Abstract Objective To assess the potential relationship of clinical status upon admission and distance traveled from geographical health district in women with gestational trophoblastic disease (GTD). Methods This is a cross-sectional study including women with GTD from the 17 health districts from the São Paulo state (I–XVII), Brazil, referred to the Botucatu Trophoblastic Disease Center (specialized center, district VI), between 1990 and 2018. At admission, hydatidiform mole was assessed according to the risk score system of Berkowitz et al. Gestational trophoblastic neoplasia was evaluated using the International Federation of Gynecology and Obstetrics / World Health Organization (FIGO/WHO) staging/risk score. Data on demographics, clinical status and distance traveled were collected. Multiple regression analyses were performed. Results This study included 366 women (335 hydatidiform mole, 31 gestational trophoblastic neoplasia). The clinical status at admission and distance traveled significantly differed between the specialized center district and other districts. Patients referred from health districts IX (β = 2.38 [0.87–3.88], p = 0.002) and XVI (β = 0.78 [0.02–1.55], p = 0.045) had higher hydatidiform mole scores than those from the specialized center district. Gestational trophoblastic neoplasia patients from district XVI showed a 3.32 increase in FIGO risk scores compared with those from the specialized center area (β = 3.32, 95% CI = 0.78–5.87, p = 0.010). Distance traveled by patients from districts IX (200km) and XVI (203.5km) was significantly longer than that traveled by patients from the specialized center district (76km). Conclusion Patients from health districts outside the specialized center area had higher risk scores for both hydatidiform mole and gestational trophoblastic neoplasia at admission. Long distances (>80 km) seemed to adversely influence gestational trophoblastic disease clinical status at admission, indicating barriers to accessing specialized centers.

Resumo Objetivo Avaliar a possível relação entre estado clínico na apresentação e distância percorrida a partir do distrito de saúde em mulheres com doença trofoblástica gestacional. Métodos Estudo transversal incluindo mulheres com doença trofoblástica gestacional dos 17 distritos de saúde do estado de São Paulo (I–XVII), Brasil, encaminhadas ao Centro de Doenças Trofoblásticas de Botucatu (distrito VI), entre 1990 e 2018. Na admissão, avaliaram-se mola hidatiforme pelo sistema de pontuação de risco de Berkowitz et al. e neoplasia trofoblástica gestacional pelo escore de risco/estadiamento Federação Internacional de Ginecologia e Obstetrícia / Organização Mundial da Saúde (FIGO/OMS). Coletaram-se dados demográficos, clínicos e distância percorrida e análises de regressão múltipla foram realizadas. Resultados Este estudo incluiu 366 mulheres (335 mola hidatiforme, 31 neoplasia trofoblástica gestacional). O estado clínico na apresentação e distância percorrida diferiram significativamente entre o centro especializado e demais distritos. Nas pacientes encaminhadas pelos distritos IX (β = 2,38 [0,87–3,88], p = 0,002) e XVI (β = 0,78 [0,02–1,55], p = 0,045), os escores de mola hidatiforme foram maiores que no centro especializado. As pacientes com neoplasia trofoblástica gestacional do distrito XVI apresentaram escores FIGO 3,32 vezes maior que no centro especializado (β = 3,32, 95% CI = 0,78–5,87, p = 0,010). A distância percorrida pelas pacientes dos distritos IX (200km) e XVI (203,5km) foi significativamente maior do que a percorrida pelas pacientes do centro especializado (76km). Conclusão Pacientes de distritos de saúde fora da cobertura do centro especializado apresentaram escores de risco mais alto para mola hidatiforme e para neoplasia trofoblástica gestacional na admissão. Longas distâncias (>80 km) pareceram influenciar negativamente o estado clínico da doença trofoblástica gestacional na apresentação, indicando barreiras no acesso a centros especializados.

Abstract Objective To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment. Methods Three independent researchers searched five electronic databases (EMBASE, LILACS, Medline, CENTRAL and Web of Science), for relevant articles up to February/2023 (PROSPERO CRD42023401453). The quality assessment was performed using the Newcastle Ottawa scale for case series and case reports. The primary outcome of this study was the occurrence of complete remission. The presentation of the case reports was approved by the Institutional Review Board. Results Of the 4 cases presented, the first was a low-risk GTN with methotrexate resistance unsuccessfully treated with avelumab, which achieved remission with sequential multiagent chemotherapy. The remaining 3 cases were high-risk multiagent-resistant GTN that were successfully treated with pembrolizumab, among which there were two subsequent gestations, one of them with normal pregnancy and healthy conceptus. Regarding the systematic review, 12 studies were included, only one of them on avelumab, showing a 46.7% complete remission rate. The remaining 11 studies were on pembrolizumab, showing an 86.7% complete remission rate, regardless of tumor histology. Both immunotherapies showed good tolerability, with two healthy pregnancies being recorded: one after avelumb and another after pembrolizumab. Conclusion Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment.

