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To assess the influence of geographies and race on the survival outcomes in patients diagnosed with cervical squamous cell carcinoma (CSCC) across three continents. This multicontinental retrospective study was conducted in 8 hospitals across Asia, Europe, and North America (NA). Clinicopathologic data of 595 patients with presumed early stages of CSCC, treated surgically, with curative intent was collected. Descriptive analysis and Cox regression models were produced. A total of 595 patients, consisting of 445 (74.8 %) white, 75 (12.6 %) Blacks, and 75 (12.6 %) Asian patients were included. Geographical distribution comprised 69 % of patients from NA, 22 % from Europe, and 9 % from Asia. The median age at diagnosis was 46 years. The median overall survival (OS) and relapse-free survival (RFS) were 22.09 years and 21.19 years, respectively. Patient characteristics varied significantly across geographical regions, except for consensus tumor grade. Patients in Europe from middle-income countries with limited CC screening had a substantially higher risk of death than those in NA (HR, 1.79; 95 % CI, 1.13 to 2.79; p = 0.015). Patients from single center in Japan had higher risk of relapse than those from the four heterogeneous NA centers (sub-distribution hazard ratio, 2.19; 95 % CI, 1.22 to 3.95; p = 0.009), although OS did not differ significantly. Race remained statistically insignificant for survival outcomes across the three continents but seemed to influence survival outcomes in NA centers. Our study highlights impact of geographies and races on CSCC survival outcomes, emphasizing the need of considering these factors when developing targeted interventions against CSCC. • Significant association between the cervical cancer relapse rate and geographical region. • No significant association between the cervical cancer survival outcomes and race across the three continents. • Race influenced cervical cancer survival outcomes in North American institutes. • No significant differences in survival outcomes when comparing Black and non-Black patients in North America. [ABSTRACT FROM AUTHOR]

To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC). We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000–12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation. Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33–91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1–234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94). Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated. • Radiation only was the most common (38%) adjuvant therapy in patients with stage I-II endometrial clear cell carcinoma (ECCC) • Positive cytology impacted risk of recurrence and age > 65 years impacted overall survival in this cohort of patients • Survival outcomes of surgically staged patients with stage I-II ECCC were not impacted by receipt of adjuvant treatment • Patients with tumors of "pure" clear cell vs "mixed" clear cell histology had no difference in survival [ABSTRACT FROM AUTHOR]

In patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2 -mutated PSROC patients, focusing on the type and location of PV. We assessed the outcomes of 100 BRCA1/2 -mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS). PFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects. In summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients. Trial registration number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015. • BRCA1/2 mutation location impacts the outcome of relapsed ovarian cancer patients on olaparib maintenance monotherapy (OMT). • Patients on OMT with BRCA1 pathogenic variant (PV) had shorter progression free survival (PFS) compared to BRCA2 PV. • Patients on OMT with PV in BRCA2 or in BRCA1 DNA binding domain had better PFS compared to PV in BRCA1 RING domain. • No significant difference in PFS between patients on OMT with germline or somatic BRCA1/2 PV was observed. • Adverse events in patients on OMT were not significantly different between germline and somatic PV in BRCA1/2. [ABSTRACT FROM AUTHOR]

Mirvetuximab soravtansine may be a potentially effective therapeutic option for ovarian low-grade serous carcinoma (LGSC), but the prevalence of folate receptor alpha (FRα) overexpression in this tumor type is unknown. We sought to characterize FRα expression in LGSC and its association with clinical and molecular features. FRα immunohistochemistry was performed on a tissue microarray comprised of 89 LGSCs and 42 ovarian serous borderline tumors (SBTs). Clinical tumor-normal panel-based sequencing was performed on 78 LGSCs. Associations between FRα-high status and clinicopathologic characteristics and survival outcomes were examined. Of 89 LGSCs, 36 (40%) were FRα-high (≥75% of viable tumor cells exhibiting moderate-to-strong membranous expression). Of 9 patients with LGSC and samples from different timepoints, 4 (44%) had discordant results, with conversion from FRα-negative to FRα-high in 3 (33%) cases. There was no association between FRα-high status with age, race, or progression-free/overall survival. A MAPK pathway genetic alteration, most commonly involving KRAS (n = 23), was present in 45 (58%) LGSCs. Those lacking MAPK pathway alterations were more likely to be FRα-high compared to MAPK-altered LGSCs (61% vs 20%, p < 0.001). In SBTs, FRα-high expression was associated with high-risk (micropapillary) histology and/or subsequent LGSC recurrence compared to conventional SBTs without malignant recurrence (53% vs 9%, p = 0.008). Future studies of FRα-directed therapy in patients with LGSC are warranted. Discordant FRα status at recurrence suggests potential benefit for retesting. A biomarker-driven approach to direct treatment selection in LGSC is recommended. As high FRα expression is more common amongst tumors lacking MAPK pathway genetic alterations, FRα testing to determine eligibility for mirvetuximab soravtansine therapy is particularly recommended for this subgroup. • Approximately 40% of ovarian low-grade serous carcinomas (LGSCs) are folate receptor α (FRα)-high. • LGSCs lacking MAPK pathway genetic alterations are more likely to be FRα-high. • Change in FRα status at recurrence suggests a possible benefit to re-testing. • Mirvetuximab soravtansine should be investigated as a treatment option for LGSC, particularly for MAPK non-altered tumors. [ABSTRACT FROM AUTHOR]

To investigate the role of BRCA1/2 mutations in early ovarian cancer (eOC) (International Federation of Gynecology and Obstetrics FIGO 2014 stage I-II), and its impact on prognosis after relapse. In this multicenter retrospective study, clinical and survival data from high-grade serous (HGS)-eOC patients at presentation and recurrence were compared according to BRCA status: BRCA-mutated (BRCAmut) vs. BRCA wild-type (BRCAwt). Among 191 HGS-eOC patients, 89 were BRCAmut and 102 BRCAwt. There was no significant difference according to the BRCA status in terms of Progression-Free Survival (PFS). A longer Overall Survival (OS) was found in BRCAmut patients. Stage I patients had significantly improved PFS vs stage II, regardless of BRCA status. At multivariate analysis, stage at diagnosis was the only variable with a significant effect on PFS. No factors were significantly relevant on OS, albeit younger age and BRCA mutation showed a slight impact. Post-Recurrence Survival (PRS) in the BRCAmut population was significantly improved compared with BRCAwt. At multivariate analysis, Secondary Cytoreductive Surgery was the strongest predictor for longer PRS, followed by PARPi maintenance at recurrence. BRCA-status is not a prognostic factor in early ovarian cancer regarding PFS. However, our data suggest a better prognosis after relapse in BRCAm population. • Recurrence rate was similar in BRCAwt and BRCAmut groups (35.3% vs 29.2%). • The recurrence patterns were similar between BRCAmut and BRCAwt • BRCA status has no impact on Progression Free Survival. • Post-recurrence Survival was significantly longer in the BRCAmut group. • A longer Overall Survival was found in BRCAmut compared with BRCAwt patients. [ABSTRACT FROM AUTHOR]

