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We aimed to explore the supportive care needs of ovarian cancer patients and their caregivers before and after the first cancer recurrence, the top unmet needs after recurrence, and the relationship between patient and caregiver needs at recurrence. Participants were 288 patients and 140 caregivers from the Australian Ovarian Cancer Study-Quality of Life (AOCS-QoL) cohort. They completed Supportive Care Needs Surveys (patients: SCNS-SF34, caregivers: SCNS-P&C44) every three-to-six months for up to two years. Linear mixed models tracked changes in needs over time. We calculated the percentage reporting moderate-to-high needs after recurrence. LASSO regression analysed patient-caregiver need relationships. Both patients' and caregivers' psychological, health system/service and information needs increased with recurrence along with patients' support and physical needs. These remained stable at nine months after recurrence. Dominant patient needs post-recurrence included 'fear of recurrence' (38%) and 'concerns about the worries of those close' (34%), while caregivers expressed 'concerns about recurrence' (41%) and 'recovery of the patient not turning out as expected' (31%). Among dyads, when patients had 'fears about the cancer spreading' this was associated with caregivers having a need for help with 'reducing stress in the patients' life'; when caregivers had concerns about 'recurrence' this was associated with patients needing help with 'uncertainty about the future' and 'information about things they can do to help themselves'. Recurrent ovarian cancer intensifies disease-related fears and concerns for patients and loved ones. Addressing dyadic concerns through supportive care interventions may enhance cohesion during the challenging journey of recurrent disease. [Display omitted] • Ovarian cancer recurrence imposes enduring psychological, service and information needs for patients and caregivers. • Patients additionally experience an increase in physical and care needs with recurrence. • At recurrence, the most prevalent unmet need for both patients and caregivers revolved around fear of cancer metastasis. • Coupled with this fear is caregivers' desire to alleviate patient stress and patient uncertainty and need for information. • Patients also worry about loved ones, while caregivers struggle with adjusting expectations about patient recovery. [ABSTRACT FROM AUTHOR]

Among cervical adenocarcinomas, well-differentiated gastric adenocarcinoma of the uterine cervix (WD-GAS), previously termed adenoma malignum (minimal deviation adenocarcinoma) is not well understood. Because of its rarity and difficulty in diagnosis, there is no standard care for WD-GAS. Thus, we conducted the first multicenter retrospective study on WD-GAS to clarify prognostic factors for long-term survival and recurrence. Patients diagnosed with WD-GAS at eight hospitals participated in this multi-center study. Overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Additionally, OS between the early and advanced FIGO stage groups were compared with the log-rank test. Cox regression analysis was conducted to identify significant factors associated with recurrence-free survival (RFS). A total of 73 patients from eight hospitals in South Korea were included in the analysis. The median follow-up period was 44.8 months, and all patients underwent curative surgical intervention as the primary treatment. Recurrence was observed in 17 patients (23.3%). Ten patients had locoregional recurrence, four patients had distant metastasis, and three patients presented with both locoregional recurrence and distant metastasis. The Cox regression analysis identified several statistically significant factors associated with RFS, including vaginal invasion (VI), parametrial invasion (PMI), resection margin (RM), and nodal and lymphovascular invasion (LVI). When considering these five factors together, patients without any of the factors exhibited recurrence-free survival (RFS) of 97.0% at three years and those with more than one of these factors had a 3-year RFS of 65.4% (P < 0.001). WD-GAS showed relatively high locoregional recurrence rate. Positive PMI, VI, RM, nodal involvement, and LVI were associated with a significant increase in recurrence or distant metastasis rates. [Display omitted] • WD-GAS showed relatively high locoregional recurrence rate, as compared to other cervical adenocarcinomas. • Positive PMI and RM, vaginal and nodal invasion, and LVI were significantly associated with decreased RFS. • Patients with any of risk factors exhibited lower 3-year RFS than those with none (69.0% vs. 97.5%, P < 0.001). [ABSTRACT FROM AUTHOR]

The prognostic significance of positive peritoneal cytology in endometrial cancer has long been debated. In 2009, the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) removed cytology as a staging criterion from the endometrial cancer staging system. However, there is still evidence that positive peritoneal cytology may decrease survival among patients with endometrial cancer. The aim of this study was to determine the prognostic significance of positive peritoneal cytology among the different molecular subgroups. This study included patients with endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Bern University Hospital, Switzerland, with molecular classification of the primary tumor and peritoneal cytology performed. A total, 250 patients with endometrial cancer were enrolled. Peritoneal cytology was assessed in 206 patients, of whom 24% were positive: 25% of the POLE mut, 16% of the MMRd, 41% of the p53abn, and 24% of the NSMP cases. The mean follow-up was 128.7 months. Presence of positive peritoneal cytology was associated with significantly decreased mean recurrence-free and overall survival in patients with p53abn (p =.003 and p =.001) and NSMP (p =.020 and p =.049) endometrial cancer. In multivariable Cox regression analysis, positive peritoneal cytology remained an independent predictor of recurrence (p =.033) and death (p =.008) in p53abn endometrial cancer patients. Positive peritoneal cytology is associated with worse oncologic outcomes in NSMP and p53abn endometrial cancer and remains an independent predictor of recurrence and death in patients with p53abn endometrial cancer. • Patients with p53abn endometrial cancer showed the highest rate of positive peritoneal cytology. • Positive peritoneal cytology is associated with worse oncological outcome in NSMP and p53abn endometrial cancer patients. • In women with p53abn endometrial cancer, positive peritoneal cytology is an independent predictor of recurrence and death. [ABSTRACT FROM AUTHOR]

The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the non‑platinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival. • The impact of platinum doublet for platinum-sensitive treatment on PARP inhibitor/platinum resistance has been questioned. • There was no difference in the development of PARP/platinum resistance between the different platinum doublets. • Further study is needed to better understand mechanisms of resistance to PARP inhibitors and platinum. [ABSTRACT FROM AUTHOR]

To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence. • Many patients are not adherent to NCCN surveillance guidelines at time of recurrence detection. • Physical exam is an important for detecting uterine cancer recurrence. • Non-NCCN directed imaging detected almost half of asymptomatic recurrences. • Asymptomatic recurrence is detected earlier in patients who adhere to NCCN posttreatment surveillance guidelines. [ABSTRACT FROM AUTHOR]

Aberrant β-catenin distribution has been theorized as a predictive biomarker for recurrence in early stage, low grade endometrioid endometrial cancer. This retrospective single-institution cohort study reviewed 410 patients with endometrial cancer from May 2018 to May 2022. Only endometrioid histology was included. Demographic and clinicopathological data were collected from the medical records. Univariate and multivariate logistic regressions, and sensitivity analyses for early stage, low grade and no specific molecular profile (NSMP) tumors were performed. 297 patients were included for analysis. Most patients were over 60 years old, White, and with a BMI >30 and early stage low grade disease. Aberrant β-catenin distribution was found in 135 patients (45.5%) and wild type membranous β-catenin distribution in 162 (54.5%). While TP53 mutation correlated with endometrial cancer recurrence in this cohort (OR = 4.78), aberrant β-catenin distribution did not correlate in the overall population (OR = 0.75), the early stage low grade cancers (OR = 0.84), or the NSMP group (OR = 1.41) on univariate or multivariate analysis. No correlation between β-catenin distribution and local (OR = 0.61) or distant recurrences (OR = 0.90) was detected. Aberrant β-catenin distribution did not significantly correlate with recurrence in endometrioid endometrial cancer, nor in the early stage, low grade and NSMP sub-cohorts. • Most patients with endometrial cancer have a good prognosis; unfortunately, a subset do recur despite initial treatment. • Prior data has debated the role of β-catenin, a molecule implicated in tumor signaling, in endometrial cancer recurrence. • In our cohort of 297 patients, we found patients with β-catenin were not more likely to recur. • Those with early stage, low grade disease and no molecular specific profile also did not have increased recurrence. [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]

