Gestational Trophoblastic Neoplasia: Clinical and Therapeutic Profile in Madagascar

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. This includes complete and partial hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). The aim of this study was to report the epidemiological, clinical and therapeutic profile of gestational trophoblastic neoplasia (GTN) over period of ten years in the department of Oncology Radiotherapy at the University Hospital Joseph Ravoahangy Andrianavalona (HJRA) Antananarivo Madagascar. Medical records of women diagnosed with GTD in the department of Oncology Radiotherapy at HJRA from January 1st, 2007 to September 2017 were retrospectively reviewed. Only patients with the FIGO diagnosis GTN were included, while those with the histological diagnosis of hydatidiform mole (HM), also sometimes classified as GTD, were not included in this study. Also excluded were all cases with incomplete or missing data. Twenty four patients were included. Median age of patients at the time of diagnosis was 37 years (range 18 - 60). Most patients developed GTN following molar pregnancy (75%), had disease duration from antecedent pregnancy of less than 6 months (58.20%), and had the pre-treatment hCG level more than 10,000 IU/L (58.27%). At diagnosis, 14 patients (58.33%) had localized disease (M0). Most common metastatic sites at initial diagnosis were the liver and brain (20.83%). After a median follow-up from initial diagnosis of six months (range 1 - 24), 58.33% were lost to follow up. This represented an increase in the percentage of patients lost to follow up prior to completion of therapy, when compared with our previous results for an earlier time period. GTN in Malagasy woman displays an aggressive clinic profile. Finding ways to increase treatment compliance provides the best way to minimize recurrences of this potentially deadly disease.

Efficacy and Risk Factors Associated to Resistance to Single-Agent Chemotherapy in Low-Risk Gestational Trophoblastic Neoplasia

Objectives: This study aimed to assess efficacy of intramuscular methotrexate 8-day protocol in the treatment of low-risk gestational trophoblastic neoplasia and also identify prognostic factors associated with treatment failure, necessitating second line chemotherapy. Methods: This study was performed at Gynaecologic and Obstetric Clinic of Dakar Teaching Hospital, the reference Centre of Gestational Trophoblastic Disease in Senegal. At the beginning of 2011, patients were followed according to FIGO’s recommendations. From 2011 to 2014, we diagnosed 88 low-risk gestational trophoblastic neoplasia (GTN) patients (WHO score < 7). Low-risk patients started their treatment with methotrexate (MTX) based on the 8-day protocol consisting of 1 mg/kg MTX in combination with 0.1 mg/kg folinic acid (FA) every other day. Resistance to treatment was the main outcome. We studied the association of different prognostic factors included in the World Health Organisation (WHO) scoring system and resistance to the initial single agent chemotherapy. Results: Eighty-eight patients were diagnosed for GTN during the study period. Average age was 31 years. The antecedent pregnancy was molar in 98.1% of cases. Seventy-four patients underwent remission after single agent-chemotherapy. Resistance rate to single-agent chemotherapy was 15.9% (14 patients). Nine of them achieved remission after second line chemotherapy. WHO score was significantly associated with the risk of resistance to single-agent chemotherapy. Other variables included in the WHO as age, antecedent pregnancy, pre-treatment hCG, tumour size and FIGO stage were not significantly associated with resistance. We report five fatal cases. Conclusion: The 8-day protocol consisting of 1 mg/kg MTX in combination with 0.1 mg/kg folinic acid (FA) every other day is effective for women with LRGTN. The only significant prognostic factor for failure is pretreatment WHO score. We highly recommend the use of this protocol particularly in developing countries where methotrexate is available, affordable and relatively safe.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia(GTN).In this trial (NCT01823315),276 patients were analyzed.Patients were allocated to three initiated regimens:single-course methotrexate(MTX),single-course MTX+dactinomycin(ACTD),and multi-course MTX(control arm).The primary endpoint was the complete remission(CR)rate by initial drug(s).The primary CR rate was 64.4%with multi-course MTX in the control arm.For the single-course MTX arm,the CR rate was 35.8%by one course;it increased to 59.3%after subsequent multi-course MTX,with non-inferiority to the control(difference-5.1%,95%confidence interval(CI)-19.4%to 9.2%,P=0.014).After further treatment with multi-course ACTD,the CR rate(93.3%)was similar to that of the control(95.2%,P=0.577).For the single-course MTX+ACTD arm,the CR rate was 46.7%by one course,which increased to 89.1%after subsequent multi-course,with non-inferiority(difference 24.7%,95%CI 12.8%-36.6%,P<0.001)to the control.It was similar to the CR rate by MTX and further ACTD in the control arm(89.1%vs.95.2%,P=0.135).Four patients experienced recurrence,with no death,during the 2-year follow-up.We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Evaluation and simplification of risk factors in FIGO 2000 scoring system for gestational trophoblastic neoplasia:a 19-year retrospective analysis