Stage IVA patients comprise a small proportion of participants in cervical cancer trials, yet survival outcomes are disproportionately poor. We aim to perform a systematic review evaluating stage IVA cervical cancer. This systematic review was completed via PRISMA 2020 guidelines using two databases. Inclusion criteria comprised Phase III trials (2004–2024) assessing stage IVA cervical cancer including patients by stage. Searches had MeSH terms: ((cervical cancer) AND (stage IVA) AND (locally advanced)). 761 were articles identified, including books, trials, reviews, and meta-analyses. Of the articles identified, 12 met inclusion criteria. A total of 133 (3.8% of study populations) stage IVA and 818 (40% of study populations) stage III-IVA cervical cancer patients were analyzed. Two studies (stage IVA n = 15; 3.1%) established cisplatin as chemoradiotherapy agent of choice, while one study (stage IVA n = 2; 1%) showed no benefit with cisplatin versus radiotherapy alone. Four studies (stage IVA n = 32; 3.6%; stages IIIB-IVA n = 220; 24%) found no benefit with adjuvant chemotherapy, with one analyzing stage IIIB-IVA patients (progression-free survival (PFS) hazard ratio (HR) = 0.84; 95% confidence interval (CI): 0.57–1.23). Three studies (stage IVA n = 71; 5%) found no benefit adding immunomodulator (stage IVA overall survival HR = 3.48; 95% CI: 0.52–23.29), hypoxic cell sensitizer, or immunotherapy (stage III-IVA PFS HR = 0.71; 95% CI: 0.49–1.03) to chemoradiotherapy. One study (stages III-IVA n = 598; 56%) found benefit adding immunotherapy to chemoradiotherapy (stage III-IVA PFS HR = 0.58; 95% CI: 0.42–0.8). One study (stage IVA n = 13; 3.5%) showed benefit with induction chemotherapy. Trials have not included substantial IVA patients to draw reasonable conclusions. Despite mixed results for immunotherapy, adjuvant chemotherapy, and induction chemotherapy, the exact benefit for stage IVA patients remains unknown. Future clinical trials should include a greater number of stage IVA cervical cancer patients and analyze them individually. • Stage IVA CC presents with distinctly poor outcomes compared to other stages of LACC. • Standard of care for stage IVA has remained chemoradiotherapy for the last 20 years. • Racial minorities have poor survival outcomes and highest incidence of stage IV CC. • Ongoing clinical trials are likely to lead to changing the standard of care for LACC. • Improving outcomes for the highest risk group (stage IVA) will continue to be important. [ABSTRACT FROM AUTHOR]

A randomized non-inferiority trial showed worse survival in women with early-stage cervical cancer treated with radical hysterectomy by minimally invasive approach compared to laparotomy; the impact of surgical approach on survival following radical trachelectomy is unknown. To examine oncologic outcomes in women with early-stage cervical cancer who underwent robotic or vaginal radical trachelectomy at Canadian cancer centers with the highest volumes of radical trachelectomy procedures. Retrospective multi-centre cohort analysis which includes patients who had surgery between 2006 and 2019. Women with International FIGO 2009 stage IA-IB cervical cancer who underwent radical trachelectomy and lymph node assessment were grouped by surgical approach (vaginal versus robotic surgery). A total of 197 patients were included from 4 regional referral centres. 56 women underwent robotic radical trachelectomy and 141 underwent vaginal radical trachelectomy. All patients had lymph node assessment by a minimally invasive technique. Median age was 32 years, median tumor size was 12 mm, and median depth of invasion was 5 mm. Recurrence-free survival was 97% in both groups at a median follow-up of 57 months. On multivariable analysis, after adjusting for previously chosen confounders (high risk pathologic criteria, tumor size, and LVSI) there was no statistically significant difference in PFS between the 2 groups (HR 2.1, 95%CI 0.3–7.1, p = 0.5). Tumor size larger than 2 cm (HR 9.4, 95%CI 2.8–26, p = 0.003) was the only variable predictive of recurrence. Survival outcomes were excellent in both cohorts of patients undergoing robotic vs. vaginal radical trachelectomy. The surgical approach was not significantly associated with risk of recurrence after adjusting for clinically important confounders. • In carefully selected patients, RRT and VRT are associated with excellent oncologic outcomes. • Tumor size >2 cm is a strong predictor of recurrence. • Further research is necessary to define the role of non-radical fertility sparing surgery in early cervical cancer. [ABSTRACT FROM AUTHOR]

Failure to deliver guideline-concordant treatment may contribute to disparities among Hispanic/Latinx cervical cancer patients. This study investigated the association between survival rates in Hispanic/Latinx subpopulations and the provision of guideline-concordant care. We analyzed patients with primary cervical cancer from 2004 to 2019 (National Cancer Database). We developed nine quality metrics based on FIGO staging (2009). Clinical and demographic covariates were analyzed using Chi-squared tests. Adjusted associations between receipt of guideline-concordant care and races and ethnicities were analyzed using multivariable marginal Poisson regression models. Adjusted Cox proportional hazard models were utilized to evaluate survival probability. A total of 95,589 patients were included. Hispanic/Latinx and Non-Hispanic Black (NHB) populations were less likely to receive guideline-concordant care in four and five out of nine quality metrics, respectively. Nonetheless, the Hispanic/Latinx group exhibited better survival outcomes in seven of nine quality metrics. Compared to Mexican patients, Cuban patients were 1.17 times as likely to receive timely initiation of treatment in early-stage disease (RR 1.17, 95% CI 1.04–1.37, p < 0.001). Puerto Rican and Dominican patients were, respectively, 1.16 (RR 1.16, 95% CI 1.07–1.27, p < 0.001) and 1.19 (RR 1.19, 95% 1.04–1.37, p > 0.01) times as likely to undergo timely initiation of treatment in early-stage disease. Patients of South or Central American (RR 1.18, 95% CI 1.10–1.27, p < 0.001) origin were more likely to undergo timely initiation of treatment in locally advanced disease. Significant differences in survival were identified among our cohort despite the receipt of guideline concordant care, with notably higher survival among Hispanic/Latinx populations. • Disparities in receiving guideline-concordant care among Hispanic/Latinx subpopulations with cervical cancer are frequent. • Hispanic/Latinx populations have higher survival rates despite disparities in receipt of guideline-concordant care. • Differences in receipt of guideline-concordant care and survival are prevalent among Hispanic/Latinx subpopulations. [ABSTRACT FROM AUTHOR]

UCS survival outcome disparities by race have been reported. We aimed to investigate social determinants of health (SDOH) and their relation to survival outcomes in women at two affiliated high-volume institutions serving a racially and economically diverse population. Women diagnosed with stage I-IV UCS treated at St. Paul University Hospital, University of Texas Southwestern (UTSW) Zale Lipshy Pavilion—William P. Clements Jr. University Hospital, and Parkland Memorial Hospital between 1992 and 2022 were eligible. Patients were identified by the local tumor registries; a retrospective study was conducted. The Pearson chi-square test was utilized for categorical variables. OS and PFS were calculated using Kaplan-Meier estimates and compared with the log-rank test. Multivariate Cox models were used to identify independent prognostic factors. All statistical analyses were performed using SAS, version 9.4. Over half of the 218 patients with UCS were NHB. 35% of the patients had stage IV disease. Most HSP and NHB patients had a lower median household income* than Asian/Pacific Islander (API) or NHW (p < 0.001). Stage at diagnosis significantly affected OS (p < 0.001) but not PFS (p = 0.46) in univariate analyses. Accounting for age at diagnosis, insurance, income*, hospital, distance between hospital and home, months from diagnosis to first treatment, stage, and adjuvant therapy, race was significant for OS (p = 0.03) and PFS (p = 0.04). *Median household income by ZIP Code. Racial disparities were seen in median household income. Most SDOH independently analyzed in this study did not affect OS. The complex interaction between race and stage in UCS survival outcomes needs further investigation. • Race predicts progression-free survival on multivariate analyses, with better outcomes in NHB than in NHW patients. • Race predicts overall survival on multivariate analyses, with better outcomes in HSP than in NHW patients. • Stage and adjuvant therapy are prognostic factors for overall survival on univariate and multivariate analyses. [ABSTRACT FROM AUTHOR]

