Zhang Yiliang, Ma Yuan, Li Yuan, Shen Xuxia, Yu Yongfu, Pan Yunjian, Zhang Yang, Yu Su, Zheng Difan, Zhao Yue, Hu Hong, Sun Yihua, Zhang Yawei, Xiang Jiaqing, Chen Haiquan
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Cancer Res Clin Oncol. 2018 Jan;144(1):165-171. doi: 10.1007/s00432-017-2526-z. Epub 2017 Oct 12.
Evidence shows that exon 19 deletions (19del) and exon 21 Leu858Arg point mutation (L858R) of EGFR are different in response to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in advanced lung cancers. However, the impact of the two mutational types in the early stage lung adenocarcinoma is unknown.
We enrolled consecutive patients with operable adenocarcinoma which harbored 19del or L858R to investigate the clinicopathologic characteristics and prognostic outcomes.
Between 2008 and 2013, a total of 607 patients with 19del (47.9%) or L858R (52.1%) were included in this study. Clinicopathologic and disease-associated factors were well-balanced between 19del and L858R patients. Both recurrence-free survival (5-year RFS: 37.9% vs. 42.9%, p = 0.075) and overall survival (5-year OS: 64.7% vs. 60.7%, p = 0.741) were similar between the two groups. After relapse, 19del was associated with a better post-recurrence survival (PRS) than L858R (p = 0.016). Multivariate analysis demonstrated that mutational types (HR = 1.521, 95% CI: 1.106-2.093, p = 0.01) and tyrosine kinase inhibitors (TKI) use after recurrence (HR = 0.422, 95% CI: 0.301-0.592, p < 0.001) were independent predictors of PRS. The 19del and L858R patients were similar regarding recurrent patterns, except on pleural/chest wall metastasis (26.0% vs. 12.2%, p = 0.007).
Patients with the early stage lung adenocarcinoma harboring either 19del or L858R share similar RFS and OS. After recurrence, both could benefit from TKI therapy without the need for a second biopsy, but 19del seemed to be associated with better PRS.
有证据表明，在晚期肺癌中，表皮生长因子受体（EGFR）的19号外显子缺失（19del）和21号外显子Leu858Arg点突变（L858R）对EGFR酪氨酸激酶抑制剂（EGFR-TKI）治疗的反应有所不同。然而，这两种突变类型在早期肺腺癌中的影响尚不清楚。
我们纳入了连续的患有可手术切除腺癌且携带19del或L858R的患者，以研究其临床病理特征和预后结果。
在2008年至2013年期间，本研究共纳入了607例患者，其中19del患者占47.9%，L858R患者占52.1%。19del组和L858R组患者的临床病理及疾病相关因素均衡。两组患者的无复发生存率（5年无复发生存率：37.9%对42.9%，p = 0.075）和总生存率（5年总生存率：64.7%对60.7%，p = 0.741）相似。复发后，19del患者的复发后生存率（PRS）优于L858R患者（p = 0.016）。多因素分析表明，突变类型（HR = 1.521，95%可信区间：1.106 - 2.093，p = 0.01）和复发后酪氨酸激酶抑制剂（TKI）的使用（HR = 0.422，95%可信区间：0.301 - 0.592，p < 0.001）是PRS的独立预测因素。19del和L858R患者的复发模式相似，但胸膜/胸壁转移情况除外（26.0%对12.2%，p = 0.007）。
携带19del或L858R的早期肺腺癌患者的无复发生存率和总生存率相似。复发后，两者均可从TKI治疗中获益，无需再次活检，但19del似乎与更好的PRS相关。
