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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]

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]

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]

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]

The purpose of this study was to investigate the impact of sarcopenia and body composition change during primary treatment on survival outcomes in patients with early cervical cancer. We retrospectively identified patients diagnosed with 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 cervical cancer who underwent primary radical hysterectomy between 2007 and 2019. From pre-treatment CT scans (n = 306), the skeletal muscle area at the third lumbar vertebra (L3) and the waist skeletal muscle volume were measured using an artificial intelligence-based tool. These values were converted to the L3 and volumetric skeletal muscle indices by normalization. We defined L3 and volumetric sarcopenia using 39.0 cm2/m2 and the first quartile (Q1) value, respectively. From pre- and post-treatment CT scan images (n = 192), changes (%) in waist skeletal muscle and fat volumes were assessed. With the use of Cox regression models, factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Between the L3 sarcopenia and non-sarcopenia groups, no differences in PFS and OS were observed. In contrast, volumetric sarcopenia was identified as a poor prognostic factor for PFS (adjusted hazard ratio [aHR], 1.874; 95% confidence interval [CI], 1.028–3.416; p = 0.040) and OS (aHR, 3.001; 95% CI, 1.016–8.869; p = 0.047). During primary treatment, significant decreases in waist skeletal muscle (median, −3.9%; p < 0.001) and total fat (median, −5.3%; p < 0.001) were observed. Of the two components, multivariate analysis revealed that the waist fat gain was associated with worse PFS (aHR, 2.007; 95% CI, 1.009–3.993; p = 0.047). The coexistence of baseline volumetric sarcopenia and waist fat gain further deteriorated PFS (aHR, 2.853; 95% CI, 1.257–6.474; p = 0.012). In conclusion, baseline volumetric sarcopenia might be associated with poor survival outcomes in patients with early cervical cancer undergoing primary RH. Furthermore, sarcopenia patients who gained waist fat during primary treatment were at a high risk of disease recurrence. [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]

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]

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]

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]

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]

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]

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]

To investigate the effectiveness and safety of pembrolizumab and lenvatinib (PEMBRO+LEN) for recurrent endometrial cancer (EC) in a real-world setting. This multicenter retrospective cohort study included patients with recurrent EC who received PEMBRO+LEN between March 2020 and May 2021 at three tertiary hospitals in Korea. We summarized patient characteristics and evaluated the response rates, survival outcomes, and treatment-related adverse events (AEs). In total, 48 patients were included in the study. The median age of the patients was 62.5 (range, 42–78) years. The most common histologic subtype was endometrioid adenocarcinoma (43.8%), followed by serous adenocarcinoma (25.0%). Most patients (91.7%) had mismatch repair-proficient tumors. Patients received PEMBRO+LEN for a median of 4.5 cycles, during which the best objective response rate and disease control rate were 23.8% (95% CI, 11.9–38.1) and 76.2% (95% CI, 61.9–88.1), respectively. Overall, 56.2% of patients experienced LEN dose reduction once or more and 16.7% experienced LEN interruption. The most common treatment-related AEs were fatigue (18.8%), hypertension (16.7%), and hypothyroidism (14.6%). Total of 8 patients (16.7%) discontinued LEN during the treatment because of treatment-related AEs. Serum CA-125 level was the only prognostic factor for progression-free survival (adjusted hazard ratio, 4.41; 95% confidence interval, 1.19–16.36; p = 0.03). In our real-world study, Korean patients with recurrent EC who received PEMBRO+LEN showed lower treatment response rate and similar treatment discontinuation rate, compared to clinical trials. • We report the real-world data of pembrolizuamb plus lenvatininb for treating recurrent endometrial cancer. • Pembrolizumab plus lenvatinib is effective in providing acceptable response rates in Korean patients. • More than half of the patients experienced dose reduction of levatinib but adverse events were manageable. [ABSTRACT FROM AUTHOR]