Primary Ovarian Cancer Patients Research Articles

Hyperthermic intraperitoneal chemotherapy (HIPEC) vs. postoperative intraperitoneal (IP) chemotherapy – Impact on health-related quality of life in primary ovarian cancer patients after cytoreductive surgery

PurposeTo compare health-related quality of life (HRQL) in primary ovarian cancer (OC) patients with peritoneal metastases (PM) after undergoing upfront cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) as part of a phase 2 trial (NCT-02124421). MethodsPatients with stage III/IV high-grade serous OC were randomized (1:1) to either CRS/HIPEC with carboplatin followed by 6 cycles of adjuvant systemic chemotherapy (carboplatin/paclitaxel) or CRS followed by 6 cycles of combination intraperitoneal/intravenous chemotherapy (cisplatin/paclitaxel). The trial outcome index (TOI) of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire was used to assess HRQL. The FACT-O was administered at randomization and postoperatively at 6 weeks and 6, 12, and 24 months, or until disease recurrence/death. HRQL was analyzed using a linear mixed model. ResultsSixteen patients were enrolled in each group. All (32/32) patients completed questionnaires at baseline and 53.1 % (17/32) at 24 months. Reasons for missing scores were similar between groups. Average TOI was similar between treatment arms at each time point. In both arms, mean TOI was below baseline at 6 weeks (p = 0.798) and 6 months (p = 0.821) after CRS, but recovered at 12 months (p = 0.518). No significant differences were found in FACT-O total score or FACT-O individual dimensions over time between groups. ConclusionsNo long-term HRQL impairment was observed when HIPEC was added to CRS in primary OC. Access to CRS/HIPEC as primary treatment of PM in OC should not be solely limited by concerns for patient HRQL. SynopsisHealth-related quality of life (HRQL) was evaluated in primary ovarian cancer patients participating in a phase 2 trial comparing cytoreductive surgery (CRS)/HIPEC vs CRS + intraperitoneal (IP) chemotherapy. No differences between groups or long-term HRQL impairment were observed.

A randomized controlled trial to compare short-term outcomes following infragastric and infracolic omentectomy at the time of primary debulking surgery for epithelial ovarian cancer with normal-appearing omentum

BackgroundOmentectomy is an important procedure in surgery for epithelial ovarian cancer, but the scope of omentectomy is not recommended in the guidelines. This study was performed to evaluate the benefits and risks of infragastric omentectomy in patients with epithelial ovarian cancer.MethodsThis trial is a single center prospective study. Primary epithelial ovarian cancer patients with normal-appearing omentum were randomly assigned to either the control or experimental group and underwent infracolic or infragastric omentectomy, respectively. The primary endpoint was progression-free survival. This trial is registered on Chinese clinical trial registry site (ChiCTR1800018771).ResultsA total of 106 patients meeting the inclusion criteria for ovarian cancer were included during the study period. Of these, 53 patients underwent infracolic omentectomy, whereas 53 patients received infragastric omentectomy. Multivariate analysis revealed that infragastric omentectomy could improve the detection rate of omental metastases (OR: 6.519, P = 0.005). Infragastric omentectomy improved progression-free survival significantly for those cases with higher than stage IIB disease (HR: 0.456, P = 0.041). Based on the short-term results, infragastric omentectomy did not cause more perioperative complications.ConclusionsCompared with infracolic omentectomy, infragrastric omentectomy may be a more appropriate surgical procedure for stage IIB-IIIC epithelial ovarian cancer patients with normal-appearing omentum.

Bevacizumab combined with platinum-based chemotherapy in primary or relapsed ovarian cancer patients: Meta-analysis and literature to review.

Earlier, patients with advanced ovarian cancer were treated with a combination of cytoreductive surgery and platinum-based chemotherapy, which had significant outcomes in the past until an increase in relapse and resistance to treatment, which led to the use or development of bevacizumab (a vascular endothelial growth factor inhibitor) in the treatment of primary or relapsed ovarian cancer. This study includes five-phase three randomized controlled clinical trials designed to study the impact of bevacizumab in combination with platinum-based chemotherapy compared with platinum-based chemotherapy alone. This study demonstrated significant improvement in the progression-free span but no improvement in overall survival in the treatment group when compared with the control group. Also, adverse effects reported with combination therapy were tolerable and easily manageable by decreasing the infusion rate or by decreasing the frequency of infusion.

