Predictors of Blood Transfusion in Patients Undergoing Cytoreductive Surgeries for Ovarian Malignancy.

OBJECTIVES: The aims of this study were to describe the baseline estimated blood loss (EBL) in surgery and transfusion rate in patients undergoing cytoreductive surgeries for ovarian malignancy, and identify perioperative variables associated with blood loss and transfusion. METHODS: A retrospective cohort study at a single institution was performed that included patients with known or suspected ovarian malignancy undergoing cytoreductive surgery between 2016 and 2021. t tests, χ2 tests, and multiple logistic regression analyses were used. RESULTS: Among 44 patients meeting inclusion criteria, 61% received perioperative blood transfusion. There were significant differences in EBL and preoperative hemoglobin levels between patients who did and did not receive transfusion (EBL 442.6 vs 236.8 mL, P = 0.0008; preoperative hemoglobin 10.2 vs 11.2 g/dL, P = 0.049). After adjusting for preoperative hemoglobin, the risk of transfusion increased for each additional 200 mL of EBL (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.5-9.5). Stratified by race, the association between EBL and transfusion risk remained statistically significant only for non-Latinx White patients (OR 6.1, 95% CI 1.7-21.9), who made up 77% of the study population, but not for patients of other races and ethnicities (OR 1.0, 95% CI 0.16-6.42). CONCLUSIONS: Perioperative blood transfusion is common in patients undergoing cytoreductive surgery. In this study, EBL and preoperative hemoglobin levels were significantly associated with transfusion receipt. Clinicians should optimize hemoglobin levels and intraoperative blood conservation strategies to reduce the need for transfusion. The results also highlight the importance of considering racial and ethnic differences when developing strategies to reduce transfusion risk.

Presence of low volume metastases does not alter management in node-negative, early-stage cervical cancer patients who underwent postoperative adjuvant therapy: A retrospective cohort study.

Objective: This study sought to determine if patients with early stage cervical cancer who possessed intermediate-high risk factors (defined by Peters or Sedlis criteria) and had pathologically negative lymph nodes at the time of surgery had higher rates of low volume metastases (LVM) on retrospective ultrastaging. Methods: This IRB-approved retrospective cohort study collected data via chart review on early stage, surgically-treated node-negative cervical cancer patients who underwent postoperative adjuvant therapy, treated at a single institution from January 2011 through June 2021. Nodal blocks were retrospectively ultrastaged per standard protocol. Descriptive statistics were performed for analysis. Results: Over the 10-year study period, n = 20 patients met study inclusion criteria. Most patients were white with squamous cell histology, with a mean number of 25.15 (SD = 12) nodes examined on initial pathologic evaluation. 85 % (n = 17) patients were pathologic stage IB. 85 % of the cohort were recommended for adjuvant radiation, with the remaining 15 % for cisplatin-based chemoradiation. LVM in the form of micrometastasis was retrospectively identified in one patient (5 %) who had received whole pelvic radiation and recurred locally within the irradiated field. Conclusions: This small retrospective series of surgically managed cervical cancer with intermediate-high risk tumor factors identified only 1 patient with LVM, representing 5% of the total population. The biologic importance of ITC and LVM remains unclear in cervical cancer, however this investigation highlights the low incidence even when all nodes are evaluated in a higher risk cohort. The presence of LVM would not have changed management decisions based on this retrospective analysis.

Metastatic Uterine Leiomyosarcoma presenting as small bowel intussusception at two independent visits.

•Metastatic disease to the small bowel may present with intussusception.•Clinical decision making for malignant bowel obstruction is difficult and individual specific.•Malignant bowel obstruction due to metastatic year has an average life expectancy of less than 200 days.

PARP inhibitors in the treatment of ARID1A mutant ovarian clear cell cancer: PI3K/Akt1-dependent mechanism of synthetic lethality.

