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Genotype-Specific Differences in Circulating Tumor DNA Levels in Advanced NSCLC.

Vincent K Lam1, Jianjun Zhang1, Carol C Wu1

  • 1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|January 3, 2021
PubMed
Summary

Plasma circulating tumor DNA (ctDNA) levels in non-small cell lung cancer (NSCLC) correlate with tumor burden and are influenced by specific gene mutations. These findings are crucial for advancing ctDNA

Keywords:
Cancer detectionGenotypeLiquid biopsyLung cancerPET/CTTumor volumectDNA

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Area of Science:

  • Oncology
  • Genomics
  • Medical Imaging

Background:

  • Plasma-based circulating tumor DNA (ctDNA) is a key biomarker for molecular profiling and disease monitoring in non-small cell lung cancer (NSCLC).
  • Understanding the factors influencing ctDNA shedding and its correlation with tumor burden, especially in advanced stages, remains incomplete.

Purpose of the Study:

  • To investigate the relationship between ctDNA variant allele frequency and tumor burden in patients with NSCLC.
  • To identify predictors of ctDNA shedding, including tumor genotype and metastatic status.

Main Methods:

  • Retrospective analysis of genomic and imaging data from 144 NSCLC patients.
  • Quantification of tumor burden using computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-CT (PET-CT).

Main Results:

  • A significant correlation was observed between ctDNA variant allele frequency and imaging-based measures of tumor burden (CT volume, metabolic tumor volume).
  • The correlation strength varied by tumor genotype, being strongest in KRAS-mutant and TP53-mutant NSCLC, and weakest in EGFR-mutated (EGFR+) tumors.
  • TP53 and EGFR mutations, visceral metastasis, and tumor burden were independent predictors of increased ctDNA shedding.

Conclusions:

  • ctDNA levels in NSCLC are influenced by both tumor burden and specific tumor genotypes, potentially due to variations in DNA shedding and cellular turnover.
  • These genotype-specific differences have significant implications for the use of ctDNA in NSCLC disease monitoring and early detection.