Management Of Epithelial Ovarian Cancer Research Articles

CXC Chemokine Signaling in Progression of Epithelial Ovarian Cancer: Theranostic Perspectives.

Patients with epithelial ovarian cancer (EOC) are often diagnosed at an advanced stage due to nonspecific symptoms and ineffective screening approaches. Although chemotherapy has been available and widely used for the treatment of advanced EOC, the overall prognosis remains dismal. As part of the intrinsic defense mechanisms against cancer development and progression, immune cells are recruited into the tumor microenvironment (TME), and this process is directed by the interactions between different chemokines and their receptors. In this review, the functional significance of CXC chemokine ligands/chemokine receptors (CXCL/CXCR) and their roles in modulating EOC progression are summarized. The status and prospects of CXCR/CXCL-based theranostic strategies in EOC management are also discussed.

Management of epithelial ovarian cancers

No abstract available

SPME-LC/MS-based serum metabolomic phenotyping for distinguishing ovarian cancer histologic subtypes: a pilot study

Epithelial ovarian cancer (EOC) is the most common cause of death from gynecological cancer. The outcomes of EOC are complicated, as it is often diagnosed late and comprises several heterogenous subtypes. As such, upfront treatment can be highly challenging. Although many significant advances in EOC management have been made over the past several decades, further work must be done to develop early detection tools capable of distinguishing between the various EOC subtypes. In this paper, we present a sophisticated analytical pipeline based on solid-phase microextraction (SPME) and three orthogonal LC/MS acquisition modes that facilitates the comprehensive mapping of a wide range of analytes in serum samples from patients with EOC. PLS-DA multivariate analysis of the metabolomic data was able to provide clear discrimination between all four main EOC subtypes: serous, endometrioid, clear cell, and mucinous carcinomas. The prognostic performance of discriminative metabolites and lipids was confirmed via multivariate receiver operating characteristic (ROC) analysis (AUC value > 88% with 20 features). Further pathway analysis using the top 57 dysregulated metabolic features showed distinct differences in amino acid, lipid, and steroids metabolism among the four EOC subtypes. Thus, metabolomic profiling can serve as a powerful tool for complementing histology in classifying EOC subtypes.

Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction.

Epithelial ovarian cancer (EOC) patients are generally diagnosed at an advanced stage, usually relapse after initial treatments, which include debulking surgery and adjuvant platinum-based chemotherapy, and eventually have poor 5-year survival of less than 50%. In recent years, promising survival benefits from maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of EOC in newly diagnosed and recurrent disease. Identification of BRCA mutations and/or homologous recombination deficiency (HRD) is critical for selecting patients for PARPi treatment. However, the currently available HRD assays are not perfect predictors of the clinical response to PARPis in EOC patients. In this review, we introduce the concept of synthetic lethality, the rationale of using PARPi when HRD is present in tumor cells, the clinical trials of PARPi incorporating the HRD assays for EOC, the current HRD assays, and other HRD assays in development.

The relationship between pre-operative lymphocyte to monocyte ratio and serum cancer antigen-125 among women with epithelial ovarian cancer in Lagos, Nigeria.

Ovarian cancer (OC) is the second most common genital cancer worldwide, and the most lethal of all genital cancers. The role of inflammation and markers of systemic inflammation such as neutrophils, lymphocytes and monocytes in cancer biology have been investigated and reported in many studies. Cancer antigen 125 (CA-125) is currently in use as an adjunct to diagnosis, prognostication and monitoring of epithelial OC (EOC). This test is not readily available in many centres in sub-Saharan Africa, creating a need to identify alternative markers that are available and affordable. This study aimed to determine the relationship between pre-operative serum lymphocyte to monocyte ratio (LMR) and CA-125 in EOC. This was a retrospective cross-sectional study among 70 women, diagnosed with EOC in Lagos University Teaching Hospital from January 2013 to December 2019. Data were extracted from the case notes of the patients. LMR was calculated as the absolute lymphocyte count divided by the absolute monocyte count and analysed using Statistical Package for Social Sciences (SPSS) version 25.0. The correlation between LMR and CA-125 was determined using Pearson’s correlation coefficient. The mean age of the patients was 48.57 ± 13.97 years. Serous adenocarcinoma was the most common subtype of EOC making up 94.3% of the cases. The median serum CA-125 was 393.5 (215.00–765.67) U/mL. The median LMR was 6.77 (1.28–43.0). There was a statistically significant negative correlation between CA-125 and LMR, r = −0.28, p = 0.02. LMR was negatively associated with CA-125 in women with EOC. LMR may be considered as a simple, affordable alternative marker to CA-125 in the management of EOC.

