Undetectable circulating tumor DNA levels correlate with low risk of recurrence/metastasis in postoperative pathologic stage I lung adenocarcinoma patients

医学 内科学 磨玻璃样改变 肿瘤科 肺癌 腺癌 置信区间 比例危险模型 阶段(地层学) 胃肠病学 转移 癌症 生物 古生物学
作者
Weixiong Yang,Na You,Minghan Jia,Sai‐Ching J. Yeung,Wei Ou,Man Yu,Yinguang Wang,Xiayu Fu,Zhanfei Zhang,Jiali Yang,Zengding Lao,Zhenguo Liu,Bo Zeng,Qiuxiang Ou,Xue Wu,Yang Shao,Xiaoyu Hong,Siyu Wang,Chao Cheng
出处
期刊:Lung Cancer [Elsevier BV]
卷期号:146: 327-334 被引量:15
标识
DOI:10.1016/j.lungcan.2020.06.009
摘要

Objectives The application of circulating tumor DNA (ctDNA) monitoring after resection in pathologic(p) stage I lung adenocarcinoma (LUAD) patients remains controversial and it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. We aim to assess the utility of ctDNA in tracking early recurrence or metastasis following surgery and reveal the genetic differences between GGO and non-GGO. Materials and methods Tumor tissues and matched postoperative plasma samples were collected from a total of 82 (p)stage I LUAD patients. Comprehensive genomic profiling was performed using capture-based hybrid next generation sequencing by targeting 422 cancer relevant genes. Results EGFR and TP53 represent commonly mutated genes in this cohort of (p)stage I lung adenocarcinoma, followed by alterations in ALK, PIK3CA, STK11 and MYC. For a median follow-up period of 22.83 months after surgery, 65 out of 67 ctDNA-negative patients remained progression-free, while 3 out of 15 ctDNA-positive patients progressed [P = 0.040; positive predictive value = 0.20, 95 % confidence interval (CI), 0.04−0.48; negative predictive value = 0.97, 95 % CI, 0.9–1]. With time-dependent Cox regression analysis, we observed that ctDNA positivity significantly correlated with increased probability of early tumor recurrence or metastasis (P = 0.02, HR=8.5). Further comparison between GGO and non-GGO subgroups indicated the frequency of TP53 mutations in non-GGO was markedly higher than that in GGO (47 % vs 21 %, P < 0.05). Pathway analysis showed the epigenetic regulation pathway was more frequently affected in GGO subgroup, while impaired apoptosis/cell cycle pathway was more enriched in non-GGO LUADs. Conclusions Our longitudinal ctDNA monitoring data showed that undetectable ctDNA may predict low risk of tumor recurrence or metastasis in postoperative (p)stage I LUAD patients, while it requires further investigation on how robust the positive ctDNA results could predict tumor relapse in these patients. Clinical registration number NCT03172156.
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