Circulating tumor DNA: An alternative to tissue biopsy for detecting epidermal growth factor receptor mutation in
Md Kabirul Islam Soroar1, Sharmistha Roy1, Hosne Ara1
1Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
Abstract:
BackgroundNon-small cell lung cancer (NSCLC) patients who have mutations in their epidermal growth factor receptor (EGFR) gene respond more favorably to tyrosine kinase inhibitors (TKIs) than to standard chemotherapy. However, tissue biopsy-based EGFR testing is invasive, costly, and technically challenging. Plasma-derived circulating tumor DNA (ctDNA) offers a minimally invasive and cost-efficient alternative for mutation profiling. This study assessed the agreement between EGFR mutation status in plasma-derived ctDNA and tissue biopsy in NSCLC patients from tertiary care hospitals in Bangladesh.MethodsIn this cross-sectional analytical study, we recruited 32 patients with NSCLC before EGFR-TKI treatment. EGFR mutations in ctDNA samples were identified using the Amplification Refractory Mutation System (ARMS) polymerase chain reaction method. Tissue biopsy results were obtained from routine diagnostic procedures. Agreement between ctDNA and tissue biopsy results was assessed using kappa statistics, and diagnostic performance metrics were calculated.ResultsMost of our study participants were male (75%) and had stage IV lung adenocarcinoma (72%). We observed substantial agreement between plasma-derived ctDNA samples and tissue biopsies (kappa, κ = 0.683). This agreement was almost perfect (κ = 0.826) when calculated for patients with stage IV disease. The overall concordance was 84.4%. Compared with tissue biopsy, ctDNA testing yielded a sensitivity of 73.3% and a specificity of 94.1%.ConclusionPlasma-derived ctDNA demonstrates substantial agreement with tissue biopsy for EGFR mutation detection in patients with NSCLC, particularly those with advanced-stage disease. These findings support ctDNA as a viable alternative for molecular profiling in settings where tissue biopsy is limited or impractical.
Insights
Plasma-derived circulating tumor DNA (ctDNA) testing shows substantial agreement with tissue biopsies for detecting epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. This minimally invasive method is a viable alternative, especially for advanced-stage disease.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations benefit from tyrosine kinase inhibitors (TKIs).
- Tissue biopsy for EGFR mutation testing is invasive, costly, and technically difficult.
- Plasma-derived circulating tumor DNA (ctDNA) offers a less invasive, cost-effective alternative for mutation profiling.
Purpose of the Study:
- To assess the agreement between EGFR mutation status in plasma ctDNA and tissue biopsy in NSCLC patients in Bangladesh.
- To evaluate ctDNA as a diagnostic tool for EGFR mutations in NSCLC.
Main Methods:
- A cross-sectional study involving 32 NSCLC patients prior to EGFR-TKI treatment.
- EGFR mutations in ctDNA identified using Amplification Refractory Mutation System (ARMS) PCR.
- Comparison of ctDNA results with routine tissue biopsy results using kappa statistics and diagnostic performance metrics.
Main Results:
- Substantial agreement between ctDNA and tissue biopsy (kappa = 0.683), particularly in stage IV disease (kappa = 0.826).
- Overall concordance rate of 84.4%.
- ctDNA testing demonstrated a sensitivity of 73.3% and a specificity of 94.1% compared to tissue biopsy.
Conclusions:
- Plasma ctDNA shows significant agreement with tissue biopsy for EGFR mutation detection in NSCLC.
- ctDNA is a practical and reliable alternative for molecular profiling, especially when tissue biopsy is challenging or unavailable.
- Findings support the use of ctDNA for guiding TKI treatment decisions in NSCLC patients.
