Search

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]

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline hydroxylation of hypoxia-inducible factor alpha in the stromal regions. Metabolites more abundant in the epithelial regions of post-NACT PR tumors were involved in the metabolism of nucleotides, and metabolites more abundant in the stromal regions of post-NACT PR tumors were related to aspartate and asparagine metabolism, phenylalanine and tyrosine metabolism, nucleotide biosynthesis, and the urea cycle. A predictive model built on ions with differential abundances allowed the classification of patients' tumor responses as ER or PR with 75% accuracy (10-fold cross-validation ridge regression model). These findings offer new insights related to differential responses to chemotherapy and could lead to novel actionable targets. [ABSTRACT FROM AUTHOR]

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) < 3.5 years) and 16 were long-term (LT) survivors (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. Analysis of whole-exome and RNA-seq data from matched primary and metastatic tumor samples in a cohort of high-grade serous ovarian cancer patients reveals distinct genomic and transcriptomic alterations associated with survival outcomes. [ABSTRACT FROM AUTHOR]

PURPOSE: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients' end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy. METHODS: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to create an external control arm (ECA). RESULTS: Fifteen OVATION-1 patients (15 of 18, 83%) were matched to 15 (37%, 15 of 41) Medidata historical trial control patients. Matching attenuated preexisting differences in attributes between the groups. The median progression-free survival time was not reached by the OVATION-1 group and was 15.8 months (interquartile range, 11.40 months to nonestimable) for the ECA. The hazard of progression was 0.53 (95% CI, 0.16 to 1.73), favoring GEN-1 patients. Compared with ECA patients, OVATION-1 patients had more nausea, fatigue, chills, and infusion-related reactions. CONCLUSION: Comparing results of a single-arm early-phase trial to those of a rigorously matched HCT ECA yielded insights regarding comparative efficacy prior to a randomized controlled trial. The effect size estimate itself informed both the decision to continue development and the randomized phase II trial (ClinicalTrials.gov identifier: NCT03393884) sample size. The work illustrates the potential of HCT data to inform drug development. Historic clinical trial data repurposed via new analytics yields early efficacy signals for GEN-1. [ABSTRACT FROM AUTHOR]

Background: Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors. Methods: Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6 months) versus more extended disease‐free intervals following initial treatment. Samples from a second subgroup of 24 patients were analyzed by mixed‐effects linear models to determine whether the progression‐predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms). Results: An RNA‐based molecular signature was identified that discriminated between individuals who had disease progression in ≤6 months versus >6 months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates. Conclusion: These data identified a novel exosome‐derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring. This study identified an exosome‐derived RNA‐based biomarker indicating propensity of ovarian cancer progression. This biomarker is sensitive to biobehavioral factors and may have possible use for risk assessment, treatment monitoring, and intervention targeting. [ABSTRACT FROM AUTHOR]

Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States. This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004–31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line of therapy were evaluated. To account for new drug approvals, patients first treated in 2018 or 2019 were also assessed separately. Among the 1317 patients who met all eligibility criteria, 520 (39.5%) and 235 (17.8%) patients received 3 or 4+ lines of treatment, respectively, during a median total follow-up time of 25.2 months (range, 2.5–173.3 months) following the index date. Chemotherapy, including platinum- and non-platinum-based regimens, was the most common treatment across all lines of therapy: 2L, 80.0%; 3L, 66.2%; 4L+, 80.4%. Overall, 2.5%, 2.3%, and 8.9% of 2L, 3L, and 4L + patients, respectively, received anti-program death 1 (anti-PD-1) immunotherapies. In patients first treated in 2018 and 2019 (n = 163), 9.8% of patients received anti-PD-1 immunotherapy in the 2L. In the overall population, median time to next treatment (TTNT) was 19.3, 10.5, and 8.1 months for patients undergoing 2L, 3L, and 4L treatment, respectively. Among patients with advanced/recurrent EC treated with 1L platinum-based therapy in clinical practice, chemotherapy was the most common treatment choice across all lines of therapy. Immunotherapy use was low overall but increased in patients who started treatment in 2018 or 2019. Overall, median TTNT decreased as lines of therapy increased. [ABSTRACT FROM AUTHOR]

