Early-stage (ES) non-small cell lung cancer (NSCLC) is diagnosed in about 30% of cases. The preferred treatment is surgery, but a significant proportion of patients experience recurrence. Neoadjuvant and adjuvant chemotherapy has a limited clinical benefit. EGFR tyrosine kinase inhibitors and immunotherapy have recently opened new therapeutic scenarios. However, only a few data are available about the ES-NSCLC molecular landscape and the impact of oncogene addiction on therapy definition. Here, we determined the prevalence of the main lung cancer driver alterations in a monocentric consecutive cohort. Molecular analysis was performed on 1122 cases, including 368 ES and 754 advanced NSCLC. The prevalence of actionable alterations was similar between early and advanced stages. ES-NSCLC was significantly enriched forMETexon-14 skipping alterations and presented a lower prevalence ofBRAFp.(V600E) mutation. PD-L1 expression levels, evaluated according to actionable alterations, were higher in advanced than early tumors harboringEGFR,KRAS,METalterations and gene fusions. Taken together, these results confirm the value of biomarker testing in ES-NSCLC. Although approved targeted therapies for ES-NSCLC are still limited, the identification of actionable alterations could improve patients’ selection for immunotherapy, favoring the enrollment in clinical trials and allowing a faster treatment start at disease recurrence.
早期非小细胞肺癌约占确诊病例的30%。手术是首选治疗方案，但相当比例患者会出现复发。新辅助与辅助化疗的临床获益有限。近年来，EGFR酪氨酸激酶抑制剂及免疫疗法为治疗开辟了新路径。然而，关于早期非小细胞肺癌分子图谱及癌基因成瘾性对治疗方案制定的影响，现有数据仍较为有限。本研究通过单中心连续队列确定了主要肺癌驱动基因变异的分布特征。对1122例样本（含368例早期及754例晚期非小细胞肺癌）进行分子分析发现，可干预变异在早晚期患者中发生率相近。早期非小细胞肺癌中MET外显子14跳跃变异显著富集，而BRAF p.(V600E)突变发生率较低。根据可干预变异类型分析PD-L1表达水平发现，携带EGFR、KRAS、MET变异及基因融合的晚期肿瘤表达水平显著高于早期肿瘤。综合而言，这些结果证实了生物标志物检测在早期非小细胞肺癌中的价值。尽管目前获批用于早期非小细胞肺癌的靶向疗法仍有限，但可干预变异的识别有助于优化免疫治疗患者筛选，促进临床试验入组，并在疾病复发时实现更快速的治疗启动。
肿瘤(癌症)患者之家