Epithelial Ovarian Cancer Patients Research Articles

Clinical Utility of the Geriatric Nutritional Risk Index Before Surgical Intervention for Epithelial Ovarian Cancer Patients: A Retrospective Study.

The aim of the study is to analyze the impact of the geriatric nutritional risk index (a patient nutritional assessment item) on the prognoses of epithelial ovarian cancer patients. In this retrospective study conducted at a single hospital, we retrospectively analyzed 75 epithelial ovarian cancer patients who underwent surgical treatment at our hospital from 2010 to 2015. The geriatric nutritional risk index cut-off value was calculated using the receiver operating characteristic curve. Patients were divided into two groups on the basis of the calculated value. Kaplan-Meier curves were prepared for each group, and the difference in survival rates was calculated using the log-rank test. Cox proportional hazards regression analysis was used to compare other factors that affect prognosis. The geriatric nutritional risk index was calculated to be 97.3. The survival rate was 61.9% for the group of patients with an index value > 97.3, and 39.4% for patients with an index value < 97.3 at 48 months (P < 0.001). A univariate analysis was performed with the following variables: age > 60 years, albumin level < 3.5 g/dL, body mass index < 22, presence of ascites, cancer antigen 125 level > 35 U/mL, type of tumor tissue, residual lesion, and geriatric nutritional risk index < 97.3. Albumin level, residual lesion, and geriatric nutritional risk index showed significant differences. A multivariate analysis was also performed, and only the geriatric nutritional risk index showed a significant difference (P = 0.0481). The geriatric nutritional risk index may have a strong influence on the prognoses of epithelial ovarian cancer patients. We recommend utilizing these findings in daily clinical practice and incorporating them into treatment strategies for epithelial ovarian cancer.

Evaluation of promoter hypermethylation of tumor suppressor gene BRCA1 in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a serious gynecological issue worldwide and its late detection is the major encumbrance in treatment procedures. Hypermethylation-mediated BRCA1 gene silencing results in failure of the repair system of damaged DNA playing an important role in ovarian carcinogenesis. BRCA1 gene hypermethylation can serve as a safe and highly specific clinical marker for EOC. The present study was conducted to evaluate the promoter hypermethylation of BRCA1 gene in EOC patients. This hospital-based case-control study carried out in the tertiary care hospital in New Delhi. Subjects and Methods: Promoter hypermethylation of BRCA1 gene was examined in 30 EOC diagnosed untreated cases confirmed by histopathological examinations and compared with 30 normal healthy controls matched for age using methylation specific-polymerase chain reaction. We found significantly higher BRCA1 promoter hypermethylation in the serum of EOC cases as compared to controls with P < 0.0001. BRCA1 gene methylation was found to have 70% sensitivity for the diagnosis of EOC with 100% specificity. A significant difference was observed in the range of CA125 levels, B12 and Folate levels between EOC cases and controls. We conclude that BRCA1 gene is significantly hypermethylated in EOC patients and thus can prove to be a noninvasive diagnostic tool. Our results provide prefatory evidence that epithelial ovarian epigenome can be influenced by dietary nutrients.

Real-world clinical data analysis of PARPi as first-line maintenance therapy in newly diagnosed epithelial ovarian cancer patients

Objective: The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored. Methods: (1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed. Results: (1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95%CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95%CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions: Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

HE4 and CA125 serum biomarker monitoring in women with epithelial ovarian cancer.

