MRI assessment of ovarian masses and correlating with CA-125.

BACKGROUND: The combined use of appropriate imaging modalities and serum biomarkers like serum Carcinoembryonic Antigen-125 (CA-125) helps plan treatment strategies and reduce overall mortality. AIMS AND OBJECTIVES: To assess ovarian masses on Magnetic Resonance Imaging (MRI) and correlate them with serum CA-125 values. To derive a new serum CA-125 cut-off value for differentiating benign from malignant ovarian masses. MATERIALS AND METHODS: This cross-sectional study was conducted from August 2020 to January 2021 on patients with suspected pelvic masses referred to the department of radio-diagnosis and meeting inclusion and exclusion criteria. Serum CA-125 values and imaging features on MRI were recorded. RESULTS: A total of 37 ovarian masses were included in the study, of which 14 were malignant and 23 were benign. The mean CA-125 values among benign [35.95 ± 25.42 (mean ± SD) IU/ml] and malignant ovarian masses [444.82 ± 232.9 (mean ± SD) IU/ml] were statistically significant (<0.001). Using the reference serum CA-125 value of 35 IU/ml, specificity and accuracy were 61% and 75.68%. A cut-off value of 80.5 IU/ml recorded specificity and accuracy of 95.7% and 94.59%, respectively, with a sensitivity of 92.86% in differentiating benign from malignant ovarian masses. CONCLUSION: The serum CA-125 cut-off value of 80.5 IU/ml is a sensitive and specific serum biomarker for ovarian malignancies. A combined approach of MR imaging and serum CA-125 correlation can be used in characterizing ovarian malignancies in routine clinical practice.

Serum anti-Müllerian hormone as a marker of ovarian reserve after cancer treatment and/or hematopoietic stem cell transplantation in childhood: proposal for a systematic approach to gonadal assessment.

OBJECTIVE: Female patients treated with alkylating agents in childhood are at risk for ovarian impairment. We aimed at describing the pattern of residual ovarian function in a cohort of survivors of hematological malignancies and/or hematopoietic stem cell transplantation (HSCT) and assessing the relationship between cyclophosphamide equivalent dose (CED) and anti-Müllerian hormone (AMH). DESIGN AND METHODS: Gonadal health was clinically and biochemically assessed in 124 post-menarchal survivors who underwent treatment for pediatric hematological malignancies and/or HSCT between 1992 and 2019. RESULTS: Overt 'premature ovarian insufficiency' (POI) was detected in 72.1 and 3.7% of transplanted and non-transplanted patients, respectively; milder 'diminished ovarian reserve' (DOR) in 16.3 and 22.2%. In non-transplanted patients, increasing CED values were associated with lower AMH-SDS (P = 0.04), with the threshold of 7200 g/m2 being the best discriminator between DOR/POI and normal ovarian function (AUC: 0.75 on ROC analysis) and with an observed decrease of 0.14 AMH-SDS for each CED increase of 1 g/m2. In addition, age at diagnosis ≥10 years played a detrimental role on ovarian reserve (P = 0.003). In the HSCT group, irradiation was associated with a statistically significant reduction in AMH-SDS (P = 0.04). CONCLUSIONS: In non-transplanted patients, CED ≥ 7200 mg/m2 was associated with a DOR, while younger age at diagnosis played a protective role on ovarian reserve. As a result of the data collected, we propose a systematic algorithm to assess iatrogenic gonadal impairment in young female patients exposed to chemo-radiotherapy in childhood for hematological disorders.

Review of biomarker systems as an alternative for early diagnosis of ovarian carcinoma.

