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Gestational trophoblastic disorders include proliferative disorders that originate from the placental trophoblastic tissue with two none-neoplastic (hydatidiform moles) and neoplastic (gestational trophoblastic neoplasia or GTN) patterns (1). GTN consists of three entities including choriocarcinoma, epithelioid trophoblastic tumor, and placental site trophoblastic tumor (2). In addition, GTN may follow term or preterm pregnancy, molar pregnancy, abortion, or ectopic pregnancy (3). This tumor can be manifested by uterine bleeding or extrauterine hemorrhages (4,5). Following the molar evacuation, serial serum human chorionic gonadotropin (hCG) levels are measured weekly until it becomes undetectable. Further, postmolar GTN is diagnosed by the International Federation of Gynecology and Obstetrics (FIGO) criteria as follows (6): • Weekly hCG levels plateau over a three-week period; • An increase of >10% in the hCG level in a two-week duration; • Existence of β-HCG six months or more after molar evacuation; • Existence of histological diagnosis of choriocarcinoma. The diagnosis of GTN after a nonmolar pregnancy is evaluated with serum hCG and ultrasound after patients become symptomatic. For patients with GTN, both a stage and a risk score are assigned before treatment. The staging and scoring system can predict the possibility of resistance to singleagent chemotherapy with methotrexate (MTX) and actinomycin D. One of the main issues in the management of GTN is to investigate the main causes of resistance to common therapeutic regimens. Some previous studies emphasized the importance of the earlier identification of chemotherapy resistance in patients (7,10). Although prognosis in GTN was shown to be excellent, chemotherapy resistance was considered as a challenging matter in the treatment of GTN patients (11). Considering the above-mentioned explanation, the present study attempted to provide a clear view of GTN Abstract Objectives: The present study attempted to provide a clear view of gestational trophoblastic neoplasia (GTN) with the focus on resistance to treatment approaches in Iran. Materials and Methods: This retrospective cohort study reviewed the medical records of 272 patients with the definitive diagnosis of GTN referring to Imam Khomeini hospital in Tehran during 2007-2017. Results: The mean age of participants was 29.19 ± 7.46 years. The abnormal uterine bleeding (AUB) was the most common clinical manifestation in 64.3% of patients. Regarding the risk scoring condition according to the World Health Organization criteria, 77.6%, 9.1%, and 13.3% were categorized as low-, intermediate-, and high-risk cases. Single therapy with methotrexate was used in 22.8% of patients and actinomycin-D was planned for 42.3% whereas 11.0% and 1.5% were considered for treatment with the EMA-CO (Etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) and EMA-EP (Etoposide methotrexate and actinomycin-D/ etoposide and cisplatin) regimens, respectively. Good response to methotrexate was 66.7% but it was 83.6% in the ACT group (P = 0.001). The resistance to single-agent chemotherapy in lowand intermediate-risk groups was 16% and 92%, respectively. In addition, 20.2% of patients in stage one had tumor invasion pattern in the uterus in pretreatment Doppler ultrasonography, but 52% and 30% had resistance to chemotherapy treatment in invasive and noninvasive groups, respectively (P = 0.008). Conclusions: In general, due to the high resistance of the intermediate-risk subgroup to a single therapy, a combination therapy may be more useful to treat this disorder. The close association between tumor invasion pattern in the uterus in Doppler ultrasonography and drug resistance can be considered as a new criterion for tumor risk scoring.

Is Not It the Time to Change the Treatment of Intermediate-Risk Patients Suffering From Gestational Trophoblastic Neoplasia?