination history, absence of cancer recurrence, time since cancer diagnosis over 5 years, and higher EuroQol Visual Analogue Scale scores. Along with the well-known factors that are positively correlated with vaccination, here, we report that patients' disease status and current health status were also associated with their acceptance of the COVID-19 vaccination. Moreover, 91.2% of cancer patients were willing to be vaccinated if their attending physicians recommend it, indicating that almost 30% could change their decision upon physicians' recommendation. Unlike other factors, which are unmodifiable, physicians' recommendation is the single modifiable factor that could change patients' behavior. In conclusion, we firstly report that Korean cancer patients' acceptance rate of the COVID-19 vaccination was 61.8% and associated with disease status and current health status. Physicians should play a major role in aiding cancer patients' decision-making concerning COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: An increased risk of relapse and death from minimally invasive radical hysterectomy has been reported in some patients with early cervical cancer. Thus, the development of an intuitive and precise decision-aid tool, which estimates recurrence and mortality rates by surgical approach, is necessary. To develop models predicting survival outcomes according to the surgical approach, we collected clinicopathologic and survival data of patients with 2009 FIGO stage IB cervical cancer who underwent a radical hysterectomy. Using only variables that could be obtained preoperatively, we developed various models predicting the probability of 5-year progression-free survival and overall survival. Among them, hybrid ensemble models, combined with logistic regression and multiple machine learning models, achieved the best predictive performance. The developed models are expected to help physicians' and patients' decision making related to the surgical approach for primary radical hysterectomy. We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with 2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients' clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and overall survival (OS) with tenfold cross validation. The developed models were validated in the test set. In terms of predictive performance, we measured the area under the receiver operating characteristic curve (AUC) values. The logistic regression models comprised of preoperative variables yielded AUCs of 0.679 and 0.715 for predicting 5-year PFS and OS rates, respectively. Combining both logistic regression and multiple machine learning models, we constructed hybrid ensemble models, and these models showed much improved predictive performance, with 0.741 and 0.759 AUCs for predicting 5-year PFS and OS rates, respectively. We successfully developed models predicting disease recurrence and mortality after primary RH in patients with early cervical cancer. As the predicted value is calculated based on the preoperative factors, such as the surgical approach, these ensemble models would be useful for making decisions when choosing between open or laparoscopic RH. [ABSTRACT FROM AUTHOR]

High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers that can occur in women. This study aimed to investigate the molecular characteristics of HGSOC through integrative analysis of multi-omics data. We used fresh-frozen, chemotherapy-naïve primary ovarian cancer tissues and matched blood samples of HGSOC patients and conducted next-generation whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Genomic and transcriptomic profiles were comprehensively compared between patients with germline BRCA1/2 mutations and others with wild-type BRCA1/2. HGSOC samples initially divided into two groups by the presence of germline BRCA1/2 mutations showed mutually exclusive somatic mutation patterns, yet the implementation of high-dimensional analysis of RNA-seq and application of epithelial-to-mesenchymal (EMT) index onto the HGSOC samples revealed that they can be divided into two subtypes; homologous recombination repair (HRR)-activated type and mesenchymal type. Patients with mesenchymal HGSOC, characterized by the activation of the EMT transcriptional program, low genomic alteration and diverse cell-type compositions, exhibited significantly worse overall survival than did those with HRR-activated HGSOC (p = 0.002). In validation with The Cancer Genome Atlas (TCGA) HGSOC data, patients with a high EMT index (≥the median) showed significantly worse overall survival than did those with a low EMT index (

Although progress has been made in developing tumor microenvironment-responsive delivery systems, the list of cargo-releasing stimuli remains limited. In this study, we report DNA nanothread-cloaked nanoparticles for reactive oxygen species (ROS)-rich tumor microenvironment-responsive delivery systems. ROS is well known to strongly induce DNA fragmentation via oxidative stress. As a model anticancer drug, hydrophobic omacetaxine was entrapped in branched cyclam ligand-modified nanoparticles (BNP). DNA nanothreads were prepared by rolling-circle amplification and complexed to BNP, yielding DNA nanothread-cloaked BNP (DBNP). DBNP was unmasked by DNA nanothread-degrading ROS and culture supernatants of LNCaP cells. The size and zeta potential of DBNP were changed by ROS. In ROShigh LNCaP cells, but not in ROSlow fibroblast cells, the uptake of DBNP was higher than that of other nanoparticles. Molecular imaging revealed that DBNP exhibited greater distribution to tumor tissues, compared to other nanoparticles. Ex vivo mass spectrometry-based imaging showed that omacetaxine metabolites were distributed in tumor tissues of mice treated with DBNP. Intravenous administration of DBNP reduced the tumor volume by 80% compared to untreated tumors. Profiling showed that omacetaxine treatment altered the transcriptional profile. These results collectively support the feasibility of using polymerized DNA-masked nanoparticles for selective activation in the ROS-rich tumor microenvironment. [Display omitted] [ABSTRACT FROM AUTHOR]

The Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Consensus Conference on Clinical Research (ECCC) was held in Incheon, South Korea, Nov 2–3, 2023. The aims were to develop consensus statements for future trials in endometrial cancer to achieve harmonisation on design elements, select important questions, and identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and finalisation of 18 statements within four topic groups, addressing adjuvant treatment in high-risk disease; treatment for metastatic and recurrent disease; trial designs for rare endometrial cancer subgroups and special circumstances; and specific methodology and adaptation for trials in low-resource settings. In addition, eight areas of unmet need were identified. This was the first GCIG Consensus Conference to include patient advocates and an expert on inclusion, diversity, equity, and access to take part in all aspects of the process and output. Four early-career investigators were also selected for participation, ensuring that they represented different GCIG member groups and regions. Unanimous consensus was obtained for 16 of the 18 statements, with 97% concordance for the remaining two. Using the described methodology from previous Ovarian Cancer Consensus Conferences, this conference did not require even one minority statement. The high acceptance rate following active involvement in the preparation, discussion, and refinement of the statements by all representatives confirmed the consensus progress within a global academic setting, and the expectation that the ECCC will lead to greater harmonisation, actualisation, inclusion, and resolution of unmet needs in clinical research for individuals living with and beyond endometrial cancer worldwide. [ABSTRACT FROM AUTHOR]

Simple Summary: High-grade serous ovarian carcinoma (HGSOC) is the most aggressive histologic type of epithelial ovarian cancer, associated with high recurrence and mortality rates despite standard treatment. In accordance with the era of precision cancer medicine, we aimed to develop machine learning models predicting platinum sensitivity in patients with HGSOC. First, we collected patients' clinicopathologic data from three tertiary hospitals. Second, we elected six variables associated with platinum sensitivity using the stepwise selection method. Third, based on these variables, predictive models were constructed using four machine learning algorithms, logistic regression (LR), random forest, support vector machine, and deep neural network. Evaluation of model performance with the five-fold cross-validation method identified the LR-based model as the best at identifying platinum-resistant cases. Lastly, we developed a web-based nomogram by fitting the LR model results for clinical utility. Based on the prediction results, physicians may implement individualized treatment and surveillance plans for each HGSOC patient. To support the implementation of individualized disease management, we aimed to develop machine learning models predicting platinum sensitivity in patients with high-grade serous ovarian carcinoma (HGSOC). We reviewed the medical records of 1002 eligible patients. Patients' clinicopathologic characteristics, surgical findings, details of chemotherapy, treatment response, and survival outcomes were collected. Using the stepwise selection method, based on the area under the receiver operating characteristic curve (AUC) values, six variables associated with platinum sensitivity were selected: age, initial serum CA-125 levels, neoadjuvant chemotherapy, pelvic lymph node status, involvement of pelvic tissue other than the uterus and tubes, and involvement of the small bowel and mesentery. Based on these variables, predictive models were constructed using four machine learning algorithms, logistic regression (LR), random forest, support vector machine, and deep neural network; the model performance was evaluated with the five-fold cross-validation method. The LR-based model performed best at identifying platinum-resistant cases with an AUC of 0.741. Adding the FIGO stage and residual tumor size after debulking surgery did not improve model performance. Based on the six-variable LR model, we also developed a web-based nomogram. The presented models may be useful in clinical practice and research. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of adjuvant radiotherapy (RT) on survival outcomes in patients with intermediate-risk, early-stage cervical cancer who underwent radical hysterectomy (RH). From the cervical cancer cohorts of two tertiary hospitals, patients with 2009 FIGO stage IB-IIA who underwent primary RH between 2010 and 2018 were identified. Patients with intermediate-risk factors that met the Sedlis criteria were included. Survival outcomes were compared between the patients who received adjuvant RT (study group; n = 53) and those who did not receive adjuvant treatment (control group; n = 30). Compared to the control group, the study group showed significantly better recurrence-free survival (RFS; 5-year survival rate, 85.6% vs. 61.0%; p = 0.009). In multivariate analysis, adjuvant RT was associated with a significantly lower risk of disease recurrence (adjusted HR, 0.241; 95% CI, 0.082–0.709; p = 0.010). In a subgroup that underwent open RH (n = 33), adjuvant RT showed a trend toward improved RFS with borderline statistical significance (adjusted HR, 0.098; 95% CI, 0.009–1.027; p = 0.053). However, in a subgroup of minimally invasive surgery (n = 50), adjuvant RT did not improve RFS. In conclusion, implementation of adjuvant RT significantly reduced the disease recurrence rate in patients with intermediate-risk, stage IB-IIA cervical cancer treated primarily with surgery. Survival benefit from adjuvant RT differed according to the surgical approach. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients. Methods: We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome. Results: We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis-diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer. Conclusion: Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients. Methods: We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome. Results: We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis-diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer. Conclusion: Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer. [ABSTRACT FROM AUTHOR]

