The impact of the distance traveled between residence and gestational trophoblastic neoplasia reference center and clinical outcomes in Brazilian women.

OBJECTIVE: To relate the distance traveled from the patient's residence to the gestational trophoblastic neoplasia (GTN) reference center (RC) and the occurrence of unfavorable clinical outcomes, as well as to estimate the possible association between this distance and the risk of metastatic disease at presentation, the need for multiagent chemotherapy to achieve remission and loss to follow-up before remission. STUDY DESIGN: Retrospective historical cohort study of patients with GTN followed at 8 Brazilian GTN-RC, from January 1st, 2000 - December 31st, 2017. RESULTS: Evaluating 1055 cases of GTN, and using a receiver operating characteristic curve, we found a distance of 56 km (km) from the residence to the GTN-RC (sensitivity = 0.57, specificity = 0.61) best predicted the occurrence of at least one of the following outcomes: occurrence of metastatic disease, need for multiagent chemotherapy to achieve remission, or loss to follow-up during chemotherapy. Multivariate logistic regression adjusted by age, ethnicity, marital status and the reference center location showed that when the distance between residence and GTN-RC was ≥56 km, there was an increase in the occurrence of metastatic disease (relative risk - RR:3.27; 95%CI:2.20-4.85), need for multiagent chemotherapy (RR:1.36; 95%CI:1.05-1.76), loss to follow-up during chemotherapy (RR:4.52; 95CI:1.93-10.63), occurrence of chemoresistance (RR:4.61; 95%CI:3.07-6.93), relapse (RR:10.27; 95%CI:3.08-34.28) and death due to GTN (RR:3.62; 95%CI:1.51-8.67). CONCLUSIONS: The distance between the patient's residence and the GTN-RC is a risk factor for unfavorable outcomes, including death from this disease. It is crucial to guarantee these patients get prompt access to the GTN-RC and receive follow-up support.

Emotional and Clinical Aspects Observed in Women with Gestational Trophoblastic Disease: A Multidisciplinary Action / Aspectos emocionais e clínicos observados em mulheres com doença trofoblástica gestacional: Uma ação multidisciplinar

Abstract Objective To evaluate the emotional and clinical aspects observed in women with gestational trophoblastic disease (GTD) followed-up in a reference center (RC) by a multidisciplinary team. Methods Retrospective cohort study of the clinical records of 186 women with GTD and of the emotional aspects (EA) observed in these women by a teamof psychologists and reported by the 389 support groups conducted from 2014 to 2018. Results The women were young (mean age: 31.2 years), 47% had no living child, 60% had planned the pregnancy, and 50% participated in two or more SG. Most women (n=137; 73.6%) reached spontaneous remission ofmolar gestation in a median time of 10 weeks and had a total follow-up time of seven months. In the group of 49 women (26.3%) who progressed to gestational trophoblastic neoplasia (GTN), time to remission after chemotherapy was 18 weeks, and total follow-up time was 36 months. EA included different levels of anxiety and depression,more evident in 9.1% of the women; these symptoms tended to occur more frequently in women older than 40 years (p=0.067), less educated (p=0.054), and whose disease progressed to GTN (p=0.018), as well as in those who had to undergo multi-agent chemotherapy (p=0.028) or hysterectomy (p=0.001) adjuvant to clinical treatment. Conclusion This study found several EA in association with all types of GTD. It also highlights the importance of specialized care only found in a RC, essential to support the recovery of the mental health of these women.