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]

The prognostic impact of intra-operative tumor spillage (ITS) during minimally invasive surgery (MIS) for endometrial cancer (EC) is not well studied. The objective of this study was to determine if there is an association between ITS and EC recurrence. We performed a case-control study of patients with a laparoscopic or robot-assisted hysterectomy with EC on final pathology between 2017 and 2022 and compared those with (case) and without (control) a subsequent EC recurrence. Electronic medical records were reviewed for demographic, intra-operative and pathologic details, and recurrence status. ITS was defined as uterine perforation with a manipulator, presence of extra-uterine tumor after colpotomy or specimen delivery, exposure of uncontained specimen into peritoneum, and/or pathology/operative reports noting specimen fragmentation. Conditional logistic regression was used to determine odds ratios for the association of cancer recurrence with ITS. We adjusted for >50% myoinvasion, tumor size, and adjuvant treatment. 1057 patients underwent MIS for EC. Approximately 8% (n = 86) developed recurrent cancer and 172 patients were selected as controls. Twenty percent of recurrent cases (17/86) had ITS compared with 4% of nonrecurrent controls (7/172). When adjusted for tumor size, deep myoinvasion, and adjuvant treatment, patients with ITS had a 5.6 times increased odds (aOR 5.63, 95% CI 1.52–20.86) of recurrence compared to patients without ITS. In patients with EC, we found an association between ITS and cancer recurrence. These findings warrant further investigation to determine if adjuvant therapy or surgical technique should be altered to improve outcomes. • Patients with intraoperative tumor spillage had 5.6 increased odds of recurrence compared to those without spillage • In patients with intraoperative tumor spillage, receiving adjuvant therapy was not associated with rates of recurrence • The most common types of spillage occurred with uterine manipulator perforation or at the time of colpotomy/specimen delivery [ABSTRACT FROM AUTHOR]

Conization plays a therapeutic and diagnostic role in cervical cancer. We conducted a systematic review and meta-analysis to compare the clinical outcomes of patients with cervical cancer who underwent hysterectomy with versus without preoperative cervical conization. In this meta-analysis, we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to May 1, 2022. Eleven studies with 4184 participants were included in this review. There were 2122 patients in the preoperative conization group and 2062 patients in the non-conization group. The meta-analysis showed that disease free survival (DFS) (hazard ratio [HR]: 0.23; 95% CI: 0.12–0.44; 1616 participants; P = 0.030) and overall survival (OS) (HR: 0.54; 95% CI: 0.33–0.86; 1835 participants; P = 0.597) were improved in the preoperative conization group compared with those in the non-conization group. The risk for recurrence was lower in the preoperative conization group than in the non-conization group (odds ratio [OR]: 0.29; 95% CI: 0.17–0.48; 1099 participants; P = 0.434). There was no significant statistical difference regarding intraoperative adverse events (OR: 0.81; 95% CI: 0.18–3.70; 530 participants; P = 0.555) and postoperative adverse events (OR: 1.24; 95% CI: 0.54–2.85; 530 participants; P = 0.170) between the preoperative conization group and non-conization group. In subgroup analysis, patients who benefited more from preoperative conization, had underwent minimally invasive surgery, had smaller local tumor lesions, and had no lymph node involvement. Preoperative conization before radical hysterectomy may have a protective effect in the treatment of early cervical cancer, with better survival and less recurrence, especially when the patient is at an early stage and undergoes minimally invasive surgery. • Better survival and less recurrence were found in the preoperative conization group in early cervical cancer. • There was no significant difference regarding intraoperative and postoperative adverse events between the two groups. • Patients who underwent MIS, had smaller local tumor lesions, had no lymph node involvement, benefited more from conization. [ABSTRACT FROM AUTHOR]

Standard treatment for endometrial cancer is a hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. In premenopausal women, removal of the ovaries may not be necessary and could increase the risk of all-cause mortality. We sought to estimate the outcomes, costs, and cost-effectiveness of oophorectomy versus ovarian preservation in premenopausal women with early-stage, low-grade endometrial cancer. A decision-analytic model was designed using TreeAge software comparing oophorectomy to ovarian preservation in premenopausal women with early-stage, low-grade endometrial cancer. We used a theoretical cohort of 10,600 women to represent our population of interest in the United States in 2021. Outcomes included cancer recurrences, ovarian cancer diagnoses, deaths, rates of vaginal atrophy, costs, and quality-adjusted life years (QALYs). The cost-effectiveness threshold was set at $100,000/QALY. Model inputs were derived from the literature. Sensitivity analyses were conducted to evaluate the robustness of the results. Oophorectomy resulted in more deaths and higher rates of vaginal atrophy, while ovarian preservation resulted in 100 cases of ovarian cancer. Ovarian preservation resulted in lower costs and higher QALYs making it cost effective when compared to oophorectomy. Sensitivity analyses demonstrated the probability of cancer recurrence after ovarian preservation and probability of developing ovarian cancer were the most impactful variables in our model. Ovarian preservation is cost-effective in premenopausal women with early-stage, low-grade endometrial cancer when compared to oophorectomy. Ovarian preservation may prevent surgical menopause, which may improve quality of life and overall mortality without compromising oncologic outcomes, and should be strongly considered in premenopausal women with early stage disease. • Ovarian preservation is the cost-effective treatment option when compared to oophorectomy. • Ovarian preservation at the time of surgery resulted in 100 more cases of ovarian cancer. • Endometrial cancer recurrence and ovarian cancer after ovarian preservation were the most impactful inputs in the model. [ABSTRACT FROM AUTHOR]

Detection of lymph node metastases in cervical cancer patients is important for guiding treatment decisions, however accuracies of current detection methods are limited. We evaluated associations of abnormal glycosylation, represented by Tn and STn antigens on mucin (MUC) proteins, in primary tumor specimens with lymph node metastasis or recurrence of cervical cancer patients. Surgical specimens were prospectively collected from 139 patients with locally-advanced cervical cancer undergoing lymphadenectomy enrolled in a nation-wide clinical trial (NCT00460356). Of these patients, 133 had primary cervix tumor, 67 had pelvic lymph node (PLN) and 28 had para-aortic lymph node (PALN) specimens. Fixed tissue serial sections were immunohistochemically stained for Tn, STn, MUC1 or MUC4. Neuraminidase was used to validate Tn versus STn antibody specificity. Stain scores were compared with clinical characteristics. Primary tumor STn expression above the median was associated with negative PLN status (p -value: 0.0387; odds ratio 0.439, 95% CI: 0.206 to 0.935). PLN had higher STn compared to primary tumor, while primary tumor had higher MUC1 compared to PALN, and MUC4 compared to PALN or PLN (p = 0.017, p = 0.011, p = 0.016 and p < 0.001, respectively). Tn and STn expression correlated in primary tumor, PALN, and PLN, Tn and MUC1 expression correlated in primary tumors only (Spearman correlation coefficient [r] = 0.301, r = 0.686, r = 0.603 and r = 0.249, respectively). STn antigen expression in primary cervical tumors is a candidate biomarker for guiding treatment decisions and for mechanistic involvement in PLN metastases. • Sialyl T antigen and T antigen levels were positively correlated in both primary tumors and lymph node metastases specimens. • Pelvic lymph node metastases had higher sialyl T antigen expression in comparison to the primary cervical tumors. • Lower sialyl T antigen levels in primary tumors correlated with positive pelvic, but not para-aortic, lymph node status. [ABSTRACT FROM AUTHOR]

