CT-based radiomic analysis for categorization of ovarian sex cord-stromal tumors and epithelial ovarian cancers.

PURPOSE: To evaluate the diagnostic potential of radiomic analyses based on machine learning that rely on contrast-enhanced computerized tomography (CT) for categorizing ovarian sex cord-stromal tumors (SCSTs) and epithelial ovarian cancers (EOCs). METHODS: We included a total of 225 patients with 230 tumors, who were randomly divided into training and test cohorts with a ratio of 8:2. Radiomic features were extracted from each tumor and dimensionally reduced using LASSO. We used univariate and multivariate analyses to identify independent predictors from clinical features and conventional CT parameters. Clinic-radiological model, radiomics model and mixed model were constructed respectively. We evaluated model performance via analysis of the receiver operating characteristic (ROC) curve and area under ROC curves (AUCs), and compared it across models using the Delong test. RESULTS: We selected a support vector machine as the best classifier. Both radiomic and mixed model achieved good classification accuracy with AUC values of 0.923/0.930 in the training cohort, and 0.879/0.909 in the test cohort. The mixed model performed significantly better than the model based on clinical radiological information, with AUC values of 0.930 versus 0.826 (p = 0.000) in the training cohort and 0.905 versus 0.788 (p = 0.042) in the test cohort. CONCLUSION: Radiomic analysis based on CT images is a reliable and noninvasive tool for identifying SCSTs and EOCs, outperforming experience radiologists.

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas.

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors.

Increased Age-Adjusted Cancer Mortality After the Third mRNA-Lipid Nanoparticle Vaccine Dose During the COVID-19 Pandemic in Japan.

During the COVID-19 pandemic, excess deaths including cancer have become a concern in Japan, which has a rapidly aging population. Thus, this study aimed to evaluate how age-adjusted mortality rates (AMRs) for different types of cancer in Japan changed during the COVID-19 pandemic (2020-2022). Official statistics from Japan were used to compare observed annual and monthly AMRs with predicted rates based on pre-pandemic (2010-2019) figures using logistic regression analysis. No significant excess mortality was observed during the first year of the pandemic (2020). However, some excess cancer mortalities were observed in 2021 after mass vaccination with the first and second vaccine doses, and significant excess mortalities were observed for all cancers and some specific types of cancer (including ovarian cancer, leukemia, prostate cancer, lip/oral/pharyngeal cancer, pancreatic cancer, and breast cancer) after mass vaccination with the third dose in 2022. AMRs for the four cancers with the most deaths (lung, colorectal, stomach, and liver) showed a decreasing trend until the first year of the pandemic in 2020, but the rate of decrease slowed in 2021 and 2022. This study discusses possible explanations for these increases in age-adjusted cancer mortality rates.

Immune pathway through endometriosis to ovarian cancer.

Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Pre-operative plasma VEGF-C levels portend recurrence in epithelial ovarian cancer patients and is a bankable prognostic marker even in the initial assessment of a patient.

PURPOSE: Our explorative study assessed a panel of molecules for their association with epithelial ovarian carcinomas and their prognostic implications. The panel included tissue expression of VEGF-C, COX-2, Ki-67 and eNOS alongside plasma levels of VEGF-C and nitric oxide. METHODS: 130 cases were enrolled in the study. Plasma levels were quantified by ELISA and tissue expressions were scored by immunohistochemistry. The Chi square and Fischer's exact test were applied to examine the impact of markers on clinicopathological factors. Non-parametric Spearman's rank correlation test was applied to define the association among test factors. RESULTS: Plasma VEGF-C levels and COX-2 tissue expression strongly predicted recurrence and poor prognosis (< 0.001). Tissue Ki-67 was strongly indicative of late-stage disease (< 0.001). The aforementioned markers significantly associated with clinicopathological factors. Nuclear staining of VEGF-C was intriguing and was observed to correlate with high grade-stage malignancies, highly elevated plasma VEGF-C, and with recurrence. eNOS tissue expression showed no significant impact while nitric oxide associated positively with ascites levels. Tissue expression of VEGF-C did not associate significantly with poor prognosis although the expression was highly upregulated in most of the cases. CONCLUSION: Plasma VEGF-C holds immense promise as a prognostic marker and the nuclear staining of VEGF-C seems to have some significant implication in molecular carcinogenesis and is a novel finding that commands further robust scrutiny. We present a first such study that assesses a set of biomarkers for prognostic implications in clinical management of epithelial ovarian carcinomas in a pan-Indian (Asian) population.

