Performance of a biomarker panel to identify malignancy within a pelvic mass population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5566-5566
Author(s):  
L. Chen ◽  
H. D. Homesley ◽  
D. R. Scribner ◽  
G. H. Cantuaria ◽  
Q. He ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Differential Diagnosis ◽  
Early Stage ◽  
Pelvic Mass ◽  
Stage Iv ◽  
Serum Levels ◽  
Borderline Tumor ◽  
Serum Samples ◽  
Early Stage Disease ◽  
Biomarker Analysis

5566 Background: We previously reported the performance of biomarker combinations that displayed utility in identifying ovarian cancer from normal sera and in monitoring for disease recurrence. In this study, we evaluated the performance of a subset of these markers in differentiating ovarian cancer from benign pelvic mass. Methods: Pre-operative serum samples were prospectively collected from 254 patients undergoing surgical evaluation for differential diagnosis of a pelvic mass. Pathology showed 76 cases of epithelial ovarian carcinoma (EOC), 17 borderline tumors, 11 other gynecologic cancers, and 150 benign masses. 18 (23.7%) of the EOC patients had stage I tumors; 6 (7.9%) stage II; 44 (57.9%) stage III; and 8 (10.5%) stage IV. Serum levels of CA125, HE4, glycodelin, SLPI, MMP7, and Plau-R were ascertained. Biomarker performance was evaluated by a logistic regression model and leave one out cross-validation analysis. All calculations compared the benign vs. EOC and borderline tumor populations. Results: Individual biomarker sensitivity ranged from 28% to 77% at 85% specificity. The combination of CA125, HE4 and glycodelin exhibited the highest overall performance in identifying malignancy from benign masses, demonstrating 80% sensitivity, 80% specificity in patients <55 years, and 89% sensitivity, 80% specificity in patients ≥55. Total cohort performance was 85% sensitivity and 80% specificity. Glycodelin identified 7/22 CA125 and HE4 double negative patients, 5/7 of these patients were early stage (borderline, I or II), while only adding 4/150 false positive cases. Conclusions: Biomarker analysis within this test cohort demonstrates potential clinical utility in the differential diagnosis of pelvic mass patients, especially for the detection of early stage disease. The addition of glycodelin improved the detection of early stage cancer in sera that were negative for both HE4 and CA125. [Table: see text]

Time Trends in Ovarian Cancer Survival in Estonia by Age and Stage

2016 ◽  
Vol 27 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Kristiina Ojamaa ◽  
Piret Veerus ◽  
Aleksei Baburin ◽  
Hele Everaus ◽  
Kaire Innos
Keyword(s):  
Ovarian Cancer ◽  
Older Women ◽  
Early Stage ◽  
Cohort Analysis ◽  
Temporal Trends ◽  
Age Groups ◽  
Stage Iv ◽  
Relative Survival ◽  
Early Stage Disease ◽  
Gynecology And Obstetrics

ObjectiveThe objective of the study was to examine temporal trends in ovarian cancer (OC) survival in Estonia during 1995 to 2009 in relation to age and stage.Materials and MethodsEstonian Cancer Registry data on all adult cases of primary OC diagnosed during 1995 to 2009 and followed up for vital status until 2014 were used to estimate relative survival ratios (RSRs). Cohort analysis was used to estimate 1-, 2-, and 5-year RSRs for patients diagnosed in 1995 to 1999, 2000 to 2004, and 2005 to 2009. Analysis was performed by age at diagnosis (<50; 50–59; 60–69; 70+ years) and stage (International Federation of Gynecology and Obstetrics 1988).ResultsAmong 2296 women included in the study, the age-adjusted 5-year RSR improved from 27% in 1995 to 1999 to 38% in 2005 to 2009. Survival increase of 10% units from 1995 to 1999 to 2005 to 2009 was seen for women aged 50 to 59 and 60 to 69 years. Among younger and older women, the respective changes were smaller. In 1995 to 1999, the difference in survival between the youngest and oldest age groups was 41% units. This decreased over the study period to 37% units. From 1995 to 1999 to 2005 to 2009, the 5-year RSR increased from 82% to 91% for stage I patients; from 48% to 67% for stage II patients; from 25% to 35% for stage III patients; and from 11% to 16% for stage IV patients.ConclusionsThe study showed an improvement of OC survival in Estonia in all age and stage groups, but particularly among younger women and those with early stage disease. Slower progress among older women is of great concern.

