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Background: In addition to the diagnostic accuracy of imaging methods, patient-reported satisfaction with imaging methods is important., Objective: To report a secondary outcome of the prospective international multicenter Imaging Study in Advanced ovArian Cancer (ISAAC Study), detailing patients' experience with abdomino-pelvic ultrasound, whole-body contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) for pre-operative ovarian cancer work-up., Methods: In total, 144 patients with suspected ovarian cancer at four institutions in two countries (Italy, Czech Republic) underwent ultrasound, CT, and WB-DWI/MRI for pre-operative work-up between January 2020 and November 2022. After having undergone all three examinations, the patients filled in a questionnaire evaluating their overall experience and experience in five domains: preparation before the examination, duration of examination, noise during the procedure, radiation load of CT, and surrounding space. Pain perception, examination-related patient-perceived unexpected, unpleasant, or dangerous events ('adverse events'), and preferred method were also noted., Results: Ultrasound was the preferred method by 49% (70/144) of responders, followed by CT (38%, 55/144), and WB-DWI/MRI (13%, 19/144) (p<0.001). The poorest experience in all domains was reported for WB-DWI/MRI, which was also associated with the largest number of patients who reported adverse events (eg, dyspnea). Patients reported higher levels of pain during the ultrasound examination than during CT and WB-DWI/MRI (p<0.001): 78% (112/144) reported no pain or mild pain, 19% (27/144) moderate pain, and 3% (5/144) reported severe pain (pain score >7 of 10) during the ultrasound examination. We did not identify any factors related to patients' preferred method., Conclusion: Ultrasound was the imaging method preferred by most patients despite being associated with more pain during the examination in comparison with CT and WB-DWI/MRI., Trial Registration Number: NCT03808792., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several diagnostic prediction models to help clinicians discriminate between benign and malignant adnexal masses are available. This study is a head-to-head comparison of the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model with that of the Risk of Ovarian Malignancy Algorithm (ROMA)., Methods: This is a retrospective study based on prospectively included consecutive women with an adnexal tumour scheduled for surgery at five oncology centres and one non-oncology centre in four countries between 2015 and 2019. The reference standard was histology. Model performance for ADNEX and ROMA was evaluated regarding discrimination, calibration, and clinical utility., Results: The primary analysis included 894 patients, of whom 434 (49%) had a malignant tumour. The area under the receiver operating characteristic curve (AUC) was 0.92 (95% CI 0.88-0.95) for ADNEX with CA125, 0.90 (0.84-0.94) for ADNEX without CA125, and 0.85 (0.80-0.89) for ROMA. ROMA, and to a lesser extent ADNEX, underestimated the risk of malignancy. Clinical utility was highest for ADNEX. ROMA had no clinical utility at decision thresholds <27%., Conclusions: ADNEX had better ability to discriminate between benign and malignant adnexal tumours and higher clinical utility than ROMA., Clinical Trial Registration: clinicaltrials.gov NCT01698632 and NCT02847832., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Previous 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., Methods: This 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., Results: A 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)., Conclusion: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Competing Interests: Disclosure CS has reported non-remunerated activities as Coordinator Gynecological Programme for the European School of Oncology. JB has reported fees for advisory board membership for AstraZeneca and Pfizer; fees paid to her institute for roles as local principal investigator for AstraZeneca, MedSire and Pfizer. SLB has reported fees as an author for UpToDate. She has also reported non-remunerated activities as the chair of the Scientific Network on Female Sexual Health and Cancer (academic organisation). MJC has reported fees as an invited speaker for Roche (industry-sponsored symposium in National Conference). She has also reported non-remunerated activities as a member of the Board of Directors of EUSOMA, faculty member of ESO, project lead/lead investigator for the Breast Research Group of INESC TEC and President of MAMA Help (non-profit association for breast cancer patients in Portugal). She serves as a Specialty Editor for The Breast. NC has reported fees for advisory board membership for AstraZeneca, BIOCAD, Clovis Oncology, Eisai, GlaxoSmithKline (GSK), ImmunoGen, Mersana, Merck Sharp & Dohme (MSD)/Merck, Nuvation Bio, OncXerna, Pfizer, PharmaMar, Pieris and Roche; fees as an invited speaker for AstraZeneca, Clovis Oncology, GSK and MSD/Merck; institutional research grants from AstraZeneca, PharmaMar and Roche. She has also reported non-remunerated activities as member of the ESMO Guidelines Steering Committee and chair of the Scientific Committee of Alleanza contro il Tumore Ovarico (ACTO). GC has reported fees for advisory board membership for AstraZeneca, Bristol Myers Squibb (BMS), Celcuity, Daiichi Sankyo, Ellipsis, Exact Sciences, Lilly, Merck, Pfizer, Roche and Veracyte; fees as an invited speaker for AstraZeneca, Daiichi Sankyo, Novartis, Pfizer and Roche; fees for a writing engagement from Pfizer; institutional research grant from Merck for an investigator-initiated trial; institutional funding for phase I studies from Astellas, AstraZeneca, Blueprint Medicine, BMS, Daiichi Sankyo, Kymab, Novartis, Philogen, Relay Therapeutics, (coordinating principal investigator), Roche and Sanofi. He has also reported non-remunerated