Ovarian cancer is a leading cause of death for women worldwide, in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker [cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4)] analyses to evaluate 591 women with ovarian cancer, with benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivities of 72%, 69%, 87%, and 100% for stages I to IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100%, and HE4 alone detected 28%, 27%, 67%, and 100% of ovarian cancers for stages I to IV, respectively. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC = 0.88, 95% confidence interval, 0.83–0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation. Significance: There is an unmet need for effective ovarian cancer screening and diagnostic approaches that enable earlier-stage cancer detection and increased overall survival. We have developed a high-performing accessible approach that evaluates cfDNA fragmentomes and protein biomarkers to detect ovarian cancer.

Gestational trophoblastic diseases (GTDs) are a group of pregnancy-related premalignant and malignant diseases with generally a favorable prognosis when treated adequately. Many different treatment protocols exist worldwide. To our knowledge, this is the first set of global consensus-based guidelines for GTD. Four international organizations (European Organisation for the Treatment of Trophoblastic Diseases, European Society of Gynecologic Oncology, Gynecologic Cancer Intergroup, and International Society for the Study of Trophoblastic Diseases) delegated 53 expert GTD clinicians from 31 countries who formulated nine consensus-based definitions and the minimum criteria required to be a GTD center. Furthermore, 18 flow diagrams were developed to diagnose, treat, and follow up all forms of primary or recurrent GTD. The definitions and flow diagrams were drafted and adapted in consecutive (online) meetings until consensus was reached followed by an external review process. Here, the final guidelines are presented together with the available supporting evidence from the literature.