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Abstract：
The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.
摘要：
在低风险妊娠滋养细胞肿瘤（GTN）患者中，甲氨蝶呤（MTX）耐药性的挑战一直很突出。尽管国际妇产科联合会（FIGO）评分为0-4名患者，其中大多数是低风险的GTN患者，对与MTX耐药相关的患病率和危险因素的全面探索一直很有限.因此,我们旨在确定FIGO评分为0~4分的GTN患者的相关危险因素.2005年1月至2020年12月，310例低危GTN患者在两家医院接受了原发性MTX化疗，265的FIGO得分为0-4。在FIGO0-4子群中，94例(35.5%)对MTX化疗耐药,34例(12.8%)需要多药化疗。临床病理诊断为磨牙后绒毛膜癌（OR=17.18，95％CI：4.64-63.70，P<0.001）和较高的治疗前人类绒毛膜促性腺激素浓度（log-hCG浓度）（OR=18.11，95％CI：3.72-88.15，P<0.001）根据多变量逻辑回归被确定为与MTX抵抗相关的独立危险因素。建立决策树模型和回归模型来预测FIGO评分为0-4的GTN患者的MTX抵抗风险。模型判别的评估，校准和净效益揭示了决策树模型的优越性，包括临床病理诊断和治疗前hCG浓度。决策树模型的高、中风险组患者发生MTX耐药的概率较高。这项研究代表了对FIGO评分为0-4的GTN患者的MTX耐药性的调查，并揭示了MTX化疗的缓解率约为65％。较高的治疗前hCG浓度和临床病理诊断是后磨牙绒毛膜癌对MTX化疗耐药的独立危险因素。决策树模型显示了关于MTX抗性风险的增强的预测能力，并且可以作为指导FIGO评分为0-4的GTN患者的临床治疗决策的有价值的工具。