Health-related quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is not different than cytoreductive surgery alone in primary ovarian cancer patients (009)

Health-related quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is not different than cytoreductive surgery alone in primary ovarian cancer patients (009)

Immune profile of primary and recurrent epithelial ovarian cancer cases indicates immune suppression, a major cause of progression and relapse of ovarian cancer

BackgroundOvarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes. Procartaplex, and ELISA were used to measure soluble ligands and cytokines of HGSOC patients.ResultsAmong the enrolled 51 EOC patients, 33 were primary high grade serous epithelial ovarian cancer (pEOC) and 18 were recurrent epithelial ovarian cancer (rEOC) patients. Blood samples from 46 age matched healthy controls (HC) were used for comparative analysis. Results revealed, frequency of circulatory CD56Bright NK, CD56Dim NK, NKT-like, and T cells was reduced with activating receptors while alterations in immune subsets with inhibitory receptors were observed in both groups. Study also highlights differential immune profile of primary and recurrent ovarian cancer patients. We have found increased soluble MICA which might have acted as “decoy” molecule and could be a reason of decrease in NKG2D positive subsets in both groups of patients. Furthermore, elevated level of serum cytokines IL-2, IL-5, IL-6, IL-10, and TNF-α in ovarian cancer patients, might be associated with ovarian cancer progression. Profiling of tumor infiltrated immune cells revealed the reduced level of DNAM-1 positive NK and T cells in both groups than their circulatory counterpart, which might have led to decrease in NK cell’s ability of synapse formation.ConclusionsThe study brings out differential receptor expression profile on CD56BrightNK, CD56DimNK, NKT-like, and T cells, cytokines levels and soluble ligands which may be exploited to develop alternate therapeutic approaches for HGSOC patients. Further, few differences in the circulatory immune profiles between pEOC and rEOC cases, indicates the immune signature of pEOC undergoes some changes in circulation that might facilitated the disease relapse. They also maintains some common immune signatures such as reduced expression of NKG2D, high level of MICA as well as IL-6, IL10 and TNF-α, which indicates irreversible immune suppression of ovarian cancer patients. It is also emphasized that a restoration of cytokines level, NKG2D and DNAM-1on tumor infiltrated immune cells may be targeted to develop specific therapeutic approaches for high-grade serous epithelial ovarian cancer.

Survival Prediction Models for Ovarian Cancer Patients with Lung Metastasis: A Retrospective Cohort Study Based on SEER Database

To develop a random forest prediction model for the and short- and long-term survival of ovarian cancer patients with lung metastasis. This retrospective cohort study enrolled primary ovarian cancer patients with lung metastasis from the surveillance, epidemiology and end results (SEER) database (2010–2015). All eligible women were randomly divided into the training (n = 1357) and testing set (n = 582). The outcomes were 1-, 3- and 5-year survival. Predictive factors were screened by random forest analysis. The prediction models for predicting the 1-, 3- and 5-year survival were conducted using the training set, and the internal validation was carried out by the testing set. The performance of the models was evaluated with area under the curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The subgroups based on the pathological classification further assessed the model’s performance. Totally 1345 patients suffered from death within 5 years. The median follow-up was 7.00 (1.00, 21.00) months. Age at diagnosis, race, marital status, tumor size, tumor grade, TNM stage, brain metastasis, liver metastasis, bone metastasis, etc. were predictors. The AUCs of the prediction model for the 1-, 3-, 5-year survival in the testing set were 0.849 [95% confidence interval (CI): 0.820–0.884], 0.789 (95% CI 0.753–0.826) and 0.763 (95% CI 0.723–0.802), respectively. The results of subgroups on different pathological classifications showed that the AUCs of the model were over 0.7. This random forest model performed well predictive ability for the short- and long-term survival of ovarian cancer patients with lung metastasis, which may be beneficial to identify high-risk individuals for intelligent medical services.

The Prognostic Value of Cancer Stem Cell Markers (CSCs) Expression-ALDH1A1, CD133, CD44-For Survival and Long-Term Follow-Up of Ovarian Cancer Patients.

