Low-risk Gestational Trophoblastic Neoplasia Research Articles

Doppler-based predictive model for methotrexate resistance in low-risk gestational trophoblastic neoplasia with myometrial invasion: prospective study of 147 patients.

ABSTRACTObjectivesThis prospective clinical study aimed to evaluate the vascularization characteristics of low‐risk gestational trophoblastic neoplasia (GTN) using Doppler imaging and to develop a predictive model for resistance to methotrexate (MTX).MethodsPatients with low‐risk GTN receiving primary MTX treatment were enrolled from the Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China, from September 2012 to August 2018. The primary endpoint was to develop and internally validate a predictive model for resistance to MTX therapy in these patients. In the training set, clinical features and Doppler hemodynamic parameters before MTX therapy were analyzed using logistic regression to identify independent predictors of MTX resistance, which were integrated into the model. The predictive performance of the model was evaluated by leave‐one‐out cross‐validation in the training dataset and internal validation in an independent‐sample test dataset.ResultsThe entire imaging protocol was completed by 147 eligible patients, of which 110 comprised the training set and 37 the test set. In the training set, cases with myometrial invasion (81.8%; 90/110) showed vascular‐enriched areas in the myometrium and high velocity and low impedance ratios of the uterine artery (UtA) compared to cases without myometrial invasion (18.2%; 20/110). On multivariate logistic regression analysis, time‐averaged mean velocity in UtA (UtA‐TAmean) and the International Federation of Gynecology and Obstetrics (FIGO) score were identified as independent predictors (P = 0.009 and P = 0.043, respectively) of MTX resistance. The Doppler‐based predictive model, developed based on the 90 cases with myometrial invasion, was y = −2.95332 + 0.41696 × FIGO score + 0.03551 × UtA‐TAmean. The model showed an area under the curve of 0.757 (95% CI, 0.653–0.862) and the optimal cut‐off value was 0.50622, which had 45.2% sensitivity and 96.6% specificity. The model stratified patients with low‐risk GTN into low (< 10%), intermediate (10–90%) and high (> 90%) probability of MTX resistance, based on the threshold values of −1.59544 and 0.10046. The model had an accuracy of 74.4% (95% CI, 64.5–82.3%) in the cross‐validation and 72.7% (95% CI, 55.8–84.9%) in the internal validation.ConclusionsThe Doppler‐based predictive model, combining a non‐invasive marker of tumor vascularity with the FIGO scoring system, can differentiate cases with low from those with high probability of developing MTX resistance and therefore has the potential to guide treatment options in patients with low‐risk GTN and myometrial invasion. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

ABCB1 and SLCO1B1gene polymorphisms predict methotrexate-resistant for low-risk gestational trophoblastic neoplasia.

Aim: The aim of this study was to explore the effects of ABCB1 and SLCO1B1 gene polymorphisms and the methotrexate (MTX)treatment response in patients with low-risk gestational trophoblastic neoplasia (GTN). Materials & methods: Low-risk GTN patients who received MTX as a first-line single agent were enrolled. DNA was extracted from peripheral blood samples from 18 patients and assessed for ABCB1 C3435T and SLCO1B1 T521C. Results:ABCB1 C3435T and SLCO1B1 T521C polymorphisms were not associated with the MTX response or toxicity in Thai patients Conclusion: The selected ABCB1 and SLCO1B1 polymorphism do not predict the risk of MTX resistance in low-risk GTN.

Treatment of low-risk gestational trophoblastic neoplasia.