Introduction: Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme involved in the repair of DNA single-strand breaks (SSB). The recent development of poly(ADP-ribose) polymerase inhibitors (PARPi) results from over 45 years of studies. When the activity of PARP1 or PARP2 is compromised, DNA SSB lesions are unresolved and can be converted to DNA double-strand breaks (DSBs) by the cellular transcription mechanisms. ARID1A (also called BAF250a) is an important component of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex. ARID1A gene demonstrates >50% of mutation rate in ovarian clear-cell carcinomas (OCCC). Mutated or downregulated ARID1A significantly compromises the Homologous Recombination Repair (HRR) of DNA DSB. Results: The present study demonstrated that downregulated or mutated ARID1A attenuates DNA HRR through stimulation of the PI3K/Akt1 pathway and makes tumor cells highly sensitive to PARPi and PARPi/ionizing radiation (IR) combination. We showed that PI3K/Akt1 pathway plays an important role in the sensitization of cancer cell lines with compromised function of ARID1A to PARPi treatment. Discussion: We believe that using of PARPi monotherapy or in combination with radiation therapy is an appealing strategy for treating ARID1A-mutated cancers, as well as many other types of PI3K/Akt1-driven cancers.

Change in vaginal length and sexual function in women who undergo surgery ± radiation therapy for endometrial cancer.

PURPOSE: Endometrial Cancer (EC) is the most common gynecologic malignancy in the United States. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk. Treatment can cause significant vaginal changes, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These are not life threatening, but affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are inconsistent recommendations on use. This prospective study compared vaginal length changes and sexual function in women compliant with dilation versus not after surgery and RT. METHODS AND MATERIALS: Enrolled patients underwent surgery for Stage I-IIIC EC ±RT. Vaginal dilator use was recommended for women receiving RT (external beam or brachytherapy). Vaginal length was measured with a vaginal sound and the Female Sexual Function Index (FSFI) was used to assess sexual function. RESULTS: Forty-one enrolled patients had sufficient data for analysis. Dilation significantly increased FSFI scores (p = 0.02) while RT without dilation showed a significant decrease (p = 0.04). Dilation helped maintain vaginal length for all patients (0 cm vs. 1.8 cm loss (p = 0.03)). Individual arms did not show statistically significant changes in length with dilation, though the trend showed RT without dilation had an average loss of 2.3 cm as compared to only 0.2 cm for regular dilation. Notably, there was no difference in length change with dilation for surgery alone versus surgery and RT (p = 0.14). CONCLUSION: This data provides novel, prospective evidence of the benefit of vaginal dilation for maintaining vaginal length and improving sexual health after any pelvic treatment for EC. This evidence also supports that the addition of RT after surgery does not appear to significantly worsen vaginal shortening. This study has important implications for providing a strong foundation for future studies and helping to establish solid clinical management criteria for the prevention of vaginal stenosis and promotion of female sexual health.

Preferential human epidermal growth factor receptor 2 expression in myometrial and lymphovascular invasion of a uterine carcinosarcoma: A case report.

This case report describes a unique pattern of human epidermal growth factor receptor 2 expression in a patient with uterine carcinosarcoma. The endometrial tumor showed biphasic morphology composed of serous carcinoma and a heterologous high-grade sarcoma component. Human epidermal growth factor receptor 2 immunostaining showed positive (3+) expression in foci of myoinvasion, lymphovascular invasion, and lymph node metastasis but was negative in both the endometrial surface tumor and sarcomatous component. Fluorescent in situ hybridization testing for human epidermal growth factor receptor 2 confirmed no amplification within the endometrial surface carcinoma component and amplification of the lymphovascular invasion component. As the use of human epidermal growth factor receptor 2 immunohistochemical evaluation becomes more commonplace for therapeutic consideration in patients with uterine carcinosarcoma, interpretation of the immunohistochemical should be performed preferentially on large tissue sections including both a surface, myoinvasive portions, and suspected areas of lymphovascular invasion and lymph node metastasis.

