Service de Gynécologie-Obstétrique et de Chirurgie Oncologique du Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France.
Centre de Référence des Maladies Trophoblastiques de Lyon, Faculté de Médecine Lyon Sud, Université Lyon 1, France; Service d'Obstétrique, Centre Hospitalier Femme-Mère-Enfant, Hospices Civils de Lyon, Université Lyon 1, France.
Am J Obstet Gynecol. 2016 Jul;215(1):80.e1-7. doi: 10.1016/j.ajog.2016.01.183. Epub 2016 Jan 30.
Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients.
This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone.
Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients.
The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86-8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98-37.9], P = .0042). A patient who received 5-8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1-4 courses (95% CI, 1.54-29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1-4 courses of methotrexate (95% CI, 1.54-42.6, P = .014).
Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted.
患有 2000FIGO 低危妊娠滋养细胞肿瘤的患者通常接受单一药物化疗。甲氨蝶呤在欧洲广泛用于该适应证。分析治疗后复发的情况并确定与复发相关的因素，有助于了解其对 2000FIGO 评分演变和妊娠滋养细胞肿瘤患者化疗管理的潜在影响。
本回顾性研究分析了单纯用甲氨蝶呤使人绒毛膜促性腺激素（hCG）正常化的低危妊娠滋养细胞肿瘤患者复发的预测因素。
1999 年至 2014 年，在法国滋养细胞疾病参考中心数据库中确定了 993 例妊娠滋养细胞肿瘤患者，其中 465 例为低危患者，hCG 经甲氨蝶呤单独治疗正常化。使用单变量和多变量分析，我们确定了甲氨蝶呤治疗后复发的显著预测因素。使用 Kaplan-Meier 方法绘制患者的结果图。
hCG 经甲氨蝶呤单独治疗正常化的低危妊娠滋养细胞肿瘤患者的 5 年复发率为 5.7%（置信区间 [CI]，3.86-8.46）。单变量分析确定了先前导致分娩的妊娠（HR=5.96；95%CI，1.40-25.4，P=.016）、甲氨蝶呤疗程数超过 5 个（5-8 个疗程比 1-4 个疗程：HR=6.19；95%CI，1.43-26.8，P=.015；9 个疗程及以上比 1-4 个疗程：HR=6.80；95%CI，1.32-35.1，P=.022）以及 hCG 正常化延迟至平均值作为复发的预测因素（HR=1.27；95%CI，1.09-1.49，P=.003）。多变量分析证实，先前的妊娠类型和甲氨蝶呤疗程数是复发的独立预测因素。与葡萄胎后妊娠滋养细胞肿瘤相比，正常分娩后发生的低危妊娠滋养细胞肿瘤复发风险高 8.66 倍（95%CI，1.98-37.9]，P=.0042）。接受 5-8 个疗程甲氨蝶呤治疗的患者复发风险比接受 1-4 个疗程甲氨蝶呤治疗的患者高 6.7 倍（95%CI，1.54-29.2，P=.011）。接受 9 个疗程或更多疗程甲氨蝶呤治疗的患者复发风险比接受 1-4 个疗程甲氨蝶呤治疗的患者高 8.1 倍（95%CI，1.54-42.6，P=.014）。
分娩后发生的低危妊娠滋养细胞肿瘤和需要超过 4 个疗程的甲氨蝶呤才能使 hCG 正常化的患者比其他低危患者更容易复发。对于产后妊娠滋养细胞肿瘤，应考虑将“先前妊娠”FIGO 项目的评分提高。需要进一步分析巩固治疗的必要性。