Low-risk gestational trophoblastic neoplasia (GTN), defined as FIGO/WHO score 0-6, is highly curable with an overall survival rate, which is approximately 100%. For most low-risk GTN patients, first-line single-agent chemotherapy with either methotrexate or actinomycin-D is recommended with overall complete human chorionic gonadotrophin (hCG) response rates of 60%-90% in mostly retrospective, non-randomised studies. The few randomised trials that exist are not appropriately powered or designed to define the optimal first-line treatment. Approximately 25%-30% of low-risk patients will develop resistance to initial single-agent chemotherapy with an increase in the FIGO score, a diagnosis of choriocarcinoma, higher pre-treatment hCG and the presence of metastatic disease being associated with an increase in the risk of resistance. The optimal treatment of patients scoring WHO 5 and 6 remains poorly defined given that approximately 70%-80% of these patients develop resistance to first-line single-agent chemotherapy, and there is an urgent need to refine the FIGO/WHO scoring system so that these patients can be identified for more intensive therapy from the outset. Despite this, almost all low-risk patients who experience treatment failure with first-line monotherapy will be cured with either sequential single-agent chemotherapy or multiagent chemotherapy with or without surgery. Given the associated increased short and longer-term toxicities associated with multi-agent chemotherapy, promising strategies to reduce the exposure of women to combination chemotherapy in low-risk disease have been investigated, including the use of carboplatin and immune check-point inhibitors. Further evaluation is required to define optimal patient selection, particularly with the use of immunotherapeutic agents given their significant increased costs and lack of longer-term safety data. Although there is a clear need to revise the FIGO/WHO (2000) scoring system, consistent international use of this is recommended to facilitate the comparison of data along with future focus in the development of international collaborative translational and clinical research, including randomised controlled trials.

Placenta accreta after remission of low-risk gestational trophoblastic neoplasia: A case report

Placenta accreta after remission of low-risk gestational trophoblastic neoplasia: A case report

The diagnostics and treatment of low-risk gestational trophoblastic neoplasia (GTN): 42-year experience

The diagnostics and treatment of low-risk gestational trophoblastic neoplasia (GTN): 42-year experience

Individualization in the treatment of resistant forms of gestational trophoblastic neoplasia

Objective: to summarize the experience of treatment patients with resistant forms of gestational trophoblastic neoplasia (GTN). Materials and methods: results of treatment of 15 patients with resistant forms of GTN treated in the N.N. Petrov Research Institute of Oncology through the period 01.01.10-12.11.19 were analyzed. Results: In three out of the 15 patients the tumor was initially characterized as the low-risk (3/15, 20%), the remaining 12 women were from the high-risk group (12/15, 80%). Four out of 12 high-risk patients were ultra-high risk (&gt; 12 points according to the FIGO classification). In low-risk patients with resistant GTN forms EMA-CO therapy proved to be effective as the second line chemotherapy. In eight high-risk patients the combined treatment included the surgical component (hysterectomy in 3 cases, thoracotomy with metastasectomy in 3 cases, hysterotomy with excision of the tumor in 1 case, excision of the tumor from the abdominal wall - in 1 case). In three cases of ultra-high risk GTN, the EMA-EP chemotherapy proved effectiveness, in one of them - without a combination with surgical treatment. Combined treatment was performed in two other cases: in one case with chemotherapy was followed by thoracotomy, metastasectomy, in another - by a gamma knife radiotherapy of brain metastasis. Conclusion: even in cases of low-risk GTN careful monitoring of patients is required, despite adequate treatment among resistant forms. After the failure of methotrexate monochemotherapy with low-risk GTN patients can be successfully treated with EMA-CO chemotherapy. Only rare histological forms (epithelioid trophoblastic tumor, placental site trophoblastic tumor) are not sensitive to drug therapy and require surgical treatment. In cases of ultrahigh-risk GTN with resistance to 1st-line chemotherapy an EMA-EP regimen is effective with or without surgical intervention. Residual “tumor nodes” after completion of treatment and normalization of the HCG level do not always require surgical removal, their dynamic observation is possible, because according to the results of observations, when they were nevertheless excised, no histologically viable tumor tissue was found.

The Curative Effect of a Second Curettage in Low-Risk Gestational Trophoblastic Neoplasia