Recurrent disease and treatment-associated chemoresistance are the two main factors accounting for poor clinical outcomes of ovarian cancer (OC) patients. Both can be associated with cancer stem cells (CSCs), which contribute to cancer formation, progression, chemoresistance, and recurrence. Hence, this study investigated whether the expression of known CSC-associated markers ALDH1A, CD44, and CD133 may predict OC patient prognosis. We analyzed their expression in primary epithelial ovarian cancer (EOC) patients using immunohistochemistry and related them to clinicopathological data, including overall survival (OS) and progression-free survival (PFS). Expression of ALDH1A1 was detected in 32%, CD133 in 28%, and CD44 in 33% of cases. While Kaplan-Meier analysis revealed no association of the expression of CD133 and CD44 with PFS and OS, ALDH1A1-positive patients were characterized with both significantly shorter OS (p = 0.00022) and PFS (p = 0.027). Multivariate analysis demonstrated that the expression of ALDH1A1, FIGO stage III-IV, and residual disease after suboptimal debulking or neoadjuvant chemotherapy correlated with shorter OS. The results of this study identify ALDH1A1 as a potential independent prognostic factor of shorter OS and PFS in EOC patients. Therefore, targeting ALDH1A1-positive cancer cells may be a promising therapeutic strategy to influence the disease course and treatment response.

Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 Is Associated with Aggressive Epithelial Ovarian Cancer

Hepatocyte growth factor receptor (HGFR), also known as c-mesenchymal-epithelial transition factor (c-MET), plays a crucial role in the carcinogenesis of epithelial ovarian cancer (EOC). In contrast, the mechanisms contributing to aberrant expression of HGFR in EOC are not fully understood. In the present study, the expression of HGFR with its prognostic and predictive role was evaluated immunohistochemically in a cohort of 42 primary ovarian cancer patients. Furthermore, we analyzed the dual expression of HGFR and other druggable biomarkers. In the multivariate Cox regression analysis, high HGFR expression was identified as an independent prognostic factor for a shorter progression-free survival (PFS) (hazard ratio (HR) 2.99, 95% confidence interval (CI95%) 1.01-8.91, p = 0.049) and overall survival (OS) (HR 5.77, CI95% 1.56-21.34, p = 0.009). In addition, the combined expression of HGFR, human epidermal growth factor receptor 2 (Her2/neu), epithelial growth factor receptor (EGFR), insulin-like growth factor 1 (IGF1R), Mucin-1 and Integrin α2β1 further significantly impaired PFS, platinum-free interval (PFI) and OS. Protein co-expression analyses were confirmed by transcriptomic data in a large, independent cohort of patients. In conclusion, new biomarker-directed treatment targets were identified to fight poor prognosis of primary EOC.

Development and validation of a nomogram to predict overall survival of epithelial ovarian cancer patients: a population-based study (381)