Resumo Objetivo Avaliar aspectos emocionais e clínicos observados em mulheres com doença trofoblástica gestacional (DTG) acompanhadas em um centro de referência (CR), por equipe multiprofissional. Método Estudo de coorte retrospectivo nos prontuários clínicos de 186 mulheres comDTG, e dos aspectos emocionais (AE) observados nessas mulheres pela equipe de psicólogas e registrados nos 389 grupos de apoio (GAs), ocorridos de 2014 a 2018. Resultados As pacientes eram jovens (idade média 31,2 anos), 47% sem filhos vivos, 60% tinham desejado ou planejado esta gravidez e 50% delas participaram de dois ou mais GAs. A maioria (n=137-73,6%) apresentou remissão espontânea da gestação molar com mediana de 10 semanas e um tempo total de seguimento de 7 meses. Quarenta e nove mulheres (26,3%) evoluíram para neoplasia trofoblástica gestacional (NTG); amediana para atingir a remissão após tratamento comquimioterapia foi de 19 semanas e o tempo total de seguimento foi de 36 meses. Os AE incluíram variados graus de ansiedade e depressão, mais evidentes em 9,1% das nossas pacientes; tais AE tenderam a ocorrer mais em mulheres com idade acima de 40 anos (p=0,067), com menor escolaridade (p=0,054), com evolução para NTG (p=0,018), e nas que necessitaram de tratamento quimioterápico com regime de múltiplos agentes (p=0,028), ou de histerectomia complementar ao tratamento clínico (p=0,001). Conclusão Este estudo mostrou presença de vários AE associados em todos os tipos de DTG. Destaca tambéma importância de umatendimento psicológico especializado, somente encontrado nos CR, que é essencial para ajudar na recuperação da saúde mental dessas mulheres.

Emotional and Clinical Aspects Observed in Women with Gestational Trophoblastic Disease: A Multidisciplinary Action.

OBJECTIVE: To evaluate the emotional and clinical aspects observed in women with gestational trophoblastic disease (GTD) followed-up in a reference center (RC) by a multidisciplinary team. METHODS: Retrospective cohort study of the clinical records of 186 women with GTD and of the emotional aspects (EA) observed in these women by a team of psychologists and reported by the 389 support groups conducted from 2014 to 2018. RESULTS: The women were young (mean age: 31.2 years), 47% had no living child, 60% had planned the pregnancy, and 50% participated in two or more SG. Most women (n = 137; 73.6%) reached spontaneous remission of molar gestation in a median time of 10 weeks and had a total follow-up time of seven months. In the group of 49 women (26.3%) who progressed to gestational trophoblastic neoplasia (GTN), time to remission after chemotherapy was 18 weeks, and total follow-up time was 36 months. EA included different levels of anxiety and depression, more evident in 9.1% of the women; these symptoms tended to occur more frequently in women older than 40 years (p = 0.067), less educated (p = 0.054), and whose disease progressed to GTN (p = 0.018), as well as in those who had to undergo multi-agent chemotherapy (p = 0.028) or hysterectomy (p = 0.001) adjuvant to clinical treatment. CONCLUSION: This study found several EA in association with all types of GTD. It also highlights the importance of specialized care only found in a RC, essential to support the recovery of the mental health of these women.

OBJETIVO: Avaliar aspectos emocionais e clínicos observados em mulheres com doença trofoblástica gestacional (DTG) acompanhadas em um centro de referência (CR), por equipe multiprofissional. MéTODO: Estudo de coorte retrospectivo nos prontuários clínicos de 186 mulheres com DTG, e dos aspectos emocionais (AE) observados nessas mulheres pela equipe de psicólogas e registrados nos 389 grupos de apoio (GAs), ocorridos de 2014 a 2018. RESULTADOS: As pacientes eram jovens (idade média 31,2 anos), 47% sem filhos vivos, 60% tinham desejado ou planejado esta gravidez e 50% delas participaram de dois ou mais GAs. A maioria (n = 137­73,6%) apresentou remissão espontânea da gestação molar com mediana de 10 semanas e um tempo total de seguimento de 7 meses. Quarenta e nove mulheres (26,3%) evoluíram para neoplasia trofoblástica gestacional (NTG); a mediana para atingir a remissão após tratamento com quimioterapia foi de 19 semanas e o tempo total de seguimento foi de 36 meses. Os AE incluíram variados graus de ansiedade e depressão, mais evidentes em 9,1% das nossas pacientes; tais AE tenderam a ocorrer mais em mulheres com idade acima de 40 anos (p = 0,067), com menor escolaridade (p = 0,054), com evolução para NTG (p = 0,018), e nas que necessitaram de tratamento quimioterápico com regime de múltiplos agentes (p = 0,028), ou de histerectomia complementar ao tratamento clínico (p = 0,001). CONCLUSãO: Este estudo mostrou presença de vários AE associados em todos os tipos de DTG. Destaca também a importância de um atendimento psicológico especializado, somente encontrado nos CR, que é essencial para ajudar na recuperação da saúde mental dessas mulheres.