The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging modalities, including Doppler ultrasound, MRI, and CT, have been investigated to improve the assessment of ovarian lesions. We hypothesized that pathologic conditions might affect the ovarian vasculature and that these changes might be detectable by optical-resolution photoacoustic microscopy (OR-PAM). In our previous work, we developed a benchtop OR-PAM and demonstrated it on a limited set of ovarian and fallopian tube specimens. In this study, we collected data from over 50 patients, supporting a more robust statistical analysis. We then developed an efficient custom analysis pipeline for characterizing the vascular features of the samples, including the mean vessel diameter, vascular density, global vascular directionality, local vascular definition, and local vascular tortuosity/branchedness. Phantom studies using carbon fibers showed that our algorithm was accurate within an acceptable error range. Between normal ovaries and normal fallopian tubes, we observed significant differences in five of six extracted vascular features. Further, we showed that distinct subsets of vascular features could distinguish normal ovaries from cystic, fibrous, and malignant ovarian lesions. In addition, a statistically significant difference was found in the mean vascular tortuosity/branchedness values of normal and abnormal tubes. The findings support the proposition that OR-PAM can help distinguish the severity of tubal and ovarian pathologies. [ABSTRACT FROM AUTHOR]

The high lethality of ovarian cancer in the United States and associated complexities of the patient journey across the cancer care continuum warrant an assessment of current practices and barriers to quality care in the United States. The objectives of this study were to identify and assess key components in the provision of high‐quality care delivery for patients with ovarian cancer, identify challenges in the implementation of best practices, and develop corresponding quality‐related recommendations to guide multidisciplinary ovarian cancer programs and practices. This multiphase ovarian cancer quality‐care initiative was guided by a multidisciplinary expert steering committee, including gynecologic oncologists, pathologists, a genetic counselor, a nurse navigator, social workers, and cancer center administrators. Key partnerships were also established. A collaborative approach was adopted to develop comprehensive recommendations by identifying ideal quality‐of‐care program components in advanced epithelial ovarian cancer management. The core program components included: care coordination and patient education, prevention and screening, diagnosis and initial management, treatment planning, disease surveillance, equity in care, and quality of life. Quality‐directed recommendations were developed across 7 core program components, with a focus on ensuring high‐quality ovarian cancer care delivery for patients through improved patient education and engagement by addressing unmet medical and supportive care needs. Implementation challenges were described, and key recommendations to overcome barriers were provided. The recommendations emerging from this initiative can serve as a comprehensive resource guide for multidisciplinary cancer practices, providers, and other stakeholders working to provide quality‐directed cancer care for patients diagnosed with ovarian cancer and their families. Quality‐directed recommendations for ovarian cancer care delivery are developed across 7 core program components, with a focus on ensuring high‐quality care delivery by addressing unmet medical and supportive care needs. These recommendations can serve as a comprehensive resource guide for multidisciplinary cancer practices, providers, and other stakeholders working to provide quality‐directed cancer care for patients diagnosed with ovarian cancer and their families. [ABSTRACT FROM AUTHOR]

Aim: Patient chart data from the USA during the period of January 2011 through October 2018 were used to assess risk factors for progression in advanced ovarian cancer after response to first-line platinum-based chemotherapy. Patients & methods: Patients with stage III/IV ovarian cancer who completed first-line platinum-based chemotherapy after primary or interval debulking surgery were identified from the Flatiron Health database. Cox proportional hazards modeling was used to assess associations between baseline factors and time to next treatment (TTNT) or overall survival (OS). Results: Patients at stage IV or who received interval debulking surgery had shorter TTNT and OS than patients at stage III or who received primary debulking surgery, respectively. OS was worse in patients with residual disease and in BRCA wild-type. Conclusion: Multiple factors were associated with shorter TTNT or OS in this retrospective real-world analysis. [ABSTRACT FROM AUTHOR]

Objectives: Gynecologic oncologists frequently care for patients at the end of life with the aid of palliative care (PC) specialists. Our primary objectives were to identify perceived barriers to integrating specialty PC into gynecologic cancer care.Materials and Methods: Members of the Society of Gynecologic Oncology (SGO) were invited to participate in an anonymous online survey. A Likert scale captured perceptions regarding primary and specialty PC, frequent barriers to use of PC, and potential interventions.Results: A total of 174 (16%) gynecologic oncologists completed the survey. The majority (75%) agreed or strongly agreed that PC should be integrated into cancer care at diagnosis of advanced or metastatic cancer. The most frequently perceived PC barriers included patients' unrealistic expectations (54%), limited access to specialty PC (25%), poor reimbursement (25%), time constraints (22%), and concern of reducing hope or trust (21%). The most agreed upon potential intervention was increased access to outpatient PC (80%).Conclusions: According to this cohort of SGO members, families' or patients' unrealistic expectations are the most frequent barriers to specialty PC. Understanding this communication breakdown is critically important. [ABSTRACT FROM AUTHOR]

