C. Landolfo

Evaluating use of two‐step International Ovarian Tumor Analysis strategy to classify adnexal masses identified in pregnancy: pilot study

ABSTRACTObjectivesThe primary aim was to validate the International Ovarian Tumor Analysis (IOTA) benign simple descriptors (BDs) followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model, if BDs cannot be applied, in a two‐step strategy to classify adnexal masses identified during pregnancy. The secondary aim was to describe the natural history of adnexal masses during pregnancy.MethodsThis was a retrospective analysis of prospectively collected data from women with an adnexal mass identified on ultrasonography during pregnancy between 2017 and 2022 at Queen Charlotte's and Chelsea Hospital, London, UK. Clinical and ultrasound data were extracted from medical records and ultrasound software. Adnexal masses were classified and managed according to expert subjective assessment (SA). Borderline ovarian tumors (BOTs) were classified as malignant. BDs were applied retrospectively to classify adnexal masses, and if BDs were not applicable, the ADNEX model (using a risk‐ of‐malignancy threshold ≥ 10%) was used, in a two‐step strategy. The reference standard was histology (where available) or expert SA at the postnatal ultrasound scan.ResultsA total of 291 women with a median age of 33 (interquartile range (IQR), 29–36) years presented with an adnexal mass during pregnancy, at a median gestational age of 12 (IQR, 8–17) weeks. Of those, 267 (91.8%) were followed up to the postnatal period. Based on the reference standard, 4.1% (11/267) of adnexal masses were classified as malignant (all BOTs) and 95.9% (256/267) as benign. BDs were applicable in 68.9% (184/267) of adnexal masses; of these, only one (0.5%) BOT was misclassified as benign. The ADNEX model was used to classify the 83 residual masses and misclassified 3/10 (30.0%) BOTs as benign and 25/73 (34.2%) benign masses as malignant, of which 13/25 (52.0%) were classified as decidualized endometrioma on expert SA. The two‐step strategy had a specificity of 90.2%, sensitivity of 63.6%, negative predictive value of 98.3% and positive predictive value of 21.9%. A total of 56 (21.0%) women underwent surgical intervention: four (1.5%) as an emergency during pregnancy, four (1.5%) electively during Cesarean section and 48 (18.0%) postnatally. During follow‐up, 64 (24.0%) adnexal masses resolved spontaneously. Cyst‐related complications occurred in four (1.5%) women during pregnancy (ovarian torsion, n = 2; cyst rupture, n = 2) and six (2.2%) women in the postnatal period (all ovarian torsion). Overall, 196/267 (73.4%) women had a persistent adnexal mass at postnatal ultrasound. Presumed decidualization occurred in 31.1% (19/61) of endometriomas and had resolved in 89.5% (17/19) by the first postnatal ultrasound scan.ConclusionsBDs apply to most adnexal masses during pregnancy. However, the small number of malignant tumors in this cohort (4.1%) restricted the evaluation of the ADNEX model, so expert SA should be used to classify adnexal masses during pregnancy when BDs do not apply. A larger multicenter prospective study is required to evaluate the use of the ADNEX model to classify adnexal masses during pregnancy. Our data suggest that most adnexal masses can be managed expectantly during pregnancy, given the high rate of spontaneous resolution and low risk of complications. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Added value of cell‐free DNA over clinical and ultrasound information for diagnosing ovarian cancer