A novel multiple biomarker assay for the detection of ovarian carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5023-5023 ◽  
Author(s):  
R. G. Moore ◽  
A. K. Brown ◽  
C. M. Miller ◽  
D. Badgwell ◽  
Z. Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Markers ◽  
Ovarian Cyst ◽  
Adnexal Mass ◽  
Pelvic Mass ◽  
Stage Iv ◽  
Stage I ◽  
Serum Samples ◽  
Prospective Trials ◽  
Multicenter Prospective Study

5023 Background: Studies show that ovarian cancer patients operated on by gyn oncologists are more often adequately staged and debulked than those operated on by non-gyn oncologists. Many benign gynecologic conditions will elevate the CA125 tumor marker decreasing its specificity. An accurate test is needed to help triage patients with a pelvic mass to centers with expertise in treating ovarian cancer. This project examined several novel tumor markers to develop a multiple biomarker assay to predict the risk of ovarian cancer in patients with an ovarian cyst or pelvic mass. Methods: Data from two separate IRB approved prospective trials from two institutions were collected. After obtaining informed consent, serum samples were obtained preoperatively from women undergoing surgery for an adnexal mass and analyzed for levels of CA125, SMRP, HE4 and CA72–4. All pathology results were compared to the tumor markers. Sensitivities at set specificities of 90, 95 and 98% were determined using logistic regression for each marker individually and all combinations of 2, 3, & 4 markers. Results: 448 samples were analyzed. There were 267 benign cases and 181 ovarian cancers (27 stage I, 20 stage II, 115 stage III and 19 stage IV). Median values for HE4, SMRP, CA125 and CA72–4 all differed significantly between benign masses and cancer (p < 0.001). In the differentiation of benign masses and stage I malignancies, the addition of HE4 to CA125 increased the sensitivity by 22.2% at a specificity of 90%. The combination of HE4 and CA125 for all stages was superior to HE4 or CA125 alone (p ≤ 0.003). Conclusions: The improvement in sensitivity shown by the addition of HE4 to CA125 suggests that this biomarker combination can be used to provide an accurate risk assessment for the presence of ovarian cancer in patients with an ovarian cyst or mass. This multiple biomarker assay is now undergoing validation in a multicenter prospective study. [Table: see text] [Table: see text]

scholarly journals Comprehensive Serum Glycopeptide Spectra Analysis Combined with Artificial Intelligence (CSGSA-AI) to Diagnose Early-Stage Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2373
Author(s):  
Kazuhiro Tanabe ◽  
Masae Ikeda ◽  
Masaru Hayashi ◽  
Koji Matsuo ◽  
Miwa Yasaka ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Ovarian Cancer ◽  
Diagnostic Accuracy ◽  
Early Stage ◽  
Low Cost ◽  
Expression Patterns ◽  
Principal Component ◽  
Serum Levels ◽  
Serum Samples ◽  
Spectra Analysis

Ovarian cancer is a leading cause of deaths among gynecological cancers, and a method to detect early-stage epithelial ovarian cancer (EOC) is urgently needed. We aimed to develop an artificial intelligence (AI)-based comprehensive serum glycopeptide spectra analysis (CSGSA-AI) method in combination with convolutional neural network (CNN) to detect aberrant glycans in serum samples of patients with EOC. We converted serum glycopeptide expression patterns into two-dimensional (2D) barcodes to let CNN learn and distinguish between EOC and non-EOC. CNN was trained using 60% samples and validated using 40% samples. We observed that principal component analysis-based alignment of glycopeptides to generate 2D barcodes significantly increased the diagnostic accuracy (88%) of the method. When CNN was trained with 2D barcodes colored on the basis of serum levels of CA125 and HE4, a diagnostic accuracy of 95% was achieved. We believe that this simple and low-cost method will increase the detection of EOC.

Patterns of care for women with ovarian cancer in the United States.