activities as an Italian National Health Council as Advisor for Ministry of Health (Consiglio Superiore di Sanità), member of the Scientific Council for the patient advocacy association Europa Donna, advisory role at the Fondazione Beretta cancer research foundation, member of the Board of Directors for Lega Italian Lotta ai Tumori (public national company for cancer prevention) and member of the Advisory Council of EUSOMA. SMD has reported personal honoraria from AstraZeneca, BMS and Clovis; fees paid to her institute as coordinating principal investigator for AstraZeneca. DGE has reported fees for advisory board membership for Recursion, SpringWorks and Syantra; consultancy fees for a writing engagement for AstraZeneca. DF has declared no conflicts of interest. NH has reported fees for advisory board membership for Aptitude Health, AstraZeneca, Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Sandoz-Hexal, Sanofi and SeaGen; fees as an invited speaker for Art Tempi, AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead, Lilly, Medscape, MSD, Novartis, Onkowissen, Pierre Fabre, Roche, Sanofi and SeaGen; institutional funding from AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Palleos, Pierre Fabre, Roche, SeaGen, TRIO and WSG; ownership interest in the West German Study Group. She has also reported non-remunerated activities as a member of the AGO Breast Guideline Committee and member of the ESO/ESCO Breast Cancer Educational Programs. She is the Founding Editor of the Breast Care journal. CK has reported fees for advisory board membership for Guerbet; fees as an invited speaker for Bayer and Bracco. BL has reported fees received from the Rising Tide Foundation as a patient reviewer. She has also reported non-remunerated activities as a member of the European Society of Gynaecological Oncology (ESGO) ENGAGe (Past Executive Board Member) and chair of KIU—Danish Patient Organisation for Women with Gynaecological Cancer. ELL has reported employment as the Director of the Medical Genetics Institute of the Shaare Zedek Medical Center. She has also reported non-remunerated activity as the vice president of the Israel National Academy of Science in Medicine (non-profit). ML has reported fees for advisory board membership and speaker fees for AstraZeneca, Exact Sciences, Gilead, Lilly, MSD, Novartis, Roche and SeaGen; fees as an invited speaker for Ipsen, Knight, Libbs, Pfizer, Sandoz, SeaGen and Takeda. JAL has reported fees for advisory board membership for Artios Pharma, AstraZeneca, BMS, Clovis Oncology, Eisai, Ellipses, GSK, ImmunoGen, Merck/MSD, Nuvation, Pfizer and VBL Therapeutics; speaker fees from AstraZeneca, Clovis Oncology, GSK and Neopharm; fees related to an independent data monitoring committee for Regeneron; institutional research grants from AstraZeneca, Clovis Oncology, Eisai, GSK, MSD/Merck and Pfizer. He has also reported non-remunerated activities as vice president of the European Society of Gynaecological Oncology (2019-2021). He serves as an associate editor of Therapeutic Advances in Medical Oncology (Sage Publishing). SL has reported fees paid to her institute for advisory board membership for AbbVie, Amgen, AstraZeneca, BMS, Celgene, DSI, EirGenix, Gilead, GSK, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Relay Therapeutics, Roche, Sanofi and SeaGen; fees paid to her institute as an invited speaker for AstraZeneca, DSI, Gilead, Novartis, Pfizer and Roche; employment as the Chief Executive officer (CEO) of GBG Forschungs GmbH; licensing fees paid to her institute by VM Scope GmbH; research grants to her institute from AstraZeneca, Celgene, Daiichi Sankyo, Immunomedics/Gilead, Novartis, Pfizer and Roche; institutional funding from AbbVie and Molecular Health; fees paid to her institute as principal investigator (Penelope/Padma) from Pfizer; fees paid to her institute from AstraZeneca (SC Capitello), Daiichi Sankyo (SC Destiny B05), Immunomedics/Gilead (SC ASCENT), Novartis (SC SOLAR1), Pfizer (SC PALOMA3), Roche (SC Inavo and SC Katherine), SeaGen (SC HERCLIMB). She has also reported non-remunerated activities as principal investigator for Aphinity, advisory role to Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Kommission Mamma (group in Germany responsible for breast cancer guidelines), membership of AGO, Deutsche Krebsgesellschaft (DKG), American Society of Clinical Oncology (ASCO) and ESMO including membership of the ESMO Guidelines Committee and past chair of the ESMO Breast Congress. She has reported institutional patents for which she has no financial interests: EP14153692.0, EP21152186.9, EP15702464.7, EP19808852.8. K-AP has reported non-remunerated activities as advisory board member for AstraZeneca, Scientific Advisory Committee member for Breast Cancer Trials, project lead in Australia for the DECRESENDO and OlympiA studies, member of the Expert Advisory Group on Cancer Clusters for the Victorian Department of Health and Human Services, Strategic Advisory Committee member for Breast Cancer Network Australia, Cancer Genetics Reference Committee Member for New South Wales Cancer Institute; advisory role on the register of experts for breast and hereditary cancer for the Medical Oncology Group of Australia and breast cancer optimal care pathway committee member for Cancer Council Victoria. She is also a leadership fellow of the National Health and Medical Research Council (Australia) and a practitioner fellow of the National Breast Cancer Foundation (Australia). SP-S has reported fees paid to her institute for advisory board membership for AstraZeneca, Eli Lilly, Exact Sciences, Medison, Pfizer and Roche; fees paid to her institute as an invited speaker for AstraZeneca, Eli Lilly, Exact Sciences, Medison, Novartis, Pfizer and Roche; fees paid to her institute for consultancy for Medison; personal and institutional research grant for an request for proposal for independent research put out by Shared Progress in Cancer Care and Pfizer.