Early diagnosis of ovarian carcinoma is bound to boost the long-term endurance rate of the patients. Most ovarian tumors happen post menopause when the ovaries have no vital operation and therefore irregular ovarian role causes no signs. According to Muinao T. et al. (Heliyon. 5(12):e02826, 2019), if we consider the frequency of ovarian carcinoma to be moderate, a screening technique must accomplish a base specificity of 99.6% and sensitivity of over 75%. The classification and approval of early diagnostic biomarkers explicit to ovarian carcinoma are essentially required. Prevailing methods for early diagnosis of ovarian carcinoma incorporate TVS, biological marker examination, or a blend of the two or other. In recent years, it has been revealed that a combination of at least two biomarkers has beaten single biomarkers in measures for early diagnosis of the illness. In the present document, we survey the ongoing exploration of innovative characteristic methodologies and possible panels of carcinoma biological markers for the early diagnosis of ovarian carcinoma and discuss biomarkers as the plausible apparatus for model improvement and other progressed approaches as an effective alternative to the prevailing methods for early diagnosis of this dreadful disease to evade bogus analysis and inordinate expense.

Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors.

OBJECTIVE: To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. METHODS: In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. RESULTS: CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. CONCLUSIONS: The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

Consolidated BRCA1/2 Variant Interpretation by MH BRCA Correlates with Predicted PARP Inhibitor Efficacy Association by MH Guide.

BRCA1/2 variants are prognostic biomarkers for hereditary breast and/or ovarian cancer (HBOC) syndrome and predictive biomarkers for PARP inhibition. In this study, we benchmarked the classification of BRCA1/2 variants from patients with HBOC-related cancer using MH BRCA, a novel computational technology that combines the ACMG guidelines with expert-curated variant annotations. Evaluation of BRCA1/2 variants (n = 1040) taken from four HBOC studies showed strong concordance within the pathogenic (98.1%) subset. Comparison of MH BRCA's ACMG classification to ClinVar submitter content from ENIGMA, the international consortium of investigators on the clinical significance of BRCA1/2 variants, the ARUP laboratories, a clinical testing lab of the University of UTAH, and the German Cancer Consortium showed 99.98% concordance (4975 out of 4976 variants) in the pathogenic subset. In our patient cohort, refinement of patients with variants of unknown significance reduced the uncertainty of cancer-predisposing syndromes by 64.7% and identified three cases with potential family risk to HBOC due to a likely pathogenic variant BRCA1 p.V1653L (NM_007294.3:c.4957G > T; rs80357261). To assess whether classification results predict PARP inhibitor efficacy, contextualization with functional impact information on DNA repair activity were performed, using MH Guide. We found a strong correlation between treatment efficacy association and MH BRCA classifications. Importantly, low efficacy to PARP inhibition was predicted in 3.95% of pathogenic variants from four examined HBOC studies and our patient cohort, indicating the clinical relevance of the consolidated variant interpretation.

Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer.

Epithelial ovarian cancer (OC) is the most deadly cancer of the female reproductive system. To date, there is no effective screening method for early detection of OC and current diagnostic armamentarium may include sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 (CA-125) and Human epididymis protein 4 (HE4). Microorganisms (bacterial, archaeal, and fungal cells) residing in mucosal tissues including the gastrointestinal and urogenital tracts can be altered by different disease states, and these shifts in microbial dynamics may help to diagnose disease states. We hypothesized that the peritoneal microbial environment was altered in patients with OC and that inclusion of selected peritoneal microbial features with current clinical features into prediction analyses will improve detection accuracy of patients with OC. Blood and peritoneal fluid were collected from consented patients that had sonography confirmed adnexal masses and were being seen at SIU School of Medicine Simmons Cancer Institute. Blood was processed and serum HE4 and CA-125 were measured. Peritoneal fluid was collected at the time of surgery and processed for Next Generation Sequencing (NGS) using 16S V4 exon bacterial primers and bioinformatics analyses. We found that patients with OC had a unique peritoneal microbial profile compared to patients with a benign mass. Using ensemble modeling and machine learning pathways, we identified 18 microbial features that were highly specific to OC pathology. Prediction analyses confirmed that inclusion of microbial features with serum tumor marker levels and control features (patient age and BMI) improved diagnostic accuracy compared to currently used models. We conclude that OC pathogenesis alters the peritoneal microbial environment and that these unique microbial features are important for accurate diagnosis of OC. Our study warrants further analyses of the importance of microbial features in regards to oncological diagnostics and possible prognostic and interventional medicine.

Adnexal mass risk assessment: a multivariate index assay for malignancy risk stratification.