Low-grade-serous-ovarian-carcinoma (LGSOC) is characterized by a high recurrence rate and limited therapeutic options. About one-third of LGSOC contains mutations in MAPK pathway genes such as KRAS/NRAS/BRAF. Avutometinib is a dual RAF/MEK inhibitor while defactinib and VS-4718 are focal-adhesion-kinase-inhibitors (FAKi). We determined the preclinical efficacy of avutometinib±VS-4718 in LGSOC patient-derived-tumor-xenografts (PDX). Whole-exome-sequencing (WES) was used to evaluate the genetic fingerprint of 3 patient-derived LGSOC (OVA(K)250, PERIT(M)17 and A(PE)148). OVA(K)250 tissue was successfully xenografted as PDX into female CB17/lcrHsd-Prkdc/SCID-mice. Animals were treated with either control, avutometinib, VS-4718, or avutometinib/ VS-4718 once daily five days on and two days off through oral gavage. Mechanistic studies were performed ex vivo using avutometinib±defactinib treated LGSOC tumor samples by western blot. WES results demonstrated wild-type KRAS in all 3 LGSOC. OVA(K)250 PDX showed gain-of-function mutations (GOF) in PTK2 and PTK2B genes, and loss-of-heterozygosity in ADRB2, potentially sensitizing to FAK and RAF/MEK inhibition. The combination of avutometinib/ VS-4718 demonstrated strong tumor-growth inhibition compared to controls starting at day 9 (p < 0.002) in OVA(K)250PDX. By 60 days, mice treated with avutometinib alone and avutometinib/VS-4718 were still alive; compared to median survival of 20 days in control-treated mice and of 35 days in VS-4718-treated mice (p < 0.0001). By western-blot assays exposure of OVA(K)250 to avutometinib, FAKi defactinib and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-ERK. Avutometinib, and to a larger extent its combination with FAK inhibitor VS-4718, demonstrated promising in vivo activity against a KRAS wild-type LGSOC-PDX. These data support the ongoing registration-directed study (RAMP201/NCT04625270). • Low grade serous ovarian carcinoma (LGSOC) has a poor response to chemotherapy compared to high grade. • The MAPK pathway is critical in the pathogenesis of LGSOC. • Avutometinib is an inhibitor of MAPK pathway and defactinib is a FAK inhibitor. • Avutometinib, combined with defactinib, show promising preclinical activity for low grade serous ovarian carcinoma. [ABSTRACT FROM AUTHOR]

We investigated whether pretreatment systemic inflammatory markers are associated with survival outcomes in patients with endometrial cancer (EC). Data from the Japanese Gynecologic Oncology Group 2043 were analyzed. Patients who did not receive chemotherapy or were lost to follow-up were excluded. Associations of pretreatment systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, with progression-free survival (PFS) and overall survival (OS) were analyzed. The optimal NLR, PLR, and HALP score cutoff values for PFS and OS were determined. Survival estimates were calculated and compared using the Kaplan–Meier method and log-rank test. We included 712 patients (median age: 55 [range, 28–74] years; body mass index [BMI]: 21.1 [15.2–38.6] kg/m2). For PFS, optimal NLR, PLR, and HALP score cutoff values were 1.48, 0.017, and 35.52, respectively, and for OS, the values were 1.88, 0.026, and 19.87, respectively. At optimal PFS-related cutoff values, NLR was associated with BMI; PLR with age, BMI, and clinical stage; and HALP score with BMI, clinical stage, and lymph node metastasis. At optimal OS-related cutoff values, NLR was associated with BMI, PLR, and BMI; the HALP score was associated with age and BMI. The HALP score was a prognostic factor for PFS (p = 0.025), while PLR and HALP scores were prognostic factors for OS (both p = 0.028). Pretreatment systemic inflammatory markers are associated with survival outcomes in patients with EC, with the HALP score being a prognostic factor for PFS and OS. • Pretreatment NLR, PLR, and HALP scores were associated with clinical and EC parameters. • NLR is not associated with PFS or OS in EC patients. • PLR is associated with OS in EC patients. • The HALP score is associated with both PFS and OS in patients with EC. [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]

BackgroundAge and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy.MethodsWomen with advanced stage ovarian, primary peritoneal, or fallopian tube cancer were enrolled in a phase III clinical trial. All women had surgical staging and received adjuvant chemotherapy with one of three regimens. Cox proportional hazards models were used to evaluate the relationship between OS with age and race/ethnicity among the study participants.ResultsOne-thousand-eight-hundred-seventy-three women were enrolled in the study. There were 280 minority women and 328 women over the age of 70. Women age 70 and older had a 34% increase risk for death when compared to women under 60 (HR = 1.34; 95% CI 1.16-1.54). Non-Hispanic Black women had a 54% decreased risk of death with the addition of maintenance bevacizumab (HR = 0.46, 95% CI:0.26-0.83). Women of Asian descent had more hematologic grade 3 or greater adverse events and a 27% decrease risk of death when compared to non-Hispanic Whites (HR = 0.73; 95% CI: 0.59-0.90).ConclusionsNon-Hispanic Black women showed a decreased risk of death with the addition of bevacizumab and patients of Asian ancestry had a lower death rate than all other minority groups, but despite these clinically meaningful improvements there was no statistically significant difference in OS among the groups.

To evaluate the survival outcomes and establish a risk stratification system in patients with ovarian yolk sac tumors (OYST). The recurrence-free survival (RFS), disease-specific survival (DSS), and prognostic factors were retrospectively evaluated in 151 OYST patients treated in our hospital between 2006 and 2022. A risk stratification system based on the identified prognostic factors was established. The median follow-up time was 5.1 years, with a 5-year RFS and DSS rate of 75.5% and 91.2%, respectively. FIGO stage III-IV and the interval between treatment and normalization of AFP were two prognostic predictors. Significant differences in RFS and DSS (both P < 0.001) were identified between patients who had normalized AFP ≤ 3 and ≥ 4 cycles of chemotherapy, or among patients who had normalized AFP after ≤2, 3–4, and ≥ 5 cycles of chemotherapy. FIGO stage I – II and stage III–IV were scored as 0 and 2, respectively. AFP normalization ≤2, 3, 4, and ≥ 5 cycles of chemotherapy were scored as 0, 1, 2, and 4, respectively. A total score of 0–1, 2–3, and ≥ 4 were stratified patients into low-risk (96 patients), intermediate-risk (35 patients), and high-risk groups (20 patients), respectively. Patients in three risk stratifications manifested significant differences in both RFS and DSS (P < 0.0001). This risk stratification system based on tumor stage and the interval between treatment and normalization of AFP may help to guide clinical management by dividing OYST patients into three risk groups. [Display omitted] • FIGO stage and the time of AFP normalization were two prognostic predictors for OYST patients. • FIGO stage I – II and stage III–IV were scored as 0 and 2, respectively. • AFP normalization ≤2, 3, 4, and ≥ 5 cycles of chemotherapy were scored as 0, 1, 2, and 4, respectively. • A total score of 0–1, 2–3, and ≥ 4 stratified patients into three groups of distinct risk of relapse and mortality. • Intensity-modulated chemotherapy refers to this risk stratification system may better balance the efficacy and toxicity. [ABSTRACT FROM AUTHOR]

