Postmolar Low-risk Gestational Trophoblastic Neoplasia Research Articles

Removal of an Intrauterine Polypoid Lesion Resolved Chemotherapy-resistant Gestational Trophoblastic Neoplasia: A Case Report.

Single-agent chemotherapy typically has curative outcomes in patients with low-risk gestational trophoblastic neoplasia (GTN). Although surgical intervention is a potential alternative, its efficacy in these patients remains unclear. This report describes a case in which surgical excision of a uterine polypoid lesion resolved chemotherapy-resistant low-risk GTN. A 43-year-old patient received pulse actinomycin D treatment for post-molar low-risk GTN without extrauterine metastasis. However, the patient showed resistance to the chemotherapy regimen. There was no initial evidence of protrusion of GTN into the uterine cavity; however, a polypoid lesion grew into the uterine cavity during therapy. This growth was successfully excised via a transvaginal approach using forceps with minimal blood loss. There was a postoperative decrease in human chorionic gonadotropin levels, which ultimately reached the predetermined threshold without the need for changing the therapeutic protocol. Surgical resection should be considered a viable therapeutic strategy for uterine polypoid growth in chemotherapy-resistant low-risk GTN.

Clinical Presentation, Treatment Outcomes, and Resistance-related Factors in South American Women with Low-risk Postmolar Gestational Trophoblastic Neoplasia.

There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers. Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed. A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p = 0.019). 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

Comparing and Evaluating Five-Day Chemotherapy Agents Actinomycin D and Methotrexate in Low-Risk Post-Molar Gestational Trophoblastic Neoplasia: A Retrospective Analysis

Background: Low-risk post-molar gestational trophoblastic neoplasia is sensitive to chemotherapy, but there is no consensus regarding the best treatment regimen for low-risk post-molar gestational trophoblastic neoplasia. This study aimed to assess the efficacy, toxicity and cost-effectiveness of actinomycin D and methotrexate in low-risk post-molar gestational trophoblastic neoplasia. Methods: 210 patients with Federation International of Gynecology and Obstetrics(FIGO)-defined low-risk post-molar gestational trophoblastic neoplasia received either a first-line five-day methotrexate intramuscular injection biweekly (MTX group) or a five-day actinomycin D infusion biweekly (Act-D group). Demographic information, disease manifestations, initial treatment plan, treatment-related adverse events, cost-effectiveness and the effects of drugs on ovarian function and quality of sexual life were recorded and retrospectively compared. Results: The complete response rates were 72.73% for the Act-D group and 75.41% for the MTX group, with no statistically significant difference. Compared to the Act-D group, the MTX group had a significantly shorter total number of chemotherapy cycles and average hospitalization expenses (p < 0.05). There was no severe adverse effect reported for either group, but the Act-D group was associated with significantly higher leukopenia (grade 1 or 2) (59.38% vs. 17.39%). The two regimens had reversible effects on ovarian function and quality of sexual life, but there was no significant difference between the two groups. Conclusions: There were similar complete response rates and no severe adverse effect reported for either group, but the total treatment course was shorter and the average hospitalization expenses were lower in the MTX group. Five-day MTX intramuscular biweekly injections remain the treatment of choice for patients with low-risk post-molar gestational trophoblastic neoplasia. Chemotherapy will have a certain impact on ovarian function. Gynecological oncologists should pay attention to the protection of ovarian function in patients with gestational trophoblastic neoplasia during perioperative chemotherapy.

Consolidation chemotherapy in postmolar low-risk gestational trophoblastic neoplasia: a systematic review protocol

IntroductionCurrent evidence remains insufficient to strongly demonstrate the benefits of consolidation chemotherapy to all women with low-risk gestational trophoblastic neoplasia (GTN). This protocol outlines a systematic review to investigate whether...

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.

State-of-the-Art Workup and Initial Management of Newly Diagnosed Molar Pregnancy and Postmolar Gestational Trophoblastic Neoplasia.

