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. 2024 May 15;130(10):1758-1765.
doi: 10.1002/cncr.35263. Epub 2024 Feb 29.

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

Aaron C Tan  1   2 , Gillianne G Y Lai  1   2 , Stephanie P L Saw  1   2 , Kevin L M Chua  2   3 , Angela Takano  4 , Boon-Hean Ong  2   5 , Tina P T Koh  1   2 , Amit Jain  1   2 , Wan Ling Tan  1   2 , Quan Sing Ng  1   2 , Ravindran Kanesvaran  1   2 , Tanujaa Rajasekaran  1   2 , Ekaterina Kalashnikova  6 , Derrick Renner  6 , Sumedha Sudhaman  6 , Meenakshi Malhotra  6 , Himanshu Sethi  6 , Minetta C Liu  6 , Alexey Aleshin  6 , Wan-Teck Lim  1   2   7 , Eng-Huat Tan  1   2 , Anders J Skanderup  8 , Mei-Kim Ang  1   2 , Daniel S W Tan  1   2   8
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Free article

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

Aaron C Tan et al. Cancer. .
Free article

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.

Keywords: circulating tumor DNA; early‐stage lung cancer; liquid biopsy; non–small cell lung cancer.

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