1. Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.
- Author
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Tan AC, Lai GGY, Saw SPL, Chua KLM, Takano A, Ong BH, Koh TPT, Jain A, Tan WL, Ng QS, Kanesvaran R, Rajasekaran T, Kalashnikova E, Renner D, Sudhaman S, Malhotra M, Sethi H, Liu MC, Aleshin A, Lim WT, Tan EH, Skanderup AJ, Ang MK, and Tan DSW
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Early Detection of Cancer methods, Biomarkers, Tumor genetics, Biomarkers, Tumor blood, Adult, Aged, 80 and over, Multiplex Polymerase Chain Reaction methods, Lung Neoplasms genetics, Lung Neoplasms blood, Lung Neoplasms pathology, Circulating Tumor DNA blood, Circulating Tumor DNA genetics, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Non-Small-Cell Lung pathology, High-Throughput Nucleotide Sequencing methods, Neoplasm, Residual genetics, Neoplasm, Residual diagnosis, Neoplasm Staging
- 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, tumor-informed 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 single-nucleotide 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., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
- Published
- 2024
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