학술논문
Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in earlystage lung cancer.
Document Type
Article
Author
Tan, Aaron C.; Lai, Gillianne G. Y.; Saw, Stephanie P. L.; Chua, Kevin L. M.; Takano, Angela; Ong, Boon-Hean; Koh, Tina P. T.; Jain, Amit; Wan Ling Tan; Quan Sing Ng; Kanesvaran, Ravindran; Rajasekaran, Tanujaa; Kalashnikova, Ekaterina; Renner, Derrick; Sudhaman, Sumedha; Malhotra, Meenakshi; Sethi, Himanshu; Liu, Minetta C.; Aleshin, Alexey; Wan-Teck Lim
Source
Subject
Language
ISSN
0008-543X
Abstract
Background: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumorinformed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay. Methods: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 singlenucleotide variants in plasma samples. Results: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001). Conclusions: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting. [ABSTRACT FROM AUTHOR]