CA125 is the gold standard serum biomarker for monitoring patients with epithelial ovarian cancer (EOC). Human epididymal protein 4 (HE4) is a novel serum biomarker for EOC patients. The objective of this trial was to examine the utility of measuring serum HE4 levels for monitoring EOC patients and to compare HE4 performance parameters to serum CA125. A retrospective trial using residual longitudinal serum samples drawn during treatment and monitoring from EOC patients. Serum CA125 and HE4 levels were analyzed at each time point, and a velocity of change was calculated and correlated with clinical status. The null hypothesis was that HE4 is inferior to CA125, and this was tested using concordance and two-sided Fisher's exact testing. McNemar's test was used to assess the overall agreement of the two assays with the clinical status. A total of 129 patients with 272 separate clinical periods and 1739 events (serum samples) were evaluated. Using a 25% change in serum biomarker levels to indicate change in disease status, the accuracy and NPV determined for HE4 versus CA125 were 81.8% versus 82.6% (p = 0.846) and 87.4% versus 89.7% (p = 0.082), respectively. Concordance comparison of HE4 accuracy / CA125 accuracy was 0.990, indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.522). Performing a velocity of change analysis, the accuracy and NPV determined for HE4 versus CA125 were 78.3% versus 78.6% (p = 0.995) and 74.9% versus 76.3% (p = 0.815), respectively. Concordance comparison of HE4 velocity accuracy / CA125 velocity accuracy was 0.996, again indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.884). The combination of HE4 and CA125 velocity changes showed a similar accuracy of 81.3% (p = 0.797 compared to HE4 and CA125 alone) and NPV of 81.1% (p≥0.172 compared to HE4 and CA125 alone), and an increased sensitivity of 70.5% (p≤0.070 compared to HE4 and CA125 alone). HE4 is equivalent to CA125 for monitoring of EOC patients. The combination of CA125 and HE4 velocities is superior to either marker alone.

Progression-free survival and overall survival after BRCA1/2-associated epithelial ovarian cancer: A matched cohort study.

Germline BRCA1/2-associated epithelial ovarian cancer has been associated with better progression-free survival and overall survival than sporadic epithelial ovarian cancer, but conclusive data are lacking. We matched 389 BRCA1-associated and 123 BRCA2-associated epithelial ovarian cancer patients 1:1 to sporadic epithelial ovarian cancer patients on year of birth, year of diagnosis, and FIGO stage (< = IIA/> = IIB). Germline DNA test was performed before or after epithelial ovarian cancer diagnosis. All patients received chemotherapy. We used Cox proportional hazards models to estimate the associations between mutation status (BRCA1 or BRCA2 versus sporadic) and progression-free survival and overall survival. To investigate whether DNA testing after epithelial ovarian cancer diagnosis resulted in survival bias, we performed additional analyses limited to BRCA1/2-associated epithelial ovarian cancer patients with a DNA test result before cancer diagnosis (n = 73 BRCA1; n = 9 BRCA2) and their matched sporadic controls. The median follow-up was 4.4 years (range 0.1-30.1). During the first three years after epithelial ovarian cancer diagnosis, progression-free survival was better for BRCA1 (HR 0.88, 95% CI 0.74-1.04) and BRCA2 (HR 0.58, 95% CI 0.41-0.81) patients than for sporadic patients. Overall survival was better during the first six years after epithelial ovarian cancer for BRCA1 (HR 0.7, 95% CI 0.58-0.84) and BRCA2 (HR 0.41, 95% CI 0.29-0.59) patients. After surviving these years, survival benefits disappeared or were in favor of the sporadic patients. For epithelial ovarian cancer patients who received chemotherapy, we confirmed survival benefit for BRCA1 and BRCA2 germline pathogenic variant carriers. This may indicate higher sensitivity to chemotherapy, both in first line treatment and in the recurrent setting. The observed benefit appears to be limited to a relatively short period after epithelial ovarian cancer diagnosis.

Artificial intelligence-based preoperative prediction system for diagnosis and prognosis in epithelial ovarian cancer: A multicenter study.

BackgroundOvarian cancer (OC) is the most lethal gynecological malignancy, with limited early screening methods and poor prognosis. Artificial intelligence technology has made a great breakthrough in cancer diagnosis.PurposeWe aim to develop a specific interpretable machine learning (ML) prediction model for the diagnosis and prognosis of epithelial ovarian cancer (EOC) based on a variety of biomarkers.MethodsA total of 521 patients with EOC and 144 patients with benign gynecological diseases were enrolled including derivation datasets and an external validation cohort. The predicted information was acquired by 9 supervised ML methods, through 34 parameters. Behind predicted reasons for the best ML were improved by using the SHapley Additive exPlanations (SHAP) algorithm. In addition, the prognosis of EOC was analyzed by unsupervised clustering and Kaplan–Meier (KM) survival analysis.ResultsML technology was superior to conventional logistic regression in predicting EOC diagnosis and XGBoost performed best in the external validation datasets. The AUC values of distinguishing EOC and benign disease patients, determining pathological type, grade and clinical stage were 0.958 (0.926-0.989), 0.792 (0.701-0.8834), 0.819 (0.687-0.950) and 0.68 (0.573-0.788) respectively. For negative CA-125 EOC patients, the AUC performance of XGBoost model was 0.835(0.763-0.907). We used unsupervised cluster analysis to identify EOC subgroups with significantly poor overall survival (p-value <0.0001) and recurrence-free survival (p-value <0.0001).ConclusionsBased on the preoperative characteristics, we proved that ML algorithm can provide an acceptable diagnosis and prognosis prediction model for EOC patients. Meanwhile, SHAP analysis can improve the interpretability of ML models and contribute to precision medicine.

