Utility of Circulating Tumor DNA Assay in Identifying Mutations and Guiding Matched Targeted Therapy in Lung Cancers.

IF 1.9 4区医学 Q3 ONCOLOGY

Clinical Medicine Insights-Oncology Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI:10.1177/11795549241285238

Kun Li, Nana Zhang, Bing Xu, Zichen Liu, Dan Zhao, Yujie Dong, Jing Mu, Haifeng Lin, Guangyu Shan, Sihang Gao, Bo Yu, Xiaoxi Pan, Yanrong Wang, Dongxing Zhang, Nanying Che, Xiaoyong Ji

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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%. EGFR T790M/C797S c.G2390C and EGFR T790M/C797S c.T2389A were detected in tissue and ctDNA, respectively, in patient 01015. Moreover, ctDNA assay identified the EGFR 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.

Conclusions: 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 EGFR 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.

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循环肿瘤 DNA 检测在识别肺癌突变和指导匹配靶向治疗中的作用

背景：肿瘤基因组图谱分析对靶向治疗的选择具有重要影响。与组织活检相比，循环肿瘤 DNA（ctDNA）是一种无创、可重复的检测方法。我们旨在评估其在确定突变和指导肺癌靶向治疗方面的作用：共有 173 名肺癌患者接受了新一代测序（NGS），使用的靶向富集面板涵盖了 20 个肺癌相关基因。将ctDNA NGS检测在鉴定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。还根据ctDNA检测结果评估了表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）疗法的治疗反应：结果：61.85%的患者检测到了ctDNA。38.57%的病例在配对的ctDNA中检测到组织突变，89.1%的病例在配对的组织中检测到ctDNA突变。ctDNA使接受NCCN推荐基因检测的晚期非小细胞肺癌（NSCLC）患者人数增加了12%。ddPCR 和 ctDNA 的一致性相对较高，达到 99.43%。在 01015 号患者的组织和 ctDNA 中分别检测到了表皮生长因子受体 T790M/C797S c.G2390C 和表皮生长因子受体 T790M/C797S c.T2389A。此外，ctDNA检测发现了组织活检漏检的表皮生长因子受体T790M突变，01149号患者在接受表皮生长因子受体-TKI治疗1年后出现耐药。根据ctDNA NGS结果接受EGFR-TKI靶向治疗的17名患者中，12名患者获得部分应答，2名患者病情稳定：结论：研究结果表明，ctDNA检测可以部分克服肿瘤异质性检测突变的问题，并提供肿瘤基因组图谱的补充信息。此外，ctDNA中存在的表皮生长因子受体突变可为晚期肺癌患者选择合适的表皮生长因子受体-TKI治疗提供有价值的指导。不过，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存在一定的局限性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Medicine Insights-Oncology Medicine-Oncology

CiteScore

2.40

自引率

4.50%

发文量

审稿时长

8 weeks

期刊介绍： Clinical Medicine Insights: Oncology is an international, peer-reviewed, open access journal that focuses on all aspects of cancer research and treatment, in addition to related genetic, pathophysiological and epidemiological topics. Of particular but not exclusive importance are molecular biology, clinical interventions, controlled trials, therapeutics, pharmacology and drug delivery, and techniques of cancer surgery. The journal welcomes unsolicited article proposals.