<b>Objectives:</b> To develop and validate a nomogram for the overall survival of epithelial ovarian cancer based on the National Union of Real- World Gynecological Oncology Research and Patient Management Platform (NUWA) in China. <b>Methods:</b> We enrolled patients with pathologically confirmed primary epithelial ovarian cancer in the NUWA platform between 2004 and 2018 as a training cohort to develop a nomogram. The cut-off for follow-up was December 2020. Patients with a history of other tumors or missing values of any variable were excluded. Variables were selected by univariate and multivariate Cox proportional hazard regression. Significant factors were applied to establish a nomogram to predict 3-year and 5-year survival, assessed by C-statistic and calibration curves. A testing cohort from SEER Database was applied to externally validate the nomogram by bootstrap resampling. Statistical analysis was conducted by SPSS version 26.0 (IL, USA) and R version 4.1.1 (www.r-project.org). <b>Results:</b> A total of 1262 primary epithelial ovarian cancer patients were filtered out from 5003 ovarian cancer patients in the NUWA platform. Total 10594 of 125682 patients in the SEER Database were screened out accordingly. Baseline age, histotype, histological grade, FIGO stage, longest diameter of the primary tumor, and residual disease after primary surgery were significant risk factors (<i>p</i><0.05). Compared with serous cancer, the hazard ratio (HR) of mucinous, endometrioid, clear cell, other epithelial cancer were 3.391 (95% CI: 2.201-5.223), 1.642 (95% CI: 1.045-2.580), 3.127 (95% CI: 2.134-4.582), and 2.071 (95% CI: 1.486-2.885), respectively. The HR of advanced stage and high grade of disease (FIGO stage III-IV vs I-II, High grade vs Low/moderate grade) were 1.921 (95% CI: 1.226-3.010) and 1.407 (95% CI: 1.048-1.889), respectively. Patients who received optimal (R1), suboptimal (R2) cytoreduction, and those who didn't receive primary debulking surgery had a higher risk of death compared to those without the residual disease (R0), with HRs of 5.530 (95% CI: 3.575-8.555), 7.757 (95% CI: 5.101-11.796) and 9.975 (95% CI: 5.831-17.063), respectively. For continuous variables, the HR of baseline age (years) was 1.024 (95% CI: 1.013-1.036), and the HR of the longest diameter of the primary tumor (cm) was 1.030 (95% CI: 1.007-1.054). The C-statistic values of the nomogram (Figure 1) in the training and testing cohorts were 0.771 (95% CI: 0.748-0.794) and 0.726 (95% CI: 0.718-0.734), respectively. The slopes of calibration curves of 3-year and 5-year survival in the training cohort were 1.165 (95% CI: 0.990-1.340) and 0.955 (95% CI: 0.920-0.990), respectively, whereas, in the testing cohort, these were 1.355 (95% CI: 1.108-1.602) and 1.374 (95% CI: 1.103-1.644), respectively. Fig. 1 <b>Conclusions:</b> The discrimination and goodness of fit of the nomogram indicated its predictive value for the survival of epithelial ovarian cancer in China. Furthermore, the nomogram also obtains certain values in external validation, which implies its feasibility in different populations.

Predictive biomarker for surgical outcome in patients with advanced primary high-grade serous ovarian cancer. Are we there yet? An analysis of the prospective biobank for ovarian cancer

BackgroundHigh-grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer and is associated with high mortality rates. Surgical outcome is one of the most important prognostic factors. There are no valid biomarkers to identify which patients may benefit from a primary debulking approach. ObjectiveOur study aimed to discover and validate a predictive panel for surgical outcome of residual tumor mass after first-line debulking surgery. Study designFirstly, “In silico” analysis of publicly available datasets identified 200 genes as predictors for surgical outcome. The top selected genes were then validated using the novel Nanostring method, which was applied for the first time for this particular research objective. 225 primary ovarian cancer patients with well annotated clinical data and a complete debulking rate of 60% were compiled for a clinical cohort. The 14 best rated genes were then validated through the cohort, using immunohistochemistry testing.Lastly, we used our biomarker expression data to predict the presence of miliary carcinomatosis patterns. ResultsThe Nanostring analysis identified 37 genes differentially expressed between optimal and suboptimal debulked patients (p < 0.05). The immunohistochemistry validated the top 14 genes, reaching an AUC Ø0.650. The analysis for the prediction of miliary carcinomatosis patterns reached an AUC of Ø0.797. ConclusionThe tissue-based biomarkers in our analysis could not reliably predict post-operative residual tumor. Patient and non-patient-associated co-factors, surgical skills, and center experience remain the main determining factors when considering the surgical outcome at primary debulking in high-grade serous ovarian cancer patients.

Serum Free Fatty Acids and G-Coupled Protein Receptors Are Associated With the Prognosis of Epithelial Ovarian Cancer.

