EGFR基因状态对高危ⅠB-ⅢA期NSCLC患者术后辅助化疗及靶向治疗疗效的影响

study on the influence of status of EGFR gene on the effect of postoperative adjuvant chemotherapy and targeted therapy for patients with NsCLC in high-risk ⅠB-Ⅲ A stages

目的：探讨 EGFR 基因状态对非小细胞肺癌（NSCLC）患者根治性术后辅助化疗及靶向治疗疗效的影响。方法选取2012年1月至2014年1月行根治手术治疗的高危ⅠB -ⅢA 期 NSCLC 患者56例，送检肿瘤组织标本行EGFR 基因检测，根据 EGFR 检测结果及患者实际情况将56例患者分为三组：A 组为26例 EGFR 野生型患者，B 组为16例 EGFR 突变型患者，C 组为14例 EGFR 突变型患者。三组患者均自术后第三周起给予铂类＋紫杉醇方案化疗4周期，3周为一个周期；C 组患者在化疗结束两周后，给予口服表皮生长因子受体酪氨酸激酶抑制剂（ EGFR - TKIs）药物维持治疗。对比三组的临床特征，治疗毒副作用情况及6、12、18个月无疾病生存期（DFS）情况。结果①A 组和 B 组、A组和 C 患者的病理类型比较差异具有统计学意义（ P ﹤0.05），A 组中鳞癌多于腺癌，B 组和 C 组中腺癌多于鳞癌；②三组的化疗毒副作用主要表现为骨髓抑制和胃肠道反应，均较轻，未发生Ⅲ度以上反应，三组间比较差异无统计学意义（ P ﹥0.05）；C 组患者口服 TKIs 药物耐受性良好，仅5例患者发生Ⅰ度皮疹反应，3例患者发生Ⅰ度腹泻反应。③A 组患者6、12、18个月 DFS 分别为74.0%、60.2%、52.6%；B 组分别为100.0%、85.5%、76.1%；C 组分别为100.0%、100.0%、91.3%。三组6个月 DFS 比较差异无统计学意义（ P ﹥0.05）；12、18个月 DFS：C 组明显高于 A 组，差异具有统计学意义（ P ﹤0.05），A 组和 B 组、B 组和 C 比较差异无统计学意义（ P ﹥0.05）。结论 EGFR 基因状态可能会影响高危ⅠB -ⅢA 期 NSCLC 患者根治性术后辅助化疗的疗效；单纯采用化疗的 EGFR 突变型患者的 DFS 较野生型有延长的趋势；采用化疗＋靶向治疗的 EGFR 突变型患者的 DFS 较单纯采用化疗的野生型患者延长，较单纯采用化疗的突变型患者有延长的趋势。

Objective To explore the influence of status of EGFR gene on the effect of postoperative adjuvant chemotherapy and targeted therapy in patients with NSCLC. Methods A total of 56 patients with NSCLC inhigh - risk ⅠB - ⅢA stages received radical surgical treatment during January 2012 to January 2014 were allocated in this study,the expression of EGFR gene had been examined in specimens of tumor tissue. All these 56 patients were divided into three groups,according to the results of expression of EGFR and the actual situation of patients. 26 patients in group A were with wild type of EGFR,and 16 and 14 cases in group B and group C showed mutant type of EGFR,and patients in these three groups were given with 4 cycles of platinum plus paclitaxel chemotherapy sincethe third week after operation,3 weeks for a cycle. Patients in group C were given with oral administration of EGFR - TKIs for maintenance treatment of two weeks after the completion of chemotherapy. The clinical features,toxicity and 6,12 and 18 months disease free survival（DFS）rates were compared among patients in these 3 groups. Results ①The difference in pathologic types between group A and group B,group A and C was statistically significant（ P ﹤ 0. 05）,the number of patients with squamous carcinoma was more than that of adenocarcinoma in group A,andthe number of patients with adenocarcinoma was more than that of squa-mous carcinoma in group B and group C. ②The main side reactions of chemotherapy in patients of these three groups were suppression of bone mar-row and gastrointestinal reactions,all of them are lighter,without Ⅲ degree reactions,there was no statistically significant difference between these three groups（P ﹥ 0. 05）. The tolerance of patients in group C during oral administration ofTKIs drug was good,only 5 patients had degree 1 rash reaction,3 patients had degree 1 diarrhea reaction. ③The 6,12 and 18 months DFS in patients of group A were 74. 0% ,60. 2% and 52. 6% re-spectively,they were 100. 0% ,85. 5% and 76. 1% respectively in patients of group B,and they were 100. 0% ,100. 0% and 91. 3% respectively＆amp;nbsp;in patients of group C. The difference in six months DFS among these three groups had no statistical significance（ P ﹥ 0. 05）. The difference in 12 and 18 months DFS：in patients of group A was significantly higher than that of patients in group Cwith statistical significance（ P ﹤ 0. 05）,but the difference between patients of group A and group B,group B and group C was not statistically significant（ P ﹥ 0. 05）. Conclusion The sta-tus of EGFR gene may affect the effect of postoperative adjuvant chemotherapy in patients with NSCLC in high - riskⅠB - Ⅲ A stages. The DFS rates in patients with mutant type of EGFR received simple chemotherapy have tendency to extend in comparison with patients withwild type. The DFS rates in patients with mutant type of EGFR received chemotherapy plus targeted therapy will beextended in comparison with those patients with wild type received simple chemotherapy,and their DFS rates havetendency to be extended in comparison with those of patients with mutant type re-ceived simple chemotherapy.