Role of Circulating Tumor DNA Tumor Fraction in Advanced Non-Small Cell Lung Cancer and Its Impact on Patient
Ben Man Fei Cheung1, Elaine Yee-Ling Ko2, David Jen Hao Shih3
1Department of Clinical Oncology, Queen Mary Hospital, Hong Kong SAR, China.
Purpose:
Comprehensive genomic profiling (CGP) using targeted panel next-generation sequencing (TP-NGS) is pivotal in the clinical management of advanced non-small cell lung cancer (aNSCLC). Despite the limitations associated with tumor tissue sampling, circulating tumor DNA (ctDNA) presents a promising alternative. This study aims to assess the prognostic value of ctDNA tumor fraction (TF) in aNSCLC.
Materials And Methods:
We conducted a multicenter prospective study in Hong Kong. Patients with aNSCLC provided blood samples within 31 days before treatment initiation, followed by CGP using a validated ctDNA assay.
Results:
Among 878 patients, those with ctDNA TF ≥1% had significantly worse outcomes, with median progression-free survival (PFS) of 13.2 months and overall survival (OS) of 17.6 months compared with the ctDNA TF <1% group (P < .05). ctDNA TF demonstrated predictive capabilities for OS at various time points, with AUC values ranging from 0.65 to 0.75 for the overall population. The predictive strength of ctDNA TF in the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) subgroup remained robust for OS at 24 months, achieving an AUC of 0.79. We validated a ctDNA TF threshold of 2.3% for inferior OS in the overall population, whereas a distinct threshold of 1.6% and 2.2% was validated for EGFR TKI and chemotherapy ± immunotherapy.
Conclusion:
Our findings establish ctDNA TF as a clinically relevant biomarker in aNSCLC, providing robust prognostic and predictive information. The findings support the integration of ctDNA TF quantification into routine clinical workflows, reinforcing its role in advancing precision oncology and improving risk stratification and outcomes for patients with aNSCLC.
