晚期非小细胞肺癌患者肿瘤轻度进展后的治疗方案选择

Exploration of the rational therapeutic regimen for advanced lung cancer patients with mild tumor enlargement

目的探讨影响肿瘤轻度进展晚期非小细胞肺癌（NSCLC）疗效的因素及合理治疗方案。方法回顾性分析103例轻度进展（肿瘤长径之和增大≤20％）NSCLC患者的临床资料，分析其临床病理特征和预后。采用Cox比例风险模型分析影响患者预后的独立因素。结果103例患者中，肿瘤轻度进展后，维持原治疗方案者54例，中位无进展生存时间（PFS）为87d。更换治疗方案者49例，中位PFS为168d，差异有统计学意义（P〈0．01）；其中更换其他化疗方案者32例，中位PFS为154d；更换靶向药物治疗者10例（轻度进展前行化疗9例，靶向治疗1例），中位PFS为287d，与维持原治疗方案者比较，差异均有统计学意义（均P〈O．01）；更换放疗7例。受试者工作特征曲线显示，肿瘤增大7％为患者PFS差异最大的临界值。在轻度进展后靶向治疗的患者中，单因素分析显示，性别、病理类型、临床分期、双肺转移和肿瘤增大比例均为影响患者预后的因素（均P〈O．05）；多因素分析显示，肿瘤增大比例〉7％为影响患者预后的独立因素（P=0．001）。在轻度进展后应用化疗的患者中，单因素分析显示，轻度进展前治疗方案和轻度进展后化疗方案均为影响患者预后的因素（均P〈O．05）；Cox多因素分析显示，轻度进展后化疗方案为影响患者预后的独立因素（P=0．004）。在肿瘤增大≤7％后行化疗的患者中，单因素分析显示，增大前化疗方案为影响患者预后的因素（P=0．030）；Cox多因素分析显示，增大前化疗方案与患者的预后无关（P=0．560）。在肿瘤增大7．1％～20％后行化疗的患者中．单因素分析显示，病理类型、骨转移和轻度进展后化疗方案均为影响患者预后的因素（均P〈0．05）；Cox多因素分析显示，病理类型、骨转移和轻度进展后化疗方案均为影响患者预后的独立因素（均P〈O．05）。结论在晚期NSCLC、肿瘤增大≤20％的患者中，更换治疗方案患者的PFS长于维持原治疗方案的患者。患者PFS差异最大的临界值为肿瘤增大7％。对于肿瘤轻度进展前已行二线及以上治疗的患者，当肿瘤增大比例为7．1％-20％时，更换治疗方案患者的PFS明显延长；对于无骨转移、腺癌患者，更换双药化疗方案可获得生存受益。

Objective To investigate the factors that impacts of therapeutic effect in advanced non- small cell lung cancer （NSCLC） patients with mild tumor enlargement and the rational therapeutic strategy for them. Methods The clinicopathologieal features and prognostic data of advanced NSCLC patients whose sum of tumor longest diameters with 0 to 20% increase were retrospectively explored, and the Cox proportional hazards model was used to analyze the independent prognostic factors in patients. Results The median progression-free survival （PFS） of 54 patients with the original regimen was 87 days, significantly less than 168 days of the median PFS of 49 patients with replacing regimen （P〈0.001）. The median PFS of other chemotherapeutic regiems （154 days） and the targeted therapy （287 days） were longer than the origional therapy （P 〈 0. 05 for all ）. The left 7 patients received radiotherapy. Receiver operating characteristic （ROC） curve indicated a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio was 7%. Univariate analysis of patients with targeted therapy after disease progression showed that gender, pathological type, clinical stage, lung metastasis and tumor enlargement ratio were the prognostic factors （all of P〈0.05）. Multivariate analysis showed that the tumor enlargement ratio was an independent prognostic factor （P = 0. 001 ）. Single factor analysis showed that the chemotherapeutic regimens before and after disease progression were prognostic factors of patients received chemotherapy after disease progression （P〈0.05）. Cox multivariate analysis showed that the chemotherapeutic regimen after disease progression was an independent prognostic factor of patients （ P = 0.004 ）. In the patients whose tumor enlargement ratio was 0 to 7%, Univariate analysis showed that chemotherapeutic regimen before tumor enlargement was a prognostic factor （ P = 0.030 ） , while Cox multivariate analysis showed that it was not an independent prognostic factor （P = 0. 560）. In the patients whose tumor enlargement ratio was 7.1% to 20%, single factor analysis showed that pathological type, bone metastasis and chemotherapeutic regimen after disease progression were prognostic factors （all of P〈0.05）, and Cox multivariate analysis showed that all of them were independent prognostic factors of these patients （ all of P〈 0.05）. Conclusions To the advanced NSCLC patients whose tumor enlargement ratio is 0 to 20%, the PFS of patients receive replacing regimen is longer than that of patients receive original regimen. There is a significant difference in the PFS when the maximal cut-off value of tumor enlargement ratio is 7%. To patients undergo second-line chemotherapy before disease progression and the tumor enlargement ratio is 7.1% to 20%, the PFS of patients receive replacing regimen is significantly extended. Dual drug replacing regimen is especially benefit to the adenocarcinoma patients without bone metastasis.