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Objectives: 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. Methods: 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). Results: The median age of the women in the

Objective: Previous work suggested that the ultrasound-based benign Simple Descriptors can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. We aim to validate a modified version of the Benign Simple Descriptors (BD), and we introduce a two-step strategy to estimate the risk of malignancy: if the BDs do not apply, the ADNEX model is used to estimate the risk of malignancy. Methods: This is a retrospective analysis using the data from the 2-year interim analysis of the IOTA5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during one year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. Results: 8519 patients were recruited at 36 centers between 2012 and 2015. We included all masses that were not already in follow-up at recruitment from 17 centers with good quality surgical and follow-up data, leaving 4905 patients for statistical analysis. 3441 (70%) tumors were benign, 978 (20%) malignant, and 486 (10%) uncertain. The BDs were applicable in 1798/4905 (37%) tumors, and 1786 (99.3%) of these were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI, 0.91-0.95). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). Conclusion: A large proportion of adnexal masses can be classified as benign by the BDs. For the remaining masses the ADNEX model can be used to estimate the risk of malignancy. This

ObjectivePrevious work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. MethodsThis was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. ResultsA total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). ConclusionA large

OBJECTIVE: To systematically review the risk of bias and applicability of published prediction models for risk of central line-associated bloodstream infection (CLA-BSI) in hospitalized patients. STUDY DESIGN AND SETTING: Systematic review of literature in PubMed, Embase, Web of Science Core Collection and Scopus up to July 10, 2023. Two authors independently appraised risk models using CHARMS and assessed their risk of bias and applicability using PROBAST. RESULTS: Sixteen studies were included, describing 37 models. When studies presented multiple algorithms, we focused on the model that was selected as the best by the study authors. Eventually we appraised 19 models, among which 15 regression models and 4 machine learning models. All models were at a high risk of bias, primarily due to inappropriate proxy outcomes, predictors that are unavailable at prediction time in clinical practice, inadequate sample size, negligence of missing data, lack of model validation, and absence of calibration assessment. 18 out of 19 models had a high concern for applicability, 1 model had unclear concern for applicability due to incomplete reporting. CONCLUSION: We did not identify a prediction model of potential clinical use. There is a pressing need to develop an applicable model for CLA-BSI.

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 th

OBJECTIVES: The primary aim is to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim is to compare our findings with published data on women with AUB.METHODS: Patients presenting in seven ultrasound centers from 2011 until 2018 for indications unrelated to abnormal vaginal bleeding underwent transvaginal ultrasound examination using the IETA examination technique and measurement technique. The ultrasonography was performed either as part of routine gynecological examination, follow-up of non-endometrial pathology, or in the workup before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using IETA terminology. Findings were compared to those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology.RESULTS: The IETA3 study includes 1745 women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). 858 women were premenopausal (49%), and 887 women were postmenopausal (51%). Histology showed endometrial cancer (EC) and/or endometrial intraepithelial neoplasia (EIN) in 29 (2%) women, endometrial polyps in 1028 (59%), intracavitary myomas in 66 (4%), proliferative or secretory changes or hyperplasia without atypia in 144 (8%), endometrial atrophy in 265 (15%) and insufficient tissue in 5 (0.3%). Most EC and EIN (25/29; 86%) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2mm (95% confidence interval [CI]: 8.9 to 13.6), which made them on average 2.5mm (95% CI: +0.3 to +4.6) thicker than t

Objective: To investigate the association between personal history, anthropometric features and lifestyle characteristics and endometrial malignancy in women with abnormal vaginal bleeding. Methods: Prospective observational cohort assessed by descriptive and multivariable logistic regression analyses. Three features—age, body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), and nulliparity—were defined a priori for baseline risk assessment of endometrial malignancy. The following variables were tested for added value: intrauterine contraceptive device, bleeding pattern, age at menopause, coexisting diabetes/hypertension, physical exercise, fat distribution, bra size, waist circumference, smoking/drinking habits, family history, use of hormonal/anticoagulant therapy, and sonographic endometrial thickness. We calculated adjusted odds ratio, optimism-corrected area under the receiver operating characteristic curve (AUC), R2, and Akaike's information criterion. Results: Of 2417 women, 155 (6%) had endometrial malignancy or endometrial intraepithelial neoplasia. In women with endometrial cancer median age was 67 years (interquartile range [IQR] 56–75 years), median parity was 2 (IQR 0–10), and median BMI was 28 (IQR 25–32). Age, BMI, and parity produced an AUC of 0.82. Other variables marginally affected the AUC, adding endometrial thickness substantially increased the AUC in postmenopausal women. Conclusion: Age, parity, and BMI help in the assessment of endometrial cancer risk in women with abnormal uterine bleeding. Other patient information adds little, whereas sonographic endometrial thickness substantially improves assessment.

OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates. RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only

Objectives: To investigate and compare post-traumatic stress (PTS), depression and anxiety in women and their partners over a 9-month period following miscarriage or ectopic pregnancy.Methods: This was a prospective cohort study. Consecutive women and their partners were approached in the early pregnancy units of three hospitals in central London. At 1, 3 and 9 months after early pregnancy loss, recruits were e-mailed links to surveys containing the Hospital Anxiety and Depression Scale and the Post-traumatic Stress Diagnostic Scale. The proportion of participants meeting the screening criteria for moderate or severe anxiety or depression and PTS was assessed. Mixed-effects logistic regression was used to analyze differences between women and their partners and their evolution over time.Results: In total, 386 partners were approached after the woman in whom the early pregnancy loss had been diagnosed consented to participate, and 192 couples were recruited. All partners were male. Response rates were 60%, 48% and 39% for partners and 78%, 70% and 59% for women, at 1, 3 and 9 months, respectively. Of the partners, 7% met the criteria for PTS at 1 month, 8% at 3 months and 4% at 9 months, compared with 34%, 26% and 21% of women, respectively. Partners also experienced lower rates of moderate/severe anxiety (6% vs 30% at 1 month, 9% vs 25% at 3 months and 6% vs 22% at 9 months) and moderate/severe depression (2% vs 10% at 1 month, 5% vs 8% at 3 months and 1% vs 7% at 9 months). The odds ratios for psychological morbidity in partners vs women after 1 month were 0.02 (95% CI, 0.004-0.12) for PTS, 0.05 (95% CI, 0.01-0.19) for moderate/severe anxiety and 0.15 (95% CI, 0.02-0.96) for moderate/severe depression. Morbidity for each outcome decreased modestly over time, without strong evidence of a different evolution between women and their partners.Conclusions: Some partners report clinically relevant levels of PTS, anxiety and depression after pregnancy loss, though to a fa

Objective: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology.Methods: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology.Results: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m(2) (range, 16.0-72.1 kg/m(2) ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% C

Objective: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. Methods: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. Results: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19–92 years), median parity was 2 (range, 0–10) and median body mass index was 24.9 kg/m2 (range, 16.0–72.1 kg/m2). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0–5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4–3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI

Objectives: The aim of this study was to quantify the impact of predictor measurement heterogeneity on prediction model performance. Predictor measurement heterogeneity refers to variation in the measurement of predictor(s) between the derivation of a prediction model and its validation or application. It arises, for instance, when predictors are measured using different measurement instruments or protocols. Study Design and Setting: We examined the effects of various scenarios of predictor measurement heterogeneity in re

Objectives: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). Methods: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The ‘subjective prediction model’ included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the ‘objective prediction model’ included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. Results: I

Objectives To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). Methods The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. Results I

Objective To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer.Methods A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread).Results Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68-0.78), the calibration slope was 1.06 (95% CI, 0.79-1.34) and the calibration intercept was 0.06 (95% CI, -0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical

Objective: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. Methods: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). Results: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68–0.78), the calibration slope was 1.06 (95% CI, 0.79–1.34) and the calibration intercept was 0.06 (95% CI, –0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was

OBJECTIVES: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). METHODS: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. RESULTS: I

Background: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. Methods: In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. Findings: Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in fo

Clinical risk prediction models are increasingly being developed and validated on multicenter datasets. In this article, we present a comprehensive framework for the evaluation of the predictive performance of prediction models at the center level and the population level, considering population-averaged predictions, center-specific predictions, and predictions assuming an average random center effect. We demonstrated in a simulation study that calibration slopes do not only deviate from one because of over- or underfitting of patterns in the development dataset, but also as a result of the choice of the model (standard versus mixed effects logistic regression), the type of predictions (marginal versus conditional versus assuming an average random effect), and the level of model validation (center versus population). In particular, when data is heavily clustered (ICC 20%), center-specific predictions offer the best predictive performance at the population level and the center level. We recommend that models should reflect the data structure, while the level of model validation should reflect the research question.