Effects of the WRITE Symptoms Interventions on Symptoms and Quality of Life Among Patients With Recurrent Ovarian Cancers: An NRG Oncology/GOG Study (GOG-0259).

PURPOSE: GOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL). METHODS: Patients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates. RESULTS: Participants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time (P < .001) for all three groups. A group by time interaction (P < .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time. CONCLUSION: Both WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study.

The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors.

Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 - 60 minute mixed mode aerobic exercises, comprising 10 - 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p<0.001], lower CXCR2 [4878 (1796) v 6330 (1299) MFI, p=0.032] and higher TLR2 [98 (32) v 72 (17) MFI, p=0.022] expression, while IL-6 [7.4 (5.4) v 4.0 (2.7) pg/mL, p=0.079] levels were marginally higher and IL-8 [6.0 (4.7) v 7.9 (5.0) pg/mL, p=0.316] levels similar. After 16 weeks of training, compared to Controls, BCS Final PRE phagocytosis [4510 (738) v 4881 (417) MFI, p=0.146] and TLR2 expression [114 (92) v 72 (17) MFI, p=0.148] were no longer different. Acute Exercise Responses. As compared to Controls, at Base, BCS phagocytic Pre-Post response was lower [mean difference, % (SD): 12% (26%), p=0.042], CD16 Pre-Post response was lower [12% (21%), p=0.016] while CD16 Pre-1Hr response was higher [13% (25%), p=0.022], TLR2 Pre-Post response was higher [15% (4%) p=0.002], while IL-8 Pre-Post response was higher [99% (48%), p=0.049]. As compared to Controls, following 16 weeks of training BCS phagocytic Pre-Post response [5% (5%), p=0.418], CD16 Pre-1Hr response [7% (7%), p=0.294], TLR2 Pre-Post response [6% (4%), p=0.092], and IL-8 Pre-Post response [1% (9%), p=0.087] were no longer different. Following cancer therapy, BCS may have impaired neutrophil functions in response to an acute bout of exercise that are partially restored by 16 weeks of exercise training. The improved phagocytosis of bacteria in BCS may represent an exercise-induced intrinsic improvement in neutrophil functions consistent with a reduced risk of infectious disease. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03760536.

Exercise-induced modulation of monocytes in breast cancer survivors.

BACKGROUND: Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. OBJECTIVES: The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. METHODS: Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. RESULTS: Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (-9989, p=0.014), IL-1ß+CD14+CD16+ MFI (-11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (-63, p=0.002) and CD14+CD16+ (-18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. CONCLUSIONS: Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

Asparagus officinalis Exhibits Anti-Tumorigenic and Anti-Metastatic Effects in Ovarian Cancer.

Ovarian cancer is one of the leading causes of female cancer death. Emerging evidence suggests that many dietary natural products have anti-tumorigenic activity, including that of asparagus officinalis. The current study aimed to assess the anti-tumorigenic and anti-metastatic effects of asparagus officinalis on serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer. Asparagus officinalis decreased cellular viability, caused cell cycle G1 phase arrest and induced apoptosis in the OVCAR5 and SKOV3 cells. Induction of apoptosis and inhibition of cell proliferation was rescued by the pan-caspase inhibitor, Z-VAD-FMK, implying that its cytotoxic effects were mainly dependent on caspase pathways. Asparagus officinalis increased levels of ROS and decreased mitochondrial membrane potential with corresponding increases in PERK, Bip, Calnexin PDI and ATF4 in both cell lines. Treatment with asparagus officinalis also reduced ability of adhesion and invasion through epithelial-mesenchymal transition and reduction of VEGF expression. The combination of Asparagus officinalis with paclitaxel had synergistic anti-proliferative activity. Furthermore, Asparagus officinalis significantly inhibited tumor growth and reduced serum VEGF in a genetically engineered mouse model of ovarian cancer under obese and lean conditions, accompanied with a decrease in the expression of Ki67, VEGF and phosphorylated S6, and in an increase in phosphorylation of AMPK in the ovarian tumor tissues. Overall, our data provide a pre-clinical rationale for asparagus officinalis in the prevention and treatment of ovarian cancer as a novel natural product.

