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1.
  • Van Calster, Ben, et al. (författare)
  • A Novel Approach to Predict the Likelihood of Specific Ovarian Tumor Pathology Based on Serum CA-125: A Multicenter Observational Study.
  • 2011
  • Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 20, s. 2420-2428
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The CA-125 tumor marker has limitations when used to distinguish between benign and malignant ovarian masses. We therefore establish likelihood curves of six subgroups of ovarian pathology based on CA-125 and menopausal status.METHODS: This cross-sectional study conducted by the International Ovarian Tumor Analysis group involved 3,511 patients presenting with a persistent adnexal mass that underwent surgical intervention. CA-125 distributions for six tumor subgroups (endometriomas and abscesses, other benign tumors, borderline tumors, stage I invasive cancers, stage II-IV invasive cancers, and metastatic tumors) were estimated using kernel density estimation with stratification for menopausal status. Likelihood curves for the tumor subgroups were derived from the distributions.RESULTS: Endometriomas and abscesses were the only benign pathologies with median CA-125 levels above 20 U/mL (43 and 45, respectively). Borderline and invasive stage I tumors had relatively low median CA-125 levels (29 and 81 U/mL, respectively). The CA-125 distributions of stage II-IV invasive cancers and benign tumors other than endometriomas or abscesses were well separated; the distributions of the other subgroups overlapped substantially. This held for premenopausal and postmenopausal patients. Likelihood curves and reference tables comprehensibly show how subgroup likelihoods change with CA-125 and menopausal status.Conclusions and Impact: Our results confirm the limited clinical value of CA-125 for preoperative discrimination between benign and malignant ovarian pathology. We have shown that CA-125 may be used in a different way. By using likelihood reference tables, we believe clinicians will be better able to interpret preoperative serum CA-125 results in patients with adnexal masses. Cancer Epidemiol Biomarkers Prev; ©2011 AACR.
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3.
  • Van Calster, Ben, et al. (författare)
  • Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively : multicentre cohort study
  • 2020
  • Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 370
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.
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4.
  • Van Holsbeke, Caroline, et al. (författare)
  • External Validation of Diagnostic Models to Estimate the Risk of Malignancy in Adnexal Masses
  • 2012
  • Ingår i: Clinical Cancer Research. - 1078-0432. ; 18:3, s. 815-825
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To externally validate and compare the performance of previously published diagnostic models developed to predict malignancy in adnexal masses. Experimental Design: We externally validated the diagnostic performance of 11 models developed by the International Ovarian Tumor Analysis (IOTA) group and 12 other (non-IOTA) models on 997 prospectively collected patients. The non-IOTA models included the original risk of malignancy index (RMI), three modified versions of the RMI, six logistic regression models, and two artificial neural networks. The ability of the models to discriminate between benign and malignant adnexal masses was expressed as the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and likelihood ratios (LR+, LR-). Results: Seven hundred and forty-two (74%) benign and 255 (26%) malignant masses were included. The IOTA models did better than the non-IOTA models (AUCs between 0.941 and 0.956 vs. 0.839 and 0.928). The difference in AUC between the best IOTA and the best non-IOTA model was 0.028 [95% confidence interval (CI), 0.011-0.044]. The AUC of the RMI was 0.911 (difference with the best IOTA model, 0.044; 95% CI, 0.024-0.064). The superior performance of the IOTA models was most pronounced in premenopausal patients but was also observed in postmenopausal patients. IOTA models were better able to detect stage I ovarian cancer. Conclusion: External validation shows that the IOTA models outperform other models, including the current reference test RMI, for discriminating between benign and malignant adnexal masses. Clin Cancer Res; 18(3); 815-25. (C)2011 AACR.
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