Kim Chul, Xi Liqiang, Cultraro Constance M, Wei Fang, Jones Gregory, Cheng Jordan, Shafiei Ahmad, Pham Trinh Hoc-Tran, Roper Nitin, Akoth Elizabeth, Ghafoor Azam, Misra Vikram, Monkash Nina, Strom Charles, Tu Michael, Liao Wei, Chia David, Morris Clive, Steinberg Seth M, Bagheri Hadi, Wong David T W, Raffeld Mark, Guha Udayan
Thoracic and GI Malignancies Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Laboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Cancers (Basel). 2021 Jul 3;13(13):3342. doi: 10.3390/cancers13133342.
: We assessed whether serial ctDNA monitoring of plasma and saliva predicts response and resistance to osimertinib in EGFR-mutant lung adenocarcinoma. Three ctDNA technologies-blood-based droplet-digital PCR (ddPCR), next-generation sequencing (NGS), and saliva-based EFIRM liquid biopsy (eLB)-were employed to investigate their complementary roles. : Plasma and saliva samples were collected from patients enrolled in a prospective clinical trial of osimertinib and local ablative therapy upon progression (NCT02759835). Plasma was analyzed by ddPCR and NGS. Saliva was analyzed by eLB. : A total of 25 patients were included. We analyzed 534 samples by ddPCR ( = 25), 256 samples by NGS ( = 24) and 371 samples by eLB ( = 22). Among 20 patients who progressed, ctDNA progression predated RECIST 1.1 progression by a median of 118 days (range: 61-272 days) in 11 (55%) patients. Of nine patients without ctDNA progression by ddPCR, two patients had an increase in mutant by eLB and two patients were found to have ctDNA progression by NGS. Levels of ctDNA measured by ddPCR and NGS at early time points, but not volumetric tumor burden, were associated with PFS. // amplifications, C797S, E545K, V9del, and S45P were key resistance mechanisms identified by NGS. : Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles.
我们评估了血浆和唾液中循环肿瘤DNA（ctDNA）的连续监测是否能预测表皮生长因子受体（EGFR）突变型肺腺癌患者对奥希替尼的反应和耐药性。我们采用了三种ctDNA检测技术——基于血液的液滴数字聚合酶链反应（ddPCR）、下一代测序（NGS）以及基于唾液的EFIRM液体活检（eLB），以研究它们的互补作用。血浆和唾液样本取自参加奥希替尼前瞻性临床试验且疾病进展时接受局部消融治疗的患者（NCT02759835）。血浆通过ddPCR和NGS进行分析。唾液通过eLB进行分析。总共纳入了25名患者。我们通过ddPCR分析了534份样本（n = 25），通过NGS分析了256份样本（n = 24），通过eLB分析了371份样本（n = 22）。在20名病情进展的患者中，11名（55%）患者的ctDNA进展比实体瘤疗效评价标准（RECIST）1.1定义的进展提前了118天（范围：61 - 272天）。在9名通过ddPCR检测无ctDNA进展的患者中，2名患者通过eLB检测到突变增加，2名患者通过NGS检测到ctDNA进展。早期通过ddPCR和NGS检测到的ctDNA水平而非肿瘤体积负荷与无进展生存期（PFS）相关。NGS鉴定出的关键耐药机制包括基因扩增、C797S、E545K、V9del和S45P。血浆和唾液中ctDNA的连续评估可预测对奥希替尼的反应和耐药性，每种检测方法都具有互补作用。
