IETA Ultrasonic Features Combined with GI-RADS Classification System and Tumor Biomarkers for Surveillance of Endometrial Carcinoma: An Innovative Study.

Lin D ，Wang H ，Liu L ，Zhao L ，Chen J ，Tian H ，Gao L ，Wu B ，Zhang J ，Guo X ，Hao Y ... -  《Cancers》

Combination IETA Ultrasonographic Characteristics Simple Scoring Method With Tumor Biomarkers Effectively Improves the Differentiation Ability of Benign and Malignant Lesions in Endometrium and Uterine Cavity.

To evaluate International Endometrial Tumor Analysis (IETA) ultrasonographic characteristics simple scoring method and tumor biomarkers for the diagnosis of uterine cavity and endometrial lesions. We classified and scored the normalized description of IETA ultrasonic characteristics, according to IETA expert consensus literature, previous IETA-related research articles, and the previous research experience of this project group. We conducted a retrospective analysis of the ultrasound images of 594 patients enrolled from January 2017 to June 2020, scored them item by item, and finally calculated the total score of each case. Meanwhile, we combined the results of seven tumor biomarkers. The objective was to evaluate the sensitivity, specificity, coincidence rate, and the area under receiver operating characteristic (ROC) curve of IETA ultrasonographic characteristics simple scoring method and tumor biomarkers for benign and malignant uterine cavity or endometrial lesions. The diagnostic efficiency between the combined method and the single method was compared. A total of 594 cases were confirmed by postoperative pathology or surgery records, including 475 benign lesions and 119 malignant lesions. In the simple ultrasound scoring method, the average score of benign lesions was 3.879 ± 1.279 and that of malignant lesions was 9.676 ± 4.491. If ≥6.5 points was taken as the cutoff value for the judgment of malignant lesions, the sensitivity, specificity, coincidence rate, and the area under receiver operating characteristic (ROC) curve (AUC) were 76.5%, 96.0%, 92.1%, and 0.935, respectively. The difference in tumor antigen 19-9 (CA19-9) and human epididymal protein 4 (HE4) between benign and malignant lesions was statistically significant (all p ≤ 0.01). The other five tumor biomarkers (CA125, CA15-3, SCC-Ag, AFP, and CEA) showed no statistically significant difference in benign and malignant lesions. If the value of CA19-9 ≥13.96 U/ml was taken as cutoff value, the sensitivity, specificity, and coincidence rate of the diagnosis of endometrial benign and malignant lesions were 54.8%, 74.7%, and 70.7%, respectively, and the AUC was 0.620. If the value of HE4 ≥ 39.075 pmol/L was taken as cutoff point, the sensitivity, specificity, coincidence rate, and AUC were 77.4%, 67.9%, 69.8%, and 0.796, respectively. The sensitivity was increased to 97.6% and the AUC was 0.939 when IETA ultrasound characteristics simple scoring method combined CA19-9 and HE4 in parallel test. In IETA ultrasound characteristics simple scoring method, with ≥6.5 points as the cutoff value, it could quickly and accurately assess the benign and malignant in uterine cavity and endometrial lesions, with high diagnostic value. The diagnostic efficacy of seven tumor biomarkers was all mediocre. Combining with these two methods, the comprehensive diagnosis could improve sensitivity and accuracy and reduce the risk of missed diagnosis.

Lin D ，Zhao L ，Zhu Y ，Huang Y ，Yuan K ，Liu W ，Li S ，Guo X ，Hao Y ... -  《Frontiers in Oncology》

Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA-1 multinomial regression model: validation study.

To assess the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. This was a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). The IETA-3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow-up of non-endometrial pathology, in the work-up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow-up of at least 1 year if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver-operating-characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). The median age of the women in the IETA-3 cohort was 51 (range, 20-85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI, 0.73-0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32-0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62-0.73) (n = 1532). The IETA-1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95-0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75-0.91), compared with 0.62 (95% CI, 0.52-0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08-0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI, 0.71-0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60-0.81) (difference in AUC, 0.11; 95% CI, 0.01-0.20). The IETA-1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Heremans R ，Wynants L ，Valentin L ，Leone FPG ，Pascual MA ，Fruscio R ，Testa AC ，Buonomo F ，Guerriero S ，Epstein E ，Bourne T ，Timmerman D ，Van den Bosch T ，IETA Consortium ... -  《-》

The use of modified TI-RADS using contrast-enhanced ultrasound features for classification purposes in the differential diagnosis of benign and malignant thyroid nodules: A prospective and multi-center study.