Gestational trophoblastic disease refers to a series of interrelated tumors arising from the placenta, including benign molar pregnancies as well as the malignant conditions termed gestational trophoblastic neoplasia (GTN). GTN most commonly follows a molar pregnancy but may develop after any gestation. The wide availability of first trimester ultrasound and serum human chorionic gonadotropin (hCG) measurement has changed the presentation of molar pregnancy in recent decades from a second trimester to a first trimester disease, such that most patients have few symptoms at diagnosis. With identification of molar pregnancy at earlier gestations, accurate diagnosis increasingly relies on expert histopathology coupled with ancillary molecular and genetic techniques. However, earlier diagnosis has not changed the risk of postmolar GTN. Although most molar pregnancies are treated with dilation and curettage, hysterectomy may be appropriate in select cases when future fertility is not desired. After treatment of molar pregnancy, close surveillance with serial hCG monitoring is essential to diagnose GTN and identify the need for chemotherapy. Physicians following hCG levels should understand the performance characteristics of the test, including common causes of false-positive and false-negative results. After a diagnosis of postmolar GTN is made, selection of single-agent or multiagent chemotherapy depends on accurate assignment of the clinical stage and risk stratification by the International Federation of Gynecology and Obstetrics (FIGO) prognostic scoring system. Surgical treatment of postmolar low-risk GTN, including both second uterine curettage and hysterectomy, may decrease subsequent need for or duration of chemotherapy. Cure rates for postmolar low-risk GTN approach 100%, and subsequent pregnancy outcomes for patients reflect those of the general population.

Effectiveness and toxicity of first-line methotrexate chemotherapy in low-risk postmolar gestational trophoblastic neoplasia: The New England Trophoblastic Disease Center experience

ObjectivesTo assess the outcomes and toxicity of first-line methotrexate (MTX) chemotherapy in low-risk postmolar gestational trophoblastic neoplasia (GTN) patients receiving 8-day methotrexate or one-day methotrexate infusion regimens. MethodsThis retrospective cohort study was conducted at the New England Trophoblastic Disease Center (NETDC), between 1974 and 2014, and included 325 patients with FIGO-defined low-risk postmolar GTN receiving first-line 8-day MTX/folinic acid (FA) or one-day MTX infusion and FA. Demographics, disease presentation, initial treatment plan, treatment outcome, and treatment-related adverse events were assessed. ResultsSustained remission (84% vs 62%, p<0.001) and need to switch to second-line therapy due to treatment-related adverse events (5.3% vs 0%, p=0.001) were higher for 8-day MTX/FA compared to one-day MTX infusion. MTX resistance, however, was more frequent with one-day MTX (34.5%) than with 8-day MTX/FA (7.3%, p<0.001). Relapse rates were similar with both regimens (3.0%). Compared to one-day MTX infusion, 8-day MTX/FA was associated with significantly higher gastrointestinal disorders (48% vs 24%), abnormal laboratory findings (48% vs 28%), eye disorders (37% vs 19%) and general disorders (22% vs 5%) (p<0.001). Only infection frequency did not differ between 8-day MTX/FA and one-day MTX infusion (20% vs 12%, p=0.083). ConclusionsThis is one of the largest studies to comprehensively catalogue toxicities associated with 8-day MTX/FA and one-day MTX infusion. Although treatment-related adverse events were more frequent with 8-day MTX/FA, these were all self-limited and resolved with no long-term sequelae. Given this and its higher effectiveness, 8-day MTX/FA remains the treatment of choice at NETDC for patients with low-risk postmolar GTN.

Comparison of 5-day MTX and 5-day ETP treatment results and early predictors of drug resistance to 5-day MTX in patients with post-molar low-risk gestational trophoblastic neoplasia