Objective: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma., Methods: This was a retrospective multicenter study. Patients with a histological diagnosis of ovarian carcinosarcoma, who had undergone preoperative ultrasound examination between 2010 and 2019, were identified from the International Ovarian Tumor Analysis (IOTA) database. Additional patients who were examined outside of the IOTA study were identified from the databases of the participating centers. The masses were described using the terms and definitions of the IOTA group. Additionally, two experienced ultrasound examiners reviewed all available images to identify typical ultrasound features using pattern recognition., Results: Ninety-one patients with ovarian carcinosarcoma who had undergone ultrasound examination were identified, of whom 24 were examined within the IOTA studies and 67 were examined outside of the IOTA studies. Median age at diagnosis was 66 (range, 33-91) years and 84/91 (92.3%) patients were postmenopausal. Most patients (67/91, 73.6%) were symptomatic, with the most common complaint being pain (51/91, 56.0%). Most tumors (67/91, 73.6%) were International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV. Bilateral lesions were observed on ultrasound in 46/91 (50.5%) patients. Ascites was present in 38/91 (41.8%) patients. The median largest tumor diameter was 100 (range, 18-260) mm. All ovarian carcinosarcomas contained solid components, and most were described as solid (66/91, 72.5%) or multilocular-solid (22/91, 24.2%). The median diameter of the largest solid component was 77.5 (range, 11-238) mm. Moderate or rich vascularization was found in 78/91 (85.7%) cases. Retrospective analysis of ultrasound images and videoclips using pattern recognition in 73 cases revealed that all tumors had irregular margins and inhomogeneous echogenicity of the solid components. Forty-seven of 73 (64.4%) masses appeared as a solid tumor with cystic areas. Cooked appearance of the solid tissue was identified in 28/73 (38.4%) tumors. No pathognomonic ultrasound sign of ovarian carcinosarcoma was found., Conclusions: Ovarian carcinosarcomas are usually diagnosed in postmenopausal women and at an advanced stage. The most common ultrasound appearance is a large solid tumor with irregular margins, inhomogeneous echogenicity of the solid tissue and cystic areas. The second most common pattern is a large multilocular-solid mass with inhomogeneous echogenicity of the solid tissue. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To compare the performance of transvaginal and transabdominal ultrasound with that of the first-line staging method (contrast-enhanced computed tomography (CT)) and a novel technique, whole-body magnetic resonance imaging with diffusion-weighted sequence (WB-DWI/MRI), in the assessment of peritoneal involvement (carcinomatosis), lymph-node staging and prediction of non-resectability in patients with suspected ovarian cancer., Methods: Between March 2016 and October 2017, all consecutive patients with suspicion of ovarian cancer and surgery planned at a gynecological oncology center underwent preoperative staging and prediction of non-resectability with ultrasound, CT and WB-DWI/MRI. The evaluation followed a single, predefined protocol, assessing peritoneal spread at 19 sites and lymph-node metastasis at eight sites. The prediction of non-resectability was based on abdominal markers. Findings were compared to the reference standard (surgical findings and outcome and histopathological evaluation)., Results: Sixty-seven patients with confirmed ovarian cancer were analyzed. Among them, 51 (76%) had advanced-stage and 16 (24%) had early-stage ovarian cancer. Diagnostic laparoscopy only was performed in 16% (11/67) of the cases and laparotomy in 84% (56/67), with no residual disease at the end of surgery in 68% (38/56), residual disease ≤ 1 cm in 16% (9/56) and residual disease > 1 cm in 16% (9/56). Ultrasound and WB-DWI/MRI performed better than did CT in the assessment of overall peritoneal carcinomatosis (area under the receiver-operating-characteristics curve (AUC), 0.87, 0.86 and 0.77, respectively). Ultrasound was not inferior to CT (P = 0.002). For assessment of retroperitoneal lymph-node staging (AUC, 0.72-0.76) and prediction of non-resectability in the abdomen (AUC, 0.74-0.80), all three methods performed similarly. In general, ultrasound had higher or identical specificity to WB-DWI/MRI and CT at each of the 19 peritoneal sites evaluated, but lower or equal sensitivity in the abdomen. Compared with WB-DWI/MRI and CT, transvaginal ultrasound had higher accuracy (94% vs 91% and 85%, respectively) and sensitivity (94% vs 91% and 89%, respectively) in the detection of carcinomatosis in the pelvis. Better accuracy and sensitivity of ultrasound (93% and 100%) than WB-DWI/MRI (83% and 75%) and CT (84% and 88%) in the evaluation of deep rectosigmoid wall infiltration, in particular, supports the potential role of ultrasound in planning rectosigmoid resection. In contrast, for the bowel serosal and mesenterial assessment, abdominal ultrasound had the lowest accuracy (70%, 78% and 79%, respectively) and sensitivity (42%, 65% and 65%, respectively)., Conclusions: This is the first prospective study to document that, in experienced hands, ultrasound may be an alternative to WB-DWI/MRI and CT in ovarian cancer staging, including peritoneal and lymph-node evaluation and prediction of non-resectability based on abdominal markers of non-resectability. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Tumors can influence peripheral immune macroenvironment, thereby creating opportunities for non-invasive serum/plasma immunobiomarkers for immunostratification and immunotherapy designing. However, current approaches for immunobiomarkers' detection are largely quantitative, which is unreliable for assessing functional peripheral immunodynamics of patients with cancer. Hence, we aimed to design a functional biomarker modality for capturing peripheral immune signaling in patients with cancer for reliable immunostratification., Methods: We used a data-driven in silico framework, integrating existing tumor/blood bulk-RNAseq or single-cell (sc)RNAseq datasets of patients with cancer, to inform the design of an innovative serum-screening modality, that is, serum-functional immunodynamic status (sFIS) assay. Next, we pursued proof-of-concept analyses via multiparametric serum profiling of patients with ovarian cancer (OV) with sFIS assay combined with Luminex (cytokines/soluble immune checkpoints), CA125-antigen detection, and whole-blood immune cell counts. Here, sFIS assay's ability to determine survival benefit or malignancy risk was validated in a discovery (n=32) and/or validation (n=699) patient cohorts. Lastly, we used an orthotopic murine metastatic OV model, with anti-OV therapy selection via in silico drug-target screening and murine serum screening via sFIS assay, to assess suitable in vivo immunotherapy options., Results: In silico data-driven framework predicted that peripheral immunodynamics of patients with cancer might be best captured via analyzing myeloid nuclear factor kappa-light-chain enhancer of activated B cells (NFκB) signaling and interferon-stimulated genes' (ISG) responses. This helped in conceptualization of an ' in sitro ' ( in vitro + in situ ) sFIS assay, where human myeloid cells were exposed to patients' serum in vitro , to assess serum-induced (si)-NFκB or interferon (IFN)/ISG responses (as active signaling reporter activity) within them, thereby 'mimicking' patients' in situ immunodynamic status. Multiparametric serum profiling of patients with OV established that sFIS assay can: decode peripheral immunology (by indicating higher enrichment of si-NFκB over si-IFN/ISG responses), estimate survival trends (si-NFκB or si-IFN/ISG responses associating