Changes in subcellular localization of Lysyl-tRNA synthetase and the 67-kDa laminin receptor in epithelial ovarian cancer metastases.

Although lysyl-tRNA synthetase (KARS1) is predominantly located in the cytosol, it is also present in the plasma membrane where it stabilizes the 67-kDa laminin receptor (67LR). This physical interaction is strongly increased under metastatic conditions. However, the dynamic interaction of these two proteins and the turnover of KARS1 in the plasma membrane has not previously been investigated. Our objective in this study was to identify the membranous location of KARS1 and 67LR and investigate if this changes with the developmental stage of epithelial ovarian cancer (EOC) and treatment with the inhibitor BC-K01. In addition, we evaluated the therapeutic efficacy of BC-K01 in combination with paclitaxel, as the latter is frequently used to treat patients with EOC. Overall survival and prognostic significance were determined in EOC patients according to KARS1 and 67LR expression levels as determined by immunohistochemistry. Changes in the location and expression of KARS1 and 67LR were investigated in vitro after BC-K01 treatment. The effects of this compound on tumor growth and apoptosis were evaluated both in vitro and in vivo. EOC patients with high KARS1 and high 67LR expression had lower progression-free survival rates than those with low expression levels of these two markers. BC-K01 reduced cell viability and increased apoptosis in combination with paclitaxel in EOC cell xenograft mouse models. BC-K01 decreased membranous KARS1 expression, causing a reduction in 67LR membrane expression in EOC cell lines. BC-K01 significantly decreased in vivo tumor weight and number of nodules, especially when used in combination with paclitaxel. Co-localization of KARS1 and 67LR in the plasma membrane contributes to EOC progression. Inhibition of the KARS1-67LR interaction by BC-K01 suppresses metastasis in EOC.

NANOG regulates epithelial-mesenchymal transition via AMPK/mTOR signalling pathway in ovarian cancer SKOV-3 and A2780 cells.

NANOG engages with tumour initiation and metastasis by regulating the epithelial–mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). However, its role in association with pAMPKα, and its clinical significance in EOC have not been elucidated even though AMPK is known to degrade NANOG in various human cancers. Hence, we investigated the role of pAMPKα and its association with NANOG as potential prognostic biomarkers in EOC. Both NANOG and pAMPKα expression were significantly overexpressed in EOCs comparing nonadjacent normal epithelial tissues, benign tissues, and borderline tumours. NANOG overexpression was significantly associated with poor disease‐free survival (DFS) and overall survival (OS), whereas pAMPKα overexpression was associated with good DFS and OS. Importantly, multivariate analysis revealed that the combination of high NANOG and low pAMPKα expression was a poor independent prognostic factor for DFS and was associated with platinum resistance. In ovarian cancer cell lines, siRNA‐mediated NANOG knockdown diminished migration and invasion properties by regulating the EMT process via the AMPK/mTOR signalling pathway. Furthermore, treatment with AMPK activator suppressed expression of stemness factors such as NANOG, Oct4 and Sox2. Collectively, these findings established that the combination of high NANOG and low pAMPKα expression was associated with EOC progression and platinum resistance, suggesting a potential prognostic biomarker for clinical management in EOC patients.