Aims: Adnexal mass risk assessment (AMRA) stratifies patients with adnexal masses, identifying the relatively small number of malignancies from benigns which might take a 'watchful waiting' approach. Methods: AMRA uses seven biomarkers and derived from women with adnexal masses scheduled for surgery. Estimated clinical performance was calculated using fixed prevalence. Results: At 5% prevalence, the high-risk group, 7.9% total, captured 75.9% of invasive malignancies at a positive predictive value of 35.8%. High risk/intermediate risk combined had a sensitivity of 89.7 and 95.6% for pre- and post-menopausal cancers, respectively. The low-risk group, 67.8% total, had an negative predictive value of 99.0%. Conclusion: With highly differentiating risk stratification capability across histological subtypes and stages, AMRA is potentially applicable to patients with adnexal masses to assist deciding whether immediate surgery is recommended.

Diagnostic significance assessment of the circulating cell-free DNA in ovarian cancer: An updated meta-analysis.

BACKGROUND: Recently, disagreements remain in increasing evidence about the potential value of circulating cell-free DNA (cfDNA) as a noninvasive diagnostic biomarker for ovarian cancer (OC). Here, this update meta-analysis was performed to further assess the diagnostic performance of circulating cfDNA in discriminating OC from non-cancerous individuals. METHODS: We performed a systemic literature search of PubMed, Embase, Web of Science, Cochrane Library, OVID, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases to obtain 22 eligible articles including a total of 1125 patients and 1244 controls. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and area under receiver operating characteristics curves (AUROC) of the included studies for cfDNA in diagnosing OC patients were used to estimate the diagnostic value. The clinical utility of cfDNA was evaluated by Fagan nomogram. Heterogeneity was explored utilizing subgroup analysis and meta-regression. RESULTS: The pooled sensitivity and specificity were 73% and 90%, the DOR and AUROC were 25.29 and 0.90, respectively. Subgroup analyses and meta-regression, according to patients' region, study design, clinical stage, specimen types, detection indicators, simple size, publication year revealed there were no significant sources of heterogeneity. Additionally, subgroup analyses showed qualitative detection (methylation detection); TNM stage I-IV, publication year 2011-2018, serum-based cfDNA assays exhibited better diagnostic performance as compared to quantitative detection, TNM stage III-IV, publication year 2002-2010; plasma-based cfDNA assays, and more participants and prospective studies manifested superior diagnostic accuracy. The result of sensitivity analysis indicated no study exclusively contributed to the heterogeneity and Deeks' funnel plot suggested no evidence of significant publication bias. CONCLUSIONS: Our meta-analysis found the qualitative detection (methylation); TNM stage I-IV, publication year 2011-2018 were related to more effective diagnostic accuracy for OC. However, serum-based cell-free DNA detection should be cautiously interpreted due to unclear factors. Hence, further large-scale longitudinal studies are required to validate the diagnostic potential of cell-free DNA. The present study provides to accrue knowledge of cell-free DNA levels for future researches.

Clinical Performance Comparison of Two In-Vitro Diagnostic Multivariate Index Assays (IVDMIAs) for Presurgical Assessment for Ovarian Cancer Risk.

INTRODUCTION: Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, especially for ovarian cancer. Proper identification prior to surgery would permit appropriate referral to a specialty center in cases likely to be ovarian cancer, as optimal outcomes in such cases are obtained when surgical staging and treatment are provided at the time of initial surgery. METHODS: We compared the screening capabilities of two in vitro diagnostic multivariate index assays (IVDMIAs), a new IVDMIA (second-generation multivariate index assay: MIA2G) and a currently used triage algorithm (Risk of Ovarian Malignancy Assay: ROMA). RESULTS: Among 245 subjects (24.7%) determined to have a malignancy, ROMA misclassified 51 malignancies (including 10 high-grade ovarian malignancies), whereas MIA2G misclassified 22 (including 5 high-grade ovarian malignancies). Early stage cancers were more frequently misclassified by ROMA (20 vs. 8 cases). The rate of "test-negative" malignancies was significantly higher for ROMA, while the rate of "test-positive" benign cases was significantly higher for MIA2G. CONCLUSION: Triage algorithms play an important role in improving clinical outcomes for women presenting with an adnexal mass regardless of the eventual diagnosis. In this study, MIA2G was shown to correctly predict more cases of ovarian cancer than the ROMA algorithm. FUNDING: Aspira Labs/Vermillion Inc.