with negative or positive prognosis, respectively), and coestimate malignancy risk (relative to benign/borderline ovarian lesions). Biologically, we documented dominance of pro-tumorigenic, myeloid si-NFκB response HIGH si-IFN/ISG response LOW inflammation in periphery of patients with OV. Finally, in an orthotopic murine metastatic OV model, sFIS assay predicted the higher capacity of chemo-immunotherapy (paclitaxel-carboplatin plus anti-TNF antibody combination) in achieving a pro-immunogenic peripheral milieu (si-IFN/ISG response HIGH si-NFκB response LOW ), which aligned with high antitumor efficacy., Conclusions: We established sFIS assay as a novel biomarker resource for serum screening in patients with OV to evaluate peripheral immunodynamics, patient survival trends and malignancy risk, and to design preclinical chemo-immunotherapy strategies., Competing Interests: Competing interests: The sFIS assay is currently the subject of an ongoing PCT patent application. ADG has received consulting/advisory/lecture honoraria from Boehringer Ingelheim and Miltenyi Biotec., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: DT: senior investigator FWO (Fund for Scientific Research Flanders), and research sponsored by Roche Diagnostics. KU Leuven has consultancy agreements with GE Healthcare, Samsung Healthcare, GSK, and Canon. TB: research sponsored by Roche Diagnostics, Samsung Medison and Illumina, and grants for traveling from Samsung Medison. LC: advisory boards for AstraZeneca, GSK, Takeda, and Roche. DC: advisory boards for Genmab, AstraZeneca, Roche, and Sotio. NC: advisory boards for AstraZeneca, Seattle Genetics, Mersana and eTheRNA Immunotherapies NV, grants for traveling from Roche, Genmab and Amgen, and educational fees from MSD and Medscape Oncology. AdB: advisory boards for Roche, AstraZeneca, GSK/Tesaro, BIOCAD, Clovis, Genmab/Seattle Genetics, Pfizer, and Amgen, and grants for traveling from Roche and AstraZeneca. IV: consulting activities for Amgen, AstraZeneca, Clovis Oncology, Carrick Therapeutics, Debiopharm International SA, Deciphera Pharmaceuticals, Elevar Therapeutics, F Hoffmann-La Roche Ltd, Genmab, GSK, Immunogen Inc, Medical University of Vienna, Mersana, Millenium Pharmaceuticals, MSD, Novocure, Octimet Oncology NV, Oncoinvent AS, Pharmamar, Sotioa.s, Tesaro Inc, Verastem Oncology, and Zentalis, contracted research (via KU Leuven) from Oncoinvent AS and Genmab, grants (corporate sponsored research) from Amgen and Roche, and accommodations/travel expenses from Amgen, MSD, Tesaro, AstraZeneca, and Roche. CF: advisory boards for Roche, GSK, Tesaro, AZ/MSD, Clovis, Sequana and Ethicon, and grants for traveling from GSK and Roche. FP, CL, DF, WF, GG, BL, AL, LM, PM, DQ, ACT, VV and GS: no conflicts of interest., (© IGCS and ESGO 2021. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

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 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.

Objective: To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor., Methods: This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition., Results: One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14-77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38-216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours., Conclusions: A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second-stage test in adnexal masses that are difficult to classify., Methods: This was a prospective observational international multicenter diagnostic accuracy study. Consecutive patients with an adnexal mass underwent standardized transvaginal two-dimensional (2D) grayscale and color or power Doppler and 3D power Doppler ultrasound examination by an experienced examiner, and those with a 'difficult' tumor were included in the current analysis. A difficult tumor was defined as one in which the International Ovarian Tumor Analysis (IOTA) logistic regression model-1 (LR-1) yielded an ambiguous result (risk of malignancy, 8.3% to 25.5%), or as one in which the ultrasound examiner was uncertain regarding classification as benign or malignant when using subjective assessment. Even when the ultrasound examiner was uncertain, he/she was obliged to classify the tumor as most probably benign or most probably malignant. For each difficult tumor, one researcher created a 360° rotating 3D power Doppler image of the vessel tree in the whole tumor and another of the vessel tree in a 5-cm 3 spherical volume selected from the most vascularized part of the tumor. Two other researchers, blinded to the patient's history, 2D ultrasound findings and histological diagnosis, independently described the vessel tree using predetermined vessel features. Their agreed classification was used. The reference standard was the histological diagnosis of the mass. The sensitivity of each test for discriminating between benign and malignant difficult tumors was plotted against 1 - specificity on a receiver-operating-characteristics diagram, and the test with the point furthest from the reference line was considered to have the best diagnostic ability., Results: Of 2403 women with an adnexal mass, 376 (16%) had a difficult mass. Ultrasound volumes were available for 138 of these cases. In 79/138 masses, the ultrasound examiner was uncertain about the diagnosis based on subjective assessment, in 87/138, IOTA LR-1 yielded an ambiguous result and, in 28/138, both methods gave an uncertain result. Of the masses, 38/138 (28%) were malignant. Among tumors that were difficult to classify as benign or malignant by subjective assessment, the vessel feature 'densely packed vessels' had the best discriminative ability (sensitivity 67% (18/27), specificity 83% (43/52)) and was slightly superior to subjective assessment (sensitivity 74% (20/27), specificity 60% (31/52)). In tumors in which IOTA LR-1 yielded an ambiguous result, subjective assessment (sensitivity 82% (14/17), specificity 79% (55/70)) was superior to the best vascular feature, i.e. changes in the diameter of vessels in the whole tumor volume (sensitivity 71% (12/17), specificity 69% (48/70))., Conclusion: Vessel morphology depicted by 3D power Doppler ultrasound may slightly improve discrimination between benign and malignant adnexal tumors that are difficult to classify by subjective ultrasound assessment. For tumors in which the IOTA LR-1 model yields an ambiguous result, subjective assessment is superior to vessel morphology as a second-stage test. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses., Methods: Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed., Results: In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P < 0.0001) and presented with a lower number of cysts with > 10 locules (18.9% vs 54.3%; P < 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%., Conclusions: CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To describe the clinical and ultrasound characteristics of ovarian pure clear cell carcinoma., Methods: This was a retrospective study involving data from 11 ultrasound centers. From the International Ovarian Tumor Analysis (IOTA) database, 105 patients who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016 were identified with a histologically confirmed pure clear cell carcinoma of the ovary. An additional 47 patients diagnosed with pure clear cell carcinoma between 1999 and 2016 and with available complete preoperative ultrasound reports were identified retrospectively from the databases of the departments of gynecological oncology in the participating centers. The ultrasound images of all tumors were described using IOTA terminology. Clinical and ultrasound characteristics were analyzed for the whole group, and separately, for patients with and those without histologically confirmed endometriosis, and for patients with evidence of tumor developing from endometriosis., Results: Median age of the 152 patients was 53.5 (range, 28-92) years and 92/152 (60.5%) tumors were FIGO Stage I. Most tumors (128/152, 84.2%) were unilateral. On ultrasound examination, all tumors contained solid components and 36/152 (23.7%) were completely solid masses. The median largest diameter of the lesion was 117 (range, 25-310) mm. Papillary projections were present in 58/152 (38.2%) masses and, in most of these (51/56, 91.1%), vascularized papillary projections were seen. Information regarding the presence, site and type of pelvic endometriosis at histology was available for 130/152 patients. Endometriosis was noted in 54 (41.5%) of these. In 24/130 (18.6%) patients, the tumor was judged to have developed from endometriosis. Patients with, compared to those without, evidence of tumor developing from endometriosis were younger (median 47.5 vs 55.0 years, respectively), and ground-glass echogenicity of cyst fluid was more common in pure clear cell cancers developing from endometriosis (10/20 vs 13/79 (50.0% vs 16.5%), respectively)., Conclusions: Ovarian pure clear cell carcinoma is usually diagnosed at an early stage and typically appears as a large unilateral mass with solid components. Patients with clear cell carcinoma developing from endometriosis are younger than other patients with clear cell carcinoma, and clear cell cancers developing from endometriosis more often manifest ground-glass echogenicity of cyst fluid. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To describe the clinical and ultrasound characteristics of ovarian pure endometrioid carcinomas., Methods: This was a retrospective multicenter study of patients with a histological diagnosis of pure endometrioid carcinoma. We identified 161 patients from the International Ovarian Tumor Analysis (IOTA) database who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016, and another 78 patients from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. In addition, one author reviewed all available ultrasound images and described them using pattern recognition., Results: Median age of the 239 patients was 55 years (range, 19-88 years). On ultrasound examination, two (0.8%) endometrioid carcinomas were described as unilocular cysts, three (1.3%) as multilocular cysts, 37 (15.5%) as unilocular-solid cysts, 115 (48.1%) as multilocular-solid cysts and 82 (34.3%) as solid masses. Median largest tumor diameter was 102.5 mm (range, 20-300 mm) and median largest diameter of the largest solid component was 63 mm (range, 9-300 mm). Papillary projections were present in 70 (29.3%) masses. Most cancers (188 (78.7%)) were unilateral. In 49 (20.5%) cases, the cancer was judged by the pathologist to develop from endometriosis. These cancers, compared with those without evidence of tumor developing from endometriosis, more often manifested papillary projections on ultrasound (46.9% (23/49) vs 24.7% (47/190)), were less often bilateral (8.2% (4/49) vs 24.7% (47/190)) and less often associated with ascites (6.1% (3/49) vs 28.4% (54/190)) and fluid in the pouch of Douglas (24.5% (12/49) vs 48.9% (93/190)). Retrospective analysis of available ultrasound images using pattern recognition revealed that many tumors without evidence of tumor developing from endometriosis (36.3% (41/113)) had a large central solid component entrapped within locules, giving the tumor a cockade-like appearance., Conclusions: Endometrioid cancers are usually large, unilateral, multilocular-solid or solid tumors. The ultrasound characteristics of endometrioid carcinomas developing from endometriosis differ from those without evidence of tumor developing from endometriosis, the former being more often unilateral cysts with papillary projections and no ascites. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To examine prospectively the accuracy of ultrasound in predicting rectosigmoid tumor infiltration in patients with epithelial ovarian cancer., Methods: Patients referred for a suspicious pelvic mass between 2012 and 2014 were examined by ultrasound following the standard protocol for assessment of tumor infiltration. Of the 245 patients examined, 191 had proven ovarian cancer and underwent primary surgery and were included in the analysis. Patients with apparently benign or inoperable disease were excluded. Rectosigmoid infiltration was evaluated by histopathology or according to perioperative findings. Clinical, pathological and laboratory parameters were analyzed as factors potentially affecting the sensitivity and specificity of sonography., Results: The sensitivity of ultrasound in detecting rectosigmoid infiltration in patients with ovarian cancer was 86.3%, with specificity of 95.8%, positive predictive value of 92.6%, negative predictive value of 91.9% and overall accuracy of 92.1%., Conclusion: Ultrasound is a highly accurate method for detecting rectosigmoid tumor infiltration in ovarian cancer patients, and thus, can be used for planning adequate management, including patient consultation, surgical team planning, suitable operating time and postoperative care. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate the utility of preoperative diagnostic models for ovarian cancer based on ultrasound and/or biomarkers for referring patients to specialized oncology care. The investigated models were RMI, ROMA, and 3 models from the International Ovarian Tumor Analysis (IOTA) group [LR2, ADNEX, and the Simple Rules risk score (SRRisk)]. Experimental Design: A secondary analysis of prospectively collected data from 2 cross-sectional cohort studies was performed to externally validate diagnostic models. A total of 2,763 patients (2,403 in dataset 1 and 360 in dataset 2) from 18 centers (11 oncology centers and 7 nononcology hospitals) in 6 countries participated. Excised tissue was histologically classified as benign or malignant. The clinical utility of the preoperative diagnostic models was assessed with net benefit (NB) at a range of risk thresholds (5%-50% risk of malignancy) to refer patients to specialized oncology care. We visualized results with decision curves and generated bootstrap confidence intervals. Results: The prevalence of malignancy was 41% in dataset 1 and 40% in dataset 2. For thresholds up to 10% to 15%, RMI and ROMA had a lower NB than referring all patients. SRRisks and ADNEX demonstrated the highest NB. At a threshold of 20%, the NBs of ADNEX, SRrisks, and RMI were 0.348, 0.350, and 0.270, respectively. Results by menopausal status and type of center (oncology vs. nononcology) were similar. Conclusions: All tested IOTA methods, especially ADNEX and SRRisks, are clinically more useful than RMI and ROMA to select patients with adnexal masses for specialized oncology care. Clin Cancer Res; 23(17); 5082-90. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Objective: Ovarian juvenile granulosa cell tumor has an interesting association with multiple enchondromatosis (Ollier disease and Maffucci syndrome) and should be considered a leading diagnosis when an ovarian mass is found in young patients with these conditions. Besides the association with nonskeletal malignancies, there is a high risk of malignant transformation of enchondroma in chondrosarcoma as was also the case in this instance., Case Report: The report uses multiple images to document the representative and characteristic markers of multiple enchondromas in a 22-year-old patient with Ollier disease complicated by malignant transformation of chondrosarcoma and in whom the disease is associated with ovarian juvenile granulosa cell tumor of the right ovary., Conclusion: It is important to recognize that when the female patient presents with enchondromatosis and a large unilateral multilocular-solid ovarian mass, the specific diagnosis of granulosa cell tumor can be made with high accuracy., (Copyright © 2017. Published by Elsevier B.V.)