1997 ◽  
Vol 15 (11) ◽  
pp. 3408-3415 ◽  
Author(s):  
K A Muñoz ◽  
L C Harlan ◽  
E L Trimble
Keyword(s):  
Ovarian Cancer ◽  
Older Women ◽  
Early Stage ◽  
Stage Iv ◽  
The United States ◽  
Stage I ◽  
Stage Iii ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Platinum Based Chemotherapy

PURPOSE To characterize treatments for ovarian cancer, to determine if recommended staging and treatment were provided, and to determine factors that influence receipt of recommended staging and treatment. METHODS A total of 785 women diagnosed with ovarian cancer in 1991 were selected from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Type and receipt of recommended staging and treatment were examined using data on surgery and physician-verified chemotherapy. RESULTS Most women with presumptive stage I and II ovarian cancer were treated with surgery alone (58%), while women with stage III or IV disease were treated with surgery plus platinum-based chemotherapy (75% stage III, 56% stage IV). Approximately 10% of women with presumptive stage I and II, 71% with stage III, and 53% with stage IV disease received recommended staging and treatment. The absence of lymphadenectomy and assignment of histologic grade were the primary reasons women with presumptive stage I and II cancer did not receive recommended staging and treatment, whereas for stages III and IV, it was due to older women not receiving surgery plus platinum-based adjuvant chemotherapy. Age, stage, comorbidity, "other" race/ethnicity, and treatment at a facility with an approved residency training program were associated with whether recommended staging and therapy were received. CONCLUSION Older women with late-stage disease did not receive recommended treatment. The majority of women with early-stage disease did not receive recommended staging and treatment.

scholarly journals Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Christopher Walker ◽  
Tuan-Minh Nguyen ◽  
Shlomit Jessel ◽  
Ayesha B. Alvero ◽  
Dan-Arin Silasi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Predictive Value ◽  
Early Stage ◽  
Ca 125 ◽  
Healthy Controls ◽  
Classification Models ◽  
Serum Samples ◽  
Protein Biomarker ◽  
Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

scholarly journals CA125 test result, test-to-diagnosis interval, and stage in ovarian cancer at diagnosis: a retrospective cohort study using electronic health records

2021 ◽  
pp. BJGP.2020.0859
Author(s):  
Garth Funston ◽  
Luke TA Mounce ◽  
Sarah Price ◽  
Brian Rous ◽  
Emma J Crosbie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Care ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Early Stage ◽  
Cancer Antigen 125 ◽  
Early Stage Disease ◽  
Cancer Registry Data ◽  
Test Result

BackgroundIn the UK, the cancer antigen 125 (CA125) test is recommended as a first-line investigation in women with symptoms of possible ovarian cancer.AimTo compare time between initial primary care CA125 test and diagnosis, tumour morphology, and stage in women with normal (<35 U/ml) and abnormal (≥35 U/ml) CA125 levels prior to ovarian cancer diagnosis.Design and settingRetrospective cohort study using English primary care and cancer registry data.MethodAssociations between CA125 test results and test-to-diagnosis interval, stage, and ovarian cancer morphology were examined.ResultsIn total, 456 women were diagnosed with ovarian cancer in the 12 months after having a CA125 test. Of these, 351 (77%) had an abnormal, and 105 (23%) had a normal, CA125 test result. The median test-to-diagnosis interval was 35 days (interquartile range [IQR] 21–53) for those with abnormal CA125 levels, and 64 days (IQR 42–127) for normal CA125 levels. Tumour morphology differed by CA125 result: indolent borderline tumours were less common in those with abnormal CA125 levels (n = 47, 13%) than those with normal CA125 levels (n = 51, 49%) (P<0.001). Staging data were available for 304 women with abnormal, and 77 with normal, CA125 levels. Of those with abnormal CA125 levels, 35% (n = 106) were diagnosed at an early stage, compared to 86% (n = 66) of women with normal levels. The odds of being diagnosed with early-stage disease were higher in women with normal as opposed to abnormal CA125 levels (odds ratio 12.2, 95% confidence interval = 5.8 to 25.1, P<0.001).ConclusionDespite longer intervals between testing and diagnosis, women with normal, compared with abnormal, CA125 levels more frequently had indolent tumours and were more commonly diagnosed at an early stage in the course of the disease. Although testing approaches that have greater sensitivity might expedite diagnosis for some women, it is not known if this would translate to earlier-stage diagnosis.