Cancer-associated fibroblasts-derived FMO2 as a biomarker of macrophage infiltration and prognosis in epithelial ovarian cancer

ObjectiveRecent molecular profiling revealed that cancer-associated fibroblasts (CAFs) are essential for matrix remodeling and tumor progression. Our study aimed to investigate the role of flavin-containing monooxygenase 2 (FMO2) in epithelial ovarian cancer (EOC) as a novel CAF-derived prognostic biomarker. MethodsPrimary fibroblasts were isolated from EOC samples. Microdissection and single-cell RNA sequencing (scRNA-seq) datasets (including TCGA, GSE9891, GSE63885, GSE118828 and GSE178913) were retrieved to determine the expression profiles. Gene set enrichment analysis (GSEA) was used to explore the correlation between FMO2 and stromal activation as well as immune infiltration. The predictive value of FMO2 and combined macrophage infiltration level was verified in an independent EOC cohort (n = 113). ResultsWe demonstrated that FMO2 was upregulated in tumor stroma and correlated with fibroblast activation. Besides, FMO2 had the predictive power for worse clinical outcome of EOC patients. In the mesenchymal subtype of EOC, the FMO2-defined signature revealed that FMO2 contributed to infiltration of tumor-infiltrating lymphocytes. Moreover, we confirmed the positive correlation between FMO2 and CD163+ cell infiltration level in EOC tissues, and showed that combination of FMO2 expression with CD163+ cell infiltration level in the tumor stroma could predict poor overall survival (HR = 3.63, 95% CI = 1.93–6.84, p = 0.0008). Additionally, FMO2 also predicted the prognosis of patients with ovarian cancer based on the expression of immune checkpoints (such as PD-L1 and PD1). ConclusionOur results address the tumor-supporting role of FMO2 in EOC and its association with immune components, and it might be a prospective target for stroma-oriented therapies against EOC.

Develop companion radiopharmaceutical YKL40 antibodies as potential theranostic agents for epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is usually diagnosed at an advanced stage and has poor prognosis. Theranostic agents are the current trend in drug development, but are lacking in EOC. YKL40 is predominantly expressed and involved in tumorigenesis in EOC. In this study, we developed a companion theranostic agent targeting YKL40. We measured YKL40 expression levels in ascites using ELISA and correlated them with the clinical outcomes of patients with EOC. We developed radionuclide labeled In-111/Lu-177-DTPA-YKL40 neutralizing antibodies and investigated their radiochemical purity, SPECT/CT imaging, bio-distribution, and therapeutic responses in ovarian cancer xenograft mice. We demonstrated that YKL40 expression levels in ascites were significantly higher in EOC patients with serous histological type, high tumor grade, advanced stage, tumor recurrence, chemoresistance, and tumor-related death. The radiochemical purity of In-111/Lu-177-DTPA-YKL40 neutralizing antibodies reached more than 90% after 24 h of labeling. SPECT/CT imaging showed significant accumulation of In-111-DTPA-YKL40 and Lu-177-DTPA-YKL40 antibodies at the tumor site of ovarian cancer xenograft mice 24 h after administration. Lu-177-DTPA-YKL40 antibodies significantly inhibited tumor growth in ovarian cancer xenograft mice. Our study indicated that In-111/Lu-177-DTPA-YKL40 neutralizing antibodies could be potential companion theranostic agents for patients with EOC.

Corrected Allele Frequency of BRCA1/2 Mutations Is an Independent Prognostic Factor for Treatment Response to PARP-Inhibitors in Ovarian Cancer Patients.

PARP inhibitors (PARPi) have increased treatment options in ovarian cancer, particularly in patients with BRCA1/2 mutations, although there are still marked differences in the duration of patients’ response to this targeted therapy. BRCA testing is routinely performed in tumor tissue of ovarian cancer patients. The resulting molecular pathological findings include the genetic nomenclature of the mutation, the frequency of the mutated allele (variant allele frequency, VAF), and the tumor cell content. VAF measures the percentage of mutated alleles from the total alleles in the cells of the examined tissue. The aim of this study was to investigate the significance of VAF on the therapeutic response to PARPis in ovarian cancer patients. Epithelial ovarian cancer patients harboring BRCA1/2 tumor mutations, who underwent germline testing and received PARPi therapy at the Medical University of Vienna (n = 41) were included in the study. Corrected VAF (cVAF) was calculated based on VAF, tumor cell content, and germline mutation. Patients were divided into two groups based on their cVAF. Median PFS under PARPi in patients with low cVAF was 13.0 months (IQR [10.3-not reached]) and was not reached in the high cVAF group. High cVAF was significantly associated with longer PFS in the multivariate analysis (HR = 0.07; 95% CI [0.01–0.63]; p = 0.017). In conclusion, high cVAF was associated with a significantly better response to PARPi in this study population.