To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2–32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081–9.757, P = 0.036). PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode. • From 2019 to 2022, the proportion of PSR maintenance therapy with PARPi increased from 29.6% to 62.2%. • There were substantial differences between the patients in actual clinical settings and the RCTs population. • The mPFS was 26.1 months in a real-world study regarding PARPi maintenance therapy in recurrent ovarian cancer patients. • CR to the primary therapy was the independent factor favorably affecting PFS in the new treatment mode. [ABSTRACT FROM AUTHOR]

To examine patients with confirmed endometrial cancer recurrence; evaluate patterns, presentation, and mode of diagnosis. A retrospective review of women with endometrial cancer diagnosis between 2014 and 2020. Disease recurrences were evaluated. Medical records were reviewed focusing on presentation at time of recurrence. Relationships were assessed using χ2, Fisher's exact test, t -test, and Wilcoxon test. The Kaplan-Meier product limit was used to estimate survival. Multiple logistic regression analysis was used to assess the impact of covariates. Endometrial cancer recurrence was identified in 201 (11.7%) patients. Sixty percent (120/201) of patients presented with symptoms. Pain was the most common presenting symptom (23.4%, 47/201) and bleeding was reported in <14% (28/201). Patients with symptomatic presentation were less likely to be able to receive treatment for their recurrent disease (76.7% vs 91.3%, p = 0.005). Asymptomatic pelvic exam diagnosed recurrence in 13.4% (27/201) and was more common in patients initially diagnosed with early-stage disease (66.7% vs 34.5% p = 0.001) of endometrioid histology (66.7% vs 36.8%, p = 0.003) without prior adjuvant therapy (48.2% vs 17.9%, p = 0.001). More than1/3 of diagnoses were made by providers outside of the oncologic care team. The majority of women with recurrent endometrial cancer were symptomatic and pain is a common complaint associated with disease recurrence. Patients with symptomatic presentation of disease recurrence were less likely to receive treatment for recurrent disease but this did not result in an overall survival (OS) difference. Given the rising mortality rate of endometrial cancer further work is needed to develop multidisciplinary surveillance strategies that will enable meaningful treatment of disease recurrence. • The majority of endometrial cancer recurrences are symptomatic, and pain is the most common symptom. • Vaginal bleeding was reported in less than a quarter of symptomatic presentations. • More than a third of recurrences were diagnosed outside of the oncologic care team and frequently in the emergency room. • Seventeen percent of patients were unable to receive treatment for recurrent disease. [ABSTRACT FROM AUTHOR]

The objective of the present study was to define and validate an anastomotic leak prognostic score based on previously described and reported anastomotic leak risk factors (OVA-LEAK: https://n9.cl/ova-leakscore) and to establish if the use of OVA-LEAK score is better than clinical criteria (surgeon's choice) selecting anastomosis to be protected with a diverting ileostomy. This is a retrospective, multicentre cohort study that included patients who underwent cytoreductive surgery for primary advanced or relapsed ovarian cancer with colorectal resection and anastomosis between January 2011 and June 2021. Data from patients already included in the previous predictive model were not considered in the present analysis. To validate the performance of our logistic regression model, we used the OVA-LEAK formula (Annex I: https://n9.cl/ova-leakscore) for estimating leakage probabilities in a new independent cohort. Then, receiver operating characteristic (ROC) analysis was performed and area under the curve (AUC) was used to measure the performance of the model. Additionally, the Brier score was also estimated. 95% confidence intervals (CI) for each of the estimated performance measures were also calculated. 848 out of 1159 recruited patients were finally included in the multivariable logistic regression model validation. The AUC of the new cohort was 0.63 for predicting anastomotic leak. Considering a cut-off point of 22.1% to be 'positive' (to get a leak) this would provide a sensitivity of 0.45, specificity of 0.80, positive predictive value of 0.09 and negative predictive value of 0.97 for anastomotic leak. If we consider this cut-off point to select patients at risk of leak for bowel diversion, up to 22.5% of the sampled patients would undergo a diverting ileostomy and 47% (18/40) of the anastomotic leaks would be 'protected' with the stoma. Nevertheless, if we consider only the 'clinical criteria' for performing or not a diverting ileostomy, only 12.5% (5/40) of the leaks would be 'protected' with a stoma, with a rate of diverting ileostomy of up to 24.3%. Compared with subjective clinical criteria, the use of a predictive model for anastomotic leak improves the selection of patients who would benefit from a diverting ileostomy without increasing the rate of stoma use. [ABSTRACT FROM AUTHOR]

Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab. In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/m2 plus pazopanib 600–800 mg daily or standard weekly paclitaxel 80 mg/m2. The primary endpoint was 4-month progression-free survival (PFS) rate. Overall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51–73%] with the combination versus 68% [95% CI, 54–85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1–6.1] versus 5.8 [95% CI, 4.8–7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone. In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery. ClinicalTrials.gov registration: NCT02383251. • We tested anti-angiogenic rechallenge for ovarian cancer progressing on bevacizumab. • Pazopanib rechallenge did not improve efficacy vs paclitaxel alone. • Adding pazopanib to paclitaxel increased toxicity, compromising paclitaxel delivery. • The combination had a detrimental effect on abdominal/gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

The role of kallikrein-related peptidase 5 (KLK5) has been studied in several diseases, including skin and ovarian cancers. However, its role in cervical cancer remains unclear, particularly in regulating the radiation resistance and growth of cervical cancer cells. Radiation resistance of cervical cancer is associated with local recurrence, distant metastasis, and reduced survival. We first analyzed radiotherapy-naive samples and relevant clinical data from patients with cervical cancer who received radiotherapy without surgery or other antitumor treatment from 2014 to 2016. Subsequently, biopsied tissues, in vitro cells, and transplanted tumors in nude mice were investigated. Gene sequencing and clinical data analysis showed that KLK5 overexpression was associated with a poor prognosis post-radiotherapy. In in vitro cell and tumor transplantation experiments, KLK5 overexpression significantly increased radiation resistance. However, downregulating KLK5 expression increased radiosensitivity. Our results confirm that KLK5 is vital to the radioresistance of cervical cancer, and provide a new target and marker for the treatment of radioresistance in cervical cancer. • KLK5 expression is significantly correlated with cervical cancer radioresistance. • KLK5 expression is correlated with negative outcomes, progression, and metastasis. • KLK5 under/overexpression decrease/increase radioresistance in vivo , respectively. • KLK5 may be a promising biomarker for targeted radiotherapy treatment. [ABSTRACT FROM AUTHOR]

Sexual dysfunction has been reported after gynecologic cancer treatment but few studies have examined sexual function during treatment. Our objectives were to describe sexual function among women receiving systemic therapy for gynecologic cancers and to compare sexual function between women receiving upfront treatment versus treatment for cancer recurrence. We conducted a prospective study of women 18yo and older receiving systemic therapy for gynecologic cancer in the upfront or recurrent setting. Patients receiving radiation were excluded. Participants completed a survey with questions from the Patient Reported Outcome Measurement Information System (PROMIS) SexFS and Female Sexual Function Index (FSFI). Clinical information was collected from chart review. Statistical analysis included t -test, Wilcoxon rank sum test, and Fisher's exact test. Of 145 patients approached, 100 (69%) enrolled and 97 (67%) completed the survey. Median age was 65yo. Most patients had ovarian cancer (58%), then endometrial cancer (34%) and cervical cancer (8%). Fifty-two (54%) were receiving recurrent treatment and 45 (46%) upfront treatment. Thirty-eight (76%) in the recurrent group and 34 (75%) in the upfront group hadn't been sexually active in the last month (p = 1.0); however, 61 (67%) participants reported a desire for future sexual activity. Of the 31 patients who completed all FSFI questions, the median FSFI score was 24.0 and 21 (68%) had sexual dysfunction. Vaginal dryness was more common among patients receiving recurrent treatment (p = 0.09) while a "health condition" was a more common reason for sexual inactivity in the upfront setting (p = 0.07). Many patients receiving systemic therapy for gynecologic cancers are willing to discuss sexual function. Most patients reported sexual dysfunction and weren't currently sexually active. Understanding patients' sexual function concerns will allow providers to intervene. • Sexual dysfunction is common among patients receiving systemic therapy for newly diagnosed and recurrent gynecologic cancers. • Most patients, in both the upfront and recurrent treatment groups, were not sexually active but desired to be in the future. • Sexual health issues should be assessed throughout gynecologic cancer treatment, and interventions tailored to patient needs. [ABSTRACT FROM AUTHOR]

