术后化疗胸腺肿瘤中的应用及对其预后的影响

Application of Postoperative Chemotherapy on Thymomas and Its Prognostic Effect

背景与目的探讨术后化疗在胸腺肿瘤中的应用及术后化疗对Masaoka Ⅲ期/Ⅳ期预后的影响。方法 1994年3月至2012年12月,中国胸腺瘤研究协作组(Chinese Alliance of Research for Thymomas,ChA RT)数据库共纳入2,306例胸腺肿瘤病例,资料相对完整1,700例患者纳入本研究,对其中Masaoka Ⅲ期/Ⅳ期665例患者进行进一步分析,初步评估术后化疗的临床价值,采用Kaplan-Meier法绘制不同亚组患者生存曲线,Cox回归进行多因素分析影响预后的因素。采用倾向值匹配研究(propensity-matched study,PSM),评估化疗的临床价值。结果 1,700例患者中未行术后化疗1,406例(82.7%),术后化疗294例(17.3%),随着Masaoka分期的增加,术后化疗患者的比例也随之增高,差异有统计学意义(P<0.001)。对Masaoka Ⅲ期/Ⅳ期患者665例进行进一步分析,其中未术后化疗组444例,术后化疗组221例。两组患者在有无重症肌无力、WHO病理类型、病理分期、手术根治性、有无术后放疗等方面分布有差异(P<0.05)。其中C型胸腺瘤、不完全切除和术后放疗明显影响患者术后复发和生存(P<0.05)。术后化疗组5年和10年无病生存率分别为51%、30%,5年和10年复发率分别为46%、68%,而未术后化疗组5年和10年无病生存率分别为73%、58%。5年和10年复发率分别为26%、40%,两组无病生存率和复发率均有明显统计学差异(P=0.001,P=0.001)。对有无重症肌无力,病理类型,病理分期,手术根治性状态,术后放疗等因素进行倾向值匹配筛选出其中158例未术后化疗和158例术后化疗共316例患者,生存分析显示:未术后化疗组和术后化疗组两组5年生存率并无明显统计学差异(P=0.332)。结论病理学类型、手术的根治性和术后放疗是影响进展期胸腺肿瘤患者术后生存和复发的主要因素。术后化疗并未给Masaoka-Koga Ⅲ期/Ⅳ期胸腺瘤患者带来生存获益。

Background and objectiveTo study the role of postoperative chemotherapy and its prognostic effect in Masaoka-Koga stage III and IV thymic tumors.Methods Between 1994 and 2012, 1,700 patients with thymic tumors who underwent surgery without neoajuvant therapy were enrolled for the study. Among them, 665 patients in Masaoka-Koga stage III and IV were further analyzed to evaluate the clinical value of postoperative chemotherapy. TheKaplan-Meier method was used to obtain the survival curve of the patients divided into different subgroups, and theCox regression analysis was used to make multivariate analysis on the factors affecting prognosis. A Propensity-Matched Study was used to evaluate the clinical value of chemotherapy.Results Two-hundred-twenty-one patients were treated with postoperative chemotherapy, while the rest 444 cases were not. The two groups showed signiifcant differences （P〈0.05） regarding the incidence of myasthenia gravis, World Health Organization （WHO） histological subtypes, pathological staging, resection status and the use of postopera-tive radiotherapy. WHO type C tumors, incomplete resection, and postoperative radiotherapy were signiifcantly related to increased recurrence and worse survival （P〈0.05）. Five-year and 10-year disease free survivals （DFS） and recurrence rates in patients who underwent surgery followed by postoperative chemotherapy were 51% and 30%, 46% and 68%, comparing with 73% and 58%, 26% and 40% in patients who had no adjuvant chemotherapy atfer surgery （P=0.001,P=0.001, respectively）. In propensity-matched study, 158 pairs of patients with or without postoperative chemotherapy （316 patients in total） were se-lected and compared accordingly. Similar 5-year survival rates were detected between the two groups （P=0.332）. Conclusion Pathologically higher grade histology, incomplete resection, and postoperative radiotherapy were found to be associated with worse outcomes in advanced stage thymic tumors. At present, there is no evidence to show that postoperative chemotherapy may help improve prognosis in patients with Masaoka-Koga-Koga stage III and IV thymic tumors.