Impact of community-based exercise program participation on aerobic capacity in women with and without breast cancer.

BACKGROUND: Evidence for exercise as an efficacious strategy to improve aerobic capacity of breast cancer survivors (BCS) has come largely from intervention studies conducted in laboratory settings. There is an increasing need to translate to community-type settings, but the efficacy of those interventions using gold standard evaluation is not well-established. AIM: To investigate whether similar improvement in aerobic capacity (maximal oxygen consumption [VO2]) measured with gold standard testing can be achieved through a community-based setting in BCS. METHODS: A peak cardiopulmonary exercise test (VO2peak), 6-min walk test (6MWT), and timed up and go test (TUG) were assessed pre- and post-16 wk of progressive intensity aerobic and strength training exercise at a community center. RESULTS: The sample consisted of 31 early BCS (< 1 year since treatment completion) and 15 controls (CTLs). Both groups significantly improved VO2peak (+1.2 mL/kg/min; P = 0.030), 6MWT (+35 meters; P < 0.001), and TUG (-0.44 s; P < 0.01) following training. Both groups improved peak cycling power during the cardiopulmonary exercise test with BCS improving by +10 watts more than the CTLs (P = 0.020). Average exercise attendance was 71% (34 of 48 possible days), but compliant days averaged only 60% of total days for aerobic, and < 40% for strength in both groups. CONCLUSION: Community-based exercise programs can be an effective strategy to improve aerobic capacity and physical function for early-stage BCS but potentially not to the same extent observed in laboratory-based randomized controlled trials. Further research is needed to explore barriers and facilitators of exercise engagement in community-based centers to maximize training benefits for adults with cancer.

Genomic profiling of endometrial cancer and relationship with volume of endometrial cancer disease spread.

OBJECTIVES: Lymph node (LN) metastasis and genomic profiles are important prognostic factors in endometrial cancer (EMCA). However, the prognostic significance of low volume metastasis found in sentinel lymph nodes (SLN) is unknown. We sought to determine if genomic mutations were associated with metastatic volume. METHODS: Surgically staged women with EC who were enrolled in both a SLN clinical trial and tumor sequencing protocol were eligible. Relevant targets were enriched by a custom designed Agilent SureSelect hybrid capture enrichment library using standard protocols. Three specific gene mutations were evaluated, TP53, PTEN and PIK3CA in the primary tumor of patients with LN negative, LN positive and ITC disease. RESULTS: 42 patients were eligible; of these, 7 (16.7%) had ITC only and 7 (16.7%) had micrometastatic or macrometastatic (LN positive) disease. No differences were seen in TP53, PIK3CA or PTEN between groups. All ITC patients with TP53 mutations were of non-endometrioid histology (2/7). Deeper myometrial invasion and lymph vascular space invasion were more likely to occur in the LN positive group (p < 0.01 for both). No patients with ITC had a recurrence in a median 67.7 months of follow-up since surgery. CONCLUSIONS: This pilot investigation did not identify differences between frequency of PIK3CA, PTEN or TP53 mutations in tumors and volume of LN metastasis. Low number of ITC limited the ability to detect genomic differences, however mutations appeared to align with expected histology. More work is needed to define the relationship between genomic mutations, histology, ITC, and prognosis.

Vulvar Hibernoma: An Unusual Lipomatous Tumor in an Adolescent.

