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

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.

摘要 目的 目前南美洲地区关于妊娠滋养细胞肿瘤（gestational trophoblastic neoplasia, GTN）治疗结局的跨国研究尚少。本研究旨在评估南美洲三家医疗中心内，接受一线单药化疗的低风险葡萄胎后GTN患者的临床表现、治疗结局以及与化疗耐药相关的影响因素。方法 本研究为多中心回顾性队列研究，纳入1990年至2014年间就诊于阿根廷、巴西、哥伦比亚三地医疗机构的、经国际妇产科联盟（International Federation of Gynecology and Obstetrics, FIGO）分期的低风险葡萄胎后GTN女性患者。收集患者基线特征、疾病表现及治疗反应相关数据，采用Logistic回归分析临床因素与一线单药治疗耐药的相关性，并对单因素分析中具有统计学意义的临床因素开展多因素分析。结果 本研究共纳入163例低风险GTN患者。一线化疗总体完全缓解率为80%（130/163）。以甲氨蝶呤（methotrexate）或放线菌素-D（actinomycin-D）作为一线治疗的完全缓解率分别为79%（125/157）、83%（5/6），甲氨蝶呤治疗失败后以放线菌素-D作为二线治疗的完全缓解率为70%（23/33）。因化疗耐药而更换二线治疗的病例占总病例数的20.2%（33/163）。多因素分析显示，FIGO风险评分为5~6分的患者，发生一线单药治疗耐药的风险是其他患者的4.2倍（P=0.019）。结论 1）就诊时，多数患者的临床特征提示预后良好；2）一线单药治疗后持续完全缓解的总体发生率与发达国家的同类研究结果相当；3）FIGO风险评分5或6分与一线单药化疗耐药的发生显著相关。