Malignant tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and mitochondria in malignant tumors remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign tissue and in high-grade epithelial ovarian carcinoma (EOC) in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n = 1435) showed that gene expression of specific mitochondrial proteins in EOC is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in tissue from 51 patients with benign ovarian masses and 128 patients with high-grade EOC revealed that compared to benign tissue, EOCs exhibit 3.3–8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P < 0.001) but similar mitochondrial DNA (mtDNA) levels (− 3.1%), documenting abnormal mitochondrial phenotypes in EOC. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r = − 0.43 to 0.47). In contrast, serous EOCs showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in EOC and warrant further research on the link between biobehavioral factors and mitochondria in cancer. [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]

Background: Social isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. In patients with ovarian cancer, social isolation has been found to be related to decreased survival and multiple biomarkers supporting tumor progression. However, to the authors' knowledge, little is known regarding the relationship between social isolation and the molecular characteristics of ovarian tumors. Herein, the authors have used genome-wide transcriptional profiling to quantify associations between social isolation and epithelial-mesenchymal transition (EMT) polarization in ovarian tumors and transcriptome-driven, promoter-based bioinformatics analyses to identify gene regulatory pathways that may potentially underlie these changes.Methods: Tumor was sampled during primary surgical resection and immediately frozen in liquid nitrogen. After RNA extraction, microarray analysis of the transcriptome was performed and samples were analyzed to assess associations between EMT-related gene transcripts and social isolation (as indicated by a Social Provisions Scale Attachment subscale score <15). Convergent validation was provided by a promoter-based bioinformatic analysis of transcription factor activity.Results: Primary analyses of 99 women demonstrated a lower average expression of gene transcripts previously associated with epithelial differentiation in women with high social isolation (-0.143 ± 0.048 log2 mRNA abundance; P = .004), but no difference in mesenchymal differentiation as a function of social isolation (+0.007 ± 0.0064 log2 mRNA abundance; P = .900). Upregulated activity was shown for 3 of the 4 targeted EMT-related transcription factors, including GATA4 (P = .014); SMAD2, SMAD3, and/or SMAD4 (P < .001); and TWIST1 (P < .001). Analyses of SNAIL2/SLUG activity indicated a directional trend toward increased activity that did not reach statistical significance (P = .123).Conclusions: The findings of the current study demonstrated differential EMT polarization and EMT-related transcription factor activity according to social isolation, a known socioenvironmental risk factor.Lay Summary: Social isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. Herein, the authors examined the relationship between social isolation and the molecular characteristics of ovarian tumors. The authors investigated the epithelial-mesenchymal transition (EMT), a process whereby tumor cells lose epithelial characteristics and become more embryonic (mesenchymal), thereby enhancing invasiveness. Primary analyses demonstrated lower expression of genes previously associated with epithelial differentiation and increased activity of specific EMT-related transcription factors in individuals with high social isolation, indicating increased EMT polarization in these patients. These findings extend the understanding of how socioenvironmental factors may modulate tumor growth. [ABSTRACT FROM AUTHOR]

Endometriosis affects approximately 10% of reproductive age women and represents a significant cause of pelvic pain and infertility. Unfortunately, the diagnosis of endometriosis is often delayed by years. Endometriosis may manifest as cystic lesions in the ovaries known as endometriomas. Superficial endometriosis is typically detected by laparoscopy along the pelvic peritoneum as these lesions tend to be difficult to detect by imaging. Deep infiltrative endometriosis may be detected by ultrasound, CT or MRI in classic locations within the pelvis, such as the posterior cul-de-sac and uterosacral ligaments. Endometriosis may also involve the thorax, gastrointestinal and urinary tracts, and locations such as the abdominal wall and abdominal organs. We present MRI and CT case examples, together with corresponding laparoscopic and histopathology images to enhance radiologists' understanding of this disease. [ABSTRACT FROM AUTHOR]