We aimed to develop a diagnostic model identifying ovarian cancer (OC) from benign ovarian tumors using metagenomic data from serum microbe-derived extracellular vesicles (EVs). We obtained serum samples from 166 patients with pathologically confirmed OC and 76 patients with benign ovarian tumors. For model construction and validation, samples were randomly divided into training and test sets in the ratio 2:1. Isolation of microbial EVs from serum samples of the patients and 16S rDNA amplicon sequencing were carried out. Metagenomic and clinicopathologic data-based OC diagnostic models were constructed in the training set and then validated in the test set. There were significant differences in the metagenomic profiles between the OC and benign ovarian tumor groups; specifically, genus Acinetobacter was significantly more abundant in the OC group. More importantly, Acinetobacter was the only common genus identified by seven different statistical analysis methods. Among the various metagenomic and clinicopathologic data-based OC diagnostic models, the model consisting of age, serum CA-125 levels, and relative abundance of Acinetobacter showed the best diagnostic performance with the area under the receiver operating characteristic curve of 0.898 and 0.846 in the training and test sets, respectively. Thus, our findings establish a metagenomic analysis of serum microbe-derived EVs as a potential tool for the diagnosis of OC. [ABSTRACT FROM AUTHOR]

Initial identification of biomarkers predicting the exact prognosis of high-grade serous ovarian carcinoma (HGSOC) is important in precision cancer medicine. This study aimed to investigate prognostic biomarkers of HGSOC through proteomic analysis. We conducted label-free liquid chromatography-mass spectrometry using chemotherapy-naïve, fresh-frozen primary HGSOC specimens, and compared the results between a favorable prognosis group (progression-free survival (PFS) ≥ 18 months, n = 6) and a poor prognosis group (PFS < 18 months, n = 6). Among 658 differentially expressed proteins, 288 proteins were upregulated in the favorable prognosis group and 370 proteins were upregulated in the poor prognosis group. Using hierarchical clustering, we selected α1-antitrypsin (AAT), nuclear factor-κB (NFKB), phosphomevalonate kinase (PMVK), vascular adhesion protein 1 (VAP1), fatty acid-binding protein 4 (FABP4), platelet factor 4 (PF4), apolipoprotein A1 (APOA1), and α1-acid glycoprotein (AGP) for further validation via immunohistochemical (IHC) staining in an independent set of chemotherapy-naïve primary HGSOC samples (n = 107). Survival analyses revealed that high expression of AAT, NFKB, and PMVK were independent biomarkers for favorable PFS. Conversely, high expression of VAP1, FABP4, and PF4 were identified as independent biomarkers for poor PFS. Furthermore, we constructed models predicting the 18-month PFS by combining clinical variables and IHC results. Through leave-one-out cross-validation, the optimal model was based on initial serum CA-125, germline BRCA1/2 mutations, residual tumors after surgery, International Federation of Gynecology and Obstetrics (FIGO) stage, and expression levels of the six proteins. The present results elucidate the proteomic landscape of HGSOC and six protein biomarkers to predict the prognosis of HGSOC. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of sarcopenia and body composition on survival outcomes in Korean patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). We retrospectively identified patients diagnosed with and treated for International Federation of Gynecology and Obstetrics stage III-IV HGSOC. Skeletal muscle index (SMI) was measured using pre-treatment computed tomography scans at the third lumbar vertebra. Sarcopenia was defined as SMI <39.0 cm2/m2. Patients' clinicopathologic characteristics and survival outcomes were compared according to sarcopenia presence. For subgroup analysis, we also measured the total fat area from the same image. In total, 76 and 103 patients were assigned to the sarcopenia and control groups, respectively. Comorbidities, stage, serum CA-125 levels, and size of residual tumor after surgery were similar between both groups. After a median follow up of 42.7 months, both groups showed similar progression-free survival (PFS) and overall survival (OS). In subgroup analysis confined to the sarcopenia group, patients with high fat-to-muscle ratio (FMR; ≥2.1, n = 38) showed significantly worse OS than those with low FMR (<2.1, n = 38) (5-year survival rate, 44.7% vs. 80.0%; p = 0.046), whereas PFS was not different (p = 0.365). Multivariate analyses identified high FMR as an independent poor prognostic factor for OS in this group (adjusted hazard ratio, 3.377; 95% confidence interval, 1.170–9.752; p = 0.024). In conclusion, sarcopenia did not influence recurrence rates and survival in Korean patients with advanced-stage HGSOC. However, among the patients with sarcopenia, high FMR was associated with decreased OS. [ABSTRACT FROM AUTHOR]

