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High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and the majority of cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. We aimed to better characterize the distinctions between primary and metastatic tumors based on short- or long-term survival. We characterized 39 matched primary and metastatic tumors by whole exome and RNA sequencing. Of these, 23 were short-term (ST) survivors (overall survival (OS)  5 years). We compared somatic mutations, copy number alterations, mutational burden, differential gene expression, immune cell infiltration, and gene fusion predictions between the primary and metastatic tumors and between ST and LT survivor cohorts. There were few differences in RNA expression between paired primary and metastatic tumors, but significant differences between the transcriptomes of LT and ST survivors in both their primary and metastatic tumors. These findings will improve the understanding of the genetic variation in HGSC that exist between patients with different prognoses and better inform treatments by identifying new targets for drug development.

ObjectivesThe ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients.MethodsSurgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated.Results361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables.ConclusionSNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.

PurposeWe conducted a randomized phase III trial to determine whether adjuvant chemotherapy improves survival in women with uterine leiomyosarcoma.MethodsWomen with uterus-confined, high-grade leiomyosarcoma who were confirmed disease free by imaging were randomly assigned to four cycles of gemcitabine plus docetaxel, followed by four cycles of doxorubicin, or to observation. All were followed for evidence of recurrence. The primary end point was overall survival (OS).ResultsWith international collaboration, 38 of the targeted accrual of 216 patients were enrolled, after which the study was closed by the National Cancer Institute for accrual futility. Twenty patients were assigned to chemotherapy, 18 to observation. Among the 17 patients treated with at least one cycle of chemotherapy, grade 3 or 4 toxicities were observed in 47%; among the 18 patients assigned to observation, one had grade 3 hypertension. There were six deaths (chemotherapy, n = 5; observation, n = 1), all due to disease. The restricted mean survival time for OS was estimated as 34.3 months (95% CI, 25.3 to 43.3 months) in the chemotherapy arm and as 46.4 months (95% CI, 43.6 to 49.1 months) in the observation arm. There were eight recurrences in each arm. The restricted mean survival time for recurrence-free survival was estimated as 18.1 (95% CI, 14.2 to 22.0) months in the chemotherapy arm and as 14.6 months (95% CI, 10.3 to 19.0 months) in the observation arm. Neither survival outcome comparison was considered statistically robust, due to the small sample size.ConclusionDespite international collaboration to test the role of adjuvant chemotherapy in uterine-confined leiomyosarcoma, this study was closed for accrual futility. Although the sample size precludes robust statistical comparison, observed OS and recurrence-free survival data do not show superior outcomes with adjuvant chemotherapy.

BackgroundThe incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. Although a few cohort studies of

IntroductionHypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment.Materials and methodsParticipants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables.ResultsEach cortisol measure was associated with decreased survival time, adjusting for covariates (all p36, all p

This study was designed to examine (1) whether ovarian cancer (OC) survivors would have greater well-being vs. elevated distress compared to community members during a universal health stressor (COVID-19) and (2) how resources and risk factors at diagnosis predicted vulnerability to a subsequent health-related stressor. One hundred seventeen OC survivors were recruited from two academic medical centers and compared to a community-based sample on COVID-related distress and disruption. Latent class analysis identified differentially impacted groups of survivors. Survivors reported lower distress than community members. Predictors of higher distress included shorter-term survivorship, greater disruption, and poorer emotional well--being (EWB) at diagnosis. Survivors were divided into high- and low-COVID-19-impact subgroups; high-impact individuals endorsed higher perceived stress and lower EWB at diagnosis. Survivors reported lower COVID-related distress than community participants. While depression at diagnosis did not predict later distress, EWB was a strong predictor of response to a novel health-related stressor. [ABSTRACT FROM AUTHOR]

Objective: Ovarian cancer is characterized by poor prognosis, high levels of distress, disturbed sleep, and compromised quality of life (QOL). Although life stressors have been shown to significantly impact physical and psychological health in cancer populations, no studies have used a high-resolution stress assessment to differentiate effects of acute versus chronic stressors among women with ovarian cancer. We addressed this issue in the present prospective longitudinal study by examining how acute and chronic stress exposure in the year pre-diagnosis relate to depressive symptoms, sleep quality, and QOL over the first year post-diagnosis in women with ovarian cancer.Methods: One hundred thirty-seven women completed the Life Events and Difficulties Schedule within a month of initial treatment for suspected ovarian cancer. Depressive symptoms, sleep, and QOL were measured pre-treatment, at six months, and one-year post-diagnosis. Mixed models were used to examine associations of acute and chronic stress pre-diagnosis with (a) change in psychosocial outcomes over the first year post-diagnosis and (b) levels of psychosocial outcomes across all time points.Results: Both the number and severity of chronic difficulties (but not acute life events) were related to significantly greater depression, and poorer sleep quality and QOL, across all time-points. In contrast, these stress indices were unrelated to changes in psychosocial functioning over time.Conclusions: Chronic but not acute stress exposure predicted average levels of depression, sleep, and QOL in the first year post-diagnosis among women with ovarian cancer. Assessing stressors and designing interventions for reducing stress may thus be beneficial for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Over the past 25 years, epidemiological and clinical studies have linked psychological factors such as stress, chronic depression, and lack of social support to the incidence and progression of cancer. Although the mechanisms underlying these observations are not completely understood, recent molecular and animal studies have begun to identify specific signaling pathways that could explain the impact of neuroendocrine effects on tumor growth and metastasis. This review will highlight the importance of known clinical, molecular, and cellular processes with regard to the neuroendocrine stress effects on tumor biology and discuss possible behavioral and pharmacological interventions to ameliorate these effects and ultimately improve cancer outcomes. [Copyright &y& Elsevier]