PurposeFatty acid metabolism plays key role in cancer development, and free fatty acid receptors (FFARs) are involved in many cancers. However, the correlation between serum free fatty acids (FFAs)/FFARs levels and ovarian cancer (OC) prognosis remains largely unclear.MethodsA retrospective review of 534 primary OC patients and 1049 women with benign ovarian tumors was performed. Serum FFA levels data were extracted from the electronic medical record system. Repeated FFA results of 101 OC patients treated with standard chemotherapy were collected. The effects of FFAs on cells migration were evaluated in OC cell lines by Transwell assay. Gene Expression Profiling Interactive Analysis (GEPIA) was used to compare FFAR mRNA expression levels in cancer and noncancer tissues. Kaplan-Meier (KM) plotter was employed to analyze their prognostic values. SPSS 23.0 and Graphpad prism 7.0 software was used for analysis and graph construction.ResultsFFA levels in the serum of epithelial ovarian cancer (EOC) women were higher than in women with benign ovarian tumors independent of pathology, tumor stage,and grade. FFA levels decreased gradually after chemotherapy. FFAs enhanced the migration of OVCAR3 cells. FFAR1 mRNA expression was lower in OC cells than in control cells. FFAR3 was related to a better prognosis, and FFAR4 was related to poor prognosis in TP-53wild-type and mutated type OC, while FFAR1 and FFAR2 were related to a better prognosis in TP53 wild-type OC but FFAR2 was related to a poor prognosis in TP53-mutant OC.ConclusionThe FFA levels are increased in OC and decreased with chemotherapy. High expression of FFARs was related to the prognosis of OC. The prognostic value of different FFARs differs depending on whether it is a TP53 wild or TP53 mutant ovarian cancer.Targeting FFARs may be an attractive treatment strategy for EOC.

VEGF-C serum level is associated with response to bevacizumab maintenance therapy in primary ovarian cancer patients.

ObjectiveAt present, maintenance therapy with the antiangiogenic agent bevacizumab or with PARP-inhibitors represent two options for BRCA-wildtype ovarian cancer patients, after platinum-based first line chemotherapy. The identification of molecular markers to predict patient response to different maintenance therapies remains a major challenge. In the present study we analyzed the predictive potential of vascular endothelial growth factor C (VEGF-C) to identify ovarian cancer patients that might benefit from an antiangiogenic therapy.Methods101 patients with primary epithelial ovarian cancer were analyzed for serum levels of VEGF-A,–C and CA-125 by ELISA. Serum levels were compared between patients with low pT-stage (pT1a-pT2c n = 11), healthy individuals (n = 27) and patients with higher pT-stage (> = pT3 n = 90). Adjusted ROC curves and an adjusted logistic regression model were carried out to evaluate the potential impact of VEGF-A and -C, as well as CA-125 serum level concentration on bevacizumab-therapy response, under consideration of covariates such as FIGO, pM, pN and residual tumor after surgery.ResultsA patient which has in comparison twice the VEGF-C concentration in serum, has a significant increased chance of response to bevacizumab by a factor of 2.79. Further, only VEGF-C serum levels were significantly higher in the group of patients with lower pT-stage compared to healthy individuals, whereas VEGF-A or CA-125 serum levels could not discriminate between healthy individuals and patients with ovarian cancer at low pT-stages.ConclusionVEGF-C serum level might serve as as a biomarker to evaluate treatment response under bevacizumab.

Cisplatin-induced nephrotoxicity in hyperthermic intraperitoneal chemotherapy (HIPEC) is mitigated by sodium thiosulfate: Clinical and toxicotranscriptomic results of a prospective trial.

5570 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC). Unfortunately, cisplatin is associated with significant renal toxicities. Sodium thiosulfate (ST) has been suggested as a nephroprotectant for patients undergoing HIPEC with cisplatin. Methods: A feasibility trial ( ClinicalTrials.gov: NCT01970722) evaluated safety outcomes of HIPEC with cisplatin 75 mg/m2 during optimal cytoreductive surgery (CRS) in patients with EOC and endometrial cancer (n = 40), with or without ST. Twenty-one patients received no sodium-thiosulfate (nST group), and nineteen patients received sodium thiosulfate (ST group). Toxicities were reported according to CTCAE v. 5. Progression-free survival was followed. Normal tissue biopsies were collected intra-operatively immediately following HIPEC and cisplatin exposure in a subset of patients (n = 21), and profiled with transcriptomic sequencing to identify RNAseq signatures correlating with toxicities. Hierarchical cluster analyses identified distinct transcriptomic signatures in post-HIPEC normal samples of patients with renal AEs (rAEs) compared to no renal AEs (nrAEs). KEGG pathway analysis identified up- or downregulated gene sets using GSEA. Results: Forty patients had HIPEC at time of optimal CRS. Renal toxicities were higher in the nST group (no sodium thiosulfate) compared to the ST group. nST patients had 17% any grade, and 9% Grade 3 AEs for acute and chronic kidney injuries. In contrast, ST patients suffered 0% renal AEs. rAE patients demonstrated upregulation of immune signaling pathways (Toll-like receptor, Natural killer cell, Nod-like receptor); and downregulation of metabolic pathways. Top upregulated genes in rAE patients included immune (e.g. neutrophil) related genes, while downregulated genes included metabolism genes. Kaplan-Meier curves demonstrated improved PFS in primary ovarian cancer patients undergoing HIPEC who were treated with ST vs no ST (p = 0.04, NR vs 13.4 mo). Conclusions: HIPEC with cisplatin results in significant renal toxicities. The mechanisms of cisplatin-induced nephrotoxicity in HIPEC are immune-related and reflect reduced metabolism. Sodium thiosulfate abrogated renal toxicities and did not decrease PFS. Clinical trial information: NCT01970722.