Objective: To analyze the accuracy of ultrasound in assessing pelvic and intra-abdominal spread in patients with ovarian cancer., Methods: This prospective study enrolled all consecutive patients referred to a single gynecological oncology center for suspected ovarian cancer. We analyzed only data from patients with histologically confirmed primary ovarian cancer who were evaluated following predefined preoperative ultrasound, intraoperative and pathology protocols. We evaluated the agreement of depth of infiltration of the rectosigmoid wall, tumor spread in different peritoneal compartments and presence of metastatic retroperitoneal and inguinal lymph nodes, as determined at ultrasound, with intraoperative and histopathological findings., Results: In total, 578 patients were enrolled between March 2008 and January 2013, of whom 394 met the study inclusion criteria and were analyzed; 74% of these suffered from advanced-stage cancer. Our results showed excellent agreement between ultrasound and histology in assessment of rectosigmoid wall infiltration (kappa value, 0.812; area under the receiver-operating characteristics curve, 0.898). The overall accuracy in evaluating different peritoneal compartments, retroperitoneal and inguinal lymph nodes and depth of rectosigmoid wall infiltration was 85.3%, 84.8%, 99.7% and 91.1%, respectively. Ultrasound showed high sensitivity only in the assessment of rectosigmoid wall infiltration (83.1%), peritoneal spread into the pelvis (81.4%) and omentum (67.3%), and inguinal metastatic lymph nodes (100%). The specificity of ultrasound in detection of all evaluated parameters was > 90%., Conclusion: This is the largest imaging study to date on ovarian cancer staging. Ultrasound can be used as the method of choice to plan rectosigmoid wall resection and dissection of infiltrated inguinal lymph nodes. In assessing different peritoneal and retroperitoneal compartments, ultrasound was accurate and highly specific. However, similar to other modern imaging techniques, it had relatively low sensitivity, further supporting the role of comprehensive surgical staging. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

We analyzed the accuracy of transvaginal sonography in detection of pelvic carcinomatosis in ovarian cancer patients and factors (age, body mass index, performance status, ascites, stage, histotype, tumor grade) influencing the performance of ultrasound. In this prospective study, all 191 consecutively included patients underwent a pre-operative ultrasound staging examination according to institutional protocol. Peritoneal spread was assessed on the basis of peri-operative findings or histology. The area under the receiver operating characteristic curve for the detection of carcinomatosis was 0.90 (0.84-0.93); the sensitivity was 84% (95% confidence interval [CI]: 75%-%90), specificity 96% (95% CI: 89%-99%), positive predictive value 96% (95% CI: 89%-99%), negative predictive value 83% (95% CI: 74%-90%) and overall accuracy 89% (95% CI: 84%-93%). We report that transvaginal sonography is clinically useful in the detection of pelvic carcinomatosis., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Ultrasound is the primary imaging modality in gynecological oncology. Over the last decade, there has been a massive technology development which led to a dramatic improvement in the quality ultrasound imaging. If performed by an experienced sonographer, ultrasound has an invaluable role in the primary diagnosis of gynecological cancer, in the assessment of tumor extent in the pelvis and abdominal cavity, in the evaluation of the treatment response, and in follow-up. Ultrasound is also a valuable procedure for monitoring patients treated with fertility-sparing surgery. Furthermore, it is an ideal technique to guide tru-cut biopsy for the collection of material for histology. Taking into consideration that besides its accuracy, the ultrasound is a commonly available, non-invasive, and inexpensive imaging method that can be carried out without any risk or discomfort to the patient; it is time to reconsider its role in gynecologic oncology and to allocate resources for a specialized education of future experts in ultrasound imaging in gynecology.

Objectives: To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours., Design: Observational diagnostic study using prospectively collected clinical and ultrasound data., Setting: 24 ultrasound centres in 10 countries., Participants: Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients., Main Outcome Measures: Histological classification and surgical staging of the mass., Results: The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate., Conclusions: The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology., (© Van Calster et al 2014.)

Background: To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3., Methods: This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery., Results: The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5., Conclusions: This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.