Evaluation of High-Dose Vitamin A Treatment in Postmolar Patients with Low and Plateauing Serum Human Chorionic Gonadotropin Levels.

OBJECTIVE: To compare the effect of high-dose vitamin A (HD Vit-A) use during postmolar follow-up of patients with low and plateauing (L&P) serum human chorionic gonadotropin (hCG) levels, from the moment serum hCG plateaued (P-hCG) to the first normal serum hCG value (< 5 IU/L). METHODS: The present retrospective series case study compared two nonconcurrent cohorts of patients. Control group (CG): 34 patients with L&P serum hCG levels who underwent expectant management for 6 months after uterine evacuation, from 1992 to 2010; study group (SG): 32 patients in similar conditions who received 200,000 IU of Vit-A daily, from the identification of a P-hCG level to the first normal hCG value or the diagnosis of progression to gestational trophoblastic neoplasia (GTN), from 2011 to 2017. The present study was approved by the Ethics Committee of the institution where it was conducted. RESULTS: In both groups, the prevalence of persistent L&P serum hCG levels was < 5%. In the SG, hCG levels at plateau were higher (CG = 85.5 versus SG = 195 IU/L; p = 0.028), the rate of postmolar GTN was lower (CG = 29.4% versus SG = 6.3%, p = 0.034) and follow-up was shorter (CG = 14 versus SG = 10 months, p < 0.001). During GTN follow-up, there were no differences in GTN staging or treatment aggressiveness in both groups. High-dose Vit-A use did not have any relevant toxic effect. There were no GTN relapses or deaths. CONCLUSION: The limited use of HD Vit-A seems to have a safe and significant effect on the treatment of postmolar patients with L&P serum hCG levels and may decrease the development of postmolar GTN in this population.

OBJETIVO: Comparar o efeito de alta dose de vitamina A (VitA) no seguimento pós-molar de pacientes com gonadotrofina coriônica humana (hCG) sérica apresentando valores baixos e em platô (L&P). MéTODOS: Estudo retrospectivo de série de casos comparando duas coortes não simultâneas. Grupo controle (CG): 34 pacientes com títulos de hCG sérico L&P submetidos a manejo expectante por 6 meses após o esvaziamento uterino, de 1992 a 2010; Grupo de Estudo (SG): de 2011 a 2017, 32 pacientes em condições semelhantes de hCG receberam Vit-A na dose de 200.000 IU por dia, do momento da identificação do hCG em platô ate o primeiro hCG normal ou diagnóstico de progressão para neoplasia trofoblástica gestacional (NTG). O presente estudo foi aprovado pelo Comitê de Ética da Instituição na qual foi desenvolvido. RESULTADOS: Em ambos os grupos, a prevalência de hCG L&P foi < 5%. No SG, os níveis de hCG em platô foram maiores (CG = 85.5 versus SG = 195 IU/L; p = 0,028), e foram significantemente menores tanto a prevalência de NTG pós-molar (CG = 29.4% versus SG = 6.3%, p = 0,034) como o tempo de seguimento (CG = 14 versus SG = 10 meses, p < 0.001). Na evolução para NTG não houve diferença no estadiamento da International Federation of Gynecology and Obstetrics (FIGO, na sigla em inglês) ou na agressividade do tratamento. Com altas doses de Vit-A não houve qualquer efeito tóxico relevante. Não houve casos de recidiva de NTG ou de óbito. CONCLUSãO: O uso limitado de altas doses de Vit-A parace ser seguro e apresenta efeitos significativos na evolução de pacientes em controle pós-molar com títulos de hCG sérico L&P, e pode diminuir o desenvolvimento de NTG pós-molar nessa população.

Gestational trophoblastic neoplasia lethality among Brazilian women: A retrospective national cohort study.