Application of Arsenic Trioxide-Based Combined Sequential Chemotherapy in Recurrent Resistant and Refractory Ovarian Cancers: A Single-Center, Open Phase II Clinical Study.

Objective Arsenic trioxide (ATO) has been effectively used for the treatment of hematological malignancies and some solid tumors, while ATO effects were not tested clinically in epithelial ovarian cancer (EOC). Methods Patients with primary or secondary platinum-resistant EOC were enrolled from October 2015 to December 2019. Patients were mainly treated with ATO-based combined sequential chemotherapy as follows: Regimen 1 (ATO combined taxanes weekly therapy); Regimen 2 (ATO + taxanes + 5-fluorouracil + adriamycin ± bevacizumab sequential chemotherapy), for 5 patients platinum-free interval >12 months, added oxaliplatin). Prespecified end points in this cohort included confirmed best overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results A total of 33 patients were enrolled in this study. After a median follow-up time of 22.1 months (range 5.5–42.9 months), ORR was 42% and DCR was 85%. The overall PFS was 9.5 months (range 1–38.4 months). The main side effect was myelosuppression. Conclusions ATO-based sequential combined chemotherapy is effective for primary and recurrent drug-resistant EOC patients in clinical phase II trials. The associated side effects could be controlled, while further study is needed.

Increased expression of MMP17 predicts poor clinical outcomes in epithelial ovarian cancer patients.

Ovarian cancer has the highest fatality rate among female reproductive system cancers, which is due to lack of biomarker for diagnosis and prognosis. We aimed to evaluate the role of matrix metalloproteinase 17 (MMP17) in ovarian cancer tumorigenesis and prognosis. Based on the epithelial ovarian cancer (EOC) in The Cancer Genome Atlas database, we determined the expression of MMP17 using the Wilcoxon rank-sum test. The biological functions of MMP17 were evaluated using the Metascape database and Gene Set Enrichment Analysis. The association between MMP17 and immune cell infiltration was investigated by single sample Gene Set Enrichment Analysis. Logistic analysis was applied to study the correlation between MMP17 expression and clinicopathological characteristics. Finally, Cox regression analysis, Kaplan–Meier analysis, and nomograms were used to determine the predictive value of MMP17 on clinical outcomes in EOC patients. The expression of MMP17 was much higher in EOC patients than in pericarcinomatous tissues (P < .001). MMP17-associated differentially expressed genes were significantly enriched in cell extracellular matrix (ECM) degrading and corresponding pathways in the high MMP17 expression phenotype. MMP17 has a high sensitivity and specificity for EOC diagnosis, with an area under the curve of 0.988. MMP17 expression was found to be an independent risk factor for overall survival (hazard ratio [HR]: 1.488, P < .001), progression-free interval (HR: 1.347, P < .01), and disease-specific survival (HR: 1.548, P < .01). Increased MMP17 expression in EOC may contribute to carcinogenesis by degrading ECM and provide diagnostic and prognostic value for clinical outcomes.

Postoperative paralytic ileus following debulking surgery in ovarian cancer patients.

AimThis study aims to evaluate the incidence of postoperative ileus (POI) following cytoreductive surgery in epithelial ovarian cancer (EOC) patients and its impact on anastomotic leakage occurrence and postoperative complications.MethodsA total of 357 surgeries were performed on 346 ovarian cancer patients between 1/2010 and 12/2020 at our institution. The postoperative course regarding paralytic ileus, anastomotic leakage, and postoperative complications was analyzed by Fisher's exact test and through ordinal logistic regression.ResultsA total of 233 patients (65.3%) returned to normal gastrointestinal functions within 3 days after surgery. A total of 123 patients (34.5%) developed POI. There were 199 anastomoses in 165 patients and 24 leakages (12.1%). Postoperative antibiotics (p 0.001), stoma creation (p 0.0001), and early start of laxatives (p 0.0048) significantly decreased POI, while anastomoses in general (p 0.0465) and especially low anastomoses (p 0.0143) showed increased POI rates. Intraoperative positive fluid excess >5,000 cc was associated with a higher risk for POI (p 0.0063), anastomotic leakage (p 0.0254), and severe complications (p 0.0012).ConclusionPostoperative antibiotics, an early start with laxatives, and stoma creation were associated with reduced POI rates. Patients with anastomoses showed an increased risk for POI. Severe complications, anastomotic leakages, and POI were more common in the case of intraoperative fluid balance exceeding 5,000 cc.