Objective Melanomas of the vulva and vagina are rare, and surgery is the gold standard of treatment [1, 2]. Since recent studies have reported pelvic exenteration by using robotic surgical system [3, 4], we showed the surgical procedures of robot-assisted anterior pelvic exenteration (rAPE) with ileal conduit urinary diversion for vulvovaginal malignant melanoma. Methods A 55-year-old woman who received vaginal wall resection due to vaginal malignant melanoma 8 months before was referred. Multiple biopsies of pigmented lesions on the vulva, vagina, and urethral orifice confirmed the recurrence, whereas preoperative image studies revealed no abnormal findings. Thus, we performed rAPE with ileal conduit urinary diversion. Results First, we performed robot-assisted bilateral inguinal and pelvic lymphadenectomy. Thereafter, we conducted en bloc resection of the bladder, uterus, vagina, and vulva through abdominal and perineal approaches ( Fig. 1 ): Under the 4-arm robotic surgical system, prevesical space was developed and laterally dissected along the undersurface of pubic bone, to the level of levator ani muscles. Bilateral infudibulopelvic ligaments, uterine arteries and parametrium, uterosacral ligaments, and pubovesical ligaments were ligated and resected. During the wide local excision of the vulva, the rectovaginal space was dissected along the posterior vaginal wall. En bloc specimen was successfully delivered. Finally, the ileal conduit urinary diversion was performed. Total operative time was 4.5 h excluding set-up and docking times of the robotic surgical system. The pathologic report ascertained clear resection margin and no lymph node involvement. Conclusion rAPE with ileal conduit urinary diversion for treatment of vulvovaginal malignant melanoma is feasible ( Fig. 1 ). [ABSTRACT FROM AUTHOR]

Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate impact of germline BRCA mutational status on prognosis in patients with advanced ovarian cancer. Methods: A total of 128 patients diagnosed with FIGO stage III-IV high-grade serous ovarian cancer (HGSOC) between 2008 and 2017 and underwent BRCA1/2 gene testing at the time of or within two years from cancer diagnosis were included in this study. We compared patients' clinicopathological characteristics and survival outcomes after primary treatment according to germline BRCA mutational status. Treatment-related factors that might affect patients' survival outcome were also investigated. Results: Germline BRCA1/2 mutations were observed in 51 women (39.8%). There were no differences in age and serum CA-125 levels at the time of HGSOC diagnosis, use of neoadjuvant chemotherapy (NAC), extent of debulking surgery, and overall survival (OS) between the BRCA mutation and wild-type BRCA groups. In contrast, the BRCA mutation group displayed longer progression-free survival (PFS) (median, 22.9 vs. 16.9 months, P = 0.001). Multivariate analyses identified germline BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted HR, 0.502; 95% CI, 0.318–0.795; P = 0.003). In the wild-type BRCA group, patients who received NAC as the primary treatment had shorter PFS compared to those who received primary debulking surgery (PDS) (median, 14.2 vs. 16.9 months, P = 0.003). However, in the BRCA mutation group, PFS did not differ between the NAC and PDS groups (P = 0.082). Conclusions: In advanced-stage HGSOC, patients with germline BRCA1/2 mutations have better prognosis with longer PFS than those lacking BRCA mutations. Prognosis after NAC was different according to the BRCA mutational status. [ABSTRACT FROM AUTHOR]