Despite its generally favorable prognosis at primary diagnosis, recurrence of endometrial cancer remains an important clinical challenge. The aim of this study was to analyze the value of molecular classification in recurrent endometrial cancer. This study included patients with recurrent endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort) with molecular classification of the primary tumor. Out of 594 molecularly classified endometrial cancer patients, 101 patients experienced recurrence, consisting of 2 POLE mut, 33 MMRd, 30 p53abn, and 36 NSMP tumors. Mean age at recurrence was 71 years and mean follow-up was 54 months. Overall, median time to first recurrence was 16 months (95% CI 12–20); with the shortest median time in MMRd patients, with 13 months (95% CI 5–21). The pattern of recurrence was distinct among molecular subgroups: MMRd tumors experienced more locoregional, while p53abn cases showed more abdominal recurrences (P =.042). Median survival after recurrence was best for MMRd cases (43 months, 95% CI 11–76), compared to 39 months (95% CI 21–57) and 10 months (95% CI 7–13) for the NSMP and p53abn cases respectively (log-rank, P =.001). Molecular classification is a significant indicator of survival after recurrence in endometrial cancer patients, and patterns of recurrence differ by molecular subgroups. While MMRd endometrial cancer show more locoregional recurrence and the best survival rates after recurrence, p53abn patients experience abdominal recurrence more often and had the worst prognosis of all recurrent patients. [Display omitted] • The pattern of recurrence in endometrial cancer differs among the molecular subgroups. • Molecular classification of the primary tumor in endometrial cancer is a significant predictor of survival after recurrence. • MMRd endometrial cancer patients experience more locoregional recurrences and show the best survival after recurrence. • p53abn endometrial cancer patients have the worst survival rate after recurrence. [ABSTRACT FROM AUTHOR]

To evaluate recurrence rates and risk factors of relapse in stage IA vulvar squamous cell carcinoma (VSCC) patients. Population-based prospectively collected data on stage IA VSCC was retrieved through the Danish Gynecological Cancer Database (DGCD) during 2011–2017. A central pathology review was performed on tumors from women with recurrent disease. 62 women diagnosed and treated for stage IA VSCC were identified. Nine (14.5%) of the included cases relapsed within the observation period. The recurrences were in the vulva, groins or both in 5 (8.1%), 3 (4.8%) and 1 (1.6%) of the women, respectively. At central pathology review, including all recurrent cases (n = 9), 5 out of 21 reviewed patients were upstaged to stage IB due to depth of invasion >1 mm and two were downstaged to Carcinoma in situ. Two of the upstaged women developed an isolated groin recurrence and one an isolated vulvar relapse. After exclusion of the seven cases the overall recurrence rate decreased to 10.9% (n = 6). Among these cases (n = 55) resection margin <8 mm and tumor size were associated with cancer recurrence. Pathological assessment of stage IA VSCC (depth of invasion ≤1 mm) may be difficult. This may result in under-staging, which impact the choice of treatment and possibly the prognosis. This suggests a need for further clarification of the FIGO measurement and may require a more radical approach when it comes to treatment and groin exploration in stage IA VSCC. Resection margins <8 mm and tumor size were associated with relapse of the disease. • Measurement of depth of invasion ≤1 mm in vulvar cancer is a challenge and understaging may occur. • The rate of recurrence went from 14.5% to 10.9% after a central pathology review was performed. • Resection margins <8 mm and tumor size were associated with recurrence. [ABSTRACT FROM AUTHOR]

Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%–44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675–0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients. • The 5-year post-recurrence disease-specific survival (PR-DSS) rate was 39.1% in patients with early-stage cervical cancer. • The strongest factors for PR-DSS were primary tumour size and the presence of symptoms at diagnosis of recurrence. • The presence of symptoms at recurrence remained a significant prognostic factor after correction for lead-time bias. • PR-DSS was best in patients without LN involvement or LVSI suffering from solitary asymptomatic recurrence. [ABSTRACT FROM AUTHOR]

While high-risk HPV (hrHPV) testing is not formally recommended as a surveillance modality in patients with a history of cervical cancer, it is often performed in routine practice. It is unclear whether the presence of hrHPV infection after cervical cancer treatment is associated with recurrent disease. Patients with a cervical cancer diagnosis who were seen in a single institution between May 2012 and December 2019 were retrospectively identified. Squamous cell, adenocarcinoma, adenosquamous, and neuroendocrine histologies were included. Those with cancer progression within 3 months of treatment or < 1 year of documented surveillance were excluded. Patients who had hrHPV testing performed were included in the primary outcome analysis. Of the 262 patients meeting inclusion criteria, 58 (22%) recurrences were diagnosed, and recurrence was most commonly detected by a surveillance imaging study (71%). Among the 169 patients that were tested for hrHPV during the surveillance period, 41 (24%) had at least one positive hrHPV test. Recurrent disease was diagnosed in 24 (14%). Of the 24 patients with recurrent disease, 5 (21%) had at least one positive hrHPV test during surveillance, versus 36 (24%) of 145 patients without recurrent disease (p = 0.67). No recurrences were detected by hrHPV testing. Positive hrHPV testing in the surveillance setting was not associated with cervical cancer recurrence but did lead to additional studies and procedures. Our findings do not support the routine use of hrHPV testing for the evaluation of cervical cancer recurrence. • Surveillance hrHPV testing was commonly performed but was not associated with cervical cancer recurrence in this cohort. • Positive hrHPV results in the surveillance setting led to significantly more additional testing procedures. • Imaging was frequently performed for surveillance and was the most common modality to detect cervical cancer recurrence. [ABSTRACT FROM AUTHOR]

The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described. In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields. The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months). Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV– tumors. • Local recurrence occurred significantly more often in N+ pts without adjuvant radiotherapy to the vulva (HR 1.79; p=0.019). • The effect of RT on local recurrence was independent of the resection status. • 50% disease free survival time (DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV + pts. [ABSTRACT FROM AUTHOR]

To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4–127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71–4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69–13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials. • Patients having bilateral negative sentinel lymph nodes or bilateral negative pelvic lymphadenectomy had similar survival. • Sentinel lymph node biopsy alone did not increase nodal-specific recurrence compared to pelvic lymphadenectomy. • The most important prognostic factor in node-negative patients is the pathologic risk assessment using the Sedlis criteria. [ABSTRACT FROM AUTHOR]

This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation. • In locally advanced cervical cancer, the risk of distant failure was predicted. • The model was more accurate in subjects with a low- and intermediate- risk. • The prediction model may be useful in designing more effective trials. [ABSTRACT FROM AUTHOR]

