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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]

Although rural residence has been related to health disparities in cancer patients, little is known about how rural residence impacts mental health and quality of life (QOL) in ovarian cancer patients over time. This prospective longitudinal study investigated mental health and QOL of ovarian cancer patients in the first-year post-diagnosis. Women with suspected ovarian cancer completed psychosocial surveys pre-surgery, at 6 months and one-year; clinical data were obtained from medical records. Histologically confirmed high grade epithelial ovarian cancer patients were eligible. Rural/urban residence was categorized from patient counties using the USDA Rural-Urban Continuum Codes. Linear mixed effects models examined differences in psychosocial measures over time, adjusting for covariates. Although disparities were not observed at study entry for any psychosocial variable (all p -values >0.22), urban patients showed greater improvement in total distress over the year following diagnosis than rural patients (p = 0.025) and were significantly less distressed at one year (p = 0.03). Urban patients had a more consistent QOL improvement than their rural counterparts (p = 0.006). There were no differences in the course of depressive symptoms over the year (p = 0.17). Social support of urban patients at 12 months was significantly higher than that of rural patients (p = 0.04). Rural patients reported less improvement in psychological functioning in the year following diagnosis than their urban counterparts. Clinicians should be aware of rurality as a potential risk factor for ongoing distress. Future studies should examine causes of these health disparities and potential long-term inequities and develop interventions to address these issues. • Rural residence is a known risk factor for health disparities in cancer patients. • Rural ovarian cancer patients show worse recovery in quality of life and distress levels in the year following diagnosis. • Education levels do not explain differences in trajectories between rural and urban patients. [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]

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]

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]

A response from the authors of the article "Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer" that was published in a 2015 issue is presented.

• Hope is a significant concern for cancer patients, caregivers, and clinicians. • Associations of hope with biomarkers relevant for ovarian cancer were studied. • Hope is associated with lower levels of inflammation (plasma and ascites IL6) and more normalized diurnal cortisol profiles. • Adjusting for negative affect and hopelessness, hope is significantly associated with lower IL-6 and nocturnal cortisol. Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. Greater hope was significantly related to a steeper cortisol slope, β = −0.193, p = 0.046, and lower night cortisol, β = −0.227, p = 0.018, plasma IL-6, β = −0.142, p = 0.033, and ascites IL-6, β = −0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol β = −0.233, p = 0.017 and ascites IL-6, β = −0.282, p = 0.003, and between hopelessness and a flatter cortisol slope, β = 0.211, p = 0.031. These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope. [ABSTRACT FROM AUTHOR]

Abstract Epithelial ovarian cancer (EOC) is the leading cause of death due to gynecologic malignancy. The majority of advanced stage EOC patients, even those who respond well to frontline therapy, will ultimately recur and succumb to their disease. In platinum-sensitive EOC patients, or those who recur ≥6 months from initial diagnosis, treatment of recurrent disease has traditionally consisted of repeat platinum-based chemotherapy. Secondary cytoreduction remains controversial. Due to recent advances in molecularly targeted treatment options, outcomes for advanced stage EOC patients are significantly improving and hold great promise. This review discusses pivotal trials establishing platinum-based combination chemotherapy as the standard of care and addresses the utility of increasing a patient's platinum-free interval. It then discusses the role of anti-angiogenesis therapeutics, specifically bevacizumab, cediranib, and trebananib and their side effects. Lastly, it reviews key trials for the three poly-adenosine diphosphate [ADP]-ribose polymerases (PARP) inhibitors that have been FDA-approved for maintenance therapy in platinum-sensitive recurrent EOC: olaparib, rucaparib, and niraparib. This review concludes with a discussion regarding ongoing and future clinical trials. Highlights • The standard of care for the treatment of platinum-sensitive recurrent ovarian cancer is platinum-combination chemotherapy. • Platinum therapy should not be delayed in order to prolong the progression free interval. • This review discusses various angiogenesis inhibitors including bevacizumab, cediranib, and trebananib. • This review assesses the benefits, side effects, and future development of PARPi in platinum-sensitive recurrent patients. • More research is necessary to optimize molecularly targeted therapy leading to improved survival for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

