Li Kun, Zhang Nana, Xu Bing, Liu Zichen, Zhao Dan, Dong Yujie, Mu Jing, Lin Haifeng, Shan Guangyu, Gao Sihang, Yu Bo, Pan Xiaoxi, Wang Yanrong, Zhang Dongxing, Che Nanying, Ji Xiaoyong
Pathology Department, Beijing Chest Hospital, Capital Medical University, Beijing, China.
Department of Bioinformatics, Beijing USCI Medical Devices Co., Ltd., Beijing, China.
Clin Med Insights Oncol. 2024 Oct 16;18:11795549241285238. doi: 10.1177/11795549241285238. eCollection 2024.
Tumor genomic profiling has a significant impact on the selection of targeted therapy. Circulating tumor DNA (ctDNA) has emerged as a noninvasive, and reproducible assay compared with tissue biopsy. We aimed to evaluate its utility in identifying mutations and guiding targeted therapy for lung cancer.
A total of 173 lung cancer patients underwent next-generation sequencing (NGS) using a targeted enrichment panel covering 20 lung cancer-related genes. The performance of the ctDNA NGS assay in identifying genetic mutations or alterations was compared with tissue biopsy and droplet digital PCR (ddPCR). The treatment response to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapies based on the ctDNA assay results was also assessed.
The ctDNA was detected in 61.85% of patients. Tissue mutations were detected in paired ctDNA in 38.57% of cases, while ctDNA mutations were detected in paired tissues in 89.1% of cases. The ctDNA increased the number of advanced non-small cell lung cancer (NSCLC) patients who received NCCN-recommended genetic testing by 12%. The concordance between ddPCR and ctDNA was relatively high reaching 99.43%. T790M/C797S c.G2390C and T790M/C797S c.T2389A were detected in tissue and ctDNA, respectively, in patient 01015. Moreover, ctDNA assay identified the T790M mutation, which was missed by tissue biopsy in patient 01149, who developed drug resistance after 1 year of EGFR-TKI therapy. Of the 17 patients who received EGFR-TKI targeted therapies based on the ctDNA NGS results, 12 patients achieved a partial response and two patients had stable disease.
The results demonstrated that the ctDNA assay could partially overcome tumor heterogeneity in detecting mutations and provide complementary information on tumor genomic profiles. Moreover, the presence of mutations in ctDNA could offer valuable guidance for selecting appropriate EGFR-TKI treatment for advanced lung cancer patients. However, it is important to note that the ctDNA NGS assay has certain limitations in fully identifying all genomic alterations present in the tumor.
肿瘤基因组分析对靶向治疗的选择有重大影响。与组织活检相比，循环肿瘤DNA（ctDNA）已成为一种非侵入性且可重复的检测方法。我们旨在评估其在识别肺癌突变和指导靶向治疗中的效用。
共有173例肺癌患者使用覆盖20个肺癌相关基因的靶向富集panel进行了下一代测序（NGS）。将ctDNA NGS检测在识别基因突变或改变方面的性能与组织活检和液滴数字PCR（ddPCR）进行了比较。还评估了基于ctDNA检测结果对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗的反应。
61.85%的患者检测到ctDNA。38.57%的病例在配对的ctDNA中检测到组织突变，而89.1%的病例在配对组织中检测到ctDNA突变。ctDNA使接受NCCN推荐基因检测的晚期非小细胞肺癌（NSCLC）患者数量增加了12%。ddPCR与ctDNA之间的一致性相对较高，达到99.43%。在患者01015中，分别在组织和ctDNA中检测到T790M/C797S c.G2390C和T790M/C797S c.T2389A。此外，ctDNA检测识别出了患者01149中组织活检遗漏的T790M突变，该患者在EGFR-TKI治疗1年后出现耐药。在基于ctDNA NGS结果接受EGFR-TKI靶向治疗的17例患者中，12例患者获得部分缓解，2例患者病情稳定。
结果表明，ctDNA检测在检测突变方面可部分克服肿瘤异质性，并提供肿瘤基因组图谱的补充信息。此外，ctDNA中突变的存在可为晚期肺癌患者选择合适的EGFR-TKI治疗提供有价值的指导。然而，需要注意的是，ctDNA NGS检测在完全识别肿瘤中存在的所有基因组改变方面有一定局限性。