Resumo Objetivo Existem poucos estudos multinacionais sobre os resultados do tratamento da neoplasia trofoblástica gestacional (NTG) na América do Sul. O objetivo deste estudo foi avaliar a apresentação clínica, os resultados do tratamento e os fatores associados a casos de quimiorresistência em NTG pós-molar de baixo risco tratados com quimioterapia de agente único de primeira linha em três centros sul-americanos. Métodos Estudo multicêntrico de coorte histórica incluindo mulheres com NTG pós-molar de baixo risco com estadiamento International Federation of Gynecology and Obstetrics (FIGO) em centros de atendimento na Argentina, Brasil e Colômbia entre 1990 e 2014. Foram obtidos dados sobre as características do paciente, apresentação da doença e resposta ao tratamento. A regressão logística foi usada para avaliar a relação entre fatores clínicos e resistência ao tratamento de primeira linha com agente único. Foi realizada uma análise multivariada dos fatores clínicos significativos na análise univariada. Resultados Cento e sessenta e três mulheres com NTG de baixo risco foram incluídas na análise. A taxa global de resposta completa à quimioterapia de primeira linha foi de 80% (130/163). As taxas de resposta completa ao metotrexato ou actinomicina-D como tratamento de primeira linha e actinomicina-D como tratamento de segunda linha após falha do metotrexato foram 79% (125/157), 83% (⅚) e 70% (23/33), respectivamente. A mudança para o tratamento de segunda linha por quimiorresistência ocorreu em 20,2% dos casos (33/163). A análise multivariada demonstrou que pacientes com pontuação de risco FIGO de 5 a 6 foram 4,2 vezes mais propensos a desenvolver resistência ao tratamento com agente único de primeira linha (p= 0,019). Conclusão 1) Na apresentação, a maioria das mulheres demonstrou características clínicas favoráveis a um bom resultado, 2) a taxa geral de remissão completa sustentada após o tratamento de primeira linha com agente único foi comparável à de países desenvolvidos, 3) um escore de risco FIGO de 5 ou 6 está associado ao desenvolvimento de resistência à quimioterapia de agente único de primeira linha.

Abstract Objective 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. Methods 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. Results 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). Conclusion 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.

OBJECTIVES: This study aimed to determine the effects of age, race/ethnicity, body mass index, and contraception on human chorionic gonadotropin (hCG) regression following the evacuation of a molar pregnancy. METHODS: This was a retrospective cohort study of 277 patients with molar pregnancies between January 1, 1994 and December 31, 2015. The rate of hCG regression was estimated using mixed-effects linear regression models on daily log-transformed serum hCG levels after evacuation. RESULTS: There were no differences in hCG half-lives among age (p=0.13) or race/ethnicity (p=0.16) groups. Women with obesity and hormonal contraceptive use demonstrated faster hCG regression than their counterparts (3.2 versus. 3.7 days, p=0.02 and 3.4 versus. 4.0 days, p=0.002, respectively). CONCLUSION: Age and race/ethnicity were not associated with hCG regression rates. Hormonal contraceptive use and obesity were associated with shorter hCG half-lives, but with unlikely clinical significance. It is important to understand whether the clinical characteristics of patients may influence the hCG regression curve, as it has been proposed as a way to predict the risk of gestational trophoblastic neoplasia.

OBJECTIVES: This study aimed to evaluate the potential relationship between oxidative stress, dietary intake, and serum levels of antioxidants in patients with a complete hydatidiform mole (CHM) compared with controls. METHODS: This was an observational cross-sectional study conducted in Rio de Janeiro, Brazil. A total of 140 women were enrolled in this study and divided into four groups: 43 patients with CHM, 33 women who had had an abortion, 32 healthy pregnant women, and 32 healthy non-pregnant women. All participants underwent blood sampling, assessment using a semiquantitative food frequency questionnaire, and anthropometric measurement. Blood samples were collected after overnight fasting (10-12 h). Vitamin levels (A, C, and E) were determined by ultra-performance liquid chromatography, and gamma-glutamyl transferase levels were assessed using an automated quantitative analysis system (Dimension®, Siemens). RESULTS: Although all groups showed sufficient serum vitamin A and E levels, the participants had inadequate dietary intake of these vitamins. Conversely, all groups had an insufficient serum level of vitamin C, despite adequate intake. The gamma-glutamyl transferase values did not differ significantly among the groups. However, elevated serum levels of this enzyme were observed in several patients. CONCLUSIONS: All groups exhibited high levels of oxidative stress, as evaluated by gamma-glutamyl transferase levels, and had inadequate intake of antioxidant vitamins. Therefore, the high exposure to oxidative stress found in our study, even in healthy pregnant and non-pregnant women, may increase the incidence of CHM in this region.

Neoplasia trofoblástica gestacional (NTG) é o termo que descreve o conjunto de anomalias malignas da placenta, incluindo a mola invasora, coriocarcinoma, tumor trofoblástico do sítio placentário e tumor trofoblástico epitelióide. Ambos a mola invasora e o coriocarcinoma respondem bem à quimioterapia, com taxas de cura superiores a 90%. Desde o advento da quimioterapia, NTG de baixo risco tem sido tratada com monoquimioterapia, pelo geral methotrexate ou actinomicina-D. Casos de NTG de alto risco, contudo, devem ser tratados com poliquimioterapia, e o regime usualmente escolhido é o EMA-CO que combina etoposide, methotrexate, actinomicina-D, ciclofosfamida e vincristina. Esse estudo revê a literatura sobre NTG a fim de discutir os conhecimentos atuais sobre seu diagnóstico e tratamento.

Gestational trophoblastic neoplasia (GTN) is the term to describe a set of malignant placental diseases, including invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Both invasive mole and choriocarcinoma respond well to chemotherapy, and cure rates are greater than 90%. Since the advent of chemotherapy, low-risk GTN has been treated with a single agent, usually methotrexate or actinomycin D. Cases of high-risk GTN, however, should be treated with multiagent chemotherapy, and the regimen usually selected is EMA-CO, which combines etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. This study reviews the literature about GTN to discuss current knowledge about its diagnosis and treatment.