Association of a Combined Cancer Exhaustion Score with Circulating Tumor Cells and Outcome in Ovarian Cancer-A Study of the OVCAD Consortium.

Simple SummaryAdvances in circulating tumor cells (CTCs) research could improve the way we diagnose, treat and monitor epithelial ovarian cancer (EOC) patients. In this study, we investigated the interplay between inflammation-induced systemic catabolic markers and the presence of CTCs and patient outcome, and showed that the presence of CTCs goes hand-in-hand with an increased protein turnover and immune activation. We integrated the information provided by measuring the plasma levels of albumin, tryptophan and its metabolite kynurenine in a combined score for cancer exhaustion (CCES). Our study indicates that not only could the CCES be a useful prognostic biomarker in women with EOC, but also that the interaction between the systemic microenvironment and CTCs is worth investigating in further studies.We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in “liquid biopsy” biomarker assessment.

Incidence and treatment outcomes of ovarian sarcoma compared to epithelial ovarian cancer from the national cancer registry

PurposeTo investigate the incidence and survival outcomes of primary ovarian sarcoma compared to those of epithelial ovarian cancer. MethodsData on primary ovarian sarcoma patients (n = 1361) and epithelial ovarian cancer patients (n = 30,366) between 1999 and 2017 were obtained from the Korea Central Cancer Registry, and their respective age-standardized incidence rate (ASR) and relative survival rate were calculated and compared. ResultsBased on the ASR, the incidence of epithelial ovarian cancer was 4.75 per 100,000 women, while that of primary ovarian sarcoma was 0.22 per 100,000 women. The ASR ratio was 21.94 without significant change of ASR during the study period. Primary ovarian sarcoma had a better survival curve compared with epithelial ovarian cancer, though the difference was not statistically significant (5 yr overall survival 64.0% vs. 61.5%; p = 0.6030). In addition, among the pure sarcomas, the fibrosarcoma histologic subtype showed the best overall survival, and that of liposarcomas and stromal cell sarcoma were behind that (5 yr overall survival 85.0%, 76.7%, and 72.7%; p < 0.0001). ConclusionsThe incidence of primary ovarian sarcoma is quite low, with an ASR of 0.22/100,000 during the last 20 years. There were no significant differences between survival rates of primary ovarian sarcoma and epithelial ovarian cancer.

Exploring ovarian cancer screening using a combined sensor approach: A pilot study

All cells release low molecular weight organic compounds that possess finite vapor pressures at body and/or ambient temperatures. These volatile organic compounds (VOCs) may possess an odor and can be found emanating from all body fluids. As cells turn malignant, analysis of changes in these VOCs can provide insight into cancer onset and diagnosis. Previous studies have demonstrated that dogs can be trained to distinguish ovarian cancer tissues of various stages and grades from normal ovarian tissue and other gynecological malignancies with sensitivity and specificity over 95%. When trained on biopsied tissue, dogs were able to detect the VOC disturbances in peripheral blood samples with the same accuracy. Building on these earlier studies, we examined the VOCs emanating from plasma samples from primary ovarian cancer patients, patients with benign reproductive tract growths, and healthy controls. We used a three-pronged sensor approach to analyze the VOCs from plasma: canines trained on tissue and plasma samples, analysis using solid phase microextraction gas chromatography–mass spectrometry, and novel single stranded DNA-coated carbon nanotube sensor field effect transistors. Each of the three experimental approaches used in this study provided preliminary evidence that plasma from ovarian cancer patients emits a volatile odor signature that can be distinguished from the VOCs of patients with benign ovarian tumors and controls. Our results provide optimism that a diagnostic approach based on the analysis of the VOC odor signature of ovarian cancer is achievable.

