B-391 Is Comprehensive Cancer Panel By Next-generation Sequencing (NGS) More Efficient Than Cancer-specific NGS Panel in the Management of Non-small Cell Lung Cancer Patients?

Abstract Background : Genetic tests play an integral part in the diagnosis, treatment and prognosis of lung cancer patients. Comprehensive cancer panels using next-generation sequencing (NGS) are gradually becoming the standard tool and replacing the previous approach of single-gene or cancer-specific testing. In this study, we compared the performance of two commercially available NGS gene panels of different sizes concerning their clinical utility in the management of non-small cell lung cancer (NSCLC) patients. Methods A total of 65 tumor samples were sequenced with both lung cancer NGS panel (Lung-panel), 12 genes, and comprehensive cancer NGS panel (Pan-panel), 161 genes, following the manufacturer’s protocol. Results The Pan-panel detected 159 variants in 93.8% (61/65) patient samples; 37.7% (60/159) of these variants were classified as clinically relevant (tier I or II) with 68.3% (41/60) containing therapy approved and 31.7% (19/60) eligible for a clinical trial. The Lung-panel covered 51 of the 159 (32.0%) variants reported by the larger panel in 72.3% (47/65) tumor samples and all genetic alterations detected (51/51) were indicated as clinically relevant with 78.4% (40/51) described therapy-related variants and 21.6% (11/51) with a genomically matched clinical trial. While the Pan-panel detected more variants, additional variants beyond those included in the Lung-panel had no impact on NSCLC patient management. Even more remarkably, the cancer-specific panel despite covering a smaller genomic region than the comprehensive panel (28.7 kbp vs 329.4 kbp) was more informative in the context of FDA-approved therapy or biomarkers included in NCCN or ESMO guidelines that predict response or resistance to therapies in this cancer type, 78.4% and 68.3%, respectively. Conclusion Overall, this comparative analysis of the clinical utility of NGS panels of different sizes indicates that cancer-specific NGS panels containing carefully selected genes are as informative as larger panels when the primary goal is to identify clinically actionable mutations, particularly in patients with NSCLC. Furthermore, this approach presents a better balance among accurate identification of genomic variants, sensitivity, turnaround time, and cost-effectiveness for cancers with well-characterized molecular targets as shown in this study. Larger panels should be used in patients with rare and understudied forms of cancer or in academic reference centers where clinical and translational research is conducted.