The recently published ASTRO cervical cancer guidelines recommend the use of modern radiotherapy. Imaging is now incorporated in the updated FIGO 2018 staging with a new stage IIIC. This study aims to evaluate the oncologic outcomes and predictors of survival using FIGO 2018 staging in a cohort of patients treated in an era of high-precision image-guided radiotherapy. We performed a retrospective cohort study of 216 adult cervical cancer patients treated with definitive chemoradiotherapy between 2010 and 2018. Eligible patients had non-metastatic cervical cancer treated at a single academic institution. All patients had pre-treatment MRI and CT/PET. Treatment protocol consisted of external beam intensity-modulated radiotherapy and 3D image-guided brachytherapy. Kaplan-Meier curves were used for survival analysis. Multivariate cox proportional-hazards model was performed to identify potential prognostic factors. Median age at diagnosis was 50 and median BMI was 26.4 kg/m2. Median follow-up time was 44.3 months. Five-year overall survival (OS), disease-free survival and loco-regional disease-free survival rates were 76.8%, 68.5% and 82.6%, respectively. FIGO 2018 showed better OS discrimination compared to FIGO 2009 classification. OS was increasingly worse with positive pelvic and para-aortic nodes (p < 0.001). In a multivariate prediction model, performance status (p = 0.044) and FIGO 2018 classification (stage III p = 0.016; stage IVA p = 0.010) were predictors of mortality; FIGO 2018 classification (stage III p = 0.003; stage IVA p = 0.001) was a predictor of any recurrence; MRI tumor diameter (p ≤ 0.001) and nodal metastases (p = 0.024) were predictors of loco-regional recurrence. Integration of state-of-the-art imaging in cervical cancer staging and in radiotherapy planning leads to good loco-regional control rates, however distant recurrence remains an important issue. FIGO 2018 staging better reflects patient prognosis, highlighting the need for new treatment strategies for stage IIIC cervical cancer. • Integrating precision imaging in cervical cancer treatment offers good outcomes. • The new FIGO 2018 staging system better reflects patient prognosis. • Distant recurrence remains a concern in the management of cervical cancer. [ABSTRACT FROM AUTHOR]

To assess preferences of women with ovarian cancer regarding features of available anti-cancer regimens for platinum-resistant, biomarker-positive disease, with an emphasis on oral PARP inhibitor and standard intravenous (IV) chemotherapy regimens. A discrete-choice-experiment preferences survey was designed, tested, and administered to women with ovarian cancer, with 11 pairs of treatment profiles defined using seven attributes (levels/ranges): regimen (oral daily, IV weekly, IV monthly); probability of progression-free (PFS) at 6 months (40%–60%); probability of PFS at 2 years (10%–20%); nausea (none, moderate); peripheral neuropathy (none, mild, moderate); memory problems (none, mild); and total out-of-pocket cost ($0 to $10,000). Of 123 participants, 38% had experienced recurrence, 25% were currently receiving chemotherapy, and 18% were currently taking a PARP inhibitor. Given attributes and levels, the relative importance weights (sum 100) were: 2-year PFS, 28; cost, 27; 6-month PFS, 19; neuropathy,14; memory problems, nausea, and regimen, all ≤5. To accept moderate neuropathy, participants required a 49% (versus 40%) chance of PFS at 6 months or 14% (versus 10%) chance at 2 years. Given a 3-way choice where PFS and cost were equal, 49% preferred a monthly IV regimen causing mild memory problems, 47% preferred an oral regimen causing moderate nausea, and 4% preferred a weekly IV regimen causing mild memory and mild neuropathy. These findings challenge the assumption that oral anti-cancer therapies are universally preferred by patients and demonstrate that there is no "one size fits all" regimen that is preferable to women with ovarian cancer when considering recurrence treatment regimens. • A survey of patient preferences for ovarian cancer recurrence regimens. • Progression-free survival (PFS) and personal cost drove treatment choice. • Patients did not prefer oral over intravenous recurrence regimens. [ABSTRACT FROM AUTHOR]

Surgery is the only treatment for cervical cancer recurrence in a previously irradiated field. Pelvic exenteration (PE) and laterally extended endopelvic resection (LEER) are indicated for select patients; however, morbidity and mortality rates remain high, and new treatment modalities are required. Laparoscopy optimizes visualization and allows meticulous dissection while also reducing intraoperative blood loss and postoperative complications without worsening the outcomes. We aimed to clarify the feasibility and outcomes of laparoscopic PE and LEER for previously irradiated recurrent cervical cancer. We prospectively investigated the outcomes of laparoscopic PE and LEER in 28 patients with recurrent cervical carcinoma after radiotherapy. Seventeen laparoscopic PEs for central recurrences and 11 laparoscopic LEERs for lateral recurrences were performed. The median operation time and blood loss were 454mins and 285 mL in the PE group, and 562mins and 325 mL in the LEER group, respectively, with no conversions to laparotomy. R0 resection was achieved in all patients in the PE group and 73% in the LEER group. The morbidity and mortality rates were 41% and 0% in PE group, and 55% and 0% in LEER group, respectively. The 2-year disease-free survival and overall survival were 68.9% and 76% in the PE group, and 27.3% and 29.6% in the LEER group, respectively. Laparoscopic PE is feasible for previously irradiated central recurrent cervical cancer and has acceptable outcomes. Laparoscopic LEER is also feasible for lateral recurrence, but oncologic outcome may be modest in this limited preliminary study. Further studies using a larger sample size with a longer follow-up period is warranted to determine the indications for laparoscopic LEER. • PE and LEER are effective surgical salvage therapies for recurrent, previously irradiated cervical cancer. • A laparoscopic approach can reduce blood loss without worsening oncologic outcomes. • This report describes the technical feasibility and outcomes of laparoscopic PE and LEER for recurrent, previously irradiated cervical cancer. [ABSTRACT FROM AUTHOR]

The spleen represents an important contributor to tumor immune escape, but the relevance of increased splenic metabolic activity remains to be fully elucidated. We retrospectively measured the spleen-to-liver standard uptake value (SLR) on 18F-FDG PET/CT examinations of 92 consecutive patients with FIGO stage IB1 to IVA cervical cancer and integrated the results with survival, response to treatment, tumor immune infiltrate, and baseline characteristics. SLR max > 0.92 (p =.026) and SLR mean > 0.94 (p =.005) were significantly associated with decreased DFS in univariable analysis. Multivariable models were built using best subset selection; ΔSLR max and either SLR max or SLR mean were consistently selected, strongly reinforcing the association between SLR variables and DFS in relation to potential confounders (all models p ≤.002). Independent associations were found for SLR max using multivariable Cox regression models for DFS (all p ≤.003). Further, uni- and multivariable analyses demonstrated the negative impact of higher SLR values on pathological complete response. A statistically significant higher proportion of patients with high SLR max had a dense infiltrate of CD20+ (p =.036) and CD68+ (p =.015) immune cells, as well as PD-L1+ tumor cells (p =.019) as compared to those with low SLR max. Finally, high SLR max status was neither associated with systemic inflammatory markers (except for an increased white blood cell count; p =.038), nor with clinically overt infection. This hypothesis-generating study provides the first evidence that increased splenic metabolic activity is a negative prognostic and predictive biomarker in locally advanced cervical cancer. In addition, it might help to discriminate immunologically 'hot' from 'cold' cervical tumors. • Splenic metabolic activity was a prognostic factor for recurrence in cervical cancer. • Splenic metabolic activity was a predictive factor for pathological complete response in cervical cancer. • Splenic metabolic activity was associated with the cervical tumor immune infiltrate. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0–3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p =.003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p <.001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p <.001 and p =.024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84–6.67; p <.001) and OS (aHR 2.00, 95%CI 1.04–3.88; p =.039) compared to HER2-negative tumors. Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease. • Twenty six percent of stage I uterine serous carcinoma tumors were HER2 positive. • HER2 positivity was associated with a 3 fold greater risk of disease recurrence. • HER2 is a potential prognostic biomarker for women with early stage disease. [ABSTRACT FROM AUTHOR]