GEN-1 is a gene-based immunotherapy, comprising a human IL-12 gene expression plasmid and a synthetic plasmid delivery system, delivered intraperitoneally (ip.) to produce local and persistent levels of a pleiotropic immunocytokine, IL-12, at the tumor site in patients with advanced ovarian cancer. The goal of local and persistent IL-12 delivery is to remodel the highly immunosuppressive tumor microenvironment to favor immune stimulation while avoiding serious systemic toxicities, a major limitation of recombinant IL-12 therapy. Safe and sustained local production of IL-12 and related immunocytokines at the tumor site could produce potentially more favorable immunological changes in the tumor microenvironment and antitumor responses than a bolus systemic delivery of recombinant IL-12. Treatment safety, clinical benefits and biological activity of GEN-1 ip. in patients with ovarian cancer and in representative animal models are described. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with ovarian cancer often report elevated anxiety at diagnosis that decreases posttreatment. However, a minority of patients experience sustained anxiety. Few studies have examined risk factors for persistent anxiety or its physiologic sequelae in ovarian cancer. Therefore, the authors investigated associations between prior life events, anxiety, inflammation (plasma levels of interleukin‐6), and diurnal cortisol profiles in patients with ovarian cancer during the first year postdiagnosis. METHODS: Participants (n = 337) completed surveys and had blood and salivary sampling prediagnosis, postchemotherapy (6 months), and 12 months after diagnosis. The Life Events and Difficulties Schedule was administered to a patient subset (n = 127) within 1 month of diagnosis. Linear mixed‐effects models were used to analyze relations between anxiety and biologic variables over time. Linear regression models assessed whether anxiety trajectories mediated associations between prior stress exposure and biologic variables. Age, chemotherapy at 1 year, and cancer stage were covariates. RESULTS: Decreased anxiety was associated with a more normalized cortisol slope over time (β = 0.092; P = .047). Early life adversity was related to flatter cortisol slopes over time (β = −0.763; P = .002); this relation was partially mediated by anxiety trajectory (P = .046). More danger‐related events prediagnosis were associated with sustained anxiety (β = 0.537; P = .019) and flatter cortisol slopes over time (β = −0.243; P = .047); anxiety partially mediated the relation between danger and cortisol slope (P = .037). Neither anxiety nor prior stress exposure was related to levels of interleukin‐6. CONCLUSIONS: Because dysregulated cortisol has been related to fatigue, poorer quality of life, and shorter survival in patients with ovarian cancer, those who have prior life events and chronic anxiety during the first year postdiagnosis may be at risk for more negative outcomes. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Social factors in the patient macroenvironment have been shown to influence molecular events in the tumor microenvironment and thereby influence cancer progression. However, biomarkers providing a window into the longitudinal effects of biobehavioral factors on tumor biology over time are lacking. Exosome analysis is a novel strategy for in vivo monitoring of dynamic changes in tumor cells. This study examined exosomal profiles from patients with low or high levels of social support for epithelial-mesenchymal transition (EMT) polarization and gene expression related to inflammation and β-adrenergic signaling.Methods: Exosomes were isolated from plasma sampled from a series of 40 women before primary surgical resection of advanced-stage, high-grade ovarian carcinoma. Samples were selected for analysis on the basis of extremes of low and high levels of social support. After exosomal isolation and RNA extraction, a microarray analysis of the transcriptome was performed.Results: Primary analyses identified significant upregulation of 67 mesenchymal-characteristic gene transcripts and downregulation of 63 epithelial-characteristic transcripts in patients with low social support; this demonstrated increased EMT polarization (P = .0002). Secondary analyses using promoter sequence bioinformatics supported a priori hypotheses linking low social support to 1) increased activity of cyclic adenosine monophosphate response element binding protein (CREB)/activating transcription factor (ATF) family transcription factors that mediate the β-adrenergic response to catecholamines via the cyclic adenosine monophosphate/protein kinase A signaling pathway (mean fold change for CREB: 2.24 ± 0.65; P = .0019; mean fold change for ATF: 2.00 ± 0.55; P = .0049) and 2) increased activity of the proinflammatory nuclear factor κB/Rel family of transcription factors (mean fold change: 2.10 ± 0.70; P = .0109).Conclusions: These findings suggest the possibility of leveraging exosomes as a noninvasive assessment of biobehavioral factors to help to direct personalized treatment approaches. Cancer 2018;124:580-6. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: Because of the poor prognosis of ovarian cancer and concomitant distress, understanding contributors to positive well-being is critical. This study examines spiritual growth as a domain of posttraumatic growth and its contribution to longitudinal emotional outcomes in ovarian cancer.Methods: Ovarian cancer patients (N = 241) completed measures assessing spirituality (Functional Assessment of Chronic Illness Therapy-Spiritual Well-being-12; subscales: faith, meaning, and peace), depression (Center for Epidemiologic Studies Depression Scale), cancer-specific anxiety (Impact of Event Scale), and total mood disturbance (TMD; Profile of Mood States) prior to surgery and 1-year postsurgery. Stressful life events in the year after diagnosis were measured at 1-year postsurgery. Regressions examined the association between changes in spirituality and depression, anxiety, and TMD at 1-year postsurgery. Additionally, spiritual change was examined as a moderator of the effect of recent life events on mood.Results: Increases in peace were related to lower depression (β = -.40, P < .001), anxiety (β = -.20, P = .004), and TMD (β = -.41, P < .001) at 1 year. Changes in meaning and faith were unrelated to all outcomes. Additionally, changes in peace moderated the effect of stressful life events on depression (β = -.14, P = .027), anxiety (β = -.16, P = .05), and TMD (β = -.17, P = .01), such that those with a high number of life events paired with a decrease in peace experienced the worst psychological outcomes at 1 year.Conclusion: These findings suggest that the quality of peace may be the most adaptive facet of spiritual growth in cancer patients. Furthermore, changes in peace appear to moderate the effect of life events on psychological well-being. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to do the following: (1) describe progression free survival (PFS) and overall survival (OS) of women with cervical cancer presenting with occult supraclavicular lymph node (SCLN) metastases, identified by positron emission tomography CT (PET-CT) and (2) compare OS of patients with isolated SCLN metastases to that of patients with SCLN and extranodal metastatic disease.Methods: Patients were identified retrospectively. Treatment intent was abstracted. PFS and OS in the high-dose chemo-radiotherapy (RT), palliative RT, and supportive treatment groups, as well as OS of patients with SCLN metastases only vs. SCLN and extranodal metastases were calculated.Results: Fourteen patients received high-dose chemo-RT, 32 received palliative RT, and 6 received supportive care (n = 52). Median PFS was 3 months in high-dose chemo-RT group and 1 month in palliative RT (p = ns). Median OS was 12 months in high-dose chemo-RT group, 7 months in palliative RT group, and 2 months in palliative care group (p = 0.05). OS was significantly different between patients with isolated SCLN disease vs. SCLN and extranodal disease, that is, 10.5 vs. 3 months (p = 0.009, χ2 = 6.9).Conclusions: In this limited analysis, median OS of cervical cancer patients with PET/CT-positive SCLN metastases was the longest when treated with high-dose chemo-RT. Patients with SCLN and extranodal metastases experienced significantly shorter OS, as compared to patients with SCLN only disease. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate if locus of control (LOC) predicts various quality of life (QOL) and mental well-being measures among terminally ill cancer patients at the time of palliative care consult.Methods: Multi-site analysis of patients with advanced cancer being seen as new patients in a Palliative and Supportive Care outpatient clinic. Patients completed the following surveys: locus of control (LOC) scale, Functional Assessment of Chronic Illness Therapy-General (FACT-G), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Hospital Anxiety Depression Scale (HADS), and Herth Hope Index (HHI). Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of age, gender, race, partnership status, education, and months since diagnosis as potential confounders.Results: This study enrolled 100 patients. After adjusting for site, race, and partnership status, higher levels of LOC chance predicted decreased QOL (FACT-G) (p < 0.01). Higher levels of LOC chance also correlated with increased depression and anxiety (p ≤ 0.01) and decreased meaning/peace and faith (p ≤ 0.01). Additionally, higher levels of LOC chance predicted decreased hope (HHI) (p ≤ 0.001).Conclusions: Terminally ill cancer patients with a high LOC chance may be at risk for decreased physical and mental well-being at the end of life. Efforts should be made to identify these patients and design interventions to increase their feeling of control over the situation in order to improve physical and mental well-being at the end of life. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients.Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained from medical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology.Results: Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR = 1.66, 95% CI = 1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR = 2.23, 95% CI = 1.19 to 4.18, two-sided P trend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors.Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted. [ABSTRACT FROM AUTHOR]