To evaluate the diagnostic efficacy of a modified thyroid imaging reporting and data system (TI-RADS) in combination with contrast-enhanced ultrasound (CEUS) for differentiating between benign and malignant thyroid nodules and to assess inter-observer concordance between different observers. This study included 3353 patients who underwent thyroid ultrasound (US) and CEUS in ten multi-centers between September 2018 and March 2020. Based on a modified TI-RADS classification using the CEUS enhancement pattern of thyroid lesions, ten radiologists analyzed all US and CEUS examinations independently and assigned a TI-RADS category to each thyroid nodule. Pathology was the reference standard for determining the diagnostic performance (accuracy (ACC), sensitivity (SEN), specificity (SPN), positive predictive value (PPV), and negative predictive value (NPV)) of the modified TI-RADS for predicting malignant thyroid nodules. The risk of malignancy was stratified for each TI-RADS category-based on the total number of benign and malignant lesions in that category. ROC curve was used to determine the cut-off value and the area under the curve (AUC). Cohen's Kappa statistic was applied to assess the inter-observer agreement of each sonological feature and TI-RADS category for thyroid nodules. The calculated malignancy risk in the modified TI-RADS categories 5, 4b, 4a, 3 and 2 nodules was 95.4%, 86.0%, 12.0%, 4.1% and 0%, respectively. The malignancy risk for the five categories was in agreement with the suggested malignancy risk. The ROC curve showed that the AUC under the ROC curve was 0.936, and the cutoff value of the modified TI-RADS classification was >TI-RADS 4a, whose SEN, ACC, PPV, NPV and SPN were 93.6%, 91.9%, 90.4%, 93.7% and 88.5% respectively. The Kappa value for taller than wide, microcalcification, marked hypoechoic, solid composition, irregular margins and enhancement pattern of CEUS was 0.94, 0.93, 0.75, 0.89, 0.86 and 0.81, respectively. There was also good agreement between the observers with regards to the modified TI-RADS classification, the Kappa value was 0.80. The actual risk of malignancy according to the modified TI-RADS concurred with the suggested risk of malignancy. Inter-observer agreement for the modified TI-RADS category was good, thus suggesting that this classification was very suitable for clinical application.

Zhou P ，Chen F ，Zhou P ，Xu L ，Wang L ，Wang Z ，Yu Y ，Liu X ，Wang B ，Yan W ，Zhou H ，Tao Y ，Liu W ... -  《Frontiers in Endocrinology》

Standardized IETA criteria enhance accuracy of junior and intermediate ultrasound radiologists in diagnosing malignant endometrial and intrauterine lesions.

To transform the standardized descriptions of the ultrasound characteristics of endometrial and intrauterine lesions devised by the International Endometrial Tumor Analysis (IETA) group into a practical scoring method and to investigate whether application of this method enhances the diagnostic accuracy of ultrasound radiologists with different levels of experience in detecting malignancy compared with subjective assessment. This was a retrospective study of 855 patients with endometrial and/or intrauterine lesions, who were divided into a training (n = 600) and a validation (n = 255) set. Ultrasound radiologists with varying levels of experience (expert, intermediate and junior) evaluated all lesions by subjective assessment and according to IETA rules. Using IETA rules, the experts identified signs of malignancy in the training set, assigned scores for each indicator and validated the scoring method in the validation set. The intermediate-level and junior ultrasound radiologists reassessed the malignancy of the lesions using the IETA scoring method and compared their classifications with those made previously by subjective assessment. Postsurgical pathological evaluation was used as the reference standard. Using subjective assessment, the experts demonstrated the highest level of diagnostic accuracy, with a sensitivity of 85.0%, specificity of 94.3% and an area under the receiver-operating-characteristics curve (AUC) of 0.897. Applying the IETA scoring method (comprising eight ultrasound characteristics that contributed to the total score) with a threshold of > 25 points for the diagnosis of malignancy achieved a sensitivity of 84.7%, specificity of 94.7% and AUC of 0.9533 in the training set, with similar performance in the validation set, when performed by experts. Using the IETA scoring method, both junior and intermediate ultrasound radiologists showed improvement in sensitivity (from 55.5% to 74.8% and from 70.2% to 77.1%, respectively), specificity (from 88.4% to 91.5% and from 87.4% to 92.2%, respectively) and AUC (from 0.704 to 0.827 and from 0.793 to 0.841, respectively) for diagnosing malignant lesions. The IETA scoring method exhibits high diagnostic efficacy for malignant endometrial and intrauterine lesions. This method compensates for the lack of experience among junior and intermediate-level ultrasound radiologists, enhancing their diagnostic skill to a level nearing that of experienced senior ultrasound radiologists. Further research is essential to validate the practicality of implementing this method and to confirm its clinical value. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Chen B ，Wang P ，He W ，Yang P ，Kong Z ，Wang D ，Huang L ，Chen X ，Zheng Y ，Chen Q ，Xu H ，Qi J ... -  《-》