BACKGROUND: Lipomatous tumors of the vulva are exceedingly rare, particularly in adolescents. We describe the work-up and management of an adolescent girl who presented with a large, well-vascularized vulvar mass. CASE: A 14-year-old girl presented with a large vulvar mass of unclear etiology. Magnetic resonance imaging of this mass revealed an ill-defined, well-vascularized mass with fat signal characteristics suggestive of a lipomatous tumor that was concerning for malignancy. We performed complete resection of the mass, and histologic evaluation revealed a vulvar hibernoma. There have been no signs of recurrence 1 year later. SUMMARY AND CONCLUSION: Although rare, a hibernoma of the vulvar region may present in adolescence and may be concerning for malignancy on imaging. Complete resection of these tumors is recommended for definitive diagnosis and treatment.

Acute extraperitoneal spontaneous bladder rupture in cervical cancer patient undergoing chemoradiation: A case report and review of the literature.

The standard of care for locally advanced cervical cancer is pelvic radiotherapy with sensitizing cisplatin, and intracavitary brachytherapy. This standard of care treatment paradigm has best survival outcomes, however is associated with genitourinary toxicities. Spontaneous bladder rupture (SBR) is a rare complication of chemoradiation that has only been reported in literature as an intraperitoneal rupture occurring years after the cessation of treatment. We herein present a novel case of extraperitoneal SBR in a 27-year-old female with FIGO Stage IIIC cervical cancer and no prior surgical history who was undergoing chemoradiation with sensitizing cisplatin. During her final planned brachytherapy treatment upon instilling the bladder under ultrasound guidance, an anterior midline extraperitoneal rupture was noted. She was managed conservatively for several weeks and during this time was ultimately able to complete her external beam therapy and last cycle of cisplatin. After approximately ten weeks of conservative management, imaging demonstrated complete resolution of the rupture. A review of the literature suggests this complication tends to occur as an intraperitoneal rupture years after the cessation of therapy. Late genitourinary complications and types of complications are rarely reported in clinical trials, so it is difficult to determine the true incidence of rare complications and identify patients that may be at risk.

SPR965, a Dual PI3K/mTOR Inhibitor, as a Targeted Therapy in Ovarian Cancer.

SPR965 is an inhibitor of PI3K and mTOR C1/C2 and has demonstrated anti-tumorigenic activity in a variety of solid tumors. We sought to determine the effects of SPR965 on cell proliferation and tumor growth in human serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer (KpB model) and identify the underlying mechanisms by which SPR965 inhibits cell and tumor growth. SPR965 showed marked anti-proliferative activity by causing cell cycle arrest and inducing cellular stress in ovarian cancer cells. Treatment with SPR965 significantly inhibited tumor growth in KpB mice, accompanied by downregulation of Ki67 and VEGF and upregulation of Bip expression in ovarian tumors. SPR965 also inhibited adhesion and invasion through induction of the epithelial-mesenchymal transition process. As expected, downregulation of phosphorylation of AKT and S6 was observed in SPR965-treated ovarian cancer cells and tumors. Our results suggest that SPR965 has significant anti-tumorigenic effects in serous ovarian cancer in vitro and in vivo. Thus, SPR965 should be evaluated as a promising targeted agent in future clinical trials of ovarian cancer.

Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition.

Uterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such as Tp53 and Pten However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressor Fbxw7 in endometrial cancer through defined genetic model systems. Inactivation of Fbxw7 and Pten resulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquired Trp53 mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial-mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.

Awareness and acceptability of population-based screening for pathogenic BRCA variants: Do race and ethnicity matter?