Background: The impact of psychological well-being on the physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, the authors examined how 2 different aspects of well-being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in patients with ovarian cancer.Methods: A total of 365 women with suspected ovarian cancer completed psychosocial assessments before surgery and clinical information was obtained from medical records. Study inclusion was confirmed after histological diagnosis. Tumor NE was measured in frozen tissue samples using high-performance liquid chromatography with electrochemical detection. Confirmatory factor analysis was used to model eudaimonic well-being, positive affect, and psychological distress, and structural equation modeling was used to examine associations between these factors and tumor NE.Results: Eudaimonic well-being, positive affect, and psychological distress, modeled as distinct but correlated constructs, best fit the data (ie, compared with unitary or 2-factor models) (root mean square error of approximation, 0.048; comparative fit index, 0.982; and standardized root-mean-squared residual, 0.035). Structural equation modeling analysis that included physical well-being, stage of disease, histology, psychological treatment history, beta-blocker use, and caffeine use as covariates was found to have good model fit (root mean square error of approximation, 0.052; comparative fit index, 0.955; and standardized root-mean-squared residual, 0.036) and demonstrated that eudaimonic well-being was related to lower tumor NE (β = -.24 [P = .045]). In contrast, no effects were found for positive affect or psychological distress.Conclusions: Eudaimonic well-being was found to be associated with lower tumor NE, independent of positive affect and psychological distress. Because adrenergic signaling is implicated in tumor progression, increasing eudaimonic well-being may improve both psychological and physiologic resilience in patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta-adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]).Methods: A multicenter review of 1425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta-blocker use during chemotherapy and those without beta-blocker use.Results: The median age of patients in the current study was 63 years (range, 21-93 years). The sample included 269 patients who received beta-blockers. Of those, 193 (71.7%) were receiving beta-1-adrenergic receptor selective agents, and the remaining patients were receiving nonselective beta antagonists. The primary indication for beta-blocker use was hypertension but also included arrhythmia and postmyocardial infarction management. For patients receiving any beta-blocker, the median overall survival (OS) was 47.8 months versus 42 months for nonusers (P =.04). The median OS based on beta-blocker receptor selectivity was 94.9 months for those receiving nonselective beta-blockers versus 38 months for those receiving beta-1-adrenergic receptor selective agents (P<.001). Hypertension was associated with decreased OS compared with no hypertension across all groups. However, even among patients with hypertension, a longer median OS was observed among users of a nonselective beta-blocker compared with nonusers (38.2 months vs 90 months; P<.001).Conclusions: Use of nonselective beta-blockers in patients with EOC was associated with longer OS. These findings may have implications for new therapeutic approaches. Cancer 2015;121:3435-43. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

