医学
循环肿瘤DNA
危险系数
肺癌
置信区间
队列
液体活检
肿瘤科
实体瘤疗效评价标准
内科学
癌症
克拉斯
突变
癌症研究
表皮生长因子受体
数字聚合酶链反应
非小细胞肺癌
临床试验
胎儿游离DNA
生物标志物
临床研究阶段
生物
遗传学
作者
Young Kwang Chae,Andrew M. Davis,Sarita Agte,Alan Pan,Nicholas W. Simon,Wade T. Iams,Marcelo Santos Cruz,Keerthi Tamragouri,Kyunghoon Rhee,Nisha Mohindra,Victoria M. Villaflor,Wungki Park,Gilberto Lopes,Francis J. Giles
出处
期刊:Oncologist
[Wiley]
日期:2019-06-01
卷期号:24 (6): 820-828
被引量:61
标识
DOI:10.1634/theoncologist.2018-0433
摘要
Abstract Background Tissue tumor mutational burden (TMB) has emerged as a potential biomarker predicting response to anti-programmed cell death-1 protein receptor (PD-1)/programmed cell death-1 protein ligand (PD-L1) therapy, but few studies have explored using circulating tumor DNA (ctDNA) TMB in non-small cell lung cancer (NSCLC). Materials and Methods A total of 136 patients with NSCLC with ctDNA testing were retrospectively evaluated from a single institution, along with a validation cohort from a second institution. ctDNA TMB was derived using the number of detected mutations over the DNA sequencing length. Results Higher ctDNA TMB was significantly correlated with smoking history (p < .05, chi-squared test). Among patients treated with immune checkpoint inhibitors (n = 20), higher ctDNA TMB was significantly correlated with shorter progressive free survival (PFS) and overall survival (OS; 45 vs. 355 days; hazard ratio [HR], 5.6; 95% confidence interval [CI], 1.3–24.6; p < .01, and OS 106 days vs. not reached; HR, 6.0; 95% CI, 1.3–27.1; p < .01, respectively). In a small independent validation cohort (n = 12), there was a nonsignificant numerical difference for higher ctDNA TMB predicting shorter OS but not PFS. ctDNA TMB was not correlated with RECIST tumor burden estimation in the subset of patients treated with immune checkpoint blockade. Conclusion The findings indicate that higher ctDNA TMB, at the current commercial sequencing length, reflects worse clinical outcomes.
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