Lin Chun-Wei, Huang Kuo-Yang, Lin Ching-Hsiung, Hou Ming-Hon, Lin Sheng-Hao
Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan, ROC.
Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40227, Taiwan, ROC.
Oncol Lett. 2025 Jan 7;29(3):125. doi: 10.3892/ol.2025.14872. eCollection 2025 Mar.
EGFR and ALK are key driver mutations in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors are recommended as the first-line treatment for advanced NSCLC with driving oncogenes because they have fewer side effects and provide better disease control than chemotherapy. The present retrospective analysis aimed to investigate how altered driver genes impact cancer outcomes and clinical presentation. A total of 628 patients with advanced-stage NSCLC and documented EGFR and ALK mutations were enrolled at Changhua Christian Hospital in Taiwan between August 2011 and January 2021. EGFR mutations were identified by PCR. ALK rearrangements were identified by immunostaining. Patients without EGFR or ALK mutations were labeled as wild-type (WT). EGFR mutation was detected in 446 (71.02%) patients, ALK rearrangement in 36 (5.73%) patients and WT in 146 (23.25%) patients. EGFR mutations resulted in higher frequency of lung, brain and multiple extrapulmonary metastases than ALK rearrangement. The ALK group exhibited the longest median overall survival (OS), followed by EGFR and WT groups (ALK: 51.60±13.32, EGFR: 24.03±1.22 and WT: 19.63±2.43 months, respectively; P=0.011). In patients with brain metastases, ALK group had a longer median OS than the EGFR group. Because there were few recruited patients with ALK rearrangement, the results were not significant. According to the results of Cox regression model analysis, driver mutations with EGFR and ALK, lower smoking pack-years, younger age, better performance status, no pleural metastasis and fewer extrapulmonary metastases were key prognostic factors. In conclusion, diverse clinical outcomes are driven by different driver mutations. EGFR mutation leads to more extrapulmonary metastases. Median OS was superior in ALK-rearranged NSCLC than EGFR-mutated NSCLC regardless of brain metastases.
表皮生长因子受体（EGFR）和间变性淋巴瘤激酶（ALK）是非小细胞肺癌（NSCLC）的关键驱动基因突变。酪氨酸激酶抑制剂被推荐作为具有驱动癌基因的晚期NSCLC的一线治疗药物，因为它们的副作用较少，并且与化疗相比能更好地控制疾病。本回顾性分析旨在研究驱动基因改变如何影响癌症预后和临床表现。2011年8月至2021年1月期间，台湾彰化基督教医院共纳入了628例晚期NSCLC患者，这些患者均记录有EGFR和ALK突变。通过聚合酶链反应（PCR）鉴定EGFR突变。通过免疫染色鉴定ALK重排。没有EGFR或ALK突变的患者被标记为野生型（WT）。446例（71.02%）患者检测到EGFR突变，36例（5.73%）患者检测到ALK重排，146例（23.25%）患者为WT。与ALK重排相比，EGFR突变导致肺、脑和多发肺外转移频率更高。ALK组的中位总生存期（OS）最长，其次是EGFR组和WT组（ALK组：51.60±13.32个月，EGFR组：24.03±1.22个月，WT组：19.63±2.43个月；P=0.011）。在有脑转移的患者中，ALK组的中位OS比EGFR组长。由于招募的ALK重排患者较少，结果无统计学意义。根据Cox回归模型分析结果，EGFR和ALK驱动突变、吸烟包年数较低、年龄较小、体能状态较好、无胸膜转移和肺外转移较少是关键预后因素。总之，不同的驱动突变导致不同的临床结果。EGFR突变导致更多的肺外转移。无论有无脑转移，ALK重排的NSCLC的中位OS均优于EGFR突变的NSCLC。
