GestaTIonal TrophoblAstic NeoplasIa Ultrasound assessMent: TITANIUM study

BACKGROUND: \r\nThere are limited data on ultrasound morphologic features of gestational trophoblastic neoplasia. A predictive model to determine predictors of response to therapy would be ideal in the management of patients with this rare disease.\r\nPRIMARY OBJECTIVES AND STUDY HYPOTHESIS: \r\nTITANIUM is a prospective, multicenter, observational study aiming to describe ultrasound features of gestational trophoblastic neoplasia and to investigate the role of ultrasound in identifying patients at high risk of resistance to single-drug therapy. The study hypothesis is that ultrasound could improve the International Federation of Gynecology and Obstetrics (FIGO) scoring system for early identification of patients predisposed to single-drug resistance.\r\nTRIAL DESIGN AND MAJOR INCLUSION/EXCLUSION CRITERIA: \r\nPatients eligible have a diagnosis of gestational trophoblastic neoplasia according to FIGO or the criteria set by Charing Cross Hospital, London, UK. At diagnosis, patients are classified as low-risk (score 0-6) or high-risk (score >6) according to the FIGO risk scoring system, and a baseline ultrasound scan is performed. Patients receive treatment according to local protocol at each institution. Follow-up ultrasound examinations are performed at 1, 4, 10, 16, and 22 months after start of chemotherapy, and at each scan, serum human chorionic gonadotropin (hCG) level, and chemotherapy treatment, if any, are recorded.\r\nPRIMARY ENDPOINTS: \r\nOur aims are to define ultrasound features of gestational trophoblastic neoplasia and to develop a predictive model of resistance to single-drug therapy in low-risk patients.\r\nSAMPLE SIZE: \r\nThe sample size was calculated assuming that 70% of patients with gestational trophoblastic neoplasia are at low risk, and estimating the rate of resistance to single-drug therapy in this group to be 40%. Assuming a dropout rate of 10%, we should recruit at least 120 patients. With this sample size, we can attempt to create a mathematical model with three variables (either two ultrasound parameters in addition to the risk score or three ultrasound variables statistically significant at univariate analysis) to predict resistance to single-drug therapy in low-risk patients.\r\nESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: \r\nThe accrual started in February 2019. Additional referral centers for gestational trophoblastic disease, with similar ultrasound expertise, are welcome to participate in the study. Enrollment should be completed by December 2021, and analysis will be conducted in December 2023.\r\nTRIAL REGISTRATION: \r\nThe study received the Ethical Committee approval of the Coordinator Center (Rome) in January 2019 (Protocol No. 0004668/19).