Objective The International Federation of Gynecology and Obstetrics(FIGO)2000 scoring system classifies gestational trophoblastic neoplasia(GTN)patients into low-and high-risk groups,so that single-or multi-agent chemotherapy can be administered accordingly.However,a number of FIGO-defined low-risk patients still exhibit resistance to single-agent regimens,and the risk factors currently adopted in the FIGO scoring system possess inequable values for predicting single-agent chemoresistance.The purpose of this study is therefore to evaluate the efficacy of risk factors in predicting single-agent chemoresistance and explore the feasibility of simplifying the FIGO 2000 scoring system for GTN.Methods The clinical data of 578 GTN patients who received chemotherapy between January 2000 and December 2018 were retrospectively reviewed.Univariate and multivariate logistic regression analyses were carried out to identify risk factors associated with single-agent chemoresistance in low-risk GTN patients.Then,simplified models were built and compared with the original FIGO 2000 scoring system.Results Among the eight FIGO risk factors,the univariate and multivariate analyses identified that pretreatment serum human chorionic gonadotropin(hCG)level and interval from antecedent pregnancy were consistently independent predictors for both first-line and subsequent single-agent chemoresistance.The simplified model with two independent factors showed a better performance in predicting single-agent chemoresistance than the model with the other four non-independent factors.However,the addition of other co-factors did improve the efficiency.Overall,simplified models can achieve favorable performance,but the original FIGO 2000 prognostic system still features the highest discrimination.Conclusions Pretreatment serum hCG level and interval from antecedent pregnancy were independent predictors for both first-line and subsequent single-agent chemoresistance,and they had greater weight than other non-independent factors in predicting single-agent chemoresistance.The simplified model composed of certain selected factors is a promising alternative to the original FIGO 2000 prognostic system,and it shows comparable performance.

Gestational Trophoblastic Disease Diagnosis and Treatment:An Analysis of 56 Cases

Objective To investigate the diagnosis and treatment of gestational trophoblastic disease （GTD）. Methods A retrospective review was conducted on 56 patients with GTD who under- went treatment in Ruijin hospital from January 2007 to December 2012. Their infor- mation of diagnosis, treatments, follow-up and efficacy were collected and analyzed Results Misdiagnosis rate was 41.1% （23/56）for the first time. Of 56 patients, 31 had direct curettage, 19 had curettage after trichosanthis （TCS） treatment, 3 had curettage after intervention treatment and 3 did not have curettage. Twenty patients with gesta- tional trophoblastic neoplasia （GTN） took fluorouracil＋vincristine＋dactinomycin （VCR ＋KSM＋5-FU） chemotherapy, but 2 of them changed to etoposide＋methotrexate＋acti- nomycetes streptozotocin-D＋cyclophosphamide＋vincristine （EMA-CO） chemo- therapy due to drug resistance. Three patients＂ with GTN took EMA-CO chemotherapy. Two patients with placental site trophoblastic tumor （PSTT） required surgeries, one took hysterectomy, another got mass and adnexectomy. Apart from 1 case who gave up treatment and was dead, all the other women went into remission from their diseases. Conclusion The diagnosis of trophoblastic disease rely on a comprehensive analysis. A reasonable choice of TCS or intervention can be effective and safe in treating GTD. Most patients with GTN could get complete remission by selecting the appropriate chemotherapy and surgery.