Background: Gestational trophoblastic neoplasia (GTN), despite its widespread metastases, is a very common cancer in women that is curable. Although the GTN cases show a good response to chemotherapy, in an effort to reduce toxic drug exposure, the second curettage has been suggested for some patients. In the current study, we have aimed to compare the benefits of the second curettage in comparison with single-agent chemotherapy for low-risk GTN patients.&#x0D; &#x0D; Methods: This retrospective observational study was carried out on GTN patients admitted to the gynecology department of Imam Khomeini Hospital in Ahvaz. The demographic profile of all participants was extracted. Patients&amp;#39; hospitalization records were also extracted from the files. Patients with an endometrial thickness above 10 mm were treated with re-curettage. The &amp;beta; hCG clearance time was estimated by the Kaplan Meier plot. &#x0D; &#x0D; Results: In the present study, 148 patients with low-risk GTN stage 1 were studied. The time required for &amp;beta;-hCG clearance in patients undergoing re-curettage was significantly lower than the chemotherapy receiving group (7 months vs. 10 months, p &amp;lt;0.0001). More than 50% of patients treated by re- curettage without needing chemotherapy. Moreover, the other 50% cases needed chemotherapy the number of courses was significantly lower than those received single-agent chemotherapy alone (p &amp;lt;0.0001). The baseline &amp;beta;-hCG levels were significantly lower in those who did not need chemotherapy (p = 0.012). &amp;beta;-hCG resolution occurred more rapidly in patients undergoing re-curettage alone, while, those who received only chemotherapy had a longer duration for &amp;beta;-hCG clearance.&#x0D; &#x0D; Conclusion: In general, the findings of this study showed that re-curettage could be used effectively in the treatment of GTN following molar pregnancy. This treatment reduces or eliminates the need for chemotherapy. Our findings also showed that the initial level of &amp;beta;-hCG could be considered as a predictive factor in response to curettage.

Efficacy of Oral Vitamin A in Reducing β-hCG Levels in Low-Risk Gestational Trophoblastic Neoplasia Patients.

Objective:Low-risk gestational trophoblastic neoplasia (GTN) is generally treated with single agent chemotherapy and methotrexate (MTX) as a first-line therapy. Vitamin A helps to increase trophoblast cell regression, as well as to decrease β-hCG levels. Vitamin A also increases the effectiveness of MTX by inducing more malignant cell death than MTX alone. Therefore, the aim of the current study was to analyze the changes in β-hCG levels in low-risk GTN patients following vitamin A administration. Methods:This study was a randomized clinical trial, which examined initial serum vitamin A and β-hCG levels in GTN patients before and after three cycles of MTX therapy. Patients were given vitamin A supplementation of 6,000 IU (1.8 mg RAEs) per day, and the changes in serum β-hCG were observed after three cycles. Patients were grouped by β-hCG levels (decreased or stagnant). Results:A total of 32 low-risks GTN patients were divided into the intervention group (16 patients who received vitamin A supplementation) and the control group (16 patients who did not receive vitamin A supplementation). In the intervention group, the average initial β-hCG level was 170,949.3 ± 354,452.1 mIU/mL, and the average β-hCG post-cycle level was 1,611.9 ± 3,652.5 mIU/mL. In the control group, the average initial β-hCG level was 178,834.1 ± 2913844.6 mIU/mL, and the average β-hCG post-cycle level was 25,388.5 ± 58,437.7 mIU/mL. Conclusion:In patients with low-risk GTN who underwent MTX chemotherapy, the levels of β-hCG and the incidence of chemo resistance in the intervention group were lower than those in the control group. Older age may also influence the incidence of chemo resistance in GTN patients. Oral administration of 6,000 IU vitamin A could help to reduce β-hCG levels in low-risk GTN patients who receive MTX chemotherapy.

Outcomes for relapsed versus resistant low risk gestational trophoblastic neoplasia following single-agent chemotherapy

ObjectiveTo compare outcomes for relapsed versus resistant low risk gestational trophoblastic neoplasia (GTN) following single-agent chemotherapy. MethodsThis was a single center retrospective study of low risk GTN. Cases failing to achieve a normal hCG with first-line therapy were defined as chemotherapy resistance. Cases achieving hCG remission, but recurring, were defined as relapse. Primary endpoints were remission rate with second-line therapy and time to remission. Univariate and multivariate analyses were performed to define prognostic factors. ResultsAmong 877 low risk GTN patients there were 124 (14.8%) chemotherapy resistant and 22 (2.6%) relapse cases. Complete remission rates with second-line therapy were similar between relapse (77.3%) and resistant (76.6%) cases (p = 0.95), but resistance was associated with a longer time to reach complete remission with second-line therapy (median 8.3 vs 4.9 weeks; p = 0.024). In multivariate analysis, the significant prognostic factors for second-line therapy remission and time to second-line therapy remission were use of multi-agent chemotherapy (OR of 9.45; 95%CI, 2.13–41.97; p = 0.003) and primary chemo-resistance (HR of 0.27; 95%CI, 0.12–0.59; p = 0.001), respectively. With additional therapies, sustained remission rates rose to 90% (18/20) for relapse and 99.2% (120/121) for chemo-resistance (p = 0.053). ConclusionsAlthough second-line therapy for resistant or relapsed low risk GTN is able to achieve complete remission in most cases, time to complete remission for relapsed disease was shorter than for resistant disease. Further studies on the biologic differences between resistant and relapsed disease may clarify the optimal treatment for these clinical situations.