The importance of adrenergic pathways in cancer has long been suspected, but now there is mounting epidemiological, preclinical, and clinical evidence of its importance in gynecologic cancers. To date, most of these effects are mediated primarily through the beta 2 adrenergic receptor activation of the tumor cell cyclic AMP-protein kinase A signaling pathway. This review will discuss the current knowledge about the neuroendocrine stress response in gynecologic tumor biology. [ABSTRACT FROM AUTHOR]

BACKGROUND Sleep disturbance is a common clinical complaint of oncology patients and contributes to substantial morbidity. However, because most sleep studies have been cross-sectional, associations between sleep quality and distress in patients with ovarian cancer over time remain unclear. This prospective longitudinal study examined rates of sleep disturbance; contributions of depression, anxiety, and medication use in sleep disturbance; and associations between sleep quality and quality of life (QOL) during the first year after diagnosis among women with ovarian cancer. METHODS Women with a pelvic mass completed measures of sleep quality, depression, anxiety, and QOL before surgery. Those diagnosed with primary epithelial ovarian, fallopian tube, or peritoneal cancer repeated surveys at 6 months and 1 year after diagnosis. Mixed modeling was used to examine trajectories of psychosocial measures over time, as well as associations between changes in distress and sleep quality. Relationships between changes in sleep and QOL were also examined. RESULTS The majority of patients reported disturbed global sleep (Pittsburgh Sleep Quality Index > 5) at all 3 time points. Medications for sleep and pain were associated with worse sleep at all time points. Greater increases in depression were associated with increased disturbances in sleep quality over time ( P < .04). Worsening sleep was also associated with declines in QOL over time ( P < .001). CONCLUSIONS Sleep disturbance is common and persistent in women with ovarian cancer, and is linked to depressive symptoms and QOL. Pharmacologic treatment does not appear to adequately address this problem. Results highlight the need for ongoing screening and intervention for sleep disturbance in this population. Cancer 2013;119:3234-3241. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK) pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3ß (GSK3ß), and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3ß inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3ß by either lithium chloride (LiCl) or specific GSK3ß inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952) and type II (ARK1) endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3ß activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth. [ABSTRACT FROM AUTHOR]