The Molecular Landscape Influencing Prognoses of Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is one of the major increasing lethal malignancies of the gynecological tract, mostly due to delayed diagnosis and chemoresistance, as well as its very heterogeneous genetic makeup. Application of high-throughput molecular technologies, gene expression microarrays, and powerful preclinical models has provided a deeper understanding of the molecular characteristics of EOC. Therefore, molecular markers have become a potent tool in EOC management, including prediction of aggressiveness, prognosis, and recurrence, and identification of novel therapeutic targets. In addition, biomarkers derived from genomic/epigenomic alterations (e.g., gene mutations, copy number aberrations, and DNA methylation) enable targeted treatment of affected signaling pathways in advanced EOC, thereby improving the effectiveness of traditional treatments. This review outlines the molecular landscape and discusses the impacts of biomarkers on the detection, diagnosis, surveillance, and therapeutic targets of EOC. These findings focus on the necessity to translate these potential biomarkers into clinical practice.

Current update on malignant epithelial ovarian tumors.

Epithelial ovarian cancer (EOC) represents the most frequently occurring gynecological malignancy, accounting for more than 70% of ovarian cancer deaths. Preoperative imaging plays an important role in assessing the extent of disease and guides the next step in surgical decision-making and operative planning. In this article, we will review the multimodality imaging features of various subtypes of EOC. We will also discuss the role of imaging in the staging, management, and surveillance of EOC.

Rationale and study design of the CHIPPI-1808 trial: a phase III randomized clinical trial evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) for stage III ovarian cancer patients treated with primary or interval cytoreductive surgery

BackgroundOvarian cancer remains the most lethal gynecologic malignancy with high recurrence rates. Because recurrence involves primarily the peritoneum, intraperitoneal chemotherapy is being evaluated as a new approach to treat microscopic peritoneal disease. One trial showed that cisplatin–paclitaxel intraperitoneal chemotherapy with intravenous paclitaxel improved survival but increased morbidity. Another trial reported a significant improvement in overall survival (OS) and disease-free survival (DFS) without increasing the morbidity (P = 0.76) or mortality rates (hazard ratio 0.67, P = 0.02) after adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreduction. The current trial aims to evaluate the impact of adding HIPEC to primary or interval cytoreductive surgery for epithelial ovarian cancer (EOC) on the efficacy, safety, treatment feasibility, and quality of life.Patients and methodsThis is an international, multicenter, open-label, randomized (1 : 1), two-arm, phase III clinical trial that will enroll 432 patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III EOC. Patients are randomized to receive or not HIPEC with the standard of care. Inclusion criteria include patients with FIGO stage III EOC, Fallopian tube carcinoma or primary peritoneal cancer who undergo complete primary or interval cytoreduction. The primary objective is to assess DFS of the addition of HIPEC. Secondary objectives are the assessment of OS, safety, return to intended oncologic treatment, quality of life and the trade-off between efficacy and morbidity.ConclusionsThe results might help extend the indications of HIPEC to include patients undergoing primary cytoreduction, providing a standardized protocol for HIPEC in EOC management and reliable information on the quality of life after adding HIPEC.

Cancers épithéliaux de l’ovaire et chirurgie de cytoréduction par voie mini-invasive après chimiothérapie néoadjuvante : revue systématique de la littérature

IntroductionAdvanced epithelial ovarian cancer (EOC) is associated with high mortality and often managed first with neoadjuvant chemotherapy (NACT) followed by debulking surgery. Laparoscopic surgery with or without robotic assistance (Minimally Invasive Surgery (MIS)) may represent a beneficial option for these patients. The objective of this literature review is to clarify the place of MIS in the management of advanced EOC for selected patients. MethodPubmed, Cochrane and Clinicaltrials.gov online databases were used for this review, to select English or French published articles. ResultsWe selected 11 original articles published between 2015 and 2020, 6 of which compared MIS and laparotomy. Among these 11 studies, 8 were retrospective cohorts, 2 were phase II trials, and one was a case-control study. In total, there were 3721 patients, of which 854 (23%) were treated with MIS. The robotic assistance was used with 224 patients (26%) of those MIS patients. Looking specifically at MIS patients, the laparoconversion rate was 9.5%, the rate of complete resection (CC-0) was 83.4%. Finally, the MIS complication rate was 1% intraoperatively and 12% postoperatively. The rate of complete resection, postoperative complication, as well as overall survival (OS) were comparable between patients treated with MIS or laparotomy. One study found an improved disease-free survival (DFS) in MIS versus laparotomy (18 months versus 12 months; P=0.027). ConclusionMIS seems feasible, effective, and reliable in comparison to laparotomy for the completion of cytoreductive surgery after NACT without compromising oncological safety. Prospective randomized controlled trials are needed to confirm the role of MIS in advanced EOC.