ABSTRACT Objective We previously proposed two cell‐free (cf) DNA‐based scores (genome‐wide Z ‐score and nucleosome score) as candidate non‐invasive biomarkers to further improve the presurgical diagnosis of ovarian malignancy. We aimed to investigate the added value of these cfDNA‐based scores in combination with the clinical and ultrasound predictors of the Assessment of Different NEoplasias in the adneXa (ADNEX) model to estimate the risk of ovarian malignancy. Methods In this prospective cohort study, 526 patients with an adnexal mass scheduled for surgery were recruited consecutively in three oncology referral centers. All patients underwent a transvaginal ultrasound examination, and adnexal masses were described according to the International Ovarian Tumor Analysis terms and definitions. cfDNA was extracted from preoperative plasma samples and genome‐wide Z ‐scores and nucleosome scores were calculated. Logistic regression models were fitted for ADNEX predictors alone and after inclusion of the cfDNA‐based scores. We report likelihood ratios, area under the receiver‐operating‐characteristics curve (AUC), sensitivity, specificity and net benefit for thresholds between 5% and 40%, to assess the diagnostic performance of the models in discriminating between benign and malignant ovarian masses. Results The study included 272 benign, 86 borderline, 36 Stage‐I invasive, 113 Stage‐II–IV invasive, and 19 secondary metastatic tumors. The likelihood ratios for adding the cfDNA‐based scores to the ADNEX model were statistically significant ( P  < 0.001 for ADNEX without CA 125; P  = 0.001 for ADNEX including CA 125). The accompanying increases in AUC were 0.013 when the cfDNA biomarkers were added to the ADNEX model without CA 125, and 0.003 when added to the ADNEX model including CA 125. Net benefit, sensitivity and specificity were similar for all models. The increase in net benefit at the recommended 10% threshold estimated risk of malignancy when adding the cfDNA‐based scores was 0.0017 and 0.0020, respectively, for the ADNEX model without CA 125 and the ADNEX model with CA 125. According to these results, adding cfDNA markers would require at least 453 patients per additional true‐positive test result at the 10% risk threshold. Conclusion Although statistically significant, cfDNA‐based biomarker scores have limited clinical utility in addition to established clinical and ultrasound‐based ADNEX predictors for discriminating between benign and malignant ovarian masses. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

Validation of ADNEX and IOTA two‐step strategy and estimation of risk of complications during follow‐up of adnexal masses in low‐risk population

ABSTRACTObjectivesTo evaluate the ability of the Assessment of Different NEoplasias in the adneXa (ADNEX) model and the International Ovarian Tumour Analysis (IOTA) two‐step strategy to predict malignancy in adnexal masses detected in an outpatient low‐risk setting, and to estimate the risk of complications in masses with benign ultrasound morphology managed using clinical and ultrasound follow‐up.MethodsThis single‐center study was performed at Hospital Universitari Dexeus, Barcelona, Spain, using interim data from the ongoing prospective observational IOTA Phase‐5 (IOTA5) study. The primary aim of the IOTA5 study is to describe the cumulative incidence of complications during follow‐up of adnexal masses classified as benign on ultrasound examination. Consecutive patients with an adnexal mass detected between June 2012 and September 2016 in a private center offering screening for gynecological cancer were included and followed up until February 2020. Tumors were classified as benign or malignant based on histology (if patients underwent surgery) or the outcome of clinical and ultrasound follow‐up at 12 (range, 10–14) months. Multiple imputation was used when outcomes were uncertain. The ability of the ADNEX model without CA125 and of the IOTA two‐step strategy to distinguish benign from malignant masses was evaluated retrospectively using the prospectively collected data. We assessed performance with regard to discrimination (area under the receiver‐operating‐characteristics curve (AUC)), calibration, classification (sensitivity and specificity) and clinical utility (Net Benefit). In the group of patients with a mass judged to be benign who were selected for conservative management, we evaluated the occurrence of spontaneous resolution or any mass complication during the first 5 years of follow‐up by assessing the cumulative incidence of malignancy, torsion, cyst rupture and minor mass complications (inflammation, infection or adhesions) and the time to occurrence of an event.ResultsA total of 2654 patients were recruited to the study. After application of exclusion criteria, 2039 patients with a newly detected mass were included for the model validation. Of those, 1684 (83%) masses were benign, 49 (2%) masses were malignant and, for 306 (15%) masses, the outcome was uncertain and therefore imputed. The AUC was 0.95 (95% CI, 0.89–0.98) for ADNEX without CA125 and 0.94 (95% CI, 0.88–0.97) for the two‐step strategy. Calibration performance could not be meaningfully interpreted because the small number of malignancies resulted in very wide confidence intervals. The two‐step strategy had better clinical utility than did the ADNEX model at malignancy risk thresholds < 3%. There were 1472 (72%) patients whose mass was judged to be benign based on pattern recognition by an experienced ultrasound examiner and were managed with clinical and ultrasound follow‐up. In this group, the 5‐year cumulative incidence was 66% (95% CI, 63–69%) for spontaneous resolution of the mass, 0% (95% CI, 0–0.2%) for torsion, 0.1% (95% CI, < 0.1–0.4%) for cyst rupture, 0.2% (95% CI, 0.1–0.6%) for a borderline tumor and 0.2% (95% CI, 0.1–0.6%) for invasive malignancy.ConclusionsThe ADNEX model and IOTA two‐step strategy performed well to distinguish benign from malignant adnexal masses detected in a low‐risk population. Conservative management is safe for masses with a benign ultrasound appearance in this population. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on pre-operative diagnosis of ovarian tumors

