Lung neoplasms are the second most frequently diagnosed cancer and are the most common cause of cancer death worldwide (1). The different types of lung cancer are described by morphologic evaluation and tumor biological characteristics. There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter being more prevalent.

SCLC is a neuroendocrine tumor that behaves most aggressively and is treated non-surgically in most cases, whereas NSCLC has a better prognosis and is managed by a combination of surgery and adjuvant therapy. The three main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma (2). In addition to histological classification, NSCLC can be further characterized into subtypes that exhibit specific genetic alterations. This molecular stratification of NSCLC tumors is critical to improving the understanding of carcinogenesis, determining the prognosis, and defining a personalized treatment. In this context, genetic testing has emerged as an integral part of NSCLC patient care and solid tumor panels using next-generation sequencing (NGS) have become a common tool in clinical practice (3).

The question is, which NGS panel is best suited to investigate clinically relevant variants in NSCLC? Currently, panels with extensive genomic coverage have been used as an initial testing approach for some patients with NSCLC, and alternatively single gene tests or those panels that contain only a few genes related to the specific cancer type are performed (3). To assess the effectiveness of this latter approach, we compared the clinical performance of two commercial NGS panels of different sizes for the treatment of NSCLC patients. Tumor sample from 65 NSCLC patients were sequenced and analyzed with a Target NGS panel for lung cancer (12 genes) and a Comprehensive Genomic Profiling (CGP) NGS panel (> 160 genes).

The CGP panel identified at least one variant in 93.8% of patients (61/65). A total of 159 variants were observed, 37.7% (60/159) of which were classified as actionable, with 25.8% (41/159) containing approved therapy and 11.9% (19/159) eligible for a clinical trial.

The target panel detects variants in 72.3% of patients (47/65) and identified 32% of variants reported by the CGP panel (51/159). All genetic alterations detected by the Target panel were classified as actionable (100% - 51/51), with 78.4% (40/51) described therapy-related variants and 21.6% (11/51) with a genomically matched clinical trial. While CGP panel detected more variants, additional variants beyond those included in the Target panel had no impact on the treatment of NSCLC patients. We conclude that target panels containing a judicious selection of genes may be more clinically efficient and as informative as larger panels when the main objective is to identify actionable mutations. This result is consistent with specialized guidelines that recommend analyzing a limited number of genes of interest for each type of cancer (4,5).

In summary, target panels have a better balance between genomic variants detection, sensitivity, turnaround time, and cost-effectiveness for well-characterized cancer types. CGP panels should be used for patients who test negative for mutations in driver genes, rare and understudied cancer forms, or clinical research.

References

  • Thandra K., Barsouk A., Saginala K. et al.. Epidemiology of lung cancer. Contemp Oncol (Pozn) 25, 45-52 (2021). https://doi.org/10.5114/wo.2021.103829.
  • Zheng M. Classification and Pathology of Lung Cancer. Surg Oncol Clin N Am. 2016 Jul;25(3):447-68. doi: 10.1016/j.soc.2016.02.003. PMID: 27261908.
  • Vail E., Song J., Xu J. et al. Comparison of Large, Medium, and Small Solid Tumor Gene Panels for Detection of Clinically Actionable Mutations in Cancer. Targ Oncol 15, 523–530 (2020). https://doi.org/10.1007/s11523-020-00743-9.
  • National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology, non-small cell lung cancer (Version 1.2022, December 7 2021). 2021. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Last accessed: 06 July 2023.
  • Planchard D et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv192-237.