HSP90 identified by a proteomic approach as druggable target to reverse platinum resistance in ovarian cancer.

Acquired resistance to platinum (Pt)‐based therapies is an urgent unmet need in the management of epithelial ovarian cancer (EOC) patients. Here, we characterized by an unbiased proteomics method three isogenic EOC models of acquired Pt resistance (TOV‐112D, OVSAHO, and MDAH‐2774). Using this approach, we identified several differentially expressed proteins in Pt‐resistant (Pt‐res) compared to parental cells and the chaperone HSP90 as a central hub of these protein networks. Accordingly, up‐regulation of HSP90 was observed in all Pt‐res cells and heat‐shock protein 90 alpha isoform knockout resensitizes Pt‐res cells to cisplatin (CDDP) treatment. Moreover, pharmacological HSP90 inhibition using two different inhibitors [17‐(allylamino)‐17‐demethoxygeldanamycin (17AAG) and ganetespib] synergizes with CDDP in killing Pt‐res cells in all tested models. Mechanistically, genetic or pharmacological HSP90 inhibition plus CDDP ‐induced apoptosis and increased DNA damage, particularly in Pt‐res cells. Importantly, the antitumor activities of HSP90 inhibitors (HSP90i) were confirmed both ex vivo in primary cultures derived from Pt‐res EOC patients ascites and in vivo in a xenograft model. Collectively, our data suggest an innovative antitumor strategy, based on Pt compounds plus HSP90i, to rechallenge Pt‐res EOC patients that might warrant further clinical evaluation.

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.

Assessing feasibility and perioperative outcomes with minimally invasive surgery compared with laparotomy for interval debulking surgery with hyperthermic intraperitoneal chemotherapy for advanced epithelial ovarian cancer

ObjectiveTo determine peri-operative outcomes in women with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) via minimally invasive interval debulking surgery (MIS) or laparotomy (LAP). MethodsA single institution, retrospective cohort study was performed in women with EOC who underwent IDS with HIPEC from 2017 to 2019 via MIS or LAP. Peri-operative outcomes were compared using univariate analysis. ResultsIn total, 50 eligible women were identified; ten (20.0%) underwent MIS + HIPEC and 40 (80.0%) LAP + HIPEC. The median age of patients in the MIS group was 71.1 vs. 64.2 years in LAP (p = 0.031). There was no significant difference in pre-operative complete radiographic response following NACT (p = 0.18). Notably, there was no difference in the rate of R0 resection (70.0% vs. 77.5%; p = 0.39). There was no significant difference in ICU admission, estimated blood loss, operative time, or use of vasopressors between the cohorts. Similarly, there was no difference in 30-day adverse events for MIS vs. LAP, but length of stay was decreased for those who underwent minimally invasive procedures (3 vs. 4 days, p = 0.016). Time to initiation of chemotherapy following surgery was not significantly different between groups (26.2 days vs 32.0 days, p = 0.090). With median follow-up of 15.1 months, there was no difference in recurrence free survival (median 15.0 vs 17.2 months log-rank, p = 0.30) for MIS vs. LAP. ConclusionsIn this retrospective cohort study, we demonstrate that in women with advanced EOC, HIPEC with MIS at the time of IDS following NACT is feasible. Our institutional experience demonstrates similar rates of R0 cytoreduction, compared to LAP. An MIS approach should not prevent surgeons from utilizing HIPEC where indicated for management of advanced EOC.

Frontline Management of Epithelial Ovarian Cancer-Combining Clinical Expertise with Community Practice Collaboration and Cutting-Edge Research.