To investigate the relation of pathologic tumor-free margins and local recurrence in patients who underwent primary surgery for vulvar squamous cell carcinoma. In this retrospective analysis, patients with stage I-III vulvar squamous cell carcinoma who underwent primary surgery between 2000 and 2018 were identified from the Mayo Clinic Cancer Registry. A total of 335 patients were included and divided into three groups according to tumor-free margins: group 1 (<3 mm, n = 32); group 2 (≥3 to <8 mm, n = 151); group 3 (≥8 mm, n = 152). The median follow-up time was 73 months (range 2–240). A total of 78 (23.3%) patients developed local recurrence. With the inverse propensity score weighing method adjusting baseline characters, margins <8 mm had inferior local control (HR 1.98, 95% CI 1.13–3.41). The 5-year local disease-free survival (DFS) was 48.2%, 81.5% and 84.6% for group 1, 2 and 3 respectively (p < 0.001). There were no differences in groin lymph nodes relapse (p = 0.850), distant metastases (p = 0.253), or disease-specific survival (DSS) (p = 0.289) among the three groups. Margins <8 mm, midline involvement, multifocal disease, precancerous lesions on margins and depth of invasion >1 mm were found to be poor prognosticators for local DFS in univariate analysis. Multifocal disease was the strongest predictor for local recurrence in multivariate analysis (HR 4.32, 95% CI 2.67–6.99). Patients undergoing primary surgery for vulvar squamous cell carcinoma with tumor free-margins <8 mm have a higher local recurrence rate. • Pathologic tumor-free margins <8 mm is associated with a higher local recurrence in vulvar cancer. • 5-year local DFS is 84.6% in patients with tumor-free margins ≥8 mm. • Local recurrence is related with midline involvement, VIN3, multifocal disease and stromal invasion >1 mm. • Multifocal disease is the strongest predictor for local recurrence. [ABSTRACT FROM AUTHOR]

To evaluate the treatment outcome and survival of patients with epithelial ovarian cancer recurrence isolated to the retroperitoneal lymph nodes compared to intraperitoneal spread. A retrospective cohort study including women with recurrence of epithelial ovarian, cancer, who were treated at a single medical center, between 2000 and 2015. Patients were classified into three groups according to the site of recurrence: intraperitoneal only, retroperitoneal lymph nodes only, and both. Response to treatment was assessed by the RECIST criteria. Out of 135 patients in our cohort, 66 were diagnosed with intraperitoneal recurrence, 30 with retroperitoneal lymph node recurrence and 39 with combined site recurrence. The clinical, pathological and surgical characteristics were similar among all groups, besides CA-125 which was significantly lower in the retroperitoneal recurrence group at diagnosis, end of treatment and recurrence. The median follow-up period was 45.8 months. Overall survival (OS) and post relapse survival (PRS) were significantly higher in the retroperitoneal recurrence group vs. the intraperitoneal and combined site recurrence groups. (OS – 93.07, 47.9 and 41.7 months, respectively, p <.001, PRS – 68.57, 29.67 and 19.7 months, respectively, p <.001). On cox's regression analysis, retroperitoneal recurrence was found to be an independent prognostic factor for survival. The site of recurrence has significant prognostic value regarding PRS and OS. Patients with recurrence limited to the retroperitoneal lymph nodes have a favourable prognosis with median survival longer than 5 years. • Treatment outcome and survival of patients with recurrent epithelial ovarian cancer by site of recurrence was evaluated • Post relapse survival was significantly longer in the retroperitoneal vs. the intraperitoneal recurrence group. • Retroperitoneal lymph nodes recurrence has a favourable prognosis with median survival longer than 5 years. [ABSTRACT FROM AUTHOR]

For over forty years, the Gynecologic Oncology Group drove progress in treating endometrial cancer. The first decades of investigation began with a meticulous prospective, surgicopathologic staging study that was the platform for development of all subsequent trials. The resultant statistical model of low risk, intermediate risk, and high-risk groups of patients led to trials where therapeutic modalities were best targeted at disease spread. A clear role for chemotherapy was established. It was realized that greater advances might be achieved with the advent of newer anti-neoplastic agents and these agents were subjected to extensive phase II testing. These agents later were integrated into comparison trials for advanced endometrial cancer. Multimodality therapy continues to show promise. Hormonal therapy was thoroughly investigated and led to combination hormonal therapy trials. Newer agents, including biologics are under active study, as well as the potential contribution of modern imaging techniques. Finally, GOG0210 established a repository of clinical specimens with detailed clinical and epidemiologic data from patients with surgically staged endometrial carcinoma. This should provide for a much greater understanding of molecular characteristics associated with risk of endometrial cancer recurrence, clinical and histological characteristics, and epidemiologic factors. • The Gynecologic Oncology Group has driven progress in the management of endometrial cancer. • These trials have changed surgical, radiation, and chemotherapy practice. • Further progress will be seen with targeted and immunologic therapies. [ABSTRACT FROM AUTHOR]

To propose an ideal patient candidate with early-stage cervical cancer for undergoing fertility-sparing trachelectomy. This nationwide, multicenter, retrospective study was conducted by the Japan Society of Obstetrics and Gynecology involving women aged <45 years with clinical stage I-II cervical cancer who had planned fertility-sparing trachelectomy and pelvic lymphadenectomy between 2009 and 2013 (n = 393). Ideal candidates were defined to have a tumor size of ≤2 cm, no lymph node metastasis, no deep stromal invasion, and no high-risk histology (n = 284, 69.6%). Less-ideal candidates were defined to have any one of these four characteristics (n = 109, 30.4%). Propensity score inverse probability of treatment weighting was used to assess survival outcomes. Less-ideal candidates were more likely to undergo hysterectomy conversion (22.9% versus 3.2%), receive postoperative radiotherapy (11.9% versus 0.4%), or chemotherapy (32.1% versus 3.2%) compared with ideal candidates (all, P < 0.05). The weighted model revealed that among those who underwent trachelectomy (ideal candidates, n = 275 and less-ideal candidates, n = 84), less-ideal candidates had significantly decreased disease-free survival (5-year rates: 85.5% versus 95.5%; HR 3.93, 95% CI 1.99–7.74; P < 0.001) and cause-specific survival (92.5% versus 98.6%; HR 5.47, 95% CI 1.68–17.8, P = 0.001) compared with ideal candidates. Similarly, less-ideal candidates were significantly associated with decreased disease-free survival compared with ideal candidates among those who were young age, had small tumors or squamous histology, and underwent surgery alone (all, P < 0.05). Less-ideal candidates had approximately four-fold higher recurrence risk and cancer mortality compared with ideal candidates. Ideal candidates for fertility-sparing trachelectomy for early-stage cervical cancer proposed in our study may be useful as the future framework for developing guidelines for fertility-sparing trachelectomy in Japan. • A retrospective study was performed for 393 women underwent fertility-sparing trachelectomy for stage I-II cervical cancer. • Women without tumor size>2cm, deep stromal invasion, nodal metastasis, or high-risk histology may be ideal candidates. • Less-ideal candidates had approximately four-fold higher recurrence risk and mortality compared with ideal candidates. • Adjuvant chemotherapy for women with large tumors may have benefit for the purpose of fertility preservation. [ABSTRACT FROM AUTHOR]

