Circulating tumor DNA profiling for non-invasive genomic analysis in Indian lung cancer patients: A real-world experience

Background

Liquid biopsy assays are an important tool for non-invasive detection of genetic alterations, providing an effective alternative to traditional tissue biopsies. The study aimed to investigate the utility of ctDNA based next generation sequencing for clinical management of lung cancer patients from India.

Methods

We conducted ctDNA targeted sequencing on 425 lung cancer patients from India using 50 gene oncomine precision assay. The assay was validated employing 7 controls and 77 clinical samples, and the performance of the assay was evaluated. The concordance analysis with matched tissue biopsy samples was performed on 162 cases.

Results

Among the 425 lung cancer samples, 47 % harbored at least one mutation. EGFR was the most frequently altered gene (25.2 %), followed by TP53 (19.8 %) and KRAS (4.5 %). Concordance with tissue biopsy data was 77 % for EGFR, 79 % for TP53 and above 97 % for low frequency mutations. The assay demonstrated 100 % specificity and around 60 % sensitivity for the majority of clinically relevant genetic alterations including EGFR, KRAS and BRAF. Notably ERBB2 alterations were detected with 100 % sensitivity and specificity.

Conclusion

The ctDNA assay demonstrates high accuracy and specificity, for both prevalent and rare genetic alterations. While further advancements are needed to enhance sensitivity and routine clinical application, our ctDNA profiling assay offers a reliable alternative for detecting genetic alterations in lung cancer patients, with significant potential for clinical integration in the Indian healthcare context.