Combination of Sonographic Morphology Score and Tumor Markers for Detecting Postoperative Recurrent Pelvic Ovarian Carcinoma: Compared With MRI Assessment.

To assess the efficacy of the combination of sonographic morphology score (SMS) with CA125 and HE4 for detecting recurrent pelvic ovarian carcinoma (OC). Data of 58 OC patients treated in our hospital between 2014 and 2016 were analyzed. After cytoreductive surgery and routine chemotherapy, all patients were followed up by transvaginal ultrasound examination (SMS for pelvic masses based on volume and structure scores) and tumor marker (serum CA125 and HE4) detection. Clinical diagnosis of recurrent OC was based on physical examination, magnetic resonance imaging, and punctured pathology for pelvic masses. Receiver operating characteristic (ROC) curves of SMS and the tumor markers were generated, and areas under the curve (AUC) values were assessed. There were 26 patients with tumor recurrence and 32 cases with no recurrence. Magnetic resonance imaging had 100% sensitivity and specificity. The areas under the ROC curves of SMS, CA125, HE4, and SMS-CA125-HE4 were 0.816, 0.825, 0.737, and 0.903, respectively. There was no significant difference in AUC values between SMS and CA125 or HE4. There were significant differences in AUC values between SMS-CA125-HE4 and SMS (Z = 2.48, P = 0.042), CA125 (Z = 2.38, P = 0.046), and HE4 (Z = 6.48, P = 0.016), respectively. With a cutoff value of SMS, 5; CA125, 35 U/mL; HE4, 105 pmol/L, the sensitivity, specificity, positive prognostic value, and negative prognostic value of SMS-CA125-HE4 for recurrent OC assessment were 0.9231, 0.8438, 0.8276, and 0.931, respectively. SMS-CA125-HE4 was correlated with recurrent OC (χ = 30.7428, P < 0.0001). Ultrasound combined with tumor markers may improve the diagnostic efficiency of recurrent OC.

Quantitative assessment of serum heat shock protein 27 for the diagnosis of epithelial ovarian cancer using targeted proteomics coupled with immunoaffinity enrichment.

BACKGROUND: Heat shock protein 27 (HSP27) may take part in the epithelial ovarian cancer (EOC) malignant process because it is elevated in the serum of EOC patients, suggesting that HSP27 may serve as an EOC biomarker to complement the standard serum carbohydrate antigen 125 (CA125) test. Thus, accurate quantification of serum HSP27 would assist the diagnosis of EOC. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics coupled with an immunoaffinity enrichment assay was developed and validated to monitor HSP27 concentrations in serum. RESULTS: Tryptic peptide 80QLSSGVSEIR89 was selected as a surrogate analyte for quantification, and an immuno-depleted serum extract was used as a surrogate matrix. Immunoaffinity enrichment was effective for protein enrichment and sensitivity enhancement, and the resulting LOQ was 500 pg/ml (>10-fold increase). Then, serum HSP27 concentrations in EOC patients, benign ovarian tumors patients and healthy volunteers were accurately determined to be 4.95 ±â€¯0.37 ng/ml, 2.98 ±â€¯0.16 ng/ml and 2.82 ±â€¯0.15 ng/ml, respectively, suggesting that the EOC samples had significantly higher concentrations of HSP27 than a sample from benign ovarian tumor patients. The experimental values for the samples were compared with those obtained from enzyme-linked immune sorbent assays (ELISAs). The ROC curve analysis showed that the combined area under the curve (AUC) for CA125 and HSP27 was 0.88, which is significantly superior to that of CA125 alone. CONCLUSIONS: Targeted proteomics coupled with immunoaffinity enrichment may provide more accurate quantification of low-abundant proteins.