ObjectiveTo determine the primary remission rates and predictors of drug resistance in patients with post-molar low-risk gestational trophoblastic neoplasia (GTN) who were treated with a 5-day intramuscular methotrexate (5-day IM MTX) or a 5-day drip infusion etoposide (5-day DIV ETP) regimen. MethodsBetween 1980 and 2014, 166 consecutive patients with low-risk post-molar GTN were initially treated with a 5-day IM MTX or a 5-day DIV ETP regimen. The primary remission rates, changes in chemotherapy due to drug resistance or toxicity, and relapse rates were compared. Furthermore, we analyzed the factors that influenced the development of resistance to MTX. ResultsPrimary remission rates were significantly higher among the ETP-treated patients than among the MTX-treated patients. Among the 42 patients who required a change in chemotherapy, 23 patients (22.6%) and 4 patients (6.3%) were diagnosed as being resistant to MTX and EPT, respectively. Maternal age and the presence of metastasis did not significantly influence the development of MTX resistance, although higher FIGO scores and pre-treatment human chorionic gonadotropin (hCG) levels of >5×104mIU/mL were significantly more common among patients who developed MTX resistance. Moreover, a <30% decrease in hCG after the first cycles of MTX chemotherapy was significantly associated with the development of MTX resistance. ConclusionsAll patients with low-risk GTN eventually achieved complete remission, although several patients developed drug resistance to the first-line chemotherapy. A <30% decrease in hCG during the first chemotherapy cycle may be an early indicator of drug resistance after commencing a 5-day MTX regimen.

Response to chemotherapy in overweight/obese patients with low-risk gestational trophoblastic neoplasia.

Despite rising global obesity rates, the impact of obesity on gestational trophoblastic neoplasia (GTN) remains uninvestigated. This study aimed at investigating whether overweight/obesity relates to response to chemotherapy in low-risk GTN patients. This nonconcurrent cohort study included 300 patients with International Federation of Gynecology and Obstetrics-defined postmolar low-risk GTN treated with a single-agent chemotherapy—methotrexate or actinomycin-D (actD)—between 1973 and 2012 at the New England Trophoblastic Disease Center. Chemotherapy dosing was based on actual body weight regardless of obesity status, except for 5-day courses or pulse regimens of actD. Patients were classified as overweight/obese (body mass index [BMI] ≥25 kg/m²) or non-overweight/obese (BMI <25 kg/m²). Information on patient characteristics and response to chemotherapy (need for second-line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles, need for combination chemotherapy, and time to human chorionic gonadotropin remission) was obtained. Of 300 low-risk GTN patients, 81 (27%) were overweight/obese. Overweight/obese patients were older than the non-overweight/obese patients (median age: 30 vs 28 years, P = 0.004). First-line therapy using actD was more frequent in overweight/obese patients (6.2% vs 1.4%, P = 0.036). Resistance and toxicity were similar between groups. No significant difference in the number of chemotherapy cycles needed for remission or time required to achieve remission was found between groups. No association between overweight/obesity and low-risk GTN outcomes was found. Current chemotherapy dosing using BMI seems to be appropriate for overweight/obese patients with low-risk GTN.

Relationship between race and clinical characteristics, extent of disease, and response to chemotherapy in patients with low-risk gestational trophoblastic neoplasia

ObjectiveTo evaluate the potential effects of race on clinical characteristics, extent of disease, and response to chemotherapy in women with postmolar low-risk gestational trophoblastic neoplasia (GTN). MethodsThis non-concurrent cohort study was undertaken including patients with FIGO-defined postmolar low-risk GTN treated with comparable doses and schedules of chemotherapy at the New England Trophoblastic Disease Center (NETDC) between 1973 and 2012. Racial groups investigated included whites, African American and Asians. Information on patient characteristics and response to chemotherapy (need for second line chemotherapy, reason for changing to an alternative chemotherapy, number of cycles/regimens, need for combination chemotherapy, and time to hCG remission) was obtained. ResultsOf 316 women, 274 (86.7%) were white, 19 (6%) African American, and 23 (7.3%) Asian. African Americans were significantly younger than white and Asian women (p=0.008). Disease presentation, and extent of disease, including antecedent molar histology, median time to persistence, median hCG level at persistence, rate of D&C at persistence, presence of metastatic disease, and FIGO stage and risk score were similar among races. Need for second line chemotherapy (p=0.023), and median number of regimens (p=0.035) were greater in Asian women than in other races. ConclusionsLow-risk GTN was more aggressive in Asian women, who were significantly more likely to need second line chemotherapy and a higher number of chemotherapy regimens to achieve complete remission than women of African American and Asian descent. Further studies involving racial differences related to clinical, biological and environmental characteristics are needed.