A Rare Case of Advanced-Stage Small Cell Carcinoma of the Ovary Identified During the Third Trimester of Pregnancy.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare form of aggressive ovarian malignancy linked with mutations in the SMARCA4 gene. This disease predominantly affects young women within the first five decades of life and is associated with poor overall long-term survival, particularly when diagnosed in the advanced stage of the disease. Due to the low incidence of the condition and limited literature, current clinical decision-making is based on a small number of case series and case reports. We present an extremely rare case of SCCOHT diagnosed in a young female during her third trimester of pregnancy, requiring preterm delivery via cesarean section with simultaneous unilateral oophorectomy and salpingectomy.

Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer.

OBJECTIVES: To evaluate the diagnostic value of plasma exosomal miR-223 and its combination with CA125 for the diagnosis of early-stage epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Exosomes derived from the plasma of 78 EOC patients, 40 patients with epithelial benign ovarian tumors, and 52 healthy participants were isolated using the ultracentrifugation method and identified by transmission electron microscopy (TEM) and western blot. RESULTS: The expression of exosomal miR-223 was significantly upregulated in the plasma of EOC patients compared to that in healthy subjects and patients with benign diseases. The combination of exosomal miR-223 and CA125 from plasma had an equivalent area under the ROC curve (AUC) to CA125 alone for discriminating between EOC and non-EOC cases, including healthy subjects and benign ovarian tumors. However, the AUC value of the combination was 0.944 (95% CI: 0.899-0.990) for differentially diagnosing early-stage EOC from healthy subjects, slightly higher than that of CA125 alone (0.928, 95% CI: 0.875-0.981), with a sensitivity and specificity of 0.9784 and 0.885, respectively. CONCLUSION: Our data suggest that plasma exosomal miR-223 can be used as a complement to CA125 to increase the diagnostic power for differentiating early-stage EOC from healthy subjects.

Getting to know ovarian cancer: Focusing on the effect of LncRNAs in this cancer and the effective signaling pathways.

This article undertakes a comprehensive investigation of ovarian cancer, examining the complex nature of this challenging disease. The main focus is on understanding the role of long non-coding RNAs (lncRNAs) in the context of ovarian cancer (OC), and their regulatory functions in disease progression. Through extensive research, the article identifies specific lncRNAs that play significant roles in the intricate molecular processes of OC. Furthermore, the study examines the signaling pathways involved in the development of OC, providing a detailed comprehension of the underlying molecular mechanisms. By connecting lncRNA dynamics with signaling pathways, this exploration not only advances our understanding of ovarian cancer but also reveals potential targets for therapeutic interventions. The findings open up opportunities for targeted treatments, highlighting the importance of personalized approaches in addressing this complex disease and driving progress in ovarian cancer research and treatment strategies.

Safety of fertility-sparing surgery in young women with stage I endometrioid epithelial and mucinous ovarian cancer: A population-based analysis.