To compare all-cause and cancer-specific mortality between women who underwent fertility-sparing surgery (FSS) versus standard surgery for stage IA and IC epithelial ovarian cancer. Reproductive aged patients (18–45) with stage IA or IC epithelial ovarian cancer diagnosed between 2000 and 2015 were identified in the California Cancer Registry. FSS was defined as retention of the contralateral ovary and the uterus, and standard surgery included at least removal of both ovaries and the uterus. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. Inverse probability of treatment weighting (IPTW) was used to create two groups balanced on covariates of interest. The Kaplan-Meier method and Cox proportional hazards analysis were used to model survival outcomes. Among 1119 women who met inclusion criteria, 390 (34.9%) underwent FSS. IPTW yielded a balanced cohort of 394 women who underwent FSS and 723 women who underwent standard surgery. Among patients who underwent FSS, there were 45 deaths corresponding to an 85.4% (95% confidence interval [CI] 0.79–0.92) 10-year all-cause survival probability, compared to 81 deaths and 86.4% 10-year all-cause survival probability (95% CI 0.83–0.90) among patients who underwent standard surgery. FSS was not associated with increased all-cause mortality (HR 1.04, 95% CI 0.72–1.49) or cancer-specific mortality (HR 1.50, 95%CI 0.97–2.31). Among reproductive-aged patients with early-stage epithelial ovarian cancer fertility-sparing surgery was not associated with an increased risk of death compared to standard surgery. • Fertility-sparing surgery was not associated with an increased risk of all-cause or cancer-specific mortality. • Among those with a higher risk for recurrence cancer specific survival remained high after fertility sparing surgery. • Fertility-sparing surgery is a safe and reasonable option to consider for patients with early-stage epithelial. [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 the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer. The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically. Prespecified PRO analyses focused on disease-related abdominal pain and bloating symptoms (European Organisation for Research and Treatment of Cancer QLQ-OV28), functioning, and health-related quality of life (HRQoL) (QLQ-C30). After 38 months' median follow-up, the OS hazard ratio in the PD-L1-positive population was 0.83 (95% CI, 0.66–1.06; p = 0.13); median OS was not estimable with atezolizumab versus 49.2 months with placebo. The hazard ratio for OS in the ITT population was 0.92 (95% CI, 0.78–1.09; median 50.5 versus 46.6 months, respectively). At week 9, similar proportions of patients in both arms of the neoadjuvant cohort showed ≥10-point improvement from baseline in abdominal pain and bloating, functioning, and HRQoL. In the primary surgery cohort, similar proportions of patients in each arm had improved, stable, or worsened physical and role function and HRQoL from baseline over time. Neither cohort showed differences between arms in treatment-related symptoms or overall side-effect bother. Incorporation of atezolizumab into standard therapy for newly diagnosed ovarian cancer does not significantly improve efficacy or impose additional treatment burden for patients. ClinicalTrials.gov registration: NCT03038100. • IMagyn050 assessed atezolizumab integrated into chemotherapy/bevacizumab for newly diagnosed stage III/IV ovarian cancer. • Overall survival was not significantly improved with atezolizumab in the PD-L1-positive or intent-to-treat populations. • Patient-reported outcomes revealed no additional treatment burden from combining atezolizumab with standard therapy. [ABSTRACT FROM AUTHOR]

BackgroundSuccessfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer. Herein we performed exploratory analyses to examine the relationship between mutations in TP53, the most commonly mutated gene in cancer, with outcomes on GOG-86P.MethodsTP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P.ResultsMutations in TP53 were associated with improved PFS and OS for patients that received bevacizumab as compared to temsirolimus (PFS: HR 0.48, 95% CI 0.31, 0.75; OS: HR: 0.61, 95% CI 0.38, 0.98). By contrast, there was no statistically significant difference in PFS or OS between arms for cases with WT TP53.ConclusionsThis exploratory study suggests that combining chemotherapy with bevacizumab, but not temsirolimus, may enhance PFS and OS for patients whose tumors harbor mutant p53. These data set the stage for larger clinical studies evaluating the potential of TP53 mutational status as a biomarker to guide choice of treatment for endometrial cancer patients. Clintrials.gov: NCT00977574.

We evaluated clinicopathologic parameters of patients with cervical squamous cell carcinoma (SCC) who were treated with initial surgical management and assessed their relation to survival outcomes. Specifically, we evaluated the relation between extent of lymphovascular invasion (LVI) and survival outcomes. All available tumor slides from patients with initially surgically treated cervical SCC were collected from 10 institutions and retrospectively analyzed. Standard clinicopathological parameters, tumor stroma, and extent of LVI were assessed (focal: <5 spaces, extensive: ≥5 spaces). PFS and OS were evaluated using Kaplan–Meier methodology. Univariable and multivariable Cox proportional hazards models were created to determine prognostic survival-related risk factors. A total of 670 tumor samples were included in the analysis. Median age at diagnosis was 47 years (IQR: 38–60), 457 patients (72%) had a 2018 International Federation of Gynecology and Obstetrics (FIGO) stage I tumor, and 155 tumors (28%) were flat and/or ulcerated. There were 303 nonkeratinizing tumors (51%), 237 keratinizing tumors (40%), and 356 histologic grade 2 tumors (61%). Quantifiable LVI was present in 321 cases (51%; 23% focal and 33% extensive). On multivariable analysis for PFS, extensive and focal LVI had worse outcomes compared to negative LVI (HR: 2.38 [95% CI: 1.26–4.47] and HR: 1.54 [95% CI: 0.76–3.11], respectively; P = 0.02). The difference did not reach statistical significance for OS. Presence of LVI is a prognostic marker for patients with cervical SCC. Quantification (extensive vs. focal vs. negative) of LVI may be an important biomarker for oncologic outcome. • Lymphovascular invasion (LVI) independently predicts worse survival outcomes in cervical squamous cell carcinoma (SCC). • Presence of extensive LVI in SCC of the cervix portends worse progression-free survival. • Quantification of LVI in SCC of the cervix should be considered in pathology reports. [ABSTRACT FROM AUTHOR]

Standard surgical treatment of FIGO stage 1B1 cervical cancer is open radical surgery. However, there is increasing evidence that for small tumours a more conservative approach can minimise fertility consequences without impacting on long term oncologic outcomes. The objective of our study is to present survival and obstetric outcomes following extended follow-up for patients who underwent conservative management of small-volume stage 1B1 disease. All patients with FIGO stage 1B1 cancer and estimated tumour volume of <500 mm3 in a loop biopsy specimen treated in Northern Gynaecological Oncology Centre between December 2000 and December 2021, were included in the study. Clinico-pathological and demographic data were collated alongside detailed follow-up and obstetric outcomes in conjunction with primary care and death register. 117 patients underwent conservative surgery for small volume stage 1B1 disease. 58 (49.5%) underwent fertility sparing conservative management with LLETZ while 59 (50.5%) underwent simple hysterectomy. Overall, 95% (111/117) of the patients underwent bilateral pelvic lymphadenectomy and 1 positive node was identified. There was no death related to cervical cancer and 1 recurrence identified during a median follow up of 8.5 years (1−20). 17 pregnancies have been recorded in patients underwent LLETZ and 17 live babies were born. No second trimester miscarriages were noted and there was one preterm delivery (36 weeks). Non-radical surgery with negative pelvic lymphadenectomy for smallvolume stage 1B1 cervical cancer ensures excellent survival without compromising obstetric outcomes. Should these results be verified by the ongoing prospective studies, radical surgery for these patients may be avoided. • Non-radical surgery in patients with small volume FIGO stage 1B1 cervical cancer demonstrate excellent oncological outcomes. • The recurrence rate after conservative surgical management was 0.9% and no deaths due to cervical cancer were recorded. • 30% of the patients treated with LLETZ achieved pregnancy, all of which resulted in live births. • No second trimester miscarriages were noted and there was only one preterm delivery in 36 weeks. [ABSTRACT FROM AUTHOR]