OBJECTIVE: To evaluate awareness and acceptability of population-based BRCA testing among an unselected population of women presenting for annual gynecologic health assessment, with secondary objective to determine if a racial disparity exists in acceptability and awareness of this screening strategy. METHODS: Women presenting for routine gynecologic care in an outpatient setting of a single academic institution were anonymously surveyed. Survey collected age, self-identified race and ethnicity, education level, personal and family history of breast and/or ovarian cancer (BOC), awareness and interest, and willingness to pay out of pocket for testing. Responses were compared with bivariate and multivariate analysis. RESULTS: Interest in testing was expressed in 150 of 301 (45.1%) of participants. Women with a family history of BOC were more likely to be interested in testing than those without (OR = 1.9 (1.0-3.6)). Interest in testing was associated willingness to pay (OR = 3.3 (1.7-6.4)). Higher education level was associated with awareness of testing (OR = 9.9 (2.0-49.7)). Interest in testing was similar between racial groups, but awareness and willingness to pay for testing were higher among White women. Multivariate analysis with adjustment for education level confirmed that Black and Hispanic women were less likely to have awareness of genetic testing compared to White women and non-Hispanic Women, respectively (OR = 0.11 (0.05-0.3); OR = 0.10 (0.01-0.8)). CONCLUSIONS: Interest in genetic testing among women in the general population is high. Despite interest, awareness of BRCA is poor among Black and Hispanic women even when adjusting for education level.

A Review of Gynecologic Oncology in the Global Setting: Educating and Training the Next Generation of Women's Health Providers.

IMPORTANCE: Women in low- and middle-income countries (LMICs) are responsible for the stability of their families. Child survival is directly linked to the health and well-being of their mother. Cancer is the leading cause of morbidity and mortality worldwide, and the incidence and mortality for women from cancer are projected to increase over the coming decades. Gynecologic cancer outcomes are improved when women are cared for by a gynecologic oncologist; however, there are limited specialized providers in LMICs. Increasing interest and involvement from specialists in the United States will improve partnerships abroad and the care of women worldwide. OBJECTIVE: To summarize the importance of global gynecologic oncology care and the current data for US trainees in obstetrics and gynecology to participate in clinical and capacity-building opportunities. EVIDENCE ACQUISITION: We performed a PubMed literature search for articles pertaining to the topic of global health education in obstetrics and gynecology and gynecologic oncology specifically. RESULTS: Many obstetric and gynecologic residency programs offer international opportunities, but these are less than those in other specialties and are more frequently focused in obstetrics. Many gynecologic oncology fellowship programs offer international experiences for fellows; however, the time and resources required are limited. Several US and international programs are ongoing to improve capacity building for gynecologic oncology in LMICs with local trainees. CONCLUSIONS AND RELEVANCE: Training and care in gynecologic oncology care worldwide are improving through efforts at multiple levels. Continued efforts are needed to improve US trainee international education and experience.

ONC201 demonstrates anti-tumorigenic and anti-metastatic activity in uterine serous carcinoma in vitro.

Uterine serous carcinoma (USC) represents an aggressive histologic subtype of endometrial cancer. It is associated with a poor prognosis, and improved therapies for women battling USCs are greatly needed. ONC201 is an orally bioavailable, first-in-class small molecule that induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) independent of p53. ONC201 has demonstrated anti-tumorigenic activity in pre-clinical models of solid tumors through induction of apoptosis and inactivation of the AKT/MAPK pathways. Recent phase I and II clinical trials have shown that ONC201 is well tolerated and may have single agent activity in high grade glioma patients among others. We sought to determine the effects of ONC201 on cell proliferation in USC and identify the mechanisms by which ONC201 inhibits cell growth in this disease. ONC201 inhibited cell proliferation in a dose-dependent manner in ARK1, ARK2 and SPEC-2 cell lines. The anti-proliferative activity of ONC201 in ARK1 and SPEC-2 cells was associated with induction apoptosis independent of p53 via both a TRAIL mediated apoptotic pathway and a mitochondrial apoptosis pathway. Treatment with ONC201 resulted in significant reduction in adhesion and invasion as well as inhibition of the AKT and MAPK pathways. In addition, ONC201 markedly potentiated the anti-tumorigenic effects of paclitaxel in USC cells. Our results suggest that ONC201 has significant anti-proliferative and anti-metastatic effects in USC cells through both induction of apoptosis and inhibition of the AKT and MAPK pathways. ONC201 and paclitaxel are a promising therapeutic combination in USC cells. Thus, ONC201 should be evaluated as a single agent and as a therapeutic partner with paclitaxel in future clinical trials of USC.