INTRODUCTION: The aim of this study was to assess the safety of fertility-sparing surgery (FSS) in stage I endometrioid epithelial cancer (EEOC) and mucinous ovarian cancer (MOC). METHODS: A retrospective case‒controlled study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on stage I EEOC and MOC between 2000 and 2016. The effects of FSS on overall survival (OS) were compared using log-rank tests. Univariate and multivariate Cox analyses were performed to control for confounders. RESULTS: The study identified 970 patients with FIGO stage I EEOC and 810 with stage I MOC. Of these patients, 116 (12.0%) EEOC and 268 (33.1%) MOC patients underwent fertility-sparing surgery. The results showed that patients with G3 EEOC had a worse 5-year OS than patients with G1 EEOC (96.1% vs. 90.1%, p = 0.020). IC stage MOC patients had a worse prognosis than IA and IB stage patients (94.9% vs. 88.7%, p = 0.001). FSS did not significantly affect the 5-year OS of patients with EEOC (94.8% vs. 95.4%, p = 0.687) or MOC (95.9% vs. 92.3%, p = 0.071). Further subgroup analysis according to tumor stage and histological grade did not show a worse OS with FSS in stage I EEOC or MOC patients, even with high-risk types such as G3 histology and IC phase. In a multivariable analysis, the application of FSS was not associated with inferior OS in EEOC or MOC. CONCLUSIONS: FSS for patients with stage I EEOC or MOC does not lead to worse outcomes than radical surgery, making it a viable option for young patients with early-stage disease wishing to preserve fertility.

The pregnancy and oncology outcome of fertility-sparing management for synchronous primary neoplasm of endometrium and ovary.

PURPOSE: To investigate the efficacy of fertility-preserving treatment for young women with synchronous primary neoplasm of endometrium and ovary. METHODS: We retrospectively reviewed eight patients with concurrent primary grade 1 presumed stage IA endometrioid endometrial adenocarcinoma (EEA) or endometrial atypical hyperplasia (EAH) and primary stage I ovarian tumors who underwent fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between April 2016 and December 2022. RESULTS: Synchronous endometrial and ovarian cancers (SEOC) accounted for 50% of these eight patients. The median age of patients was 30.5 years (range, 28-34 years). None of them received chemotherapy. The median treatment time was 4 months (range, 3-8 months). 87.5% (7/8) cases achieved complete response (CR), and the median time to CR was 3.8 months (range, 1.5-7.7 months). Among patients who got CR, none of them showed any signs of recurrence. Pregnancies and successful deliveries were achieved in 4 of 5 patients. Till September 2023, the median follow-up period was 50.5 months (range:15.2-85.2 months). CONCLUSION: Fertility-sparing treatment is feasible for highly selected patients with synchronous neoplasm of the endometrium and ovary, but strict screening and monitoring are mandatory. Though the results of our limited cases are encouraging, long follow-up and more clinical data are required. Enrolled patients must be fully informed of the risks during conservative treatment.

Possible Ovarian and Peritoneal Carcinoma Presenting in a Mediastinal Lymph Node and Pleural Effusion: A Case Report and Review of the Literature.

Ovarian carcinoma often doesn't show noticeable symptoms and is frequently diagnosed at an advanced stage. It is the most fatal cancer within the gynecologic system. Our understanding of ovarian pathology is limited, necessitating the use of multiple markers to accurately detect ovarian cancer, particularly when it presents abnormally, such as in pleural effusion or lymph nodes. A 45-year-old woman presented to the emergency room (ER) due to abdominal pain lasting for two weeks. A computed tomography (CT) scan revealed peritoneal carcinomatosis accompanied by ascites and calcification in the lymph nodes. The likely primary sources were determined to be mucinous adenocarcinomas from either the colon or ovary. Following the CT findings, a fine needle aspiration was conducted on a perigastric lymph node. Histopathology results indicated a "poorly differentiated carcinoma [with] malignant cells present." Subsequently, a PowerPort was inserted, and adjuvant chemotherapy commenced two days later, utilizing a combination of carboplatin, bevacizumab, and paclitaxel. Paracentesis was performed, yielding clear-yellow fluid. However, abdominal fullness gradually increased again after paracentesis. The patient began experiencing more intense abdominal pain, particularly in the left lower quadrant. Surgical exploration revealed widespread disease involvement throughout the intestines. Our patient exhibited an atypical manifestation of ovarian carcinoma, challenging its identification due to ectopic foci and the absence of many distinctly identifiable markers. Through comprehensive testing and a process of elimination, we successfully differentiated ovarian carcinoma from other potential cancers. The conclusive histopathological report, along with a markedly elevated CA-125 level, provided substantial support for the probable final diagnosis of ovarian carcinoma. Despite numerous advancements in staining and identification techniques, the diagnosis of ovarian carcinoma remains inadequately understood. Identifying ovarian carcinoma without clear visualization is often challenging, and further research is warranted to enhance our understanding of pathological methods. Moreover, there is a need to prioritize the development and exploration of ovarian carcinoma screening and testing methods to prevent delayed disease detection.

