KRAS Mutations in Circulating Tumor DNA for Lung Cancer Diagnosis: A Comprehensive Meta-Analysis

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• KRAS gene mutations are critical drivers in lung cancer development and progression.
• Circulating tumor DNA (ctDNA) detection offers a minimally invasive method for identifying these mutations.
• Existing studies report variable accuracy for ctDNA-based KRAS mutation detection.

Purpose of the Study:

• To systematically review and meta-analyze the diagnostic accuracy of ctDNA-based KRAS mutation detection in lung cancer.
• To provide pooled estimates of sensitivity, specificity, and likelihood ratios for this diagnostic approach.

Main Methods:

• Systematic review and meta-analysis following PRISMA-DTA guidelines.
• Inclusion of studies evaluating KRAS mutations in ctDNA from plasma or serum for lung cancer diagnosis.
• Calculation of pooled sensitivity, specificity, and likelihood ratios using aggregated 2x2 contingency tables and a bivariate random-effects model.

Main Results:

• Nine study arms with 691 patients were included.
• Pooled sensitivity was 65.2% and pooled specificity was 93.7%.
• The diagnostic odds ratio was 28.0, indicating strong rule-in capability, with moderate heterogeneity in sensitivity and minimal heterogeneity in specificity.

Conclusions:

• ctDNA-based KRAS mutation detection exhibits high specificity and moderate sensitivity for lung cancer diagnosis.
• A KRAS liquid biopsy can serve as a valuable complementary tool, especially when tissue biopsy is challenging.
• This approach supports personalized treatment decisions as technology advances.