As vulvar and vaginal cancers are rare malignancies, treatment is extrapolated from the cervical cancer field. Further studies are necessary to evaluate whether surgery, radiotherapy (RT), or combined chemoRT is most beneficial. A retrospective chart review was conducted on patients diagnosed with vulvar or vaginal cancer in 2000–2017. Descriptive statistics was used to summarize demographic factors. Kaplan-Meier curves, log-rank tests, multivariate analysis with hazard ratios (HR) were conducted to compare survival outcomes, including overall survival (OS), disease-free survival, and cancer-specific survival, between surgery, RT, and chemoRT. This study included 688 patients with either vulvar (n = 560, 81%) or vaginal cancer (n = 128, 19%). Median age of diagnosis was 68 (27–98) years. In multivariate survival analysis, vulvar cancer was associated with more likelihood of death (HR: 1.50, p = 0.042) compared to vaginal cancer. For patients who received definitive RT, median OS was 63.8 months with concurrent chemotherapy vs. 46.3 months without for vulvar cancer (p = 0.75); for vaginal, median OS 100.4 with chemotherapy vs. 66.6 months without (p = 0.31). For vulvar cancer patients who received RT (n = 224), adding chemotherapy (n = 100) was not associated with statistically significant OS improvement (HR: 0.989, p = 0.957). Similarly, vaginal cancer patients who received chemoRT (n = 51) did not have significant OS benefit (HR: 0.720, p = 0.331) over patients who received RT (n = 49). In this retrospective study, chemoRT was not associated with significant improvements in survival compared to RT in vulvar or vaginal cancer. Future studies investigating novel therapies to treat these cancers are needed to improve patient outcomes. • Retrospective study evaluating survival outcomes of patients with vulvar and vaginal cancers. • Multivariate analysis of prognostic factors for overall survival, disease-free survival, and cancer-specific survival. • No statistically significant difference in overall survival between radiotherapy with and without concurrent chemotherapy. • Age, prior surgery, and stage of disease are independent prognostic factors for survival. [ABSTRACT FROM AUTHOR]

We sought to provide a contemporary report on stage IVB endometrial carcinoma (2009 FIGO criteria) and applied the 2023 FIGO staging criteria to this population. Retrospective review of patients who underwent cytoreduction for stage IVB endometrial carcinoma (2009 FIGO criteria) from 2014 to 2020 was performed. Demographics, clinicopathologic factors, and outcomes were recorded. Disease burden and distribution were determined by imaging, operative notes, and pathology reports. Patients were re-staged according to 2023 FIGO staging criteria. Categorical variables were compared using χ2 or Fisher's exact test, and Kaplan-Meier curves compared survival outcomes using the log-rank test. Eighty-eight cases were included. Most patients (63.6%) were not suspected to have stage IVB (2009 FIGO criteria) disease prior to surgery. Seventy-two percent of patients underwent primary cytoreduction, and 12 (19%) were suboptimal. Median progression-free survival (PFS) was 12 months (95% CI 10–16 months), and median overall survival (OS) was 38 months (95% CI 19–61 months). Degree of cytoreduction (p = 0.0101) and pelvic-confined metastatic disease (p = 0.0149) were significant prognostic factors, while distant metastases were not associated with worse outcomes. For those patients who underwent primary cytoreduction, number (p = 0.0453) and diameter (p = 0.0192) of tumor deposits were associated with PFS. When 2023 FIGO staging criteria were applied, 58% of patients underwent change in stage, and 8% did not meet criteria for complete staging. PFS was significantly different based on 2023 FIGO staging (p = 0.0307); a trend in OS was also noted (p = 0.0550). Stage IVB endometrial carcinoma (2009 FIGO criteria) encompasses a diverse cohort of patients, where certain clinicopathologic features, tumor burden, and degree of cytoreduction are associated with outcomes. The 2023 FIGO staging criteria significantly improves our ability to risk-stratify patients. • FIGO stage IVB endometrial cancer comprises a heterogenous patient population with varying outcomes. • Cytoreduction degree and pelvic-confined disease are prognostic; distant metastases are not associated with worse survival. • Patients who were down-staged following application of the new FIGO 2023 staging criteria had improved survival. • Future conversations are needed regarding contemporary surgical staging and role of lymphadenectomy for advanced disease. [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]

Robotic-assisted laparoscopy (RALS) has gained widespread acceptance in the field of gynecological oncology. However, whether the prognosis of endometrial cancer after RALS is superior to conventional laparoscopy (CLS) and laparotomy (LT) remains inconclusive. Therefore, the aim of this meta-analysis was to compare the long-term survival outcomes of RALS with CLS and LT for endometrial cancer. A systematic literature search was conducted on electronic databases (PubMed, Cochrane, EMBASE and Web of Science) until May 24, 2022, followed by a manual search. Based on inclusion and exclusion criteria, publications investigating long-term survival outcomes after RALS vs CLS or LT in endometrial cancer patients were collected. The primary outcomes included overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and disease-free survival (DFS). Fixed effects models or random effects models were employed to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) as appropriate. Heterogeneity and publication bias were also assessed. RALS and CLS had no difference in OS (HR = 0.962, 95% CI: 0.922–1.004), RFS (HR = 1.096, 95% CI: 0.947–1.296), and DSS (HR = 1.489, 95% CI: 0.713–3.107) for endometrial cancer; however, RALS was significantly associated with favorable OS (HR = 0.682, 95% CI: 0.576–0.807), RFS (HR = 0.793, 95% CI: 0.653–0.964), and DSS (HR = 0.441, 95% CI: 0.298–0.652) when compared with LT. In the subgroup analysis of effect measures and follow-up length, RALS showed comparable or superior RFS/OS to CLS and LT. In early-stage endometrial cancer patients, RALS had similar OS but worse RFS than CLS. RALS is safe in the management of endometrial cancer, with long-term oncological outcomes equivalent to CLS and superior to LT. • It is of great interest to evaluate the long-term safety of minimally invasive surgery in gynecologic oncology. • RALS and CLS had equivalent survival outcomes for endometrial cancer. • Compared with laparotomy, RALS was significantly associated with favorable OS, RFS and DSS in endometrial cancer. • Providing non-inferior survival outcomes to CLS and LT, RALS is oncologically safe for endometrial cancer. [ABSTRACT FROM AUTHOR]

Malignancy-associated bowel obstruction (MBO) is a potential sequela of advanced gynecologic cancers, adversely impacting both quality of life and prognosis. The Henry score (HS) was developed in a gastrointestinal cancer-predominant population to predict 30-day mortality. We aim to characterize MBO in gynecologic cancers and assess the utility of the HS in this population. This is a retrospective review of patients with gynecologic cancer and MBO admitted to a single academic institution from 2016 to 2021. The primary outcome is to characterize malignant small and large bowel obstructions in primary and recurrent gynecologic cancer using readmission and mortality rates. Secondary outcomes are to assess the Henry score and inpatient MBO management. 179 patients totaling 269 were admissions identified, most commonly affecting patients with ovarian cancer. The majority (89.4%) were managed non-operatively while 10.6% were managed surgically. No significant differences were observed in survival for medical versus surgical management. Thirty-day mortality increased with increasing HS (0%, 0–1; 14.3%, 2–3; 40.9%, 4–5). Over 1/3 (34.1%) of patients were readmitted for recurrent or persistent MBO. Goals of care conversations were documented for 56.8% of patients with HS 4–5. Mortality rates across the entire cohort were high—20.1% and 60.9% had died by 1 and 6 months, respectively. Survival rates following an initial MBO admission are poor. The HS has utility in gynecologic cancers for assessing 30-day mortality and may be a useful tool to aid in the management and counseling of patients with gynecologic cancer and MBO. • Higher Henry scores were associated with increased 30-day mortality for this cohort of solely gynecologic cancer patients • There was no statistically significant difference in overall survival for surgical versus medical management of MBO • Median survival was poor for patients with MBO during first line treatment and in the recurrent cancer setting [ABSTRACT FROM AUTHOR]

