痰游离 DNA：晚期肺腺癌患者对 EGFR-TKIs 获得性耐药后，检测 EGFR 外显子 20 p.T790M 突变的有价值替代样本。
Sputum cell-free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR-TKIs.
机构信息
Department of Pathology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.
Department of Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.
出版信息
Cancer Med. 2021 May;10(10):3323-3331. doi: 10.1002/cam4.3817. Epub 2021 May 1.
BACKGROUND
Sputum cell-free DNA (cfDNA) is a valuable surrogate sample for assessing EGFR-sensitizing mutations in patients with advanced lung adenocarcinoma. Detecting EGFR exon 20 p.T790 M (p.T790 M) is much more challenging due to its limited availability in tumor tissues. Exploring sputum cfDNA as an alternative for liquid-based sample type in detecting p.T790 M requires potential improvement in clinical practice.
METHODS
A total of 34 patients with EGFR-sensitive mutation-positive lung adenocarcinoma and acquired resistance to the first generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled. The sputum samples, and paired tumors and/or plasma samples were tested for p.T790 M mutation and concordance of p.T790 M status among the three sample types was analyzed.
RESULTS
The overall concordance rate of p.T790 M mutation between sputum cfDNA and tumor tissue samples was 85.7%, with a sensitivity of 66.7% and a specificity of 100%. The sensitivity for detecting p.T790 M in sputum cfDNA was 100%, 66.7%, and 0% in the three sputum groups of malignant, satisfactory but no malignant cells, and unsatisfactory, respectively. The combined results of plasma cfDNA testing and sputum cfDNA testing further increased the sensitivity to 100% for p.T790 M detection in satisfactory but no malignant cells sputum group.
CONCLUSION
These findings revealed that cfDNA from malignant or satisfied but no malignant cells sputum is considered suitable for detecting p.T790 M mutation in patients with acquired resistance to first or second-generation EGFR-TKIs. The sputum cytological pathological evaluation-guided sputum cfDNA testing assists in significantly improving the sensitivity of p.T790 M detection, bringing significant value for the maximal application of third-generation EGFR-TKIs in second-line treatment.
背景
无细胞游离 DNA（cfDNA）是评估晚期肺腺癌患者表皮生长因子受体（EGFR）敏感突变的有价值的替代样本。由于肿瘤组织中 EGFR 外显子 20 p.T790M（p.T790M）的含量有限，检测该突变更加具有挑战性。为了在临床上进行改进，需要探索以 cfDNA 作为液体活检样本类型替代物检测 p.T790M。
方法
共纳入 34 例 EGFR 敏感突变阳性的肺腺癌患者，这些患者对第一代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）产生了获得性耐药。对这些患者的痰液样本，以及配对的肿瘤组织和/或血浆样本进行了 p.T790M 突变检测，并分析了三种样本类型之间 p.T790M 状态的一致性。
结果
cfDNA 与肿瘤组织样本中 p.T790M 突变的总一致性率为 85.7%，敏感性为 66.7%，特异性为 100%。在恶性、满意但无恶性细胞和不满意三组痰液中，cfDNA 检测 p.T790M 的敏感性分别为 100%、66.7%和 0%。联合检测血浆 cfDNA 和 cfDNA 进一步将满意但无恶性细胞组的 p.T790M 检测敏感性提高至 100%。
结论
这些结果表明，来源于恶性或满意但无恶性细胞的 cfDNA 适合检测接受第一代或第二代 EGFR-TKIs 治疗后获得性耐药的患者的 p.T790M 突变。基于痰细胞学病理评估的 cfDNA 检测有助于显著提高 p.T790M 检测的敏感性，为第三代 EGFR-TKIs 在二线治疗中的最大应用带来显著价值。
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