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group, and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the pre-operative diagnosis of ovarian tumors, including imaging techniques, biomarkers, and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the pre-operative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when a consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the pre-operative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumors

ABSTRACTThe European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence‐based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models.ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence‐based, the current literature was reviewed and critically appraised.Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements.This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

Imaging in gynecological disease (29): clinical and ultrasound features of primary ovarian immature teratoma

ABSTRACT Objective To describe the clinical and ultrasound characteristics at the time of diagnosis of primary ovarian immature teratoma with no other germ cell tumor components described on histopathology. Methods This was a retrospective study of women with a histological diagnosis of primary ovarian immature teratoma who had undergone a preoperative ultrasound examination between 1998 and 2024. Cases were identified from the databases of 17 contributing ultrasound centers and the International Ovarian Tumor Analysis (IOTA) database. The descriptions of the ultrasound images of the tumors made by the original ultrasound examiners using IOTA terminology were reported. In addition, grayscale and color or power Doppler ultrasound images or videoclips were retrieved for all tumors. Two independent ultrasound examiners reviewed the retrieved material and searched for specific ultrasound characteristics of immature teratomas using pattern recognition. We present their agreed description of the tumors. Results In total, 64 patients with ovarian immature teratoma were included, of which 38 (59.4%) were obtained from the IOTA database (IOTA studies phase 1, 1b, 2, 3, 5 and 7). The median age of the patients at diagnosis was 24.5 (interquartile range (IQR), 18.8–31.0; range, 12–50) years. The most common presenting symptoms were abdominal or pelvic pain (38/60, 63.3%) and abdominal swelling (30/60, 50.0%). All immature teratomas were unilateral. The median largest diameter of the tumor was 149.5 (IQR, 125.0–183.8; range, 27–400) mm. Using IOTA terminology, most tumors were described as multilocular‐solid (32/64, 50.0%) or solid lesions (22/64, 34.4%). When present, the solid component had a median largest diameter of 98.5 (IQR, 59.8–146.8; range 6–400) mm. Most masses showed minimal (19/63, 30.2%) or moderate (35/63, 55.6%) vascularization on color or power Doppler ultrasound examination. Using pattern recognition, the most typical ultrasound feature was heterogeneous, bizarre echogenicity of the solid components, with hyperechogenic areas, cystic spaces and acoustic shadows. This feature, which we consider pathognomonic, was present in 48/57 (84.2%) immature teratomas in which the solid components were adequately assessable. Conclusions The typical ultrasound appearance of an ovarian immature teratoma is a large unilateral adnexal mass with large solid components that is poorly or moderately vascularized. The pathognomonic feature is heterogeneous echogenicity of the solid components with hyperechogenic areas, cystic spaces and acoustic shadows. Preoperative suspicion of immature teratoma can guide treatment, such as offering fertility‐sparing surgery. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.