Response to first-line single agent chemotherapy impacts subsequent response to second-line therapy in low-risk gestational trophoblastic neoplasia

Response to first-line single agent chemotherapy impacts subsequent response to second-line therapy in low-risk gestational trophoblastic neoplasia

Uterine artery pulsatility index and serum BMP-9 predict resistance to methotrexate therapy in gestational trophoblastic neoplasia: A cohort study

Methotrexate is the most common first-line chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Uterine artery pulsatility index (UAPI) is an ultrasound marker for tumor vascularity that has been associated with an increased risk of methotrexate resistance. The combination of circulating angiogenic factor levels with UAPI data may improve the capacity of this model to predict chemoresistance. This was a single-center cohort study of women newly diagnosed between January 2008 and June 2012 with low-risk GTN during postmolar surveillance and treated with single-agent methotrexate at Charing Cross Hospital, a UK national center for treatment of gestational trophoblastic disease. Two hundred seventeen women underwent an ultrasound for UAPI measurement prior to initiation of chemotherapy. To examine serologic markers of methotrexate resistance among this cohort, we performed a case-control study using archived serum from 76 patients who could be matched based on prognostic risk score. Serum samples were examined by immunoassay to measure 8 different angiogenic factors (VEGF-A, FGF-basic, PLGF-1, PDGF-BB, EGF, ANGPT2, BMP-9, and ENG). Receiver-operator characteristic area under the curve (AUC) values were calculated for the ability of each analyte to correctly classify patients as methotrexate sensitive (MTX-S) or resistant (MTX-R). Total human chorionic gonadotropin levels were similar between the MTX-S and MTX-R groups. UAPI values were significantly higher in MTX-S (median 1.30 [interquartile range {IQR} = 0.80-1.90]) compared to MTX-R patients (median 0.875 [IQR = 0.60-1.30]; P < 0.0001) with AUC 0.68 (95% confidence interval 0.61-0.76; P < 0.0001). In univariate analysis, only BMP-9 concentrations were significantly different between groups, lower among MTX-S (median of 225 ng/L, IQR = 170-287) compared to MTX-R patients (median 280 ng/L [IQR = 200-339]; P= 0.03). Combining UAPI with BMP-9 concentration improved prediction for chemoresistance with AUC 0.77 (95% confidence interval 0.66-0.88; P < 0.0001). Circulating levels of BMP-9 are elevated in newly diagnosed women with low-risk GTN destined to fail primary methotrexate therapy. A combined test using serum BMP-9 plus UAPI might improve prediction of MTX-R in low-risk GTN.

Validation of an online tool for early prediction of the failure-risk in gestational trophoblastic neoplasia patients treated with methotrexate.

In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics.org/hCG . The objective was to confirm the validity of the website estimations with respect to NM. The consistencies of modeled hCGres estimated by NM and by the website were assessed in a dataset of 60 fictive patients with simulated hCG profiles, as well as in an independent database of 531 actual patients. Moreover, the hCGres predictive values regarding MTX failure-risk were assessed. The values of hCGres obtained with both methods were highly consistent in the fictive patient and in the actual patient datasets: median relative prediction errors (RPE) were - 0.059 and 9.9 × 10-7, respectively. The ROC AUCs for predictions of MTX failure-risk were 0.90 (95% CI 0.87,0.93) with both NM and the website. The gradual association between increasing hCGres and the 2-year MTX failure-free survival was confirmed. There is a high consistency of hCGres estimates obtained with the two methods. The website is meant to help clinicians in the interpretation of hCG decline curves of MTX-treated GTN patients. hCGres is now validated for more than 1690 patients in four independent datasets, and its recognition as an early predictor of MTX resistance for treatment adjustment and for the future studies should be considered.