OBJECTIVE: To investigate GTN lethality among Brazilian women comparing cases of death by GTN with those who survived, thereby identifying factors associated with GTN lethality. METHODS: We retrospectively reviewed medical records of women with GTN treated at ten Brazilian GTN Reference Centers, from January 1960 to December 2017. We evaluated factors associated with death from GTN and used Cox proportional hazards regression models to identify independent variables with significant influence on the risk of death. RESULTS: From 2186 patients with GTN included in this study, 2092 (95.7%) survived and 89 (4%) died due to GTN. When analyzing the relative risk (RR), adjusted for WHO/FIGO score, patients with low risk disease had a significantly higher risk of death if they had choriocarcinoma (RR: 12.40), metastatic disease (RR: 12.57), chemoresistance (RR: 3.18) or initial treatment outside the Reference Center (RR: 12.22). In relation to patients with high-risk GTN, these factors were significantly associated with death due to GTN: the time between the end of antecedent pregnancy and the initiation of chemotherapy (RR: 4.10), metastatic disease (RR: 14.66), especially in brain (RR: 8.73) and liver (RR: 5.76); absence of chemotherapy or initial treatment with single agent chemotherapy (RR: 10.58 and RR: 1.81, respectively), chemoresistance (RR: 3.20) and the initial treatment outside the Reference Center (RR: 28.30). CONCLUSION: The risk of mortality from low and high-risk GTN can be reduced by referral of these patients to a Reference Center or, if not possible, to involve clinicians in a Reference Center with consultation regarding management.

Can carboplatin or etoposide replace actinomycin-d for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia?

OBJECTIVE: To evaluate the impact of periodic shortage of actinomycin-d (Act-d) in the treatment of Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN) after methotrexate and folinic acid rescue (MTX/FA) resistance, treated alternately with carboplatin or etoposide as a second-line regimen. METHODS: Retrospective cohort that included patients with failure of first-line MTX/FA regimen for low-risk GTN treated at Rio de Janeiro Federal University, Universidade Federal de São Paulo and Irmandade da Santa Casa de Misericórdia de Porto Alegre, from January/2010- December/2017. RESULTS: From 356 patients with low-risk GTN treated with MTX/FA, 75 (21.1%) developed resistance, of which 40 (53.3%) received Act-d, 23 (30.7%) carboplatin and 7 (9.3%) etoposide. Although patients treated with single-agent chemotherapy as a second-line regimen had comparable clinical and primary treatment characteristics, those treated with Act-d (80%, p = 0.033) or etoposide (71.4%, p = 0.025) had higher remission rates when compared with carboplatin (47.8%). Only 29% of patients treated with carboplatin received the chemotherapy cycles without delay compared to Act-d (98%, p < 0.001) or etoposide (85%, p = 0.009). Patients treated with carboplatin had significantly more hematological toxicity, notably anemia (30.4%, p = 0.008), lymphopenia (47.7%, p < 0.001) and thrombocytopenia (43.4%, p < 0.001), as well as a higher occurrence of febrile neutropenia (14.4%, p = 0.044) and vomiting (60%, p < 0.001) than those receiving Act-d (5%, none, 2.5%, none, 10%, respectively). CONCLUSION: Carboplatin did not have a satisfactory clinical response rate, likely due to severe hematological toxicity, which postponed chemotherapy. Our results reinforce the preference for Act-d as a second-line agent in patients with low-risk GTN after MTX/FA resistance.

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.

Centralized Coordination of Decentralized Assistance for Patients with Gestational Trophoblastic Disease in Brazil: A Viable Strategy for Developing Countries.