Prognostic factors associated with time to hCG remission in patients with low-risk postmolar gestational trophoblastic neoplasia

ObjectiveThe purpose of this study was to identify the clinical factors associated with time to hCG remission among women with low-risk postmolar GTN. MethodsThis study included a non-concurrent cohort of 328 patients diagnosed with low-risk postmolar GTN according to FIGO 2002 criteria. Associations of time to hCG remission with history of prior mole, molar histology, time to persistence, use of D&C at persistence, presence of metastatic disease, FIGO score, hCG values at persistence, type of first line therapy and use of multiagent chemotherapy were investigated with both univariate and multivariate analyses. ResultsOverall median time to remission was 46days. Ten percent of the patients required multi-agent chemotherapy to achieve hCG remission. Multivariate analysis incorporating the variables significant on univariate analysis confirmed that complete molar histology (HR 1.45), metastatic disease (HR 1.66), use of multi-agent therapy (HR 2.00) and FIGO score (HR 1.82) were associated with longer time to remission. There was a linear relationship between FIGO score and time to hCG remission. Each 1-point increment in FIGO score was associated with an average 17-day increase in hCG remission time (95% CI: 12.5–21.6). ConclusionsComplete mole histology prior to GTN, presence of metastatic disease, use of multi-agent therapy and higher FIGO score were independent factors associated with longer time to hCG remission in low-risk GTN. Identifying the prognostic factors associated with time to remission and effective counseling may help improve treatment planning and reduce anxiety in patients and their families.

The management and outcome of women with post-hydatidiform mole ‘low-risk’ gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l−1

Background:Gestational trophoblastic neoplasia (GTN) after a hydatidiform mole is either treated with single- or multi-agent chemotherapy determined by a multifactorial scoring system. Women with human chorionic gonadotrophin (hCG) levels >100 000 IU l−1 can remain within the low-risk/single-agent category and usually choose one drug therapy. Here we compare the success and duration of single- vs multi-agent chemotherapy in this patient group.Methods:Between 1980 and 2008, 65 women had a pre-treatment hCG >100 000 IU l−1 and were low risk. The initial hCG level, treatment regimens, changes and duration and overall survival were recorded.Results:Of 37 patients starting low-risk/single-agent treatment, 11 (29.7%) were treated successfully, whereas 26 (70.3%) required additional multi-agent chemotherapy to achieve complete remission (CR). Combination chemotherapy was initially commenced in 28 women, and 2 (7%) required additional drugs for CR. The overall duration of therapy for those commencing and completing single- or multi-agent chemotherapy was 130 and 123 days (P=0.78), respectively. The median-treatment duration for patients commencing single-agent but changing to multi-agent chemotherapy was 13 days more than those receiving high-risk treatment alone (136 vs 123 days; P=0.07). All 3 patients with an initial hCG >400 000 IU l−1 and treated with single-agent therapy developed drug resistance. Overall survival for all patients was 100%.Conclusion:Low-risk post-molar GTN patients with a pre-treatment hCG >100 000 and <400 000 IU l−1 can be offered low-risk single-agent therapy, as this will cure 30%, is relatively non-toxic and only prolongs treatment by 2 weeks if a change to combination agents is required. Patients whose hCG is >400 000 IU l−1 should receive multi-agent chemotherapy from the outset.

Evaluating Methotrexate Treatment in Patients With Low-Risk Postmolar Gestational Trophoblastic Neoplasia