A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen.

We described progression-free survival and overall survival in patients with primary mucinous ovarian cancer receiving adjuvant gynecologic versus gastrointestinal chemotherapy regimens. We identified all primary mucinous ovarian cancer patients receiving adjuvant gynecologic or gastrointestinal chemotherapy regimens at a single institution from 1994 to 2016. Gynecologic pathologists using strict pathologic/clinical criteria determined diagnosis. Adjuvant therapy was coded as gynecologic or gastrointestinal based on standard agents and schedules. Clinical/pathologic/treatment characteristics were recorded. Wilcoxon rank-sum test was used for continuous variables, and Fisher's exact test for categorical variables. Progression-free and overall survival were calculated using the Kaplan-Meier method, applying landmark analysis. Of 62 patients identified, 21 received adjuvant chemotherapy: 12 gynecologic, 9 gastrointestinal. Median age (in years) at diagnosis: 58 (range 25-68) gynecologic cohort, 38 (range 32-68) gastrointestinal cohort (p=0.13). Median body mass index at first post-operative visit: 25 kg/m2 (range 18-31) gynecologic cohort, 23 kg/m2 (range 18-31) gastrointestinal cohort (p=0.23). History of smoking: 6/12 (50%) gynecologic cohort, 3/9 (33%) gastrointestinal cohort (p=0.66). Stage distribution in gynecologic and gastrointestinal cohorts, respectively: stage I: 9/12 (75%) and 3/9 (33%); stage II: 2/12 (17%) and 1/9 (11%); stage III: 1/12 (8%) and 5/9 (56%) (p=0.06). Grade distribution in gynecologic and gastrointestinal cohorts, respectively: grade 1: 8/12 (67%) and 1/9 (13%); grade 2/3: 4/12 (33%) and 7/9 (88%) (p=0.03). Three-year progression-free survival: 90.9% (95% CI 50.8% to 98.7 %) gynecologic, 53.3% (95% CI 17.7% to 79.6%) gastrointestinal. Three-year overall survival: 90.9% (95% CI 50.8% to 98.7%) gynecologic, 76.2% (95% CI 33.2% to 93.5%) gastrointestinal. Ongoing international collaborative research may further define associations between chemotherapy regimens and survival.

Increased expression of plakophilin 3 is associated with poor prognosis in ovarian cancer.

Considering the essential role of plakophilin 3 (PKP3) in the maintenance cell-cell adhesion, dysregulation of PKP3 is involved in human diseases. This study aimed to explore the clinical significance of PKP3 in ovarian cancer. Immunohistochemistry was performed to examine the PKP3 expression in 157 cancer specimens from primary ovarian cancer patients. PKP3 was expressed in both the cytoplasm and nucleus. Eighty-one (51.6%) out of 157 ovarian cancer tissues showed PKP3 expression, while absent expression was observed in normal ovarian tissues. High PKP3 expression was associated with lymph node metastasis (LNM, P = .004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = .013). Patients with high PKP3 expression had shorter overall survival (OS) than those with low PKP3 expression (60.2 months vs 74.2 months, P = .021). However, no association between PKP3 expression and progression-free survival (PFS) was observed (P = .790). Cox regression analysis indicated that PKP3 expression was an independently predictive factor for the OS of patient with ovarian cancer (adjusted HR = 1.601, 95%CI: 1.014-2.528, P = .043), especially those with FIGO stages III and IV disease (adjusted HR = 1.607, 95%CI: 1.006-2.567, P = .047). The gene expression profiling interactive analysis (GEPIA) databases also showed that PKP3 was upregulated in ovarian cancer (P < .001) and patients with high PKP3 expression had shorter OS (P = .004). In conclusion, our findings suggest that PKP3 is upregulated in ovarian cancer and is likely involved in the progression of ovarian cancer. PKP3 might therefore serve as a prognostic biomarker for patients with ovarian cancer.