OBJECTIVE: To report on the Brazilian Association of Gestational Trophoblastic Disease's (GTD) formation of a network of regional care at specialized centers for women with GTD. STUDY DESIGN: We developed a questionnaire composed of 15 questions, which was sent by email to the 38 Brazilian GTD Reference Center (BGTDRC) Directors who are members of the Brazilian Association of GTD, in order to characterize the professionals involved in the care of patients with GTD and the type of assistance provided. RESULTS: The Directors of the BGTDRCs are usually specialists in Gynecology and Obstetrics (97%), with a median experience of a decade in treating women with GTD. The BGTDRCs are linked to university hospitals in 75% of centers and provide completely free medical care in 87%. However, 52% of centers do not perform chemotherapy in their reference center, and patients are referred elsewhere for chemotherapy. Despite some difficulties, the rate of patients lost to follow-up before human chorionic gonadotropin remission is 9%, and the GTD mortality rate is 0.9%. CONCLUSION: Due to large regional disparities, the BGTDRCs are not uniformly organized. However, under the coordination of the Brazilian Association of GTD there is now strong communication and collaboration among reference centers, which has significantly advanced both patient care and research into the management of these diseases.

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.

Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among Brazilian women / Tratamento da neoplasia trofoblástica gestacional de baixo-risco, comparando aplicação quinzenal de oito dias de Metotrexato com ácido folínico versus Actinomicina D em bolo, em mulheres brasileiras

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. ...

OBJETIVO: Em mulheres brasileiras com neoplasia trofoblástica gestacional (NTG) de baixo-risco, de acordo com a Federação Internacional de Ginecologia e Obstetrícia (FIGO) 2002, comparar dois regimes de quimioterapia (Qt) por agente único avaliando resposta e efeitos colaterais no tratamento de primeira linha, e a eficácia no tratamento final por agente único de Qt. MÉTODOS: Análise retrospectiva de duas coortes concorrentes com 194 pacientes com NTG de baixo risco: de 1992 a 2012; como primeira linha, 115 pacientes receberam 4 doses intramusculares de metotrexato alternado com 4 doses orais de ácido folínico (MTX/FA) repetidos a cada 14 dias e, desde 1996, 79 pacientes receberam quinzenalmente dose em bolo de actinomicina D (Act-D) por via endovenosa. No momento do diagnóstico da NTG, a opinião da paciente foi levada em consideração para definir o regime de Qt por agente único inicial e, quando havia resistência ou toxicidade a um regime, o outro fármaco era usado preferentemente. Este estudo foi aprovado pelo Comitê de Ética da Irmandade da Santa Casa de Misericórdia de Porto Alegre. RESULTADOS: Ambos os grupos eram clinicamente semelhantes (p>0,05). Nos tratamentos de primeira linha, a frequência de resposta completa foi semelhante (75,7% com MTX/FA e 67,1% com Act-D em bolo); não houve diferença entre os grupos quanto ao número de séries de Qt - mediana 3 (intervalo: 1-10) com MTX/FA e 2 (intervalo: 1-6) com Act-D em bolo - e ao tempo para remissão - mediana 9 semanas (intervalo: 2-16) com MTX/FA e 10 semanas (intervalo: 2-16) com Act-D em bolo. Em ambos os grupos, foi elevada a frequência de efeitos colaterais no tratamento de primeira linha, mas com intensidade baixa; estomatite foi mais frequente com MTX/FA (p<0.01) e náuseas e vômitos com Act-D (p<0.01). A resposta final à Qt por agente único foi alta nos dois grupos (94,8% com MTX/FA e 83,5% com Act-D em bolo; p<0,01) e 13% maior no grupo inicialmente tratado com ...

Epidemiological report on the treatment of patients with gestational trophoblastic disease in 10 Brazilian referral centers: results after 12 years since International FIGO 2000 Consensus.

OBJECTIVE: To evaluate treatment of Brazilian patients with gestational trophoblastic disease (GTD). STUDY DESIGN: A retrospective cohort study with analysis of medical reports performed in 10 Brazilian referral centers from January 2000 to December 2011. RESULTS: Of 5,250 patients 3 died (0.06%) at the time of uterine evacuation. Spontaneous remission of GTD (group G1) was observed in 4,103 cases, and 1,144 (21.8%) progressed to gestational trophoblastic neoplasia (GTN) (G2). In G1 2,716 (66.2%) had complete hydatidiform mole (HM) and 1,210, partial HM (29.5%); 3,772 patients (92.7%) recovered as noted in December 2012. In G2, of 1,118 patients treated, initial histopathological results of previous gestation were complete HM (77.5% [n = 886]), partial HM (8.8% [n = 100]), and choriocarcinoma (8.0% [n = 92]); 930 (81.3%) were low-risk, 200 (17.5%) were high-risk GTN, and 14 had placental site trophoblastic tumor (PSTT) (1.2%); cure was achieved in 1,078 cases (96.4%), but 26 patients (2.3%) died (4 low-risk [0.4%], 19 high-risk [9.5%], and 3 PSTT [21.4%]). CONCLUSION: The highest death rates were due to high-risk GTN and PSTT. Patients with molar pregnancy should be referred to a referral center for an early diagnosis and prompt treatment of GTN in order to reduce the morbidity and mortality found in advanced stages.