Platelet Activation in Ovarian Cancer Ascites: Assessment of GPIIb/IIIa and PF4 in Small Extracellular Vesicles by Nano-Flow Cytometry Analysis

Simple SummaryPlatelets play a critical role in coagulation and fibrinolysis processes, but recent literature also indicates their central involvement in immune response, cancer progression and metastasis. During platelet activation, small extracellular vesicles (EVs) are released. The ascites are a fluid developing in the peritoneum of ovarian cancer patients in an advanced stage. This study analysed the expression of platelet markers GPIIb/IIIa and PF4 in small-EVs populations isolated from the ascitic fluid of patients with advanced ovarian cancer. The percentage of platelet-derived small-EVs was positively correlated with platelet distribution width to platelet count in sera (PDW/PLT), a surrogate indicator of platelet activation. Overall, we presented a method that can be helpful in future studies to determine the correlation between the extent of platelet activation in ascites and disease status.In ovarian cancer, ascites represent the microenvironment in which the platelets extravasate to play their role in the disease progression. We aimed to develop an assay to measure ascites’ platelet activation. We enriched small extracellular vesicles (EVs) (40–200 nm) from ascites of high-grade epithelial ovarian cancer patients (n = 12) using precipitation with polyethylene glycol, and we conducted single-particle phenotyping analysis by nano-flow cytometry after labelling and ultra-centrifugation. Atomic force microscopy single-particle nanomechanical analysis showed heterogeneous distributions in the size of the precipitated particles and their mechanical stiffness. Samples were fluorescently labelled with antibodies specific to the platelet markers GPIIb/IIIa and PF4, showing 2.6 to 18.16% of all particles stained positive for the biomarkers and, simultaneously, the EV membrane labelling. Single-particle phenotyping analysis allowed us to quantify the total number of non-EV particles, the number of small-EVs and the number of platelet-derived small-EVs, providing a platelet activation assessment independent of the ascites volume. The percentage of platelet-derived small-EVs was positively correlated with platelet distribution width to platelet count in sera (PDW/PLT). Overall, we presented a high-throughput method that can be helpful in future studies to determine the correlation between the extent of platelet activation in ascites and disease status.

CDC50A might be a novel biomarker of epithelial ovarian cancer-initiating cells

BackgroundThe aim of this work was to screen and validate biomarkers of ovarian cancer-initiating cells to detect the mechanisms of recurrence of epithelial ovarian cancer (EOC).MethodsStably labelled the amino acid in side population (SP) cells of epithelial ovarian cancer which were rich in cancer-initiating cells and non-SP cells with isotope in culture and differentially expressed cellular membrane proteins in SP cells were identified through proteomics technology. The new candidate biomarker was screened and validated through RT-PCR and western blot. Both in cell lines and primary EOC, cancer-initiating biofunctions of CDC50A positive cells were validated. Moreover, the characteristics of mesenchymal transition (EMT) was also detected and the correlation between the biomarker and clinical prognosis was observed.ResultsThrough proteomics technology, candidate protein CDC50A was screened, and its significantly differential expression in SP cells was validated. CDC50A-positive cells from cell lines and primary ovarian cancer tissues were validated to show characteristics of cancer-initiating cells both in vitro and in vivo, including sphere-forming, self-renewal, differentiation, tumor metastasis and tumorigenicity in mice. The relationship between CDC50A-positive cells from primary tissues and tumour metastasis was confirmed based on their mesenchymal transition characteristics. Among 16 high-grade ovarian serous cancer patients, a high ratio of CDC50A-positive cells in primary tumours was correlated with a shorter platinum-free interval (p = 0.031, HR 0.260, 95% CI 0.77 ~ 0.885).ConclusionCDC50A could be used to screen ovarian cancer-initiating cells and might be a new target to resolve tumour development in EOC patients.