Combination Treatment Strategies to Overcome PARP Inhibitor Resistance.

Poly(ADP-ribose) polymerase (PARP) enzymes have been shown to be essential for DNA repair pathways, including homologous recombination repair (HRR). Cancers with HRR defects (e.g., BRCA1 and BRCA2 mutations) are targets for PARP inhibitors (PARPis) based on the exploitation of "synthetic lethality". As a result, PARPis offer a promising treatment option for advanced ovarian and breast cancers with deficiencies in HRR. However, acquired resistance to PARPis has been reported for most tumors, and not all patients with BRCA1/2 mutations respond to PARPis. Therefore, the formulation of effective treatment strategies to overcome resistance to PARPis is urgently necessary. This review summarizes the molecular mechanism of therapeutic action and resistance to PARPis, in addition to emerging combination treatment options involving PARPis.

Triple combination of palliative oral metronomic chemotherapy in recurrent and metastatic epithelial ovarian cancer: A retrospective study.

Background: Ovarian cancer is a leading cause of death from gynecological cancer in the world and in India. This study aims to evaluate the efficacy and toxicity profile of oral metronomic chemotherapy (MCT) in the form of etoposide, cyclophosphamide, and tamoxifen in recurrent and metastatic ovarian cancer. Methods: This was a retrospective observational study that included those post-treatment patients who had the recurrent or metastatic disease after completion of treatment in 2018 at Regional Cancer Centre, Bikaner, Rajasthan. Forty patients who were unfit for further intensive intravenous chemotherapy were included. The oral MCT constituted etoposide, cyclophosphamide, and tamoxifen. Descriptive statistics and Kaplan-Meier analyses were performed. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: Forty women with a median age of 62 (range: 35-80) years were enrolled in the study to receive oral MCT. The Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) was 0-1 in 28 patients and 2-3 in 12 patients. The best clinical response rate post-oral MCT was seen in the first 4 months. Objective response was observed in 24 (60%) of patients in the form of stable disease (19, 47.5%) and partial response (5, 12.5%). Disease progression was observed in 10 (25%) of patients. The median follow-up was 6.4 months (4.5-9.2 months). The median estimated OS was 6.5 months. The median estimated PFS was 3.7 months. Nineteen (47.5%) patients had grade-I/II mucositis. Grade-III/IV mucositis were observed in 9 (22.5%) patients. Thirty-seven (92.5%) patients died at the end of the study at 1 year. Dose reduction was required in 15 (37.5%) patients. Conclusion: Oral MCT was found to be an effective and well-tolerated regime with good symptomatic control and low-moderate toxicity profile in patients with relapsed and metastatic ovarian cancer. However, 22% of patients showed grade-III/IV thrombocytopenia.

Preliminary Results of Deep Learning Approach for Preoperative Diagnosis of Ovarian Cancer Based on Pelvic MRI Scans.

BACKGROUND/AIM: To predict the pathological diagnosis of ovarian tumors using preoperative MRI images, using deep learning models. PATIENTS AND METHODS: A total of 185 patients were enrolled, including 40 with ovarian cancers, 25 with borderline malignant tumors, and 120 with benign tumors. Using sagittal and horizontal T2-weighted images (T2WI), we constructed the pre-trained convolutional neural networks to predict pathological diagnoses. The performance of the model was assessed by precision, recall, and F1-score on macro-average with 95% confidence interval (95%CI). The accuracy and area under the curve (AUC) were also assessed after binary transformation by the division into benign and non-benign groups. RESULTS: The macro-average accuracy in the three-class classification was 0.523 (95%CI=0.504-0.544) for sagittal images and 0.426 (95%CI=0.404-0.446) for horizontal images. The model achieved a precision of 0.63 (95%CI=0.61-0.66), recall of 0.75 (95%CI=0.72-0.78), and F1 score of 0.69 (95%CI=0.67-0.71) for benign tumor. Regarding the discrimination between benign and non-benign tumors, the accuracy in the binary-class classification was 0.628 (95%CI=0.592-0.662) for sagittal images and AUC was 0.529 (95%CI=0.500-0.557). CONCLUSION: Using deep learning, we could perform pathological diagnosis from preoperative MRI images.

Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer.

Somatic/germline BRCA1/2 mutations (m)/(likely) pathogenic variants (PV) (s/gBRCAm) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic TP53m, combined tumor-based BRCA1/2 (tBRCA) and TP53 mutation testing (tBRCA/TP53m) may improve the quality of results in somatic BRCAm identification and interpretation of the 'second hit' event, i.e., loss of heterozygosity (LOH). A total of 237 patients with HGSOC underwent tBRCA/TP53m testing. The ratio of allelic fractions (AFs) for tBRCA/TP53m was calculated to estimate the proportion of cells carrying BRCAm and to infer LOH. Among the 142/237 gBRCA results, 16.2% demonstrated a pathogenic/deleterious variant (DEL) gBRCA1/2m. Among the 195 contributive tumor samples, 43 DEL of tBRCAm (22.1%) were identified (23 gBRCAm and 20 sBRCAm) with LOH identified in 37/41 conclusive samples. The median AF of TP53m was 0.52 (0.01-0.93), confirming huge variability in tumor cellularity. Initially, three samples were considered as wild type with <10% cellularity. However, additional testing detected a very low AF (<0.05) in both BRCA1/2m and TP53m, thus reidentifying them as sBRCA1/2m. Combined tBRCA/TP53m testing is rapid, sensitive, and identifies somatic and germline BRCA1/2m. AF TP53m is essential for interpreting sBRCA1/2m in low-cellularity samples and provides indirect evidence for LOH as the 'second hit' of BRCA1/2-related tumorigenesis.

Synchronous ovarian and Bartholin gland carcinoma: Case report and review of literature.

To our knowledge, this is the first reported case of synchronous ovarian and vulva (Bartholin gland) cancer. A postmenopausal woman presented with a complex multiloculated left adnexal mass and 2-cm right Bartholin gland mass. CA 125 was 59 IU/mL. Computed tomography of chest, abdomen, and pelvis showed a very large (32 × 13.5 × 22.5 cm) complex mass arising from the pelvis and extending to the level of the T12/L1 disk space. A right Bartholin mass with suspicious right inguinal nodes was seen. Midline laparotomy, total abdominal hysterectomy, bilateral salpingo-oophrectomy, infracolic omentectomy, pelvic peritoneal biopsies, and peritoneal washings were carried out. Wide local excision of the right Bartholin gland mass was carried out in the same setting. Histopathology came back as Stage 2B left ovarian clear-cell carcinoma and synchronous right Bartholin gland adenoid cystic carcinoma with lymphovascular invasion, incompletely excised, staged at least FIGO Stage 1B. Following local multidisciplinary team discussion and positron emission tomography scan review, the local committee agreed to start three cycles of adjuvant chemotherapy then proceed with Bartholin gland scar re-excision and bilateral groin lymph node dissection. After the three cycles, the groin lymph nodes came back as metastatic adenocarcinoma with overall morphologic and immunohistochemical features consistent with metastatic ovarian clear-cell carcinoma. Postoperative adjuvant chemotherapy was given. Initial follow-up period over 9 months was uneventful.

The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies.