More than 80 % of women with advanced ovarian cancer relapse either during or after adjuvant therapy. Platinum-sensitive women are rechallenged with a platinum-combination therapy and platinum-resistant women are challenged with non-platinum drugs. Gemcitabine is one of many treatments that can be used both as single-agent or as combination therapy for the treatment of recurrent ovarian cancer. We included all randomised controlled trials investigating patients treated with gemcitabine for recurrent ovarian cancer and reporting data on overall survival, progression-free survival and toxicity. CENTRAL, EMBASE and MEDLINE were searched on the 31st of May 2019. We included six randomised controlled trials that evaluated gemcitabine either alone or as combination therapy. Two studies compared gemcitabine to pegylated liposomal doxorubicin in women with platinum-resistant recurrent ovarian cancer. Difference in overall and progression-free survival was non-significant. Gemcitabine treatment was associated with significantly more neutropenia, whereas pegylated liposomal doxorubicin was associated with significantly more hand-foot syndrome. One study evaluated carboplatin and gemcitabine to carboplatin. Difference in overall survival was non-significant, but progression-free survival was longer with gemcitabine and carboplatin (HR: 0.72, 95% CI 0.58–0.9). One study evaluated gemcitabine with gemcitabine and pertuzumab. Overall survival and progression-free survival was similar between the two arms. One study compared gemcitabine and carboplatin to gemcitabine, carboplatin and bevacizumab. Overall survival was similar in the two arms. Progression-free survival was significantly better in the bevacizumab arm (HR 0.48 95% CI 0.39–0.61). One study compared etoposide and gemcitabine to etoposide. The study showed similar overall survival and progression-free survival. The results show that gemcitabine is an active and safe agent in the treatment of both platinum-sensitive and resistant recurrent ovarian cancer but might highlight the need of new randomised studies in heavily pre-treated patients. • First systematic review and metaanalysis on gemcitabine for recurrent ovarian cancer. • Six RCTs evaluating the efficacy and safety of gemcitabine in recurrent ovarian cancer. • The evidence for single-agent gemcitabine might not reflect the way it is used today. [ABSTRACT FROM AUTHOR]

This study was to analyze patterns and risk factors of relapse after postoperative adjuvant chemotherapy for endometrial cancer. Among patients enrolled in a randomized phase III trial (JGOG2043) investigating the efficacy of adjuvant chemotherapy for endometrial cancer at a high risk of progression, the recurrent patients were studied. Clinical information were collected, and correlation between relapse-related factors and clinicopathological factors were analyzed. Among 193 patients analyzed, 50% had local relapse and 63% had distant relapse. Local relapse involved regional lymph nodes in 30%, while distant relapse involved the abdominal cavity in 42%. Imaging was used to confirm relapse in 83%, and the median disease-free interval (DFI) was 11.5 months. Factors showing a significant correlation with DFI ≤12 months were residual tumor at surgery (p < 0.01), Grade 3 histology (p < 0.01), and lymph node metastasis (p = 0.03). In contrast, treatment with paclitaxel and carboplatin showed a significant correlation with DFI >12 months (p = 0.04). The median post-relapse overall survival (RS) was 23.9 months. In multivariate analysis, CA125 ≥ 100 U/mL prior to relapse (p < 0.01), distant metastasis (p < 0.01), DFI ≤ 12 months (p = 0.02), and not performing para-aortic lymphadenectomy (p = 0.01) were independently related to poor RS. Relapse of endometrial cancer following adjuvant chemotherapy often occurs by 1 year after treatment, with common relapse sites of the abdominal cavity and regional lymph nodes. Among treatment-related factors, RS was correlated with DFI and para-aortic lymphadenectomy. • Analysis of relapse of endometrial cancer was done using a phase III randomized trial data. • Local relapse and distant relapse are similar in frequency after adjuvant chemotherapy. • Median disease-free interval is about 12 months. • Post-relapse overall survival is correlated with disease-free interval and para-aortic lymphadenectomy. [ABSTRACT FROM AUTHOR]

To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice. Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy. One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125. Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy. • We report a cohort of 115 ovarian cancer patients treated with olaparib. • Median PFS was 12.7 months and median OS was 35.4 months, comparable to Study 19. • PFI ≥ 12 months, CR and normalized CA-125 are associated with prolonged PFS and OS [ABSTRACT FROM AUTHOR]

To analyze our institutional experience and oncologic outcomes for salvage treatment for the recurrence of early-stage endometrial cancer patients. We included women of all ages diagnosed with FIGO stage I-II, any grade endometrial cancer from 2000 to 2016 at our institutions who were treated with at least a hysterectomy. Recurrences in the pelvis and/or vagina were considered locoregional recurrences (LRR). Overall survival (OS) was assessed using Kaplan-Meier survival analysis. Univariate (UV) and multivariate (MV) Cox proportional hazards modeling was also used. A total of 2691 women were analyzed. The majority had endometrioid histology (91%), stage IA disease (61%), and were grade 1 (57%). With a median follow-up of 6.1 years, the overall rate of recurrence was 7.2%, and the rate of LRR was 3.7%. Women with vaginal-only recurrences had a longer median OS after recurrence (14.0 years) compared to both pelvic (1.2 years) and distant (1.0 year) failures. For women with vaginal-only recurrences, salvage radiotherapy (RT) was the only factor associated with improved OS on MVA (HR 0.1, p =.04). For women with pelvic recurrences, salvage surgery (HR 0.3, p =.01), salvage RT (HR 0.3, p <.01), and salvage chemotherapy (HR 0.4, p =.03) were associated with improved OS. Failure rates for women with early-stage endometrial cancer are low. Women with vaginal-only recurrences have improved OS compared to pelvic or distant recurrences. Salvage RT appears to be an important factor for treatment of women with vaginal-only recurrences. Aggressive multimodality treatment may be beneficial for women with pelvic recurrences. • Women with vaginal recurrences had significantly longer survival than women with pelvic or distant recurrences. • Salvage radiotherapy was the only factor we found associated with improved survival for vaginal recurrences. • Salvage surgery, radiotherapy, and chemotherapy were associated with improved survival for pelvic recurrences. • In the rare situation of a second locoregional recurrence, 50% of patients can be salvaged at 5 years. [ABSTRACT FROM AUTHOR]

Abstract Background Limited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT. Methods A retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to <75 Gy and <90 Gy, respectively. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities, defined according to CTCAE v4, were recorded. Results Prior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6–75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3–81.8), 70.6 Gy (range: 32.0–80.5), and 52.7 Gy (range: 29.6–75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities. Conclusion Re-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation. Highlights • 22 patients treated with definitive re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. • No ≥G3 rectosigmoid or bladder toxicities when cumulative rectosigmoid and bladder D2cc (EQD2) limited to <75 Gy and <90 Gy. • 3-year local control, disease-free survival, and overall survival rates were 65.8%, 40.8%, and 68.1%, respectively. • Re-irradiation with 3D conformal brachytherapy is feasible and safe when cumulative dose to organs-at-risk is limited. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)–expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial. Methods Key inclusion criteria were age ≥18 years; advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of previous therapy; and tumor PD-L1 positivity. Patients received pembrolizumab (10 mg/kg every 2 weeks) for ≤24 months or until disease progression/intolerable toxicity. Tumor response was assessed per RECIST v1.1 (investigator review). Adverse events (AEs) were graded using CTCAE version 4.0. Primary end point was confirmed objective response rate (ORR) per RECIST v1.1 (investigator review); data cutoff date was February 20, 2017. Results Twenty-six patients (median age, 57.5 years) with PD-L1–positive advanced metastatic ovarian cancer received pembrolizumab; 38.5% had metastatic disease, and 73.1% previously received ≥3 lines of therapy. Treatment-related AEs (TRAEs) occurred in 19 (73.1%) patients, most commonly arthralgia (19.2%), nausea (15.4%), and pruritus (15.4%). One grade 3 TRAE (increased plasma transaminase level) occurred. No deaths and no treatment discontinuations due to TRAEs occurred. After a median follow-up duration of 15.4 months, ORR was 11.5% (1 complete response, 2 partial responses); 7 patients (26.9%) achieved stable disease. Median progression-free and overall survival were 1.9 (95% CI, 1.8–3.5) and 13.8 (95% CI, 6.7–18.8) months, respectively. Conclusion Pembrolizumab conferred durable antitumor activity with manageable safety and toxicity in patients with advanced PD-L1–positive ovarian cancer and is under further investigation in an ongoing phase II trial, KEYNOTE-100. Highlights • Most patients with ovarian cancer eventually relapse and ultimately die of chemoresistant disease • Sustained responses are less likely after second-line and subsequent therapies, suggesting a need for new treatment options • Responses to pembrolizumab were modest but durable in patients with advanced ovarian cancer expressing PD-L1 • The safety profile of pembrolizumab was acceptable, with no deaths or treatment-related discontinuations • Further evaluation of pembrolizumab is warranted to identify the tumors most likely to respond in this patient population [ABSTRACT FROM AUTHOR]