The response of low-risk persistent gestational trophoblastic neoplasia (GTN) to methotrexate (MTX) monotherapy is close to 100%. With use of various MTX regimens, 48%–92% of patients go into remission. There is limited data on potential clinical risk factors indicating the need for additional courses of MTX or alternative chemotherapy following an initial course of MTX. This retrospective observational study identified possible clinical factors predictive of the requirement for additional MTX or alternative chemotherapy to obtain a remission in patients with postmolar low-risk GTN who had received MTX initially. Data was analyzed for 1801 women diagnosed with molar pregnancies between 1973 and 2003. Of the 150 women in the final study population, 110 had been diagnosed as complete mole and 40 as partial mole, and all had received MTX as initial therapy for GTN. All women had low-risk disease according to the combined International Federation of Obstetrics and Gynecology (FIGO) stage and the World Health Organization prognostic scores. Remission was defined as achievement and maintenance of undetectable serum beta human chorionic gonadotropin (β-hCG) levels for 1 year. All 150 patients ultimately achieved remission. Of the 70 women (47%) requiring additional courses of chemotherapy including MTX, 45 (64%) required alternative chemotherapy. Multivariate analysis showed that independent prognostic factors predicting increased risk of requiring additional MTX or alternative chemotherapy were complete mole histology, presence of metastasis, single day MTX infusion and any increase in β-hCG levels 1 week after MTX therapy. Dilatation and curettage within 1 week after the diagnosis of persistence was not an independent risk factor for additional or alternative chemotherapy. For GTN following complete mole, β-hCG levels ≥2000 mIU/ml at 1 week post-MTX were associated with an 89% risk of requiring additional MTX chemotherapy and a 64% risk of alternative chemotherapy to achieve remission. These data identify several independent risk factors that predispose women with low-risk GTN to require additional MTX cycles and alternative chemotherapy after initial MTX.

Weekly intramuscular methotrexate in the treatment of low-risk gestational trophoblastic neoplasia

The objective of this study was to determine the efficacy of weekly intramuscular (IM) methotrexate without dose escalation as first-line chemotherapy for low-risk gestational trophoblastic neoplasia (LRGTN). Thirty-three women with post-molar LRGTN in the division of gynecology oncology at the Shiraz University of Medical Sciences were treated with weekly IM methotrexate at 30 mg/m(2) without dose escalation. The serum level of beta-hCG was detected every week. After the first negative beta-hCG level, one more cycle was administered as consolidation. Complete response (CR) was defined as the attainment of serum beta-hCG level of 5 IU/L or less measured on three consecutive weeks. Twenty-one of 33 women (63.6%) achieved CR with weekly IM injection of 30 mg/m(2) methotrexate. Ten of 12 patients with weekly IM methotrexate failure had a CR after one to three courses of dactinomycin administered at 1.25 mg/m(2) intravenously every 2 weeks. Two patients needed multiple-agent chemotherapy for remission. Weekly methotrexate without dose escalation may be an appropriate option for primary chemotherapy of patients with LRGTN.

Evaluating methotrexate treatment in patients with low-risk postmolar gestational trophoblastic neoplasia

Objective To identify clinical factors associated with requiring more than a single course of Methotrexate (MTX) to achieve remission among women with low-risk postmolar gestational trophoblastic neoplasia (GTN). Methods We studied 150 women with persistent GTN after diagnosis of complete ( n = 110) or partial mole ( n = 40) to identify possible predictors of requiring additional treatment after a single treatment of methotrexate (MTX). All women had low-risk disease using FIGO and WHO scoring systems. Results Seventy women (47%) required additional courses of chemotherapy, of whom 45 (64%) received chemotherapy other than MTX. Multivariate analysis revealed that complete mole histology, presence of metastasis, single day MTX infusion and any increase in serum beta human chorionic gonadotropin (β-hCG) level 1 week after MTX therapy were independent predictors of requiring additional MTX or alternative chemotherapy. Dilatation and curettage (D+C) within 1 week after the diagnosis of persistence did not affect future chemotherapy requirements ( p > 0.64). Following complete mole, β-hCG levels > 2000 mIU/mL at 1 week post MTX were associated with a 89% risk of additional cycles chemotherapy including MTX and a 65% risk of alternative chemotherapy. Conclusions Metastatic disease, MTX infusion protocol and complete mole histology were independently associated with the need for additional chemotherapy after an initial course of MTX for women with low risk GTN. D+C at persistence did not alter the chemotherapy requirement. Elevated β-hCG level at 1 week after the initial course of MTX was also an independent factor predicting the need for additional courses of MTX or alternative chemotherapy.