PurposePrior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival.MethodsData from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery.ResultsUse of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend

Gestational Trophoblastic Neoplasia (GTN) is a rare group of malignant placental-related tumours requiring systemic anti-cancer treatment. Leptomeningeal disease (LMD) related to GTN is not well reported with no consensus in optimal treatment. We offer recommendations for management of these patients. We discuss five patients with GTN who presented with features of LMD and were diagnosed with gadolinium-enhanced MRI brain, all of whom received low dose induction etoposide-cisplatin (EP) followed by either EP-etoposide, methotrexate (CNS) and actinomycin-D (EMA) or EMA(CNS)-cyclophosphamide and vincristine (CO). Four out of the five patients additionally received intrathecal methotrexate. Four patients had complete hCG response to first line multi-agent chemotherapy, one patient required second line paclitaxel, cisplatin alternating with paclitaxel, etoposide (TP/TE), where paclitaxel was substituted with nab-paclitaxel due to anaphylaxis, followed by hysterectomy. One of the four initial complete hCG responders relapsed in the lung requiring further systemic treatment with subsequent lobectomy. Patient reported outcomes indicate persistent neurological symptoms are mild and do not affect functionality and quality of life. With a follow-up range of 2–6 years, all five patients remain cured demonstrating excellent survival outcomes with the avoidance of whole-brain radiotherapy in all cases. • Leptomeningeal disease (LMD) due to GTN is rarely reported, and consequently there is no consensus for optimal management. • Diagnostic workup should include gadolinium-enhanced MRI brain +/− completion MRI spine. • We recommend low-dose induction EP followed by platinum-based chemotherapy and intrathecal MTX. • Whole brain radiotherapy can be avoided and should not be recommended. • We report a 100% cure rate of all five of our patients with GTN with LMD. [ABSTRACT FROM AUTHOR]

The aim of the present analysis was to explore the efficacy of Bevacizumab (Bev) on survival outcome in advanced low grade serous ovarian cancer (LGSOC) both in first line and in recurrent setting. In retrospective observational multicenter study, we described the outcome of LGSOC patients enrolled in the MITO 22 study and treated with chemotherapy (CT) with or without Bev. Patients receiving Bev in first-line or in recurrence were considered and compared with patients receiving CT alone (stage III and IV in first line; platinum based-CT in second line). Descriptive and survival analyses were performed for each group. Out of 128 patients included in MITO 22, 46 LGSOC patients receiving Bev in first line setting or at the time of first recurrence were identified. In first line, 30 patients received Bev + CT and 65 CT alone and the median PFS were 47.86 months (95% CI: 31.48 - NR) and 22.63 months (95% CI 15–39.24) (p -value 0.0392), respectively. In the recurrent setting, 16 patients who received Bev + CT were compared to 33 women treated with platinum-based CT alone. Median PFS were 37.1 months (95% CI: 13.42–40.56) and 11.22 months (95% CI: 8.26–15.63) (p-value 0.013), respectively. Our study suggests that Bev might be effective in LGSOC both at diagnosis and at the time of relapse. These data warrants further studies. • Bevacizumab shows antitumor activity in LGSC at the time of diagnosis and at the time of first recurrence. • A total of 46 LGSC patients received Bevacizumab in combination with CT and were compared to patients treated with CT alone. • A statistically significant advantage in terms of PFS were reported in the group of patients treated with Bev + CT. [ABSTRACT FROM AUTHOR]

HER2 status is not routinely evaluated in endometrioid endometrial cancer (E-EMCA), though it is frequently overexpressed or amplified in high grade E-EMCA and uterine serous carcinoma. Defining characteristics and survival outcomes of HER2+ E-EMCA could reveal subsets of patients who may benefit from targeted therapies. 2927 E-EMCA tumors from the Caris Life Sciences database were analyzed by next-generation sequencing and whole exome sequencing, whole transcriptome sequencing, and immunohistochemistry for molecular and genomic features in a CLIA/CAP-certified laboratory (Caris Life Sciences, Phoenix, AZ). HER2 status was determined by transcriptomic cutoff extrapolated from uterine serous carcinoma. The relationship between HER2 status and patient outcomes was determined by Kaplan-Meier analysis. HER2 positivity was detected in 5.47% of E-EMCA. Differences in molecular alterations based on HER2 status were most apparent in microsatellite stable (MSS) tumors, which displayed increased TP53 mutations and loss of heterozygosity (LOH) and decreased PTEN and CTNNB1 mutations. HER2+ tumors had increased immune checkpoint gene expression and immune cell infiltration, particularly among MSS tumors. All HER2+ tumors displayed increased MAPK pathway activation scores (MPAS) and patients with HER2+ tumors experienced worse overall survival. HER2 positivity in E-EMCA corresponds with a unique molecular landscape, particularly in MSS tumors. HER2+ tumors are also associated with increased MAPK pathway activation and exhibit features of a more active immune microenvironment. These findings suggest a potential benefit of HER2 and MAPK targeted therapies as well as immunotherapies in this patient population. • HER2+ is present in 5.47% of endometrioid endometrial cancer (E-EMCA) and is associated with microsatellite stable disease. • HER2+ disease is a negative prognostic factor in E-EMCA. • HER2+ microsatellite stable E-EMCA displays increased TP53 mutations and reduced PTEN and CTNNB1 mutations. • HER2+ E-EMCA possesses many features of a more active immune microenvironment and MAPK pathway activation. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze morbidity and survival after pelvic exenteration for gynecologic malignancies and evaluate prognostic factors influencing postoperative outcome. We retrospectively reviewed all patients who underwent a pelvic exenteration at the departments of gynecologic oncology of three tertiary care centers in the Netherlands, the Leiden University Medical Centre, the Amsterdam University Medical Centre, and the Netherlands Cancer Institute, during a 20-year period. We determined postoperative morbidity, 2- and 5-year overall survival (OS) and 2- and 5-year progression free survival (PFS), and investigated parameters influencing these outcomes. A total of 90 patients were included. The most common primary tumor was cervical cancer (n = 39, 43.3%). We observed at least one complication in 83 patients (92%). Major complications were seen in 55 patients (61%). Irradiated patients had a higher risk of developing a major complication. Sixty-two (68.9%) required ≥1 readmission. Re -operation was required in 40 patients (44.4%). Median OS was 25 months and median PFS was 14 months. The 2-year OS rate was 51.1% and the 2-year PFS rate was 41.5%. Tumor size, resection margins and pelvic sidewall involvement had a negative impact on OS (HR = 2.159, HR = 2.376, and HR = 1.200 , respectively). Positive resection margins and pelvic sidewall involvement resulted in decreased PFS (HR = 2.567 and HR = 3.969 , respectively). Postoperative complications after pelvic exenteration for gynecologic malignancies are common, especially in irradiated patients. In this study, a 2-year OS rate of 51.1% was observed. Positive resections margins, tumor size, and pelvic sidewall involvement were related to poor survival outcomes. Adequate selection of patients who will benefit from pelvic exenteration is important. • Pelvic exenteration is a rare surgical procedure with a 2-year OS rate of 51.1%. • Postoperative complications after pelvic exenteration are common, especially in irradiated patients. • Positive resections margins, tumor size, and pelvic sidewall involvement are related to poor survival outcomes. • Adequate selection of patients who will benefit from pelvic exenteration is of utmost importance. [ABSTRACT FROM AUTHOR]

We investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer. We conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006–9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded. Among 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7–61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%–56.2%). Median OS was 81.3 months (95% CI: 68.9–103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P <.001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P =.003). Intrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS. • Intrathoracic surgery for advanced ovarian cancer is both safe and feasible. • Complete gross resection of ovarian cancer can be obtained in patients with intrathoracic disease. • Primary cytoreductive surgery with intrathoracic procedures can offer excellent survival outcomes in select patients. [ABSTRACT FROM AUTHOR]

To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%–81.7% for patients meeting GOG-249 inclusion criteria, 40.2%–81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%–75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results. • Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogenous cohorts of patients. • 5-year survival was 60–82% for patients meeting GOG-249 criteria, 40–82% for PORTEC-3, and 18–75% for GOG-258 criteria. • The variation in expected survival for subsets of patients may result in underpowered studies or misleading results. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the relationship between molecular subtype, intraperitoneal (IP) disease dissemination patterns, resectability, and overall survival (OS) in advanced high-grade serous ovarian cancer (HGSOC).MethodsPatients undergoing primary surgery for stage III-IV HGSOC at Mayo Clinic from 1994 to 2011 were categorized into three IP disease dissemination patterns: upper abdominal or miliary; lower abdominal; and pelvic. Residual disease was defined as 0 (RD0), 0.1-0.5, 0.6-1.0, or >1 cm. Molecular subtypes were derived from Agilent 4x44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES).ResultsOperative and molecular data was available for 334 patients. Median OS was shorter in patients with MES compared to non-MES subtypes (34.2 vs 44.6 months; P = 0.009). Patients with MES subtype were more likely to have upper abdominal/miliary disease compared to non-MES subtype (90% vs. 72%, P

Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma. This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall survival. There were 737 patients included. Most patients had Stage IA disease (75%), 49% of which had no myometrial invasion. Only 164 (24%) tumors had lymphatic/vascular space invasion. Adjuvant treatment varied: 22% received no adjuvant therapy, 17% had chemotherapy alone, 19% had cuff brachytherapy, 35% had cuff brachytherapy with chemotherapy, and 6% underwent pelvic radiation. Adjuvant treatment was significantly associated with a decreased risk of recurrence (p = 0.04). Compared with no adjuvant therapy, patients who received brachytherapy or brachytherapy/chemotherapy had improved recurrence-free survival (HR 0.59, 95% CI 0.40–0.86; HR 0.65, 95% CI 0.49–0.88, respectively) and overall survival (HR 0.53, 95% CI 0.35–0.79; HR 0.49, 95% CI 0.35–0.69, respectively). Improved survival with brachytherapy and brachytherapy/chemotherapy persisted on multivariable analyses. Chemotherapy alone was also associated with improved overall survival compared with no adjuvant treatment (HR 0.55, 95% CI 0.37–0.81). Adjuvant therapy was associated with a decreased risk of recurrence relative to observation alone. Adjuvant cuff brachytherapy with and without chemotherapy was associated with improved survival outcomes in patients with early stage uterine serous carcinoma. • Treatment approaches for patients with early stage uterine serous carcinoma vary. • Use of adjuvant therapy is associated with decreased risk of recurrence relative to surveillance. • Vaginal cuff brachytherapy both with and without chemotherapy is associated with improved survival outcomes. • Patients with early stage uterine serous carcinoma should be offered vaginal cuff brachytherapy. [ABSTRACT FROM AUTHOR]

Determining whether cytoreductive surgery (CRS) is feasible in patients with advanced ovarian cancer and whether extensive surgery is justified is challenging. Accurate patient selection for CRS based on pre- and peroperative parameters will be valuable. The aim of this study is to assess the association between the extent of peritoneal metastases as determined during surgery and completeness of interval CRS and survival. This single-center observational cohort study included consecutive patients with newly diagnosed stage III-IV epithelial ovarian cancer who received neoadjuvant chemotherapy and underwent interval CRS. The 7 Region Count (7RC) was recorded during surgical exploration to systematically quantify the extent of peritoneal metastases. Logistic regression analysis was performed to predict surgical outcomes, and Cox regression analysis was done for survival outcomes. A total of 316 patients were included for analyses. The median 7RC was 4 (interquartile range: 2–6). Complete CRS was performed in 58%, optimal CRS in 30%, and incomplete CRS in 12% of patients. A higher 7RC was independently associated with lower odds of complete or optimal CRS in multivariable analysis (odds ratio [OR] = 0.45, 95% confidence interval [CI]: 0.33–0.63, p < 0.001). Similarly, a higher 7RC was independently associated with worse progression-free survival (hazard ratio [HR] = 1.17, 95% CI 1.08–1.26, p < 0.001) and overall survival (HR = 1.14, 95% CI 1.04–1.25, p = 0.007). The extent of peritoneal metastases, as expressed by the 7RC during surgery, is an independent predictor for completeness of CRS and has independent prognostic value for progression-free survival and overall survival in addition to completeness of CRS. • 7 Region Count (7RC) is a concise assessment tool to systematically quantify the extent of peritoneal metastases. • Extent of peritoneal metastases, as expressed by the 7RC, is an independent predictor for completeness of interval CRS. • The 7RC has independent prognostic value for progression-free and overall survival in addition to completeness of CRS. [ABSTRACT FROM AUTHOR]

Cervical adenocarcinoma (CAC) comprises a heterogeneous group of tumors that are not universally associated with HPV infection. As has been shown in other organs, it is becoming increasingly apparent that HPV status significantly affects the prognosis of adenocarcinoma. We conducted a systematic review and meta-analysis to investigate the infection status of high-risk Human papillomavirus (hrHPV) in CAC and evaluate its impact on the survival of patients. PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to May 1st, 2022. Data on HPV infection status and survival outcomes were evaluated using STATA 16.0. Seventy-one studies with 11,278 participants were included in HPV infection analysis and eight studies with 1099 participants were included in prognosis analysis. The HPV infection rate (including high-risk and low-risk) and hrHPV infection rate in CAC were 75% (95% CI 0.70–0.80, 6978 participants) and 75% (95% CI 0.70–0.81, 4906 participants), respectively. HPV-16 and -18 were the most common HPVs in CAC, with pooled infection rates of 37% (95% CI 0.33–0.41, 7848 participants) and 34% (95% CI 0.30–0.38, 7730 participants), respectively. hrHPV infection was associated with better overall survival (HR 0.23, 95% CI 0.11–0.47, 1013 participants), better disease-free survival (HR 0.18, 95% CI 0.07–0.43, 292 participants), better progression-free survival (HR 0.20, 95% CI 0.08–0.47, 271 participants) and less recurrence (RR 0.30, 95% CI 0.07–0.43, 181 participants). HPV infection rates were high in CAC. HPV-16 and -18 had the highest infection rates in CAC. However, hrHPV infection was associated with better survival and less recurrence. Future studies should clarify the relationship between hrHPV infection and other prognostic factors and make reasonable treatment strategies for CAC with different HPV status. Protocol registration: CRD42022319390. • The HPV infection rates in cervical carcinoma are high. • HPV-16 and -18 are high-risk HPVs with the highest infection rates in cervical carcinoma. • High-risk HPV infection is associated with better survival and less recurrence in cervical carcinoma. [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]