Role of hysterectomy in the management of patients with gestational trophoblastic neoplasia: importance of receiving treatment in reference centers.

OBJECTIVE: To evaluate hysterectomy prevalence, indications and impact on clinical outcomes in a reference center in southern Brazil. STUDY DESIGN: Institutional Ethical Committee approval was granted for this study. In a cohort study spanning 21 years, all patients who underwent hysterectomy for gestational trophoblastic neoplasia (GTN) were included, and technical differences between hysterectomy performed in the reference center and those performed elsewhere were evaluated as well. RESULTS: Of 1,023 patients with gestational trophoblastic disease, 57 (5.6%) underwent hysterectomy (95% CI, 4.3-7.1). Hysterectomy incidence in 230 GTN patients was 17.7% (95%CI, 15.1-23.3). Indications for 41 hysterectomies in the reference center were as follows: primary treatment in 14 (34.1%) cases and secondary treatment in 27 (65.9%); of these, the main indications were GTN recurrence (7 [25.9%] cases), hemorrhage (6 [22.2%]), resistance to single-agent chemotherapy in patients who refused more aggressive treatment (6 [22.2%]), and tumor mass reduction (5 [18.5%]). Twelve (92.3%) of the 13 hysterectomies with bilateral oophorectomy were performed elsewhere (p < 0.001). Thirty-five (85.4%) patients had no complications, and median hospitalization time was short (3 +/- 4 days). None of the 4 deaths were associated with hysterectomy. In the reference center, when associated with hysterectomy, GTN cure rates reached 93% after 63 +/- 87 months of follow-up. CONCLUSION: When treatment is in a reference center, hysterectomy frequency and morbidity may be low, and indications due to hemorrhage are significantly lower. Furthermore, at a reference center there is significantly greater ovarian preservation at the time of hysterectomy, and significantly more patients who undergo hysterectomy have low-risk GTN.

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.

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. METHODS: In a 13-year prospective cohort study, between March 1987 and March 2000, 124 adolescents with gestational trophoblastic disease were followed up and/or treated by a multidisciplinary team. Adolescents underwent strict clinical and laboratory control after mole evacuation to guarantee adhesion to follow up, early diagnosis, and prompt treatment of persistent disease. The Student-Fischer t-test and the chi-square test were used for the statistic analysis of the results. RESULTS: Adolescents represented 21.3% of the 583 patients with gestational trophoblastic disease: 102 (82.3%) had uncomplicated hydatidiform moles, and 22 (17.7%) underwent chemotherapy for persistent gestational trophoblastic disease or a gestational trophoblastic tumor. Complications were diagnosed earlier (p < 0.001) in patients managed and treated at the referral center. Of the adolescents with complications, 81.8% were low risk, 54.5% were at the International Federation of Gynecology and Obstetrics stage I, and 90.9% were treated with chemotherapy only. Time to remission and follow up were shorter for uncomplicated hydatidiform moles (9.8 +/- 3.4 weeks and 8.8 +/- 1.8 months, respectively) than for persistent disease (16.2 +/- 5.8 weeks and 45 +/- 24.5 months, respectively). Adhesion to follow up was similar in the two groups (84.2% and 91.8%). To this date, 50% of the adolescents have had one or more gestations, and 82% of these pregnancies were normal. CONCLUSIONS: Adolescents comprise approximately 20% of all gestational trophoblastic disease patients and have high adhesion to follow up. The disease did not affect their reproductive capacity, and chances of a normal subsequent gestation were high.