Factors Predicting Severe Myelosuppression and Its Influence on Fertility in Patients with Low-Risk Gestational Trophoblastic Neoplasia Receiving Single-Agent Methotrexate Chemotherapy.

PurposeTo investigate the potential factors to predict severe myelosuppression among low-risk gestational trophoblastic neoplasia (GTN) patients with single-agent methotrexate (MTX) chemotherapy. To analyze reproductive outcomes of patients with or without severe myelosuppression after achieving complete remission (CR).Patients and MethodsThe retrospective study included 319 low-risk GTN patients registered from January 2008 to December 2018 in our hospital. Patients were divided into two groups according to myelosuppression grading. Their clinical data and reproductive outcomes were compared and analyzed.ResultsA higher proportion of patients in group A received second-line chemotherapy than group B (P<0.001). The number of total chemotherapy courses was more in group A than group B (P=0.001), while the number of MTX chemotherapy courses was more in group B than group A (P=0.001). When the joint predictor of pretreatment albumin (ALB) was not more than 44.5 g/L, pretreatment serum creatinine (Scr) was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses was not less than four, there was a moderate predictive value. There was no significant difference of reproductive outcomes between the two groups after achieving CR.ConclusionAlthough some patients developed severe myelosuppression, MTX was still the effective first-line treatment for low-risk GTN patients. Patient’s pretreatment ALB was not more than 44.5 g/L, pretreatment Scr was not less than 75.6 μmol/L, and the number of MTX chemotherapy courses not less than four could be used as combined predictors to recognize the risk of severe myelosuppression. Severe myelosuppression had no significant adverse influence on fertility after achieving CR.

Cost-effectiveness of second curettage for treatment of low-risk non-metastatic gestational trophoblastic neoplasia

ObjectiveLow-risk non-metastatic gestational trophoblastic neoplasia (GTN) has been treated with single agent chemotherapy, but second curettage is emerging as an alternative strategy with reported cure rates of 40%. We sought to estimate the cost-effectiveness of second curettage as the first line treatment of low-risk GTN. MethodsA decision-analytic model was created using TreeAge software to compare costs and outcomes for women with WHO staged low-risk GTN undergoing treatment with 5-day methotrexate (MTX), biweekly pulsed actinomycin-D, or second curettage. Probabilities were derived from the literature. Outcomes of interest included side effects from chemotherapy, need for additional agents, hemorrhage, uterine perforation, and cure rates. Utilities were applied to discounted life expectancy at a rate of 3% to generate quality adjusted life years (QALYs). Sensitivity analyses were then performed in order to assess the robustness of our assumptions. ResultsOf the three treatment arms, MTX was associated with the lowest cost and had similar QALYs to the other studied modalities. Second curettage was associated with 49 additional cures when applied to a theoretic cohort of 1000 women, as well as an additional 83 hemorrhages and 17 uterine perforations. Sensitivity analysis on the cure rate of second curettage revealed that second curettage was not cost-effective over MTX unless its probability of cure was 98%. ConclusionOur study found 5-day MTX was the cost-effective strategy for treatment of women with low-risk, non-metastatic GTN when compared to second curettage and actinomycin-D. In a carefully selected patient population, second curettage may be an additional treatment strategy.

Practical clinical guidelines of the EOTTD for treatment and referral of gestational trophoblastic disease

Background and aimGestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterised by abnormal proliferation of trophoblastic tissue. Since GTD and its malignant sequel gestational trophoblastic neoplasia (GTN) are rare diseases, little evidence is available from randomised controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centres within countries. One of the goals of the ‘European Organisation for Treatment of Trophoblastic Diseases’ (EOTTD) is to harmonise treatment in Europe. To provide a basis for European standardisation of definitions, treatment and follow-up protocols in GTD, we composed a set of guidelines for minimal requirements and optimal management of GTD. MethodsMembers from each EOTTD country attended multiple workshops during annual EOTTD meetings. Clinical guidelines were formulated by consensus and evidence where available. The following guidelines were discussed: diagnostics of GTD and GTN, treatment of low-risk GTN, high-risk GTN, ultra-high-risk GTN, placental site and epithelioid trophoblastic tumours and follow-up. ResultsBetween 40 and 65 EOTTD members from 17 European countries and 7 non-European countries attended the clinical workshops held on 6 occasions. Flow diagrams for patient management were composed to display minimum and best practice for most treatment situations. New agreed definitions of recurrence and chemotherapy resistance were formulated. ConclusionsDespite the many differences between and within the participating countries, an important step in uniform treatment of GTD and GTN within Europe was made by the Clinical Working Party of the EOTTD. This is an example on how guidelines and harmonisation can be achieved within international networks.