Assessment of diagnostic utility of multivariate diagnostic models in differential diagnosis of ovarian tumors.

INTRODUCTION: Ovarian cancer (OC) diagnosis remains a clinical challenge due to lack of early symptoms and insufficient accuracy of the available diagnostic methods. The purpose of this study was to determine whether osteopontin could be useful in differential diagnosis of ovarian tumors. MATERIAL AND METHODS: Serum samples from 92 patients qualified for surgical treatment due to ovarian mass were divided into 2 groups according to the histopathological result: OC including borderline ovarian tumors (n = 39) and benign ovarian tumors (BOTs) (n = 53). CA125, HE4 and osteopontin concentrations were measured in all patients. Areas under the receiver operating characteristic curves (AUC of ROC) were used to compare the discriminative ability of the univariate and multivariate diagnostic models. RESULTS: The addition of osteopontin to ROMA significantly improved the diagnostic performance of the test in 3 of the 5 analyses: 1) in the OC vs BOT group (from AUC of 0.955 to 0.975), 2) in premenopausal women OC vs BOT (from AUC of 0.828 to 0.892) and 3) in the FIGO I-II stage OC vs BOT (from AUC of 0.865 to 0.895). It did not alter the diagnostic performance of multifactor tests in the group of postmenopausal women nor in OC FIGO III-IV stage group. Osteopontin was also the best single marker to differentiate between early stage OC and BOTs (AUC of 0.863). CONCLUSIONS: Osteopontin improves the diagnostic performance of a multimarker OC diagnostic test and could be useful in differential diagnosis of ovarian tumors, especially in pre-menopausal women and for early stage OC.

Diagnostic value of the gynecology imaging reporting and data system (GI-RADS) with the ovarian malignancy marker CA-125 in preoperative adnexal tumor assessment.

OBJECTIVES: The purpose of this study is to assess the preoperative evaluation of an adnexal mass using the GI-RADS classification and to verify whether CA-125 measurement can offer any additional benefits to the GI-RADS-based prediction of ovarian tumor malignancy. MATERIAL AND METHODS: In this study, we assessed a total of 215 women with an adnexal tumor using the GI-RADS classification combined with CA-125 measurement. All adnexal masses underwent histological verification. RESULTS: Of a total of 215 lesions, we classified 2 lesions as GI-RADS 2 (0.9%), 118 lesions as GI-RADS 3 (54.9%), 86 lesions as GI-RADS 4 (40.0%) and 9 lesions as GI-RADS 5 (4.2%). For GI-RADS 4-5 lesions, the sensitivity, specificity, PPV, NPV, ACC and OR were as follows: 94.3, 72.2, 52.6, 97.5, 77.7%, and 43.3 (CI 12.0-146), respectively. The corresponding parameters resulting from combining the GI-RADS classification with the CA-125 marker were as follows: 66.0, 93.8, 77.8, 89.4, 87.0%, and 29.6 (CI 12.6-69.6), respectively, with p < 0.001. For Ca-125 > 30 IU/mL alone, the results were as follows: 70.0, 80.3, 53.8, 89.1, 77.7%, and 9.5 (4.6-19.6), respectively, with p < 0.0001. Additionally, 47.8% of the patients had no symptoms, 36.5% had back pain, 5.2% had an increased abdominal size, 4.3% had menstrual irregularities and 2.6% had constipation. There were 152 benign and 18 malignant cases in the low risk group (GIRADS 1-3 and GIRADS 4 + CA-125 < 30 IU/mL) and 10 benign and 35 malignant tumors in the high-risk group (GIRADS 4 + CA125 > 30 IU/mL and GIRADS 5). CONCLUSIONS: GI-RADS classification had good performance in discriminating ovarian tumors. The additional measurement of CA-125 improves the system specificity, PPV and ACC for preoperative adnexal tumor assessment.

Trends and Outcomes of Venous Thromboembolism in Hospitalized Patients With Ovarian Cancer: Results From Nationwide Inpatient Sample Database 2003 to 2011.