Epithelial ovarian cancer (EOC) is the most common histology of ovarian cancer defined as epithelial cancer derived from the ovaries, fallopian tubes, or primary peritoneum. It is the fifth most common cause of cancer-related death in women in the United States. Because of a lack of effective screening and non-specific symptoms, EOC is typically diagnosed at an advanced stage (FIGO stage III or IV) and approximately one third of patients have malignant ascites at initial presentation. The treatment of ovarian cancer consists of a combination of cytoreductive surgery and systemic chemotherapy. Despite the advances with new cytotoxic and targeted therapies, the five-year survival rate for all-stage EOC in the United States is 48.6%. Delivery of up-to-date guideline care and multidisciplinary team efforts are important drivers of overall survival. In this paper, we review our frontline management of EOC that relies on a multi-disciplinary approach drawing on clinical expertise and collaboration combined with community practice and cutting edge clinical and translational research. By optimizing partnerships through team medicine and clinical research, we combine our cancer center clinical expertise, community practice partnership, and clinical and translational research to understand the biology of this deadly disease, advance therapy and connect our patients with the optimal treatment that offers the best possible outcomes.

Long non-coding RNA AOC4P suppresses epithelial ovarian cancer metastasis by regulating epithelial-mesenchymal transition

ObjectiveCurrently, the function and mechanisms of long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer (EOC), especially those of the lncRNAs participated in the epithelial-mesenchymal transition (EMT) process, remains largely unknown. Here, we focused on a lncRNA named AOC4P and analysed its role in EOC.Materials and methodsThe expression of AOC4P gene was examined with quantitative real-time quantitative PCR (qRT-PCR). The cell migration and invasion were detected by Transwell and scratch assays. The in vivo metastatic activity was evaluated by intraperitoneal metastasis model. The downstream genes were investigated by a tumour EMT real-time polymerase chain reaction (RT-PCR) array, and validated by qRT-PCR and Western blot.ResultsThe results showed that AOC4P expression levels were decreased in EOC tissues and cell lines, and that the under-expression of AOC4P was positively correlated with FIGO stage and lymph node metastasis. Furthermore, the knockdown of AOC4P expression in poorly metastatic EOC cell lines remarkably facilitated cell migration/invasion while the overexpression of AOC4P in highly metastatic EOC cell lines reduced the metastatic ability of these cells in vitro. Consistently, the anti-metastatic role of AOC4P in vivo was also verified by bioluminescence imaging and tumour dissection. Mechanistically, the anti-metastatic effect of AOC4P in EOC was partially mediated by the EMT process accompanied by the alterations in MMP9 and COL1A2 expression.ConclusionThese data highlight that AOC4P plays a critical role in EOC invasion/metastasis and could function as a novel and effective target for the lncRNA-based anti-metastatic clinical management of EOC.

Rethinking the Role of Radiation Therapy in the Management of Epithelial Ovarian Cancer.

Radiation has been relegated to a palliative role in the management of epithelial ovarian cancer (EOC). Contemporary radiation techniques, including intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and image-guided radiation therapy, enable conformal treatment that controls local disease with minimal morbidity. Recent studies from multiple institutions support the role of radiation in the ablative treatment of oligometastatic disease and control of locally recurrent and metastatic disease. Effective local treatment with radiation complements the role of systemic therapy in the management of EOC; reduces symptoms and disease burden, and may contribute to a prolonged drug free interval.

30 Years of Experience in the Management of Stage III and IV Epithelial Ovarian Cancer: Impact of Surgical Strategies on Survival.

Objective: to analyze the evolution of surgical techniques and strategies, and to determine their influence on the survival of patients with stage III or IV epithelial ovarian cancer (EOC). Methods: a retrospective data analysis was performed in two French tertiary cancer institutes. The analysis included clinical information, cytoreductive outcome (complete, optimal and suboptimal), definitive pathology, Overall Survival (OS), and Progression-Free Survival (PFS). Three surgical strategies were compared: Primary Cytoreductive Surgery (PCS), Interval Cytoreductive Surgery (ICS) after three cycles of Neo-Adjuvant Chemotherapy (NAC), and Final Cytoreductive Surgery (FCS) after at least six cycles of NAC. We analyzed four distinct time intervals: prior to 2000, between 2000 and 2004, between 2005 and 2009, and after 2009. Results: data from 1474 patients managed for International Federation of Gynecology and Obstetrics (FIGO) stages III (80%) or IV (20%) EOC were analyzed. Throughout the four time intervals, the rate of patients who were treated only medically increased significantly (10.1% vs. 22.6% p < 0.001). NAC treatment increased from 20.1% to 52.2% (p < 0.001). Complete resection rate increased from 37% to 66.2% (p < 0.001). Of our study population, 1260 patients (85.5%) underwent surgery. OS was longer in cases of complete cytoreduction (Hazard Ratio (HR) = 2.123 CI 95% [1.816–2.481] p < 0.001) but the surgical strategy itself did not affect median OS. OS was 44.9 months, 50.3 months, and 42 months for PCS, ICS, and FCS, respectively (p = 0.410). After adjusting for surgical strategies (PCS, ICS, and FCS), all patients with complete cytoreduction presented similar OS with no significant difference. However, PFS was three months shorter when FCS was compared to PCS (p < 0.001). Conclusion: In our 30 years’ experience of EOC management, complete resection rate was the only independent factor that significantly improved OS and PFS, regardless of the surgical strategy.