To identify differential survival outcomes and immune checkpoint inhibitor (ICI) response in MLH1 hypermethylated versus MLH1 mutated ("Lynch-like") endometrial tumors and determine whether their molecular profiles can elucidate the differential outcomes. 1673 mismatch repair deficient endometrial tumors were analyzed by next-generation sequencing and whole transcriptome sequencing (Caris Life Sciences, Phoenix, AZ). PD-L1, ER, and PR were tested by immunohistochemistry and immune cell infiltrates were calculated using MCP-counter. Significance was determined using Chi-square and Mann-Whitney U tests and adjusted for multiple comparisons. Overall survival (OS) was depicted using Kaplan-Meier survival curves. The endometrial cancer cohort comprised 89.2% patients with MLH1 hypermethylated tumors and 10.8% with MLH1 mutated tumors, with median ages of 67 and 60 years, respectively (p < 0.01). Patients with MLH1 hypermethylated tumors had significantly worse OS and trended toward worse OS following ICI treatment than patients with MLH1 mutated tumors. The immune microenvironment of MLH1 hypermethylated relative to MLH1 mutated was characterized by decreased PD-L1 positivity, immune checkpoint gene expression, immune cell infiltration, T cell inflamed scores, and interferon gamma (IFNγ) scores. MLH1 hypermethylation was also associated with decreased mutation rates in TP53 and DNA damage repair genes, but increased rates of JAK1 , FGFR2 , CCND1 , and PTEN mutations, as well as increased ER and PR positivity. Endometrial cancer patients with MLH1 hypermethylation display significantly decreased survival and discrepant immunotherapy responses compared to patients with MLH1 mutated tumors, which was associated with differential mutational profiles, a more immune cold phenotype, and increased ER/PR expression in MLH1 hypermethylated tumors. Providers may consider early transition from single agent ICI to a multi-agent regimen or hormonal therapy for patients with MLH1 hypermethylated tumors. • MLH1 hypermethylated patients display discrepant survival and immunotherapy outcomes compared to MLH1 mutated patients. • MLH1 hypermethylated tumors have an altered mutational profile compared to MLH1 mutated tumors. • MLH1 hypermethylated tumors display a more immune cold phenotype than MLH1 mutated tumors. • MLH1 tumors have greater estrogen receptor and progesterone receptor positivity than MLH1 mutated tumors. • The MLH1 hypermethylated cohort may benefit from multiple targeted agents rather than sole checkpoint inhibition. [ABSTRACT FROM AUTHOR]

Visceral adiposity has been established as a predictor of outcomes in various cancers. We aimed to determine the association of radiographic measurements of visceral fat with clinical outcomes in patients with endometrial cancer. A retrospective review of patients with stage III-IV endometrial cancer who underwent surgery between 2004 and 2014 was performed. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT;VAT+SAT) were assessed on preoperative computed tomography (CT) scans. Exploratory analysis was performed to establish the optimal cut-off values for VAT, SAT, and TAT to identify patients with poor prognostic body composition. Survival rates were analyzed using Kaplan-Meier analysis, log-rank tests, and cox-regression. Eighty-three patients were included. Forty-two (51%) patients had a low VAT/SAT ratio (<0.45) and 41 (49.4%) had a high VAT/SAT ratio (>0.45). There were no significant differences in demographics between the groups. The mean VAT, SAT, and TAT were 176.3 cm2, 379.3 cm2, and 555.3 cm2 respectively. Compared to patients with low VAT/SAT ratios, patients with high VAT/SAT ratios had a shorter recurrence-free survival (median 29.6 vs 32.3 months, P = 0.01) and shorter overall survival (median 56 vs 93.7 months, P = 0.03). Visceral fat measurements are predictive of outcomes in patients with advanced stage endometrial cancer. Specifically, VAT to SAT ratios are predictive of overall survival. Future studies should be pursued to identify potential therapeutic targets and biological mechanisms that underlie obesity's relationship with endometrial cancer. • Advanced stage endometrial cancer can be difficult to treat as there is no definitive optimal treatment regimen. • Visceral and subcutaneous fat stores can be easily measured on preoperative CT scans. • High visceral to subcutaneous fat ratios were associated with poorer outcomes in this patient cohort. • Preoperative CT scans could be used as a screening tool to determine which patients may require more aggressive treatment. [ABSTRACT FROM AUTHOR]