OBJECTIVE: Venous thromboembolism (VTE) is a major cause of mortality and morbidity in hospitalized patients with malignancy. Nationwide Inpatient Sample database was analyzed to determine the trends in the rate of hospitalization and mortality from VTE in hospitalized ovarian cancer patients and assess its economic impact and resource utilization. METHOD: We queried the 2003 to 2011 Nationwide Inpatient Sample database from Healthcare Cost and Utilization project (Agency of Healthcare Research and Quality) to identify all adults (age ≥18 years) ovarian cancer. Patients hospitalized with VTE as one of the top 3 discharge diagnoses were also identified. Demographic characteristics and in-hospital outcomes of this population were compared with ovarian cancer patients without VTE. Binary logistic regression analysis was used to obtain adjusted odds ratios (ORs). RESULTS: A total of 34,249 (3.5%) of a total of 981,386 hospitalized ovarian cancer patients had an accompanying diagnosis of VTE. Mean age of the study population was 64 years. After adjusting for potential confounders, compared with those without VTE, ovarian cancer patients with VTE had significantly higher inpatient mortality (6.2% vs 4.3%; OR, 1.12 [confidence interval (CI), 1.06-1.17]; P < .001), longer length of stay (5 vs 4 days; OR, 1.40 [CI, 1.36-1.43]; P < .001), higher average cost of hospitalization (US $26,000 vs US $22,000; OR, 1.10 [CI, 1.07-1.13]; P < .001), and greater disability at discharge (OR, 1.34 [CI, 1.31-1.38]; P < .001). Although the annual number of VTE admissions in ovarian cancer patients increased, in-hospital mortality declined from 10.9% in 2003 to 5.3% in 2011. CONCLUSIONS: Venous thromboembolism in hospitalized patients with ovarian cancer is associated with higher inpatient mortality, length of stay, higher cost of hospitalization, and disability at discharge. The hospitalization rate has increased, but the inpatient mortality rate has declined over study period.

Preoperative assessment of ovarian tumors using a modified multivariate index assay.

BACKGROUND: Preoperative differentiation between benign and malignant masses can be challenging. The aim of this research was to evaluate the performance of a modified multivariate index assay (MIA) in detecting ovarian cancer and to compare the effectiveness of gynecologist assessment, cancer antigen (CA) 125, and MIA for identifying ovarian masses with high suspicion of malignancy. RESULTS: This prospective observational study included 150 women with ovarian masses who underwent surgery in the Maternity Teaching Hospital from December 2014 to May 2016. Preoperative estimation of modified MIA, assessment by a gynecologist, and CA 125 level correlated with the surgical histopathology. A modified MIA was implemented because of lack of access to the software typically used. Among 150 enrolled women there were 30 cases of malignancy, including 8 cases (26%) of early-stage ovarian cancer and 22 cases (74%) of late-stage cancer. MIA showed high specificity (96.7%) in detecting cancer and a sensitivity of 70%, with a positive predictive value of 84% and a negative predictive value of 92.8%. No significant differences were detected between the MIA results and the histopathology results (P = 0.267). For early-stage ovarian cancer, the sensitivity of MIA was 100% compared with 75% for CA 125 alone. CONCLUSION: MIA seems to be effective for evaluation of ovarian tumors with higher specificity and positive predictive value than CA 125 while maintaining high negative predictive value and with only a slightly lower overall sensitivity. For evaluation of early-stage ovarian cancer, MIA showed a much higher sensitivity that markedly outperformed CA 125 alone. This modified MIA strategy may be particularly useful in low resource setting.

Suitability assessment of baseline concentration of MMP3, TIMP3, HE4 and CA125 in the serum of patients with ovarian cancer.

