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.
Cancer
; 130(10): 1758-1765, 2024 May 15.
Article
in En
| MEDLINE
| ID: mdl-38422026
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
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Neoplasm, Residual
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High-Throughput Nucleotide Sequencing
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Circulating Tumor DNA
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Lung Neoplasms
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Neoplasm Recurrence, Local
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Neoplasm Staging
Limits:
Adult
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Aged
/
Aged80
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Cancer
Year:
2024
Type:
Article
Affiliation country:
Singapore