EGFR突变与EML4-ALK融合共存的非小细胞肺癌的临床病理特征及治疗分析

目的:探讨表皮生长因子受体(EGFR)基因突变与棘皮动物微管相关样蛋白4与间变性淋巴瘤激酶(EML4-ALK)融合基因共存(以下简称双基因异常)的非小细胞肺癌的临床病理特征及治疗策略。方法:回顾性收集并分析2012年1月至2016年12月我院收治的EGFR突变与EML4-ALK融合基因共存的非小细胞肺癌患者的临床资料及病理特点。结果:11例双突变非小细胞肺癌占医院同期入院非小细胞肺癌患者的0.68%(11/1620);男性6例,女性5例;年龄23-70岁,平均年龄51.6岁;11例患者均不吸烟;腺癌9例,肉瘤样癌2例;临床分期,ⅠA期3例,ⅡB期1例,ⅢA期1例,ⅢB期1例,ⅠV期5例;6例行手术治疗,4例使用传统化疗,最好疗效为稳定(SD),最长无进展生存期(PFS)为6月;5例患者使用表皮生长因子酪氨酸激酶抑制剂(EGFR-TKⅠ)治疗,使用EGFR-TKⅠ最好疗效为部分缓解(PR),PFS为3-23月,中位PFS为9月;截止2017年12月,死亡4例,11例患者的生存时间为1-67月,中位存活时间为21月。结论:EGFR基因突变与EML4-ALK融合基因共存型非小细胞肺癌临床少见,多见于不吸烟或少吸烟的肺腺癌患者,双基因异常的非小细胞肺癌的靶向药物的治疗缺乏统一性,有待进一步研究,基于EGFR及EML4-ALK的磷酸化水平或肿瘤突变负荷选择靶向药物的个体化精准治疗是非常重要的。

Clinicopathological Features and Therapeutic Analysis of Non-small-cell lung Cancer patients with Concomitant EGFR Mutation and EML4-ALK Fusion

ABSTRACT Objective: To investigate the clinicopathological features and therapeutic strategy of non-small-cell lung cancer with concomitant EGFR mutation and EML4-ALK fusion. Methods: A retrospective analysis of clinicopathological data of concomitant in Tangdu hospital from May 2012 to December 2016 was performed. Results: There were a total of 11 cases with concomitant EGFR mu- tation and EML4-ALK fusion, accounting for 0.68%(11/1620) of all non-small-cell lung cancer patients diagnosed in our hospital in the same period. There were 6 males and 5 females, the mean age of the patients was 51.9(23 to 70) years and all of the patients had no smoking history. The histological type of 9 patient was adenocarcinoma and 2 was sarcomatoid carcinoma. Clinical stage: stage IA was in 3 cases, stage IIB was in 1 case, stage IIIA was in 1 case, stage IIIB was in 1 case, stage IV was in 5 cases. 6 patients underwent surgical treatment, 4 patients received traditional chemotherapy and the best response was stable disease, the longest progression-free survival of chemotherapy was 6 months. 5 patient received epidermal growth factor receptor tyrosine kinase inhibitors and the best response was par- tial response, the progression-free survival of TKIs were 3-23 months(median 9 months). As of December 2017, 4 patients died, and the survival time of the 11 cases was 1-67months(median 21 months). Conclusion: Non-small-cell lung cancer patients with concomitant EGFR mutation and EML4-ALK fusion is rare, most of them do not smoke or smoke slightly and are patients with adenocarcinoma. Tar- geted therapy based on phosphorylated level of EGFR and EML4-ALK or tumor mutational burden is important.