Abstract Despite the surgical and chemotherapeutic advances over the past few decades, ovarian cancer remains the leading cause of gynecological cancer-related mortality. The absence of biomarkers in early detection and the development of drug resistance are principal causes of treatment failure in ovarian cancer. Recent progress in RNA sequencing (RNA-Seq) with Next Generation Sequencing technology has expanded the understanding of the molecular pathogenesis of ovarian cancer. As compared to previous hybridization-based microarray and Sanger sequence-based methods, RNA-Seq provides multiple layers of resolutions and transcriptome complexity, with less background noise and a broader dynamic range of RNA expression. Beyond quantifying gene expression, the data generated by RNA-Seq accelerates the identification of alternatively spliced genes, fusion genes, mutations/SNPs, allele-specific expression, novel transcripts and non-coding RNAs. RNA-Seq has been successfully applied in ovarian cancer research for earlier detection, ascertaining pathological origin, and defining the aberrant genes and dysregulated molecular pathways across patient groups. This review outlines the distinct advantages of RNA-Seq compared to other transcriptomics methods and its recent applications in ovarian cancer. Highlights • Absence of biomarkers in early detection and drug resistance are principal causes of treatment failure in ovarian cancer. • RNA-Seq has expanded the knowledge of molecular tumorigenesis and novel transcriptional changes in ovarian cancer. • RNA-Seq has revealed novel biomarkers and advanced the areas of ovarian cancer diagnostics and classification. [ABSTRACT FROM AUTHOR]

Abstract Purpose To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients. Methods Patients with recurrent, platinum-sensitive epithelial ovarian or fallopian tube cancer were enrolled. Eligibility included a minimum requirement of tumor FRα positivity (≥25% of cells with ≥2+ staining intensity). Patients received escalating doses of mirvetuximab soravtansine and carboplatin on day 1 of a 21-day cycle (once every 3 weeks). Mirvetuximab soravtansine maintenance therapy was permitted, at the investigators discretion, following cessation of carboplatin treatment. Adverse events, tumor response, and progression-free survival (PFS) were determined. Results Eighteen patients were enrolled and dosed with combination therapy; thirteen continued with mirvetuximab soravtansine maintenance following carboplatin discontinuation. Mirvetuximab soravtansine dosing was escalated from 5 to 6 mg/kg (adjusted ideal body weight) and carboplatin from AUC4 to AUC5. Adverse events were generally mild (≤ grade 2) with nausea, diarrhea, thrombocytopenia, blurred vision, and fatigue being the most common treatment-emergent toxicities. For all evaluable patients (n = 17), the confirmed objective response rate (ORR) was 71%, including three complete responses and nine partial responses, and the median PFS was 15 months. A median duration of response was not reached. Conclusion These data demonstrate that mirvetuximab soravtansine combined with carboplatin is a well-tolerated and highly active regimen in recurrent, platinum-sensitive ovarian cancer. Further evaluation of this combination in a randomized fashion is warranted. Highlights • Combining mirvetuximab soravtansine and carboplatin is a promising approach for platinum-sensitive ovarian cancer. • The combination was well tolerated; low incidence of severe hematologic/neuropathic toxicities, and no new safety signals. • A highly active regimen, with a confirmed objective response rate of 71%. • Better median PFS (15 months) compared to historical carboplatin plus chemotherapy phase III trials. [ABSTRACT FROM AUTHOR]

Objectives To determine the efficacy and tolerability of sunitinib in recurrent or persistent clear cell ovarian cancer patients. Methods All patients had one or two prior regimens with measurable disease. Tumors were at least 50% clear cell histomorphology and negative for WT-1 antigen and estrogen receptor expression by immunohistochemistry. Sunitinib 50 mg per day for 4 weeks was administered in repeated 6-week cycles until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response. The study was designed to determine if the drug had a response rate of at least 20% or 6-month PFS of at least 25%. Results Of 35 patients enrolled, 30 were treated and eligible (median age: 51, range: 27–73). Twenty-five (83%) were White, 4 (13%) Asian, and 1 (3%) unknown. The majority 28 (83%) patients, underwent ≤3 but 2 (7%) had 16 courses of study therapy. Five (16.7%) patients had PFS ≥6 months (90% CI: 6.8%–31.9%). Two (6.7%) patients had a partial or complete response (90% CI: 1.2%–19.5%). The median PFS was 2.7 months. The median overall survival was 12.8 months. The most common grade 3 adverse events were fatigue (4), hypertension (4), neutropenia (4), anemia (3), abdominal pain (3), and leukopenia (3). Grade 4–5 adverse events included: thrombocytopenia (5), anemia (2), acute kidney Injury (1), stroke (1), and allergic reaction (1). Conclusion Sunitinib demonstrated minimal activity in the second- and third-line treatment of persistent or recurrent clear cell ovarian carcinoma. ClinicalTrials.gov number, NCT00979992. [ABSTRACT FROM AUTHOR]

Objective The aim of this systematic review and meta-analysis was to pool association effects of serum squamous cell carcinoma antigen (SCC-Ag) on recurrence and mortality in mainly squamous cell cervical cancer patients. Methods MEDLINE and Scopus databases were searched up to June 29, 2016. Studies assessing effects of SCC-Ag on recurrence and death in cervical cancer patients were included. Data extraction was independently performed by two reviewers. A meta-analysis was applied for pooling the effects (i.e., risk ratio (RR), hazard ratio (HR), and unstandardized mean difference (USMD)) of SCC-Ag measured before and after treatment on recurrence and death. Results A total of 61 studies were included. For pretreatment SCC-Ag and recurrence, the pooled RR, HR, and USMD for high versus low serum SCC-Ag were 2.44(95% CI: 1.91, 3.13), 2.23(95% CI: 2.03, 2.45), −7.7(95% CI: -31.7, 16.4), respectively. The corresponding effects for the posttreatment period were 3.91(95% CI: 2.96, 5.16), 3.14(95% CI: 1.29, 7.65), and 3.2(95% CI: -10.6, 17.0), respectively. In addition, patients with high level of pretreatment serum SCC-Ag were also at a higher risk for death than patients with low serum SCC-Ag with a pooled RR of 3.66(95% CI: 2.24, 5.98), pooled HR of 2.50(95% CI: 1.85, 3.37), and pooled USMD of 7.10(95% CI: 4.26, 9.94). The posttreatment serum SCC-Ag effects also reflected a similar trend. Conclusions The serum SCC-Ag was consistently associated with recurrence and mortality of newly diagnosed cervical cancer. This marker may be useful in monitoring disease progression in cervical cancer patients. Prospero registration number is: CRD42016044024. [ABSTRACT FROM AUTHOR]