BACKGROUND: MMP and TIMP play an important role in the degradation of extracellular matrix components which are essential for tumor growth, invasion and metastasis. Aim of this research was to assess MMP3 and TIMP3 as prognostic factors among patients with ovarian cancer. RESULTS: It was found that high levels of output MMP3 correlated with shortened overall survival time of patients by 9.7 months. In addition, it has been shown that high concentrations of output MMP3 were significantly associated with a shorter disease free time in median concentrations implemented p = 0.0059. Statistically significant dependence has been shown between an average concentration of TIMP3 protein to the overall survival of patients. The higher output concentration of TIMP3, the longer patients' survival by 8.9 month. In addition, it was found that high TIMP3 concentrations output were associated with a significantly longer disease free duration at a median concentrations p = 0.007. CONCLUSION: Preliminary research shows that output levels of MMP3 and TIMP3 proteins correlate with overall survival of patients. In some cases also time free of illness.

Assessment of Circulating Tumor Cells as a Predictive Biomarker of Histology in Women With Suspected Ovarian Cancer.

BACKGROUND: The clinical assessment of circulating tumor cells (CTCs) as a blood-based biomarker is FDA-approved for use in breast, colorectal, and prostate cancers. The objective of this prospective clinical study was to determine whether pretreatment CTCs are a useful diagnostic biomarker in women with complex pelvic masses. METHODS: Whole blood was collected from 49 women with newly diagnosed pelvic masses. The presence of CTCs was compared between women with and without ovarian cancer histopathologic diagnosis after surgery using a Chi-squared test. RESULTS: CTCs were absent in those with benign disease (0/14), present in 17% (5/29) of patients with a histologic diagnosis of ovarian carcinoma, and present in 80% (4/5) of patients with ovarian metastases from other cancers (P = 0.001). All 5 women with ovarian cancer who had CTCs present presented stage III or IV of the disease (P = 0.13). CONCLUSIONS: CTCs were more prevalent in patients with metastases to the ovary than in primary ovarian carcinomas.

Comparison of the Copenhagen Index versus ROMA for the preoperative assessment of women with ovarian tumors.

OBJECTIVE: To compare the Copenhagen Index (CPH-I) and the Risk of Ovarian Malignancy Algorithm (ROMA) in the differential diagnosis of ovarian tumors. METHODS: In a retrospective study, data were reviewed from women with ovarian tumors who attended University Hospital Brno, Czech Republic, between July 2011 and June 2015. The women were classified into the benign tumor group or malignant tumor group (borderline and malignant tumors). Serum levels of CA125 and HE4 were extracted from medical records. The two tumor indices were calculated using relevant clinical data. RESULTS: Among 267 included women, 110 had benign tumors, 42 had borderline ovarian tumors, and 115 had malignant tumors. The two indices showed similar discriminatory performance with no significant differences (P>0.05). In the differentiation of benign tumors from all stages of borderline tumor and ovarian cancer, ROMA showed a sensitivity of 71% at a specificity of 88%, whereas CPH-I showed a sensitivity of 69% at a specificity of 85%. CONCLUSION: CPH-I is a potential tumor index that is independent of menopausal status. It might be applied as a simple alternative to ROMA in settings of basic medical care.

Synergistic Tailoring of Electrostatic and Hydrophobic Interactions for Rapid and Specific Recognition of Lysophosphatidic Acid, an Early-Stage Ovarian Cancer Biomarker.

Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetylenes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through the synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone with a concomitant blue-to-red color change. The detailed mechanism underlying the high selectivity of PDAs toward LPA is revealed by comprehensive theoretical calculation and experiments. Moreover, the level of LPA can be quantified in plasma samples from both mouse xenograft tumor models and patients with ovarian cancer. Impressively, this approach can be introduced into a portable point-of-care device to successfully distinguish the blood samples of patients with ovarian cancer from those of healthy people, with 100% accuracy. This work provides a valuable portable tool for early diagnosis of ovarian cancer and thus holds a great promise to dramatically improve the overall survival.

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: To assess the within-trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy. METHODS: Within-trial economic evaluation of no screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second-line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model. RESULTS: Using a CA125-ROCA cost of £20, the within-trial results show USS to be strictly dominated by MMS, with the MMS vs C comparison returning an incremental cost-effectiveness ratio (ICER) of £91 452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15, the ICER becomes £77 818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30 033 per LYG, while Markov modelling produces an ICER of £46 922 per QALY. CONCLUSION: Analysis suggests that, after accounting for the lead time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared with the within-trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort.