Elza Maria Hartmann Uberti

Prevention of postmolar gestational trophoblastic neoplasia using prophylactic single bolus dose of actinomycin D in high-risk hydatidiform mole: A simple, effective, secure and low-cost approach without adverse effects on compliance to general follow-up or subsequent treatment

OBJECTIVE To evaluate the efficacy of actinomycin D (Act-D) as prophylactic chemotherapy (P-Chem) to reduce postmolar gestational trophoblastic neoplasia (GTN) in patients with high-risk hydatidiform mole (Hr-HM). METHODS From 1987 to 2006, 265 Hr-HM were selected in a retrospective analysis of a nonrandomized clinical trial of 1090 patients with gestational trophoblastic disease (GTD) followed up at a Trophoblastic Disease Center (TDC) in southern Brazil. From 1996 to 2006, 163 received a single bolus dose of Act-D at time of uterine evacuation (Hr-HM-chem group); 102 with the same risk factors did not get P-Chem (Hr-HM-control group). Variables were: number of patients with postmolar GTN who required chemotherapy during follow-up, postmolar GTN morbidity, compliance and operational costs. RESULTS Postmolar GTN was diagnosed in 18.4% of the Hr-HM-chem patients (95% CI: 12.7-24.7) and in 34.3% of the Hr-HM-control patients (95% CI: 25.1-43.5). Postmolar GTN was 46% lower in P-Chem (RR=0.54; 95% CI: 0.35-0.82; NNT=7). P-Chem adverse effects were occasional and minor. When disease progressed to postmolar GTN, severity was the same, but costs were lower for the Hr-HM-chem group. Compliance with follow-up was high and similar in both groups. CONCLUSIONS Follow-up of patients with Hr-HM showed that a single bolus dose of prophylactic Act-D reduced the incidence of postmolar GTN. Compliance and postmolar GTN morbidity were not affected. Treatment costs and emotional complications were reduced. This prophylactic approach can be adopted before uterine evacuation in any TDC that treats Hr-HM patients that present with undelivered moles.

Gestational trophoblastic disease: one more risk in adolescent pregnancy

Background.  An evaluation of the performance of a Referral Center in the diagnosis, treatment and follow up of adolescents with gestational trophoblastic disease.

Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy

OBJECTIVE To evaluate whether prophylactic chemotherapy (P-chem) with one bolus dose of actinomycin D (Act-D) during the uterine evacuation of patients with high-risk hydatidiform mole (Hr-HM) affects reproductive outcomes in subsequent pregnancies. METHODS From 1987 to 2006, 1090 patients with gestational trophoblastic disease (GTD) were evaluated at a Trophoblastic Disease Center in southern Brazil; 265 with Hr-HM were selected and retrospectively analyzed. From 1996 to 2006, 163 received one bolus dose of Act-D at the time of uterine evacuation (Hr-HM-chem group); 102 with the same risk factors did not get P-chem (Hr-HM-control group). In March 2009, the number of pregnancies, progression of first pregnancy, and association of low age and low parity with subsequent pregnancy were evaluated. RESULTS The percentage of patients that became pregnant was similar in both groups (Hr-HM-control: 59.5%; Hr-HM-chem group: 45.7%; p=0.069) and independent of HM progression. Percentages of no pregnancies because of age (> or =40 years) or hysterectomy were also similar. Type of subsequent pregnancy was not statistically different between groups, and the rate of live births associated with pregnancies for which US showed a live fetus was high. Frequency of repeat GTD was unexpectedly high in both groups (4.2% and 6.3%; p=1.00). CONCLUSIONS P-chem did not affect reproductive outcomes for patients with Hr-HM. Patients allowed to become pregnant again in both groups had high rates of live births associated with normal pregnancies. Chances of a subsequent pregnancy were higher in the low age and low parity subgroups.

Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women

PURPOSE To compare two single-agent chemotherapy (ChT) regimens evaluating, in first-line treatment, response and side effects and, in final single-agent treatment, the outcomes, among Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN), according to International Federation of Gynecology and Obstetrics (FIGO) 2002. METHODS Retrospective analysis of two concurrent cohorts with 194 low-risk GTN patients: from 1992 to 2012, as first-line treatment, 115 patients received 4 intramuscular doses of methotrexate alternated with 4 oral doses of folinic acid (MTX/FA) repetead every 14 days and, since 1996, 79 patients received an endovenous bolus-dose of actinomycin D (Act-D), biweekly. At GTN diagnosis, patient opinion was taken into consideration when defining the initial single-agent ChT regimen, and when there was resistance or toxicity to one regimen, the other drug was used preferentially. This study was approved by the Irmandade da Santa Casa de Misericórdia de Porto Alegre Ethical Committee. RESULTS Both groups were clinically similar (p>0.05). In first-line treatments, frequency of complete response was similar (75.7% with MTX/FA and 67.1% with bolus Act-D); the number of ChT courses -median 3 (range: 1-10) with MTX/FA and 2 (range: 1-6) with bolus Act-D - and the time to remission -median 9 weeks (range: 2-16) with MTX/FA and 10 weeks (range: 2-16) with bolus Act-D) - were not different between the groups. In both groups, first-line side effects frequency were high but intensity was low; stomatitis was higher with MTX/FA (p<0.01) and nausea and vomit with Act-D (p<0.01). Final single-agent ChT responses were high in both groups (94.8% with MTX/FA and 83.5% with bolus Act-D; p<0.01) and 13% higher in the group initially treated with MTX/FA. Rates of hysterectomy and of GTN recurrence were low and similar. No patient died due to GTN. CONCLUSION The two regimens had similar first-line ChT response. Final single-agent response rates were high and similar in both groups but the final single-agent remission rate was higher in the MTX/FA group.

Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma

OBJECTIVE To evaluate expectant management versus immediate chemotherapy following pathological diagnosis of gestational choriocarcinoma (GCC) in patients with nonmetastatic disease. METHODS Multicenter retrospective cohort that included patients with histological diagnosis of GCC with nonmetastatic disease followed at one of thirteen Brazilian referral centers for gestational trophoblastic disease from January 2000 to December 2016. RESULTS Among 3191 patients with gestational trophoblastic neoplasia, 199 patients with nonmetastatic GCC were identified. Chemotherapy was initiated immediately in 152 (76.4%) patients per FIGO 2000 guideline, while 47 (23.6%) were managed expectantly. Both groups presented with similar characteristics and outcomes. All patients (n=12) who had normal human chorionic gonadotropin (hCG) in the first 2-3weeks of expectant management achieved complete sustained remission with no chemotherapy. Only 44.7% (21 patients) of patients who were expectantly managed needed to receive chemotherapy due to plateauing or rising hCG level in the first 2-3weeks of follow up. The outcome of patients receiving chemotherapy after initial expectant management was similar to those who received chemotherapy immediately after the diagnosis in terms of need for multi-agent chemotherapy or number of cycles of chemotherapy. There was no case of relapse or death in either group. Logistic regression analysis showed that age≥40years and hCG≥92,428IU/L at GCC diagnosis were risk factors for needing chemotherapy after initial expectant management of nonmetastatic GCC. CONCLUSION In order to avoid exposing patients unnecessarily to chemotherapy, close surveillance of women with pathological diagnosis of nonmetastatic GCC seems to be a safe practice, particularly for those who have a normal hCG at the time of diagnosis. If confirmed by other studies, the FIGO guidelines may need to be revised.

Is chemotherapy necessary for patients with molar pregnancy and human chorionic gonadotropin serum levels raised but falling at 6months after uterine evacuation

OBJECTIVE To compare the outcomes of Brazilian patients with molar pregnancy who continue human chorionic gonadotropin (hCG) surveillance with those treated with chemotherapy when hCG was still positive, but falling at 6months after uterine evacuation. METHODS Retrospective chart review of 12,526 patients with hydatidiform mole treated at one of nine Brazilian reference centers from January 1990 to May 2016. RESULTS At 6months from uterine evacuation, 96 (0.8%) patients had hCG levels raised but falling. In 15/96 (15.6%) patients, chemotherapy was initiated immediately per FIGO 2000 criteria, while 81/96 (84.4%) patients were managed expectantly. Among the latter, 65/81 (80.2%) achieved spontaneous remission and 16 (19.8%) developed postmolar gestational trophoblastic neoplasia (GTN). Patients who received chemotherapy following expectant management required more time for remission (11 versus 8months; p=0.001), had a greater interval between uterine evacuation and initiating chemotherapy (8 versus 6months; p<0.001), and presented with a median WHO/FIGO risk score higher than women treated according to FIGO 2000 criteria (4 versus 2, p=0.04), but there were no significant differences in the need for multiagent treatment regimens (1/15 versus 3/16 patients, p=0.60). None of the women relapsed, and no deaths occurred in either group. CONCLUSION In order to avoid unnecessary exposure of women to chemotherapy, we no longer follow the FIGO 2000 recommendation to treat all patients with molar pregnancy and hCG raised but falling at 6months after evacuation. Instead, we pursue close hormonal and radiological surveillance as the best strategy for these patients.