Development and validation of a model that includes two ultrasound parameters and the plasma D-dimer level for predicting malignancy in adnexal masses: an observational study

Abstract

Background Pre-operative discrimination of malignant from benign adnexal masses is crucial for planning additional imaging, preparation, surgery and postoperative care. This study aimed to define key ultrasound and clinical variables and develop a predictive model for calculating preoperative ovarian tumor malignancy risk in a gynecologic oncology referral center. We compared our model to a subjective ultrasound assessment (SUA) method and previously described models. Methods This prospective, single-center observational study included consecutive patients. We collected systematic ultrasound and clinical data, including cancer antigen 125, D-dimer (DD) levels and platelet count. Histological examinations served as the reference standard. We performed univariate and multivariate regressions, and Bayesian information criterion (BIC) to assess the optimal model. Data were split into 2 subsets: training, for model development (190 observations) and testing, for model validation ( n = 100). Results Among 290 patients, 52% had malignant disease, including epithelial ovarian cancer (72.8%), metastatic disease (14.5%), borderline tumors (6.6%), and non-epithelial malignancies (4.6%). Significant variables were included into a multivariate analysis. The optimal model, included three independent factors: solid areas, the color score, and the DD level. Malignant and benign lesions had mean DD values of 2.837 and 0.354 μg/ml, respectively. We transformed established formulae into a web-based calculator ( http://gin-onc-calculators.com/gynonc.php ) for calculating the adnexal mass malignancy risk. The areas under the curve (AUCs) for models compared in the testing set were: our model (0.977), Simple Rules risk calculation (0.976), Assessment of Different NEoplasias in the adneXa (ADNEX) (0.972), Logistic Regression 2 (LR2) (0.969), Risk of Malignancy Index (RMI) 4 (0.932), SUA (0.930), and RMI3 (0.912). Conclusions Two simple ultrasound predictors and the DD level (also included in a mathematical model), when used by gynecologist oncologist, discriminated malignant from benign ovarian lesions as well or better than other more complex models and the SUA method. These parameters (and the model) may be clinically useful for planning adequate management in the cancer center. The model needs substantial validation. Electronic supplementary material The online version of this article (10.1186/s12885-019-5629-x) contains supplementary material, which is available to authorized users.

Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively: multicentre cohort study

“…Calibration analysis indicated that the risk of malignancy was overestimated in this subgroup (supplementary figs[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. The results obtained in the sensitivity analyses were similar to those in the primary analysis (supplementary figs[35][36][37][38][39][40][41][42][43].…”

“…These studies showed that IOTA models distinguished better between benign and malignant adnexal masses than RMI, and that ADNEX might be the best performing model. 12 13 14 16 35 36 37 38 The studies also showed that SRRisk and ADNEX had good overall calibration (the authors did not report centre specific results) and better clinical utility than other models, including RMI, to refer patients to an oncology centre. 10 11 17 18 To distinguish between benign and malignant masses in patients who underwent surgery, the following AUCs have been reported for ADNEX with CA125: 0.94 in the original study, between 0.91 and 0.97 in external validation studies, and 0.92 in the subgroup that underwent surgery in the current study.…”

“… 10 11 17 18 To distinguish between benign and malignant masses in patients who underwent surgery, the following AUCs have been reported for ADNEX with CA125: 0.94 in the original study, between 0.91 and 0.97 in external validation studies, and 0.92 in the subgroup that underwent surgery in the current study. 10 17 37 38 39 40 41 42 …”

Comparison of ultrasound−based ADNEX model with magnetic resonance imaging for discriminating adnexal masses: a multi-center study

“…Besides, previous studies also demonstrated that the CA125 level had no significant impact on the diagnostic accuracy of the ADNEX model ( 22 – 24 ). This is because CA125 is not a specific marker for ovarian cancer, and it can be increased in cases with benign lesions, such as endometriosis and uterine fibroids ( 25 , 26 ). Human epididymal protein-4 (HE-4) has been identified as a new tumor marker for ovarian cancer ( 27 ), and research has verified that HE-4 is more valuable than CA125 for ovarian cancer ( 28 ).…”

Accuracy of Pretreatment Ultrasonography Assessment of Intra-Abdominal Spread in Epithelial Ovarian Cancer: A Prospective Study

“…Inclusion criteria were age > 18 years, presence of a suspicious adnexal mass that was detected in a transvaginal ultrasound performed at our center, feasible for surgery (open or laparoscopic evaluation), agreed to undergo comprehensive transvaginal and abdominal ultrasonography. Prediction of malignancy was based on the examiner's subjective assessment, or if ambiguous in appearance, multivariable predictive models described elsewhere were used [20,21]. In addition, patients without an apparent adnexal mass who were otherwise suspected for primary peritoneal cancer were included.…”