scholarly journals BRAF Mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer

Cancer ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 548-554 ◽  
Author(s):  
Rachel N. Grisham ◽  
Gopa Iyer ◽  
Karuna Garg ◽  
Deborah DeLair ◽  
David M. Hyman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Braf Mutation ◽  
Early Stage ◽  
Low Grade ◽  
Serous Ovarian Cancer ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Improved Outcome

scholarly journals International Study of Primary Mucinous Ovarian Carcinomas Managed at Tertiary Medical Centers

2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  
Keyword(s):  
Early Stage ◽  
Statistical Tests ◽  
Stage Iv ◽  
Stage I ◽  
Stage Iii ◽  
Oncologic Outcomes ◽  
Disease Stage ◽  
Ovarian Carcinomas ◽  
Early Stage Disease ◽  
Medical Centers

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.

Gonadotropin Levels in Ovarian Cyst Fluids: A Predictor of Malignancy?

1998 ◽  
Vol 13 (3) ◽  
pp. 165-168 ◽  
Author(s):  
S. Krämer ◽  
M. Leeker ◽  
W. Jäger
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Elevated Serum ◽  
Serum Levels ◽  
Ovarian Tumors ◽  
Surgical Removal ◽  
Serum Samples ◽  
Benign Ovarian Tumors ◽  
Surprising Finding ◽  
Cyst Fluids

Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not lead to growth restriction, which means that serum levels of gonadotropins may not play the most important role in ovarian cancer. We therefore analyzed the LH and FSH concentrations in cyst fluids of ovarian cancer. Patients with preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum samples of the patients were obtained during surgery, while the fluids within the cysts were aspirated after surgical removal of the tumor. FSH and LH levels in serum and cyst fluids were measured using single antibody EIA (Boehringer Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated. While there were no significant differences in the FSH and LH serum concentrations, highly significant differences in the FSH and LH levels in cyst fluids were found. Only cancer cysts contained FSH and LH, while the corresponding concentrations in benign cysts were always below the measuring range of the assays. This clear division between high gonadotropin levels in cysts of serous ovarian cancer and low or absent concentrations in benign ovarian tumors further supports the hypothesis that FSH and LH may play a role in ovarian cancer; however, explanations for this surprising finding are still lacking.

scholarly journals Osteopontin, Macrophage Migration Inhibitory Factor and Anti-Interleukin-8 Autoantibodies Complement CA125 for Detection of Early Stage Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 596 ◽  
Author(s):  
Jing Guo ◽  
Wei-Lei Yang ◽  
Daewoo Pak ◽  
Joseph Celestino ◽  
Karen H. Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Late Stage ◽  
Early Stage ◽  
Characteristic Curve ◽  
Stage I ◽  
Inhibitory Factor ◽  
Early Stage Disease ◽  
Biomarker Panel ◽  
Early Stage Ovarian Cancer

Early detection of ovarian cancer promises to reduce mortality. While serum CA125 can detect more than 60% of patients with early stage (I–II) disease, greater sensitivity might be observed with a panel of biomarkers. Ten protein antigens and 12 autoantibody biomarkers were measured in sera from 76 patients with early stage (I–II), 44 patients with late stage (III–IV) ovarian cancer and 200 healthy participants in the normal risk ovarian cancer screening study. A four-biomarker panel (CA125, osteopontin (OPN), macrophage inhibitory factor (MIF), and anti-IL-8 autoantibodies) detected 82% of early stage cancers compared to 65% with CA125 alone. In early stage subjects the area under the receiver operating characteristic curve (AUC) for the panel (0.985) was significantly greater (p < 0.001) than the AUC for CA125 alone (0.885). Assaying an independent validation set of sera from 71 early stage ovarian cancer patients, 45 late stage patients and 131 healthy women, AUC in early stage disease was improved from 0.947 with CA125 alone to 0.974 with the four-biomarker panel (p = 0.015). Consequently, OPN, MIF and IL-8 autoantibodies can be used in combination with CA125 to distinguish ovarian cancer patients from healthy controls with high sensitivity. Osteopontin appears to be a robust biomarker that deserves further evaluation in combination with CA125.

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