There is an increasing understanding of the molecular and cytogenetic background of various tumors that helps us better conceptualize the pathogenesis of specific diseases. Additionally, in many cases, these molecular and cytogenetic alterations have diagnostic, prognostic, and/or therapeutic applications that are heavily used in clinical practice. Given that there is always room for improvement in cancer treatments and in cancer patient management, it is important to discover new therapeutic targets for affected individuals. In this review, we discuss mitochondrial changes in breast and gynecological (endometrial and ovarian) cancers. In addition, we review how the frequently altered genes in these diseases (BRCA1/2, HER2, PTEN, PIK3CA, CTNNB1, RAS, CTNNB1, FGFR, TP53, ARID1A, and TERT) affect the mitochondria, highlighting the possible associated individual therapeutic targets. With this approach, drugs targeting mitochondrial glucose or fatty acid metabolism, reactive oxygen species production, mitochondrial biogenesis, mtDNA transcription, mitophagy, or cell death pathways could provide further tailored treatment.

NIPEC with Single-Dose Intraperitoneal Cisplatin and Paclitaxel in Stage III Epithelial Ovarian Cancer.

Sanjay M. DesaiObjectives Epithelial ovarian cancer (EOC) is a heterogeneous, essentially peritoneal disease. Standard treatment consists of staging, cytoreductive surgery (CRS), and adjuvant chemotherapy. In this study, we intended to assess the effectiveness of single-dose intraperitoneal (IP) chemotherapy in optimally debulked advanced EOC patients. Materials and Methods A prospective randomized study of 87 patients with advanced EOC was done from January 2017 to May 2021 in a tertiary care center. Patients who underwent primary and interval cytoreduction received a single dose of IP chemotherapy for 24 hours after being divided into four groups: group A, IP cisplatin; group B, IP paclitaxel; group C, IP paclitaxel and cisplatin; and group D, saline. Pre- and postperitoneal IP cytology was assessed along with possible complications. Statistical Analysis Logistic regression analysis was used to assess for intergroup significance in cytology and complications. Kaplan-Meir analysis was done to assess disease-free survival (DFS). Results Of 87 patients, 17.2% of patients had FIGO stage IIIA, 47.2% had IIIB, and 35.6% had IIIC. Also, 22 (25.3%) patients were in group A (cisplatin), 22 (25.3%) patients in group B (paclitaxel), 23 (26.4%) in group C (cisplatin and paclitaxel), and 20 (23%) in group D (saline). Cytology samples taken during staging laparotomy were positive, and 48 hours post-IP chemotherapy, 2 (9%) of 22 samples in cisplatin group and 14 (70%) of 20 samples in saline group were positive; all of the post-IP samples in groups B and C were negative. No major morbidity was noted. In our study, DFS in saline group was 15 months, while in IP chemotherapy group it was 28 months and was statistically significant based log-rank test. However, there was no significant difference in DFS between different IP chemotherapy groups. Conclusion Complete or optimal CRS in advanced EOC does have a possibility of microscopic peritoneal residue. Adjuvant locoregional strategies should be considered to prolong DFS. Single-dose normothermic IP chemotherapy can be offered to the patients with minimal morbidity, and its prognostic benefits are comparable to hyperthermic IP chemotherapy. Future clinical trials are required to validate these protocols.

Cultural adaptations to a telephone genetic counseling protocol and booklet for Latina breast cancer survivors at risk for hereditary breast and ovarian cancer.

Telephone genetic counseling (TGC) is accepted as standard clinical care for people seeking hereditary cancer risk assessment. TGC has been shown to be non-inferior to in-person genetic counseling, but trials have been conducted with a predominantly highly educated, non-Hispanic White population. This article describes the process of culturally adapting a TGC protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at risk for hereditary breast and ovarian cancers. The adaptation process included two phases. Phase 1 involved a review of the literature and recommendations from an expert team including community partners. Phase 2 included interviews and a pilot with the target population (n = 14) to collect feedback about the adapted protocol and booklet following steps from the Learner Verification and Revision Framework. We describe the adaptation process and report the main adaptations following the Framework for Reporting Adaptations and Modifications to Evidence-based Interventions (FRAME). Adaptations in Phase 1 were responsive to the target population needs and characteristics (e.g., delivered in Spanish at an appropriate health literacy level, addressing knowledge gaps, targeting cultural values). Phase 2 interviews were crucial to refine details (e.g., selecting words) and to add components to address GCT barriers (e.g., saliva sample video). Cultural adaptations to evidence-based TGC protocols can increase the fit and quality of care for historically underserved populations. As TGC visits become routine in clinical care, it is crucial to consider the needs of diverse communities to adequately promote equity and justice in cancer care.

This article describes the process of adapting a telephone genetic counseling protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at increased risk for hereditary breast and ovarian cancer (HBOC). The cultural adaptation process followed two phases. In the first phase, the authors reviewed the literature and obtained insights from interdisciplinary experts. In the second phase, the authors received iterative feedback from fourteen Latina women who were breast cancer survivors, spoke Spanish as a first language, and met criteria to be considered at increased risk for HBOC. Revisions to the protocol and visual aid booklet were conducted iteratively following feedback from the expert team, after the first five women reviewed the booklet, after the second five women reviewed the booklet, and after the final four women completed the entire culturally adapted telephone genetic counseling protocol with the booklet. The final adaptations to the protocol and visual aid booklet were responsive to the target population's needs. Most adaptations made were regarding content. For example, simplifying the material presented, adding culturally relevant images, and developing a video explaining how to collect a saliva sample. Culturally adapting health interventions can improve health outcomes in historically marginalized populations and promote equity.

Patient-Derived Primary Cancer-Associated Fibroblasts Mediate Resistance to Anti-Angiogenic Drug in Ovarian Cancers.

Ovarian cancers rank first in both aggressiveness and dismal prognosis among gynecological neoplasms. The poor outcome is explained by the fact that most patients present with late-stage disease and progress through the first line of treatment. Ovarian neoplasms, especially epithelial ovarian cancers, are diagnosed at advanced/metastatic stages, often with a high angiogenesis index, one of the hallmarks of ovarian cancers with rapid progression and poor outcome as resistance to anti-angiogenic therapy develops. Despite therapy, the metastatic progression of aggressive ovarian cancer is a spectacularly selective function of tumor cells aided and abetted by the immune, mesenchymal and angiogenic components of the tumor microenvironment (TME) that enforces several pro-metastatic event(s) via direct and indirect interactions with stromal immune cells, cancer-associated fibroblasts (CAFs), and vascular endothelial cells. Since transdifferentiation of tumor endothelium is one of the major sources of CAFs, we hypothesized that ovarian CAF plays a critical role in resisting anti-angiogenic effects via direct crosstalk with endothelium and hence plays a direct role in the development of resistance to anti-angiogenic drugs. To test the hypothesis, we set up a hybrid ex vivo model for co-culture comprising Patient-Derived ex vivo primary CAFs from ovarian tumor samples and human umbilical vein endothelial cells (HUVEC). Patient-Derived CAFs were characterized by the mRNA and protein expression of positive (SMA, S100A4, TE-7, FAP-A, CD90/THY1), negative (EpCAM, CK 8,18, CD31, CD44, CD45), functional (PDGFRA, TGFB1, TGFB2, TGFRA) and immunological markers (PD-L1, PD-L2, PD-1) associated with CAFs by qRT-PCR, flow cytometry, Western blot, and ICC. Data from our HUVEC-on-CAF ex vivo Hybrid Co-Culture (HyCC) study demonstrate the pro-angiogenic effect of Patient-Derived ovarian CAFs by virtue of their ability to resist the effect of anti-angiogenic drugs, thereby aiding the development of resistance to anti-angiogenic drugs. Ascertaining direct experimental proof of the role of CAFs in developing resistance to specific anti-angiogenic drugs will provide an opportunity to investigate new drugs for counteracting CAF resistance and "normalizing/re-educating" TME in aggressive ovarian cancers. Our data provide a unique experimental tool for the personalized testing of anti-angiogenic drugs, positively predicting the development of future resistance to anti-angiogenic drugs well before it is clinically encountered in patients.