The article focuses on a study about DICER1 expression and outcomes related to endometroid endometrial adenocarcinoma. The processes undertaken for the study are discussed which include loss of heterozygosity, methylation and statistical analyses. Results show that DICER1 expression levels tend to differ in primary endometroid endometrial tumors while lower transcripts are said to lead to the worse clinical outcomes. It suggests the future use of DICER1 expression assessment in risk assessment.

BACKGROUND: The effect of body mass index (BMI) on treatment outcomes for patients with locally advanced cervical carcinoma who receive definitive chemoradiation is unclear. METHODS: The cohort in this study included all patients with cervical carcinoma (n = 404) who had stage IB1 disease and positive lymph nodes or stage ≥IB2 disease and received treatment at the authors' facility between January 1998 and January 2008. The mean follow-up was 47.2 months. BMI was calculated using the National Institute of Health online calculator. BMI categories were created according to the World Health Organization classification system. Primary outcomes were overall survival, disease- free survival, and complication rate. Univariate and multivariate analyses were performed. Kaplan-Meier survival curves were generated and compared using Cox proportional hazard models. RESULTS: On multivariate analysis, compared with normal weight (BMI 18.5-24.9 kg/m²), a BMI <18.5 kg/m² was associated with decreased overall survival (hazard ratio, 2.37; 95% confidence interval, 1.28-4.38; P < .01). The 5-year overall survival rate was 33%, 60%, and 68% for a of BMI <18.5 kg/m², a BMI from 18.5 kg/m² to 24.9 kg/m², and a BMI >24.9 kg/m², respectively. A BMI <18.5 kg/m² was associated with increased risk of grade 3 or 4 complications compared with a BMI >24.9 kg/m² (radiation enteritis: 16.7% vs 13.6%, respectively; P = .03; fistula: 11.1% vs 8.8%, respectively; P = .05; bowel obstruction: 33.3% vs 4.4%, respectively; P < .001; lymphedema: 5.6% vs 1.2%, respectively; P = .02). CONCLUSIONS: Underweight patients (BMI <18.5 kg/m²) with locally advanced cervical cancer had diminished overall survival and more complications than normal weight and obese patients. [ABSTRACT FROM AUTHOR]

Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)–protein kinase A (PKA) signaling pathway by the β2 adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify β-adrenergic activation of the cAMP–PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Uterine serous cancer (USC) is an aggressive form of endometrial cancer. USC constitutes less than 10% of endometrial cancer cases but is responsible for up to 40% of endometrial cancer deaths. Response to standard platinum and taxane therapy is modest, particularly in the recurrent setting. Thus, novel therapeutic strategies are needed to overcome this drug resistance. We hope that our findings provide strong preclinical support for the combination of an AXL inhibitor with bevacizumab in USC clinical trials in the recurrent setting. Endometrial cancer remains the most prevalent gynecologic cancer with continued rising incidence. A less common form of this cancer is uterine serous cancer, which represents 10% of endometrial cancer cases. However, this is the most aggressive cancer. The objective was to assess whether inhibiting the receptor tyrosine kinase AXL with AVB-500 in combination with bevacizumab would improve response in uterine serous cancer. To prove this, we conducted multiple angiogenesis assays including tube formation assays and angiogenesis invasion assays. In addition, we utilized mouse models with multiple cells lines and subsequently analyzed harvested tissue through immunohistochemistry CD31 staining to assess microvessel density. The combination treatment arms demonstrated decreased angiogenic potential in each assay. In addition, intraperitoneal mouse models demonstrated a significant decrease in tumor burden in two cell lines. The combination of AVB-500 and bevacizumab reduced tumor burden in vivo and reduced morphogenesis and migration in vitro which are vital to the process of angiogenesis. [ABSTRACT FROM AUTHOR]