How I Treat Epithelial Ovarian Cancer during COVID-19 Pandemic

Coronavirus disease 2019 (COVID-19) pandemic is accelerating in an unprecedented manner, with 3,175,207 confirmed cases and 224,172 deaths worldwide.[1] Studies from China and Italy reported that individuals with cancer have a two-fold higher rate of COVID-19 infection and a ten-fold higher risk of mortality as compared to individuals patients without cancer.[2], [3], [4] Cancer caregivers are battling in the wake of a scarcity of workforce, personal protective equipment, medications, and risk of COVID-19 infection. This catastrophic situation warrants a relook of management of epithelial ovarian cancer adapted to the local context. Various guidelines on ovarian cancer management and publications of landmark trials were reviewed in this regard, and the latest literature on COVID-19 was studied.[5], [6] These are the suggestions from science and cost-care consortium for managing ovarian cancer patients during the COVID-19 pandemic [Table 1].

The Value of PET-CT in Ovarian Epithelial Carcinoma: A Population-Based Study in British Columbia, Canada

IntroductionIn epithelial ovarian cancer (EOC), consensus regarding optimal use of PET/CT is lacking. Limited evidence suggests its accuracy in preoperative staging, investigating recurrence and predicting optimal secondary debulking. This study evaluated indications for PET/CT, impact of PET/CT results on EOC management, and its added value over conventional imaging. MethodsPatients with EOC aged 19 years and older who underwent PET/CT at BC Cancer Vancouver between January 2007 and September 2017 were eligible. Medical records were retrospectively reviewed with the following data abstracted: patient demographics, PET/CT indications and results, recent conventional imaging results, and application of PET/CT findings. Basic descriptive analysis was performed to determine most common use of PET/CT and its management impact. Results257 PET/CTs in 216 patients were eligible. Most PET/CTs (135/257, 52.6%) were performed for suspected disease recurrence/progression. Management after PET/CT changed in 1/3 of cases with the greatest impact seen when assessing suitability in recurrent disease for focal radiotherapy or secondary surgical debulking. For 106/257 cases with recent conventional imaging available, although differences in disease extent were found in ~50%, clinical conclusions drawn were the same in ~75%. DiscussionAlthough PET/CT is most commonly used to investigate suspected recurrence/progression, its impact on management here is low. Greater impact is seen when considering localized therapy in EOC recurrence. When compared with recent conventional imaging, although PET/CT may detect differences in disease extent, clinical conclusions are frequently the same. ConclusionImpact of PET/CT on management is greatest in EOC recurrence when considering local therapies, beyond which clinical presentation and conventional imaging may suffice.

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: an update.

In the treatment of advanced-stage epithelial ovarian cancer (EOC)-associated surgery and chemotherapy with intravenous platinum/taxane-based therapy most patients had early or late recurrence. Prevention of progression and recurrence is a major objective for the management of EOC. Recently, many clinical studies have evaluated the strategy with hyperthermic intraoperative intraperitoneal (IP) drug delivery. This is an update of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in EOC and a view for future strategies. Until recently studies on HIPEC in patients with EOC were mostly retrospective and heterogeneous. Thanks to recent clinical trials, it is reasonable to conclude that surgical cytoreduction and HIPEC is an interesting approach in the management of EOC without increasing morbidity.

Syndrome héréditaire de prédisposition au cancer du sein et de l’ovaire : diagnostic et implications thérapeutiques

Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification. BRCA1/2 carriers have to be followed up regularly and may justify breast and/or adnexal prophylactic surgery, according to the French National Cancer Institute guidelines (INCa). Poly- (DNA-riboses) polymerases inhibitors, notably olaparib, have a major role in the management of epithelial ovarian cancer in patients with BRCA mutation and many studies are ongoing to expand their indications in a near future.