Objective: The purpose of this study was to examine the functional and therapeutic significance of pericytes in ovarian cancer vasculature. Study Design: Tumor vessel morphologic condition and efficacy of endothelial and pericyte targeting were examined with the use of in vivo ovarian cancer models. The expression of platelet-derived growth factor (PDGF) ligands and receptors was examined in endothelial, pericyte-like, and ovarian cancer cells. Results: Relative to normal vessels, tumor vasculature was characterized by loosely attached pericytes in reduced density. PDGF-BB was expressed predominantly by the endothelial and cancer cells, whereas PDGFRβ was present in pericyte-like cells. PDGF-BB significantly increased the migration of and VEGF production by pericyte-like cells; PDGFRβ blockade abrogated these effects. Dual VEGF (VEGF-Trap) and PDGF-B (PDGF-Trap) targeted therapy was more effective in inhibiting in vivo tumor growth than either agent alone. Conclusion: Aberrations in the tumor microenvironment contribute to endothelial cell survival. Strategies that target both endothelial cells and pericytes should be considered for clinical trials. [Copyright &y& Elsevier]

To compare FIGO 2009 and FIGO 2018 cervical cancer staging criteria with a focus on stage migration and treatment outcomes. This study is based on a database cohort of 1282 patients newly diagnosed with cervical cancer from 1997 to 2019. All underwent standard clinical examination and whole-body FDG-PET. Tumor stage was recorded using the FIGO 2009 system, which excluded surgical pathologic, FDG-PET and other advanced imaging findings, and then re-classified to the FIGO 2018 system, including surgical pathologic and imaging findings. Patient management was based on clinical, surgical, and imaging findings. Stage migration and prognosis were evaluated. The distribution per the 2009 staging system was stage I in 593 (46%), stage II in 342 (27%), stage III in 263 (21%), and stage IV in 84 (7%) and the 2018 staging system was stage I in 354 (28%), stage II in 156 (12%), stage III in 601 (47%), and stage IV in 171 (13%). No patients were down-staged. Stage migration occurred in 53% (676/1282) and was attributable to detection of occult lymph node metastasis in 520 (41%), occult distant metastasis in 90 (7%), and tumor size and extent in 66 (5%). The 5-year progression-free survivals (PFS) by FIGO 2009 versus FIGO 2018 were as follows: stage I, 80% vs. 87% (p = 0.02); stage II, 59% vs. 71% (p = 0.002); stage III, 35% vs. 55% (p < 0.001), and stage IV, 20% vs. 16% (p = 0.41). Inclusion of surgical pathologic and imaging findings resulted in upward stage migration in the majority, mostly related to nodal and distant metastasis. While FIGO 2018 improves survival discriminatory ability for stages I and IV patients, survival remains heterogeneous among stage III substages. • Most patients are upstaged with the 2018 staging system. • Upstaging is due primarily to nodal and distant metastases. • Survival discriminatory ability is improved. • There is heterogeneous survival among the stage III substages. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC). Methods: Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500mg/m2 IV and bevacizumab 15mg/kg IV were administered every 3weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS). Results: Thirty-four patients received a median of 7 treatment cycles (range, 2–26). Median follow-up was 25.7months (range, 3.0–47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38–71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25–59), 18 stable disease (53%; 35–70) and 2 progressive disease (6%; 1–20). Median PFS was 7.9months (95% CI, 4.6–10.9), with a median OS of 25.7months (95% CI, 15.4–29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6months prior to enrollment. Grade 3–4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3–4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment. Conclusions: Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted. [Copyright &y& Elsevier]

The article discusses the results of a study that examines the effectiveness of vaginal cytology in postoperative surveillance in detecting the recurrent of endometrial cancer and the optimal management of squamous abnormalities. The study finds no case of recurrent cancer in women with atypical squamous cells. It concludes that there is no need for colposcopy after a Pap test result showed atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL).

Abstract: Objectives: The aim of this study was to evaluate the effect of number of chemotherapy cycles and other clinical and pathologic factors on progression-free (PFS) and overall survival (OS) in patients with newly diagnosed cervical cancer. Methods: We identified 118 patients with locally advanced cervical cancer (stages IB2–IVA) treated with combination weekly cisplatin (40 mg/m2) and radiation therapy (RT) between 2003 and 2007. Kaplan–Meier and Cox proportional hazard models were utilized to evaluate PFS and OS for associations with number of chemotherapy cycles and other factors. Results: The majority of patients had stage IB2 or II disease (70%), squamous histology (91%), and size <6 cm (65%). Median RT duration was 50 days and 95% received brachytherapy. Thirty percent of patients completed <6 cycles of chemotherapy, and estimated PFS and OS were 63% and 75%, respectively. In multivariate analyses, the number of chemotherapy cycles was independently predictive of PFS and OS. Patients who received <6 cycles of cisplatin had a worse PFS (HR 2.65; 95% CI 1.35–5.17; p =0.0045) and OS (HR 4.47; 95% CI 1.83–10.9; p =0.001). Advanced stage, longer time to RT completion, and absence of brachytherapy were also associated with decreased OS and PFS (p <0.05). Similar results were found when analysis was conducted using a breakpoint of at least five but not less than five chemotherapy cycles. Higher grade was associated with decreased PFS (p =0.03) but not OS. Age, race, BMI, tumor size, smoking, histology, and IMRT were not statistically significant for OS or PFS. Conclusions: Aggressive supportive care to minimize missed chemotherapy treatments may improve survival after chemoradiation. [Copyright &y& Elsevier]