Risk factors for second-line dactinomycin failure after methotrexate treatment for low-risk gestational trophoblastic neoplasia: a retrospective study.

ObjectiveTo find risk factors for second‐line dactinomycin failure in patients with low‐risk gestational trophoblastic neoplasia (GTN).DesignRetrospective multicentre study.SettingTertiary reference centre.PopulationPatients with low‐risk GTN, treated with dactinomycin after methotrexate (MTX) failure.MethodsRetrospective analysis of 45 patients with low‐risk GTN treated with dactinomycin after MTX failure, registered between 2006 and 2018.Main outcome measuresTreatment outcome and risk factors for second‐line dactinomycin failure.ResultsThirty patients (66.7%) were cured and 15 patients (33.3%) required third‐line therapy. Type of antecedent pregnancy and hCG levels pre‐dactinomycin were risk factors for failure in univariate analysis (odds ratio [OR] 19.30, 95% CI 2.04–182.60, P = 0.01 and OR 2.77, 95% CI 1.18–6.50, P = 0.02, respectively). Level of hCG pre‐dactinomycin remained a significant risk factor in multivariate analysis (OR 2.93, 95% CI 1.02–8.40, P = 0.045). Complete remission (CR) was achieved in 83.3% of patients with pre‐dactinomycin hCG levels <10 ng/ml, in 75% with hCG levels between 10 and 20 ng/ml, in 66.7% with hCG levels between 20 and 30 ng/ml, and in 50% with hCG levels between 30 and 40 ng/ml. No patients with hCG levels >40 ng/ml achieved CR. Patients with dactinomycin failure were treated surgically and/or with multi‐chemotherapy; all except one achieved CR.ConclusionsTreatment with dactinomycin after MTX failure in patients with low‐risk GTN resulted in CR in 66.7%. Chance of curative treatment with dactinomycin is strongly related to the hCG level.Tweetable abstractChance of curative treatment with dactinomycin after MTX failure in GTN patients is strongly related to the level of hCG pre‐dactinomycin.

Second Curettage for Treatment of Low-Risk Gestational Trophoblastic Neoplasia: A Cost-Effectiveness Analysis

OBJECTIVES: Low risk non-metastatic gestational trophoblastic neoplasia (GTN) is typically treated with methotrexate (MTX) or actinomycin D with second curettage emerging as an alternative treatment modality; we sought to estimate the cost-effectiveness of second curettage for the treatment of low-risk GTN.

Effectiveness and toxicity of second-line actinomycin D in patients with methotrexate-resistant postmolar low-risk gestational trophoblastic neoplasia

ObjectivesThe purpose of this study was to evaluate both the outcomes and toxicity of second-line actinomycin D (ActD) chemotherapy in methotrexate (MTX) - resistant low-risk postmolar gestational trophoblastic neoplasia (GTN) with 5-day ActD versus pulsed ActD. MethodsThis retrospective cohort study included patients with MTX-resistant low-risk postmolar GTN from 1974 to 2016. Second-line chemotherapy consisted of 5-day ActD (10–12 μg/kg per day for 5 days every 14 days) or biweekly ActD (1.25 mg/m2 every 2 weeks). Data on patient characteristics, disease presentation, treatment outcome, and toxicity were collected. ResultsSixty-eight MTX-resistant patients receiving ActD as second-line chemotherapy were identified (5-day ActD, 53 patients; pulsed ActD, 15 patients). No significant differences were observed in patient/disease characteristics and sustained remission (overall rate 72%) between second-line ActD regimens. Time to hCG remission was significantly faster (median 21 vs 47 days, p = .04) and required fewer treatment cycles (median 1 vs 2, p < .001) with 5-day ActD. Thrombocytopenia was only observed with 5-day ActD (64.6 vs 0%, p < .001). The frequency (60.4 vs 16.7%, p = .009) and severity (grade 3: 37.9 vs 0%, p = .045) of oral mucositis was significantly higher with 5-day ActD. Grade 2 alopecia was significantly more frequent (70.6 vs 16.7%, p = .02) with 5-day ActD. ConclusionsWhile 5-day ActD and pulsed ActD achieve comparable remission rates, due to its reduced toxicity, ease of administration, and patient convenience, pulsed ActD should be the treatment of choice for MTX-resistant postmolar low-risk GTN.