Impact of surgery and chemotherapy timing on outcomes in older versus younger epithelial ovarian cancer patients: A nationwide Danish cohort study

IntroductionTo explore differences in surgical complexity, chemotherapy administration, and treatment delays between younger and older Danish patients with epithelial ovarian cancer (EOC). Materials and MethodsWe included a nationwide cohort diagnosed with EOC from 2013 to 2018. We described surgical complexity and outcomes, the extent of chemotherapy and treatment delays stratified by age (<70 and ≥ 70 years), and surgical modality (primary, interval, or no debulking surgery). ResultsIn total, we included 2946 patients. For patients with advanced-stage disease, 52% of the older patients versus 25% of the younger patients did not undergo primary debulking surgery (PDS) or interval debulking surgery (IDS). For patients undergoing PDS or IDS, older patients underwent less extensive surgery and more often had residual disease after surgery >0 cm compared to younger patients. Furthermore, older patients were less often treated with chemotherapy. Older patients had PDS later than younger. We did not find any differences between age groups concerning treatment delays. Two-year cancer-specific survival differed significantly between age groups regardless of curatively intended treatment. DiscussionThis study demonstrates that older patients are treated less actively concerning surgical and oncological treatment than younger patients, leading to worse cancer-specific survival. Older patients do not experience more treatment delays than younger ones.

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.

Is There a Survival Benefit of Adjuvant Chemotherapy in Stage IC1 Epithelial Ovarian Cancer Patients? A Meta-Analysis

The purpose of the present systematic review is to clarify whether adjuvant chemotherapy improves survival rates in women with stage IC1 ovarian cancer. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar. We considered comparative observational studies and randomized trials that investigated survival outcomes (progression-free (PFS) and overall survival (OS)) among women with intraoperative rupture of early-stage epithelial ovarian cancer who received adjuvant chemotherapy and those that did not. Eleven studies, which recruited 7556 patients, were included. The risk of bias was defined as moderate after assessment with the Risk of Bias in non-Randomized Trials tool. Meta-analysis was performed with RStudio. Seven studies investigated the impact of adjuvant chemotherapy on recurrence-free survival of patients experiencing intraoperative cyst rupture for otherwise stage I ovarian cancer. The outcome was not affected by the use of adjuvant chemotherapy as the effect estimate was not significant (HR 1.24, 95% CI 0.74, 2.04). The analysis of data from 5 studies similarly revealed that overall survival rates were comparable among the two groups (HR 0.75, 95% CI 0.54, 1.05). This meta-analysis did not detect any benefit from adjuvant chemotherapy for stage IC ovarian cancer patients with cyst rupture. However, conclusions from this investigation are limited by a study population which included multiple histologic subtypes, high and low grade tumors and incompletely staged patients.

Correlation between clinicopathological factors and clinical outcomes of recurrent epithelial ovarian cancer at a tertiary hospital in Surabaya, Indonesia

Introduction: Ovarian cancer is one of the leading causes of cancer death in women globally. The objective of this study was to determine the correlation and the association between age, stage, histopathology, grade, ascites, tumor residual, CA-125 level, and type of surgery on recurrence, disease-free survival, overall survival and mortality of epithelial ovarian cancer patients. Methods: An analytical retrospective study using medical records and interviews of epithelial ovarian cancer patients was conducted in Dr. Soetomo Hospital. The study included the data from January 2016-December 2020. Kaplan-Meier and log-rank test were used to assess the factors associated with disease-free survival (DFS) and overall survival (OS). Results: A total of 358 patients with epithelial ovarian cancer from 2016 to 2020 were included in the study of which 153 of recurrence cases. Clinicopathological factors that correlated with disease-free survival were stage, histopathology, grade, ascites, tumor residual, CA-125, and type of surgery (p&lt;0.05). The factors that correlated with overall survival were stage, histopathology, grade, ascites, residual tumor, and CA-125 value (p&lt;0.05). The most significant factors associated with recurrence and mortality were stage, grade, and ascites. Stage II and III had an HR (hazard ratio) of 1.9 and 2.1 for recurrence compared to stage I, respectively. Grade II and III patients had HRs of 2.1, and 3.4 for recurrence compared to stage I, respectively. The presence of ascites had an HR of 1.5 compared to those had no ascites. Stage III had an HR of 1.9 for mortality compared to stage I, respectively. Grade II and III patients had HRs of 3.6, and 5.0 for death compared to stage I, respectively. The presence of ascites had an HR of 1.6 compared to patients with no ascites. Compared to serous type, those patients with mucinous and clear cell had HR of 1.8 and 3.1 for mortality, respectively Conclusion: Stage, grade, and ascites were the most significant factors in the incidence of recurrence and mortality of epithelial ovarian cancer.