Next-generation sequencing-based genomic profiling analysis reveals novel mutations for clinical diagnosis in Chinese primary epithelial ovarian cancer patients

BackgroundOvarian cancer (OC) is one of the most malignant gynecological tumors, associated with excess death rate (50–60%) in ovarian cancer patients. Particularly, among newly occurred ovarian cancer patients, 70% of clinical cases are diagnosed at the advanced stage, which definitely delay the timely treatment and lead to high mortality rate within 5 years post diagnosis. Therefore, identification of sensitive gene markers, as well as development of reliable genetic diagnosis, are important for the early detection and precise therapy for OC patients. This study aims to identify novel genetic mutations and develop a feasible clinical approach for early OC diagnosis.MethodsThe OC tissue-derived DNA sample was acquired from 31 OC patients, and the somatic gene mutations will be identified after comparison with normal samples, using Genome-wide analysis and next-generation sequencing.ResultsA total of 463 somatic mutations, which were considered as potential pathogenic sites, were assigned to 473 genes. Among them, 15 genes (TP53, TTN, MUC16, OR4N2, BRCA1, CAD, CCDC129, INSR, NAV3, NELL2, NRAS, OBSCN, PGLYRP4, RBM15B and TRPC7) were mutated on at least two sites. These genes were mapped to RNA sequencing (RNAseq) data, and a total of 117 genes had an absolute fold- change ≥ 2 and p ≤ 0.01. Five genes were mutated in at least two OC patients. Gene ontology (GO) classification indicated that a majority of genes participated in biological processes. Kyoto Enrichment of Genes and Genomes (KEGG) enrichment pathway analysis revealed that the genes were mainly involved in the regulation of metabolic signaling pathways.ConclusionsTaken together, this study identified several novel genetic alterations pathway for early clinical diagnosis and provided abundant information for understanding molecular mechanisms of the OC occurrence and development.

Evaluation of trace elements associated with antioxidant enzymes in blood of primary epithelial ovarian cancer patients

Epithelial ovarian cancer (EOC) has been associated with oxidative stress (OS) due to epithelial inflammation which makes ovaries more vulnerable to the deleterious effects of reactive oxygen species (ROS). However, antioxidant enzymes (AOEs) such as manganese-superoxide dismutase (Mn-SOD), copper,zinc-superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GPx1) protect cells against the biological damage of ROS-induced OS and support cancer prevention by maintaining normal cell cycle progression, inhibiting proliferation, tumor invasion, angiogenesis, inflammation or inducing apoptosis.In the present study, we aimed to measure the levels of trace elements [manganese (Mn), copper (Cu), zinc (Zn) and selenium (Se)] which are structurally and/or functionally associated with the AOEs by inductively coupled plasma/mass-spectrometry (ICP/MS) in blood samples of patients with EOC (M, n = 26) and compare the data with healthy subjects (C, n = 46). Serous EOC (M1, n = 18) data were also evaluated according to the tumor grading [well or moderately well differentiated (G 1-2) vs. poorly differentiated or undifferentiated (G3)] and staging of disease [stage I-II (SI-II) vs. stage III (SIII)]. We obtained; i) The Mn and Se levels of M were significantly lower than C, ii) only Mn levels were changed [(G3(Mn) < G 1-2 (Mn)] in M1, iii) significant correlations were observed between [Cu and Zn levels (r = 0.701, p = 0.036) in G 1-2 and (r = 0.686, p = 0.041) in G3; Cu and Se levels (r = 0.960, p = 0.000) in G3; Mn levels and Mn-SOD expression (r = 0.551, p = 0.006) in M, (r = 0.857, p = 0.007) in G 1-2 and (r = 0.690, p = 0.056) in G3; Se levels and erythrocyte GPx1 activity (r = 0.660, p = 0.053) in G 1-2 ; Se levels and erythrocyte Cu,Zn-SOD activity (r = 0.693, p = 0.038) in G3]. The study revealed that trace elements, particularly low Mn and Se levels along with high Cu/Se ratios might be of value in all histologic subtypes of EOC. Although Mn level was important in terms of discriminating tumor grades, positive correlation between Cu-Se levels was also remarkable in patients with G 1-2 tumors of M1. Moreover, high erythrocyte Cu/Se ratios might be a favourable marker for EOC.