Post-Molar Stage I Low-Risk Gestational Trophoblastic Neoplasia: Transvaginal Ultrasound Findings and Their Correlation with Chemotherapy Response

Background: Early diagnosis of gestational trophoblastic neoplasia and its complications are pivotal for prompt and efficacious treatment. Transvaginal pelvic ultrasound could detect myometrial invasion and endometrial thickening following dilation and evacuation of hydatiform mole and also in the assessment of response to chemotherapy. Objectives: In this study we aimed to investigate transvaginal ultrasound findings of stage I low-risk gestational trophoblastic neoplasia (GTN) and whether there is an association between ultrasound findings and chemotherapy response. Patients and Methods: This study included 31 consecutive patients with postmolar stage I low-risk GTN. We recorded International Federation of Gynecology and Obstetrics (FIGO) score, and transvaginal ultrasound findings including color and pulsed Doppler interrogation at the time of beta human chorionic gonadotropin (β-hCG) rise. The number of Act-D cycles that each patient needed to achieve complete remission was also recorded. Results: Of the 31 patients with post-evacuation trans-vaginal ultrasound evaluation, 2 (6.5%) patients had no detectable finding, 4 (12.9%) had lesions limited to the endometrium, 12 (38.7%) had lesions with 50% invasion into myometrium, 4 (12.9%) had lesions that reached uterine serosal surface and 2 (6.5%) had arteriovenous malformation (AVM)-like myometrial lesions. The number of Act-D cycles patients needed to achieve remission was 6 cycles in patients with no finding, lesion limited to endometrium and less than 50% myometrial invasion and was 8 cycles in patients with > 50% invasion ± involvement of serosal surface. One patient in first group and two in second group need multi-agent chemotherapy. But these differences were not significant (P = 0.172). Conclusion: There was a non-significant increase in treatment duration and need of multiagent chemotherapy with more extensive ultrasound findings among patients with stage I low risk GTN.

Comparison of treatment for low-risk GTN with standard 8-day MTX/FA regimen versus modified MTX/FA regimen without chemotherapy on the weekend

ObjectiveTo compare the outcomes of patients with low-risk gestational trophoblastic neoplasia (GTN) treated with standard 8-day methotrexate/folinic acid (MTX/FA) versus modified regimen. MethodsRetrospective cohort study of patients with low-risk GTN followed at Rio de Janeiro Federal University, from January/1990-December/2017 with standard 8-day MTX/FA or modified regimen (MTX administered on the 8th day rather than 7th) to avoid treatment on the weekend. ResultsFrom 937 patients with low-risk GTN, 538 were treated with standard MTX/FA and 98 patients received modified regimen. Both groups were comparable in age (p = .749), antecedent pregnancy (p = .221), time to initiate chemotherapy (p = .926), hCG pretreatment level (p = .112) and WHO/FIGO prognostic risk score (p = .723). Patients treated with modified MTX/FA had twice of cases of metastatic lung disease compared with the standard regimen (22.5% vs 10.6%; p = .002). The rate of remission (p = .999), number of cycles to remission in the first-line (p = .966), chemoresistance (p = .500), time to switch to second-line therapy (p = .176), need for multiagent chemotherapy (p = .084), relapse (p = .122) or death (p = .475) was the same for both MTX/FA regimen. However, although patients receiving modified MTX/FA required a higher total number of remission cycles (6 vs 5 cycles; p = .004) and longer time to remission (19 vs 16 weeks; p < .001) when compared with the standard regimen, these variables showed no significant differences after multivariate logistic regression adjusted for lung metastasis. ConclusionThe modified 8-day MTX/FA regimen didn't compromise oncologic outcomes for women with low-risk GTN. This regimen appears to be an acceptable alternative to standard 8-day MTX/FA when treatment on weekend isn't an option.