Women with ovarian cancer often present at advanced stage of disease. The outcome depends mainly on the stage of disease at first diagnosis, but also on the quality of treatment. For individualised tumour treatment, detailed assessment of tumour extension using modern imaging is crucial. Ultrasound remains the initial and most important imaging method for ovarian cancer detection. Although increasing evidence shows that ultrasound is an accurate technique to stage and follow up ovarian cancer, it requires an experienced examiner capable of examining both the pelvis and the abdomen. Computed tomography is the most commonly used imaging modality for preoperative staging and follow up. Magnetic resonance imaging remains a second-line imaging method for solving problems, mainly in the pelvis. Positron emission tomography combined with computed tomography is the optimal imaging technique for suspected recurrence, particularly in women with rising CA 125 levels, but negative results of conventional imaging methods., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: To develop a logistic regression model for discrimination between benign and malignant unilocular solid cysts with papillary projections but no other solid components, and to compare its diagnostic performance with that of subjective evaluation of ultrasound findings (subjective assessment), CA  125 and the risk of malignancy index (RMI)., Methods: Among the 3511 adnexal masses in the International Ovarian Tumor Analysis (IOTA) database there were 252 (7%) unilocular solid cysts with papillary projections but no other solid components ('unilocular cysts with papillations'). All had been examined with transvaginal ultrasound using the IOTA standardized research protocol. The ultrasound examiner had also classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for all unilocular cysts with papillations (175 tumors in the training set and 77 in the test set) and for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy (113 tumors in the training set and 53 in the test set). The gold standard was the histological diagnosis of the surgically removed adnexal mass., Results: A model containing six variables was developed for all unilocular cysts with papillations. The model had an area under the receiver-operating characteristics curve (AUC) on the test set of 0.83 (95% CI, 0.74-0.93). The optimal risk cut-off, as defined on the training set (0.35), resulted in sensitivity 69% (20/29), specificity 79% (38/48), positive likelihood ratio (LR +) 3.31 and negative likelihood ratio (LR-) 0.39 on the test set. The corresponding values for subjective assessment when using the ultrasound examiner's dichotomous classification of the mass as benign or malignant were 97% (28/29), 79% (38/48), 4.63 and 0.04. A model containing four variables was developed for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy. The model had an AUC of 0.74 (95% CI, 0.60-0.88) on the test set. The optimal risk cut-off of the model, as defined on the training set (0.30), resulted in sensitivity 57% (12/21), specificity 78% (25/32), LR + 2.61 and LR- 0.55 on the test set. The corresponding values for subjective assessment were 95% (20/21), 78% (25/32), 4.35 and 0.06. CA  125 and RMI had virtually no diagnostic ability., Conclusions: Even though logistic regression models to predict malignancy in unilocular cysts with papillations can be developed, they have at most moderate performance and are not superior to subjective assessment for discrimination between benignity and malignancy., (Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To describe the sonographic characteristics of borderline ovarian tumor (BOT) recurrence., Methods: From the databases of five ultrasound centers, we retrospectively identified 68 patients with histological diagnosis of recurrent BOT who had undergone preoperative ultrasound examination. All recurrences were detected during planned follow-up ultrasound examinations. Recurrent lesions were described using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group., Results: Sixty-two patients had a serous BOT recurrence and six a mucinous BOT recurrence. All patients except one were premenopausal, 84% of them being < 40 years old. All but one patient were asymptomatic at diagnosis of the recurrence. Fertility-sparing surgery of the recurrent tumor was performed in 57/68 (84%) patients. The most frequent ultrasound feature of recurrent serous BOT was a unilocular solid cyst (49/62, 79%) and almost half of the recurrent serous BOTs (29/62, 47%) had multiple papillary projections. In 89% of the recurrent serous BOTs there was at least one papillation with irregular surface and in 73% there was at least one papillation vascularized at color Doppler examination. Recurrent mucinous BOTs appeared mainly as multilocular or multilocular solid cysts (5/6, 83%)., Conclusion: Sonographic features of recurrent BOT resemble those described by others for different subtypes of primary BOT., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: The aim of this study was to estimate the rate of malignancy in adnexal lesions described as unilocular cysts at transvaginal ultrasound examination and to investigate if there are differences in clinical and ultrasound characteristics between benign and malignant unilocular cysts., Methods: A total of 3511 patients with an adnexal mass underwent transvaginal ultrasound examination between 1999 and 2007. Sonologists used the International Ovarian Tumor Analysis terms and definitions to describe their ultrasound findings. Only masses operated on within 120  days after the ultrasound examination were included in the analysis and the histopathological diagnosis of the mass was used as the gold standard., Results: Of the 3511 masses, 1148 (33%) were classified as unilocular cysts on ultrasound. Of these, 11 (0.96% (95% CI, 0.48-1.71)) were malignant. The malignancy rate was lower in premenopausal than in postmenopausal women: 0.54% (5/931; 95% CI, 0.17-1.25) vs. 2.76% (6/217; 95% CI, 1.02-5.92); P = 0.009. More patients with malignant unilocular cysts had a personal history of breast cancer (18% vs. 2%; P = 0.02) or ovarian cancer (18% vs 0.6%; P = 0.003). Hemorrhagic cyst contents on ultrasound were more common in malignant than in benign unilocular cysts (18% vs. 2%; P = 0.03). In seven of the 11 malignancies judged to be unilocular cysts at scan, papillary projections or other solid components were seen at macroscopic inspection of the surgical specimen., Conclusions: The malignancy rate in surgically removed adnexal lesions judged to be unilocular cysts at transvaginal scan is c 1%. Postmenopausal status, personal history of breast or ovarian cancer and hemorrhagic cyst contents on ultrasound increase the risk of malignancy. To avoid misclassifying adnexal lesions as unilocular cysts at scan, it is important to scrutinize unilocular cysts for the presence of solid components., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type-easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients.

Objective: To develop a logistic regression model that can discriminate between benign and malignant adnexal masses perceived to be difficult to classify by subjective evaluation of gray-scale and Doppler ultrasound findings (subjective assessment) and to compare its diagnostic performance with that of subjective assessment, serum CA 125 and the risk of malignancy index (RMI)., Methods: We used data from the 3511 patients with an adnexal mass included in the International Ovarian Tumor Analysis (IOTA) studies. All patients had been examined using transvaginal gray-scale and Doppler ultrasound following a standardized research protocol carried out by an experienced ultrasound examiner using a high-end ultrasound system. In addition to prospectively collecting information on > 40 clinical and ultrasound variables, the ultrasound examiner classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for the unclassifiable masses (n = 244, i.e. 7% of all tumors) using a training set (160 tumors, 45 malignancies) and then tested on a test set (84 tumors, 28 malignancies). The gold standard was the histological diagnosis of the surgically removed adnexal mass. The area under the receiver-operating characteristics curve (AUC), sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were used to describe diagnostic performance and were compared between subjective assessment, CA 125, the RMI and the logistic regression model created., Results: One variable was retained in the logistic regression model: the largest diameter (in