Rural residence has been related to health disparities and greater mortality risk in cancer patients, including gynecologic cancer patients. Lower survival rates for rural cancer survivors have been attributed to limited access to specialized healthcare, including surgery. Here, we examined whether a rural/urban survival gap existed in ovarian cancer patients receiving surgery at tertiary-care facilities, and potential causes for this gap, including educational attainment. Rural and urban patients with high grade invasive ovarian cancer (n = 342) seeking treatment at two midwestern tertiary-care university hospitals were recruited pre-surgery and followed until death or censoring date. Rural/urban residence was categorized using the USDA Rural-Urban Continuum Codes. Stratified Cox proportional hazards regression analyses, with clinical site as strata, adjusting for clinical and demographic covariates, were used to examine the effect of rurality on survival. Despite specialized surgical care, rural cancer survivors showed a higher likelihood of death compared to their urban counterparts, HR = 1.39 (95% CI: 1.04, 1.85) p = 0.026, adjusted for covariates. A rurality by education interaction was observed (p = 0.027), indicating significantly poorer survival in rural vs. urban patients among those with trade school/some college education, adjusted HR = 2.49 (95% CI: 1.44, 4.30), p = 0.001; there was no rurality survival disparity for the other 2 levels of education. Differences in ovarian cancer survival are impacted by rurality, which is moderated by educational attainment even in patients receiving initial care in tertiary settings. Clinicians should be aware of rurality and education as potential risk factors for adverse outcomes and develop approaches to address these possible risks. • Rural ovarian cancer patients have poorer survival than their urban counterparts even with access to specialized care. • Rural patients with trade school/some college showed markedly poorer outcomes than urban patients with similar education. • There was no rural-urban survival disparity for those completing college or those with high school or less education. • Clinicians should be aware of rurality and education as potential risk factors for compromised care and survival disparities. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effect of palliative care (PC) consultation on hospice enrollment and end-of-life care in gynecologic oncology patients. Methods A retrospective chart review of gynecologic oncology patients who died 1 year before and after 2014 implementation of a PC initiative for patients at a single NCI-designated comprehensive cancer center. Patient demographics, admission and procedural history, anti-cancer therapy, and end-of- life care were collected retrospectively. Data was analyzed using Student's t -test, Mann-Whitney U test, Chi-Square test, or Fisher's exact test. Results We identified 308 patients. Median age at death was 63 years (range 17 to 91). Most patients were white (78.2%), married (47.4%), and had ovarian (35.7%) or uterine cancers (35.4%). Introduction of the PC initiative was associated with increased PC consultations (40%, 53%, p = 0.02), increased hospice enrollment (57%, 61%, p = 0.29), and fewer procedures in the last 30 days of life (44%, 31%, p = 0.01). The rate of enrollment to inpatient hospice doubled from 12.5% to 25.7% ( p = 0.02) while time from inpatient hospice enrollment to death increased from 1.9 to 6.0 days ( p = 0.02). Time from outpatient hospice enrollment to death increased from 26.2 to 35.4 days ( p = 0.18). PC consultation was associated with a doubling of outpatient (40%) and inpatient (80%) hospice enrollment. Conclusions The PC quality improvement initiative was associated with more palliative care consults, increased rates of inpatient and outpatient hospice utilization, increased time on hospice, and fewer procedures in the last 30 days of life, although most women were not enrolled until the last days of life. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate survival after detection of recurrent cervical cancer by FDG-PET in symptomatic versus asymptomatic patients. Methods: This is a prospective registry study of 103 patients treated with definitive chemoradiation for advanced cervical cancer who demonstrated no abnormal FDG uptake (a complete metabolic response, CMR) on their 3-month posttherapy FDG-PET. Their median age was 48 years (range 26–84). The clinical stages were Ib in 38, IIa in 1, IIb in 39, and IIIb in 25. All patients underwent subsequent surveillance FDG-PET. Patients were grouped according to symptom status at the time of the surveillance FDG-PET. Recurrence sites and survival data were analyzed. Results: The median time from the 3-month posttherapy FDG-PET to the first surveillance FDG-PET was 13 months. 25 patients (25/103; 24%) were symptomatic at the time of surveillance FDG-PET and 21 of these had FDG-PET findings indicative of recurrence. 78 patients (78/103; 76%) were asymptomatic and 9 of these had tumor recurrence detected by PET. All recurrences were confirmed by biopsy or radiologic progression. The recurrences in the 21 symptomatic patients were loco regional in 4 and distant in 17. The 9 asymptomatic patients had isolated loco regional disease in 8 and distant disease in 1. All patients received treatment for recurrence. The three-year cause-specific survival for symptomatic recurrences was 19% versus 59% for asymptomatic recurrences (p =0.09). Conclusions: Surveillance FDG-PET can detect asymptomatic recurrent disease that is potentially amenable to salvage therapy. Prospective investigation of surveillance PET is warranted. [Copyright &y& Elsevier]