Patients with advanced epithelial ovarian cancer (EOC) alive without progression at a landmark time-point of 10 years from diagnosis are likely cured. We report the proportion of patients with Stage III EOC who were long-term disease-free survivors (LTDFS≥10 years) following either intraperitoneal (IP) or intravenous (IV) chemotherapy as well as the predictors of LTDFS. Data from 3 mature NRG/GOG trials (104, 114, 172) were analyzed and included demographics, clinicopathologic details, route of administration, and survival outcomes of patients living ≥10 years assessed according to the Kaplan-Meier method. Cox regression survival analysis was performed to evaluate independent prognostic predictors of LTDFS. Of 1174 patients randomized, 10-year overall survival (OS) was 26% (95% CI, 23–28%) and LTDFS ≥10 years was 18% (95% CI, 16–20%). Patients with LTDFS ≥10 years had a median age of 54.6 years (p < 0.001). Younger age (p < 0.001) was the only independent prognostic factor for LTDFS≥10 years on multivariate Cox analysis. Approximately 18% of patients were LTDFS ≥10 years. They form the tail end of the survival curve and are likely cured. Our results provide a comparative benchmark to evaluate the impact of PARP inhibitors in 1st line maintenance trials on survival outcomes. • Long term survivors with advanced ovarian cancer are uncommon and include patients alive with or without disease recurrence • Clinical trials don't report the patients who are long term disease free survivors (LTDFS ≥10 years) and likely cured • Almost 20% of patients were LTDFS ≥10 years in GOG trials of intravenous vs intraperitoneal chemotherapy • Apart from younger patient age at diagnosis there were no other factors associated with LTDFS ≥10 years [ABSTRACT FROM AUTHOR]

The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007–12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. We identified 1093 cases for analysis—715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03–149.51) and 54.98 months (range, 0.03–145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9–90.4%) and 89% (95% CI: 84.9–92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47–1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6–97.2%) and 96.6% (95% CI: 93.8–98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43–1.52; P = 0.5). This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS. • Minimally invasive (MIS) compared to open radical hysterectomy did not compromise outcomes in early-stage cervical cancer • Our findings are contrary to those of the Laparoscopic Approach to Cervical Cancer (LACC) trial favoring laparotomy • As the NCCN has changed guidelines in accordance with LACC, women may miss out on the benefits of MIS radical hysterectomy [ABSTRACT FROM AUTHOR]

Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. Our study highlighted that SNM provides similar long-term oncologic outcomes than LND. • Sentinel node mapping (SNM) allows an accurate detection of nodal involvement. • Low volume disease accounts for about 50% of nodal disease diagnosed with SNM. • Backup lymphadectomy does not improve oncologic outcomes in comparison to SNM alone. [ABSTRACT FROM AUTHOR]

In patients with recurrent/advanced endometrial cancer who have progressed after first-line treatment, there are a lack of real-world data on treatment patterns, characteristics, and survival outcomes. A novel study was conducted to determine real-world treatment patterns and outcomes in England. This non-interventional study used routine, administrative health data from the National Cancer Registration and Analysis Service in England to identify patients diagnosed with recurrent/advanced endometrial cancer between 1 January 2013 and 31 December 2018, inclusive. A cohort of patients who progressed to second-line treatment were identified as the 'immune checkpoint inhibitor-eligible second-line' cohort. The co-primary objectives were to summarise baseline demographics, disease characteristics, treatments received, and depict overall survival and time-to-next-treatment (a proxy for progression-free survival) from the start of second-line therapy using Kaplan–Meier methodology. Overall, 12,058 patients were diagnosed with recurrent/advanced endometrial cancer; 999 patients were included in the immune checkpoint inhibitor-eligible second-line cohort and 77.9% (778 of 999) had advanced disease (Stage III/IV). The most common treatments received at second-line were carboplatin plus paclitaxel (27.9%), carboplatin plus liposomal doxorubicin (14.1%), liposomal doxorubicin monotherapy (13.0%), and paclitaxel monotherapy (11.6%). From initiation of second-line therapy, median (95% confidence interval) overall survival was 10.3 months (9.2–11.1), and median time-to-next-treatment was 7.7 months (7.1–8.2). Treatments received in the relapsed setting were variable and survival outcomes poor at second-line, highlighting the need for standard of care guidance and innovative therapies to improve patient outcomes in England and in countries with similar treatment patterns. GSK. • Analysis of recurrent/advanced endometrial cancer treatment patterns and outcomes in England • Results demonstrate the highly variable treatment patterns in the relapsed setting. • Clinical outcomes (median OS and time-to-next treatment) were poor at second-line. • Results highlight the need for standard of care guidance and innovative therapies. [ABSTRACT FROM AUTHOR]

PurposeWe examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC).MethodsWe reviewed data from FIGO stage I-IV epithelial ovarian cancer patients who participated in 12 prospective randomized GOG protocols. Proportional hazards models were used to compare progression-free survival (PFS) and overall survival (OS) by cell type (clear cell versus serous).ResultsThere were 10,803 patients enrolled, 9531 were eligible, evaluable and treated with platinum, of whom 544 (6%) had OCCC, 7054 (74%) had SOC, and 1933 (20%) had other histologies and are not included further. In early stage (I-II) patients, PFS was significantly better in OCCC than in SOC patients. For late stage (III, IV) patients, OCCC had worse PFS and OS compared to SOC, OS HR=1.66 (1.43, 1.91; p

BackgroundBrivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients.MethodsEligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response.ResultsOf 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1-20). Seven (25%) patients had PFS >6months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 1.3%-20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1-4.4). The median overall survival was 7.9months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension.ConclusionsBased on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability.

ObjectiveGynecologic Oncology Group (GOG) 177 demonstrated that addition of paclitaxel to a backbone of adriamycin/cisplatin improves overall survival (OS) and progression-free survival (PFS) for patients with advanced or recurrent endometrial cancer. Using patient specimens from GOG-177, our objective was to identify potential mechanisms underlying the improved clinical response to taxanes. Stathmin (STMN1) is a recognized poor prognostic marker in endometrial cancer that functions as a microtubule depolymerizing protein, allowing cells to transit rapidly through mitosis. Therefore, we hypothesized that one possible mechanism underlying the beneficial effects of paclitaxel could be to counter the impact of stathmin.MethodsWe analyzed the expression of stathmin by immunohistochemistry (IHC) in 69 specimens from patients enrolled on GOG-177. We also determined the correlation between stathmin mRNA expression and clinical outcomes in The Cancer Genome Atlas (TCGA) dataset for endometrial cancer.ResultsWe first established that stathmin expression was significantly associated with shorter PFS and OS for all analyzed cases in both GOG-177 and TCGA. However, subgroup analysis from GOG-177 revealed that high stathmin correlated with poor PFS and OS particularly in patients who received adriamycin/cisplatin only. In contrast, there was no statistically significant association between stathmin expression and OS or PFS in patients treated with paclitaxel/adriamycin/cisplatin.ConclusionsOur findings demonstrate that high stathmin expression is a poor prognostic marker in endometrial cancer. Paclitaxel may help to negate the impact of stathmin overexpression when treating high risk endometrial cancer cases.