mm) of the largest solid component of the tumor (odds ratio (OR) = 1.04; 95% CI, 1.02-1.06). The model had an AUC of 0.68 (95% CI, 0.59-0.78) on the training set and an AUC of 0.65 (95% CI, 0.53-0.78) on the test set. On the test set, a cut-off of 25% probability of malignancy (corresponding to the largest diameter of the largest solid component of 23 mm) resulted in a sensitivity of 64% (18/28), a specificity of 55% (31/56), an LR+ of 1.44 and an LR- of 0.65. The corresponding values for subjective assessment were 68% (19/28), 59% (33/56), 1.65 and 0.55. On the test set of patients with available CA 125 results, the LR+ and LR- of the logistic regression model (cut-off = 25% probability of malignancy) were 1.29 and 0.73, of subjective assessment were 1.45 and 0.63, of CA 125 (cut-off = 35 U/mL) were 1.24 and 0.84 and of RMI (cut-off = 200) were 1.21 and 0.92., Conclusions: About 7% of adnexal masses that are considered appropriate for surgical removal cannot be classified as benign or malignant by experienced ultrasound examiners using subjective assessment. Logistic regression models to estimate the risk of malignancy, CA 125 measurements and the RMI are not helpful in these masses., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: To describe the clinical history and ultrasound findings in patients with ovarian dysgerminoma., Methods: This was a retrospective study of patients with a histological diagnosis of ovarian dysgerminoma who had undergone preoperative ultrasound examination. The patients were identified from the databases of 11 ultrasound centers. The tumors were described by the principal investigator at each contributing center on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, three authors reviewed all available electronic ultrasound images (gray-scale images and color/power Doppler images were available for 18 patients and 14 patients, respectively) and described them using subjective evaluation of gray-scale and color Doppler ultrasound findings (here called pattern recognition)., Results: Twenty-one patients with ovarian dysgerminoma were identified (including one woman with bilateral masses). Twenty patients had a primary ovarian dysgerminoma (including the one with bilateral masses) and one patient had a recurrence of dysgerminoma in her retained ovary. One of the 21 patients was pregnant. All tumors except one were pure dysgerminomas, one being a mixed germinal cell tumor with 30% dysgerminoma component. Median age was 20 (range, 16-31) years. Information on clinical symptoms was available for 18 patients. In four patients, the tumor was detected incidentally, whereas 14 patients presented with one or more of the following symptoms: acute pain (n = 4), chronic pain (n = 8), bloating (n = 8), menstrual disorders (n = 5) and infertility problems (n = 1). One (5%) patient had ascites. Using the IOTA terms and definitions, all but one dysgerminoma were moderately (43%) or very well (50%) vascularized solid tumors. One tumor was multilocular-solid. According to pattern recognition, most dysgerminomas were highly vascularized, purely solid tumors with heterogeneous internal echogenicity divided into several lobules, had a smooth and sometimes lobulated contour and were well-defined relative to the surrounding organs., Conclusion: The ultrasound finding of a highly vascularized, large, solid, lobulated adnexal mass with irregular internal echogenicity in a woman 20-30 years old should raise the suspicion of ovarian dysgerminoma., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: The aims of the study were to temporally and externally validate the diagnostic performance of two logistic regression models containing clinical and ultrasound variables in order to estimate the risk of malignancy in adnexal masses, and to compare the results with the subjective interpretation of ultrasound findings carried out by an experienced ultrasound examiner ('subjective assessment')., Methods: Patients with adnexal masses, who were put forward by the 19 centers participating in the study, underwent a standardized transvaginal ultrasound examination by a gynecologist or a radiologist specialized in ultrasonography. The examiner prospectively collected information on clinical and ultrasound variables, and classified each mass as benign or malignant on the basis of subjective evaluation of ultrasound findings. The gold standard was the histology of the mass with local clinicians deciding whether to operate on the basis of ultrasound results and the clinical picture. The models' ability to discriminate between malignant and benign masses was assessed, together with the accuracy of the risk estimates., Results: Of the 1938 patients included in the study, 1396 had benign, 373 had primary invasive, 111 had borderline malignant and 58 had metastatic tumors. On external validation (997 patients from 12 centers), the area under the receiver-operating characteristics curve (AUC) for a model containing 12 predictors (LR1) was 0.956, for a reduced model with six predictors (LR2) was 0.949 and for subjective assessment was 0.949. Subjective assessment gave a positive likelihood ratio of 11.0 and a negative likelihood ratio of 0.14. The corresponding likelihood ratios for a previously derived probability threshold (0.1) were 6.84 and 0.09 for LR1, and 6.36 and 0.10 for LR2. On temporal validation (941 patients from seven centers), the AUCs were 0.945 (LR1), 0.918 (LR2) and 0.959 (subjective assessment)., Conclusions: Both models provide excellent discrimination between benign and malignant masses. Because the models provide an objective and reasonably accurate risk estimation, they may improve the management of women with suspected ovarian pathology.

Objective: To determine the sensitivity and specificity of the 'ovarian crescent sign' (OCS)-a rim of normal ovarian tissue seen adjacent to an ipsilateral adnexal mass-as a sonographic feature to discriminate between benign and malignant adnexal masses., Methods: The patients included were a subgroup of patients participating in the International Ovarian Tumor Analysis (IOTA) Phase 2 study, which is an international multicenter study. The subgroup comprised 1938 patients, with an adnexal mass, recruited from 19 ultrasound centers in different countries. All patients were scanned using the same standardized ultrasound protocol. Information on more than 40 demographic and ultrasound variables were collected, but the evaluation of the OCS was optional. Only patients from centers that had evaluated the OCS in > or = 90% of their cases were included. The gold standard was the histological diagnosis of the adnexal mass. The ability of the OCS to discriminate between borderline or invasively malignant vs. benign adnexal masses, as well as between invasively malignant vs. other (benign and borderline) tumors, was determined and compared with the performance of subjective evaluation of ultrasound findings by the ultrasound examiner., Results: The OCS was evaluated in 1377 adnexal masses from 12 centers, 938 (68%) masses being benign, 86 (6%) borderline, 305 (22%) primary invasive and 48 (3%) metastases. The OCS was present in 398 (42%) of 938 benign masses, in 14 (16%) of 86 borderline tumors, in 18 (6%) of 305 primary invasive tumors (one malignant struma ovarii, one uterine clear cell adenocarcinoma and 16 epithelial carcinomas, i.e. four Stage I and 12 Stage II-IV) and in two (4%) of 48 ovarian metastases. Hence, the sensitivity and specificity for absent OCS to identify a malignancy was 92% and 42%, respectively, and the positive and negative likelihood ratios (LR+ and LR-, respectively) were 1.60 and 0.18. Subjective impression performed significantly better than the OCS. Sensitivity and specificity were 90% and 92%, respectively, LR+ was 11.0 and LR- was 0.10. For discrimination between invasive vs. benign or borderline tumors, the sensitivity for absent OCS was 94%, the specificity was 40%, the LR+ was 1.58 and the LR- was 0.14., Conclusion: This study confirms previous reports that the presence of the OCS decreases the likelihood of invasive malignancy in adnexal masses. However it is a poor discriminator between benign and malignant adnexal masses., (Copyright 2010 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas., Methods: All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated., Results: Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was 'an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable., Conclusions: Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy., ((c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.)