Review Outlines Potential Benefits, Challenges of Next-Generation Sequencing for Early-Stage NSCLC

Investigators examined the current bodies of evidence surrounding the emergence of next-generation gene sequencing, and the challenges that come with it, for identifying oncogenic drivers of early-stage non–small cell lung cancer (NSCLC).

As the body of evidence demonstrating the use of next-generation sequencing (NGS) in patient with earlier-stage non–small cell lung cancer (NSCLC) continues to grow, so does the evidence showing the potential for NGS to be used as a prognostic and predictive tool, according to a recent review.

The review, published in Cancers, highlights some of the increasing bodies of research assessing the use of NGS and tumor genomic-based therapies in earlier-stage cancer, which previously has been reserved for patients with advanced and metastatic NSCLC. It also looked at possible challenges as a result of using NGS, including data compiling, cost, and accessibility.

“With time, this trend should only continue, with technological advancements leading to better understanding of NSCLC and more personalized treatment approaches. In the future, NGS will play a critical role in further elucidating the genomic features of tumor biology, identifying new treatment targets, and improving risk-stratification in early-stage disease,” wrote the investigators.

NGS is typically used to identify specific oncogenic drivers and help in the development of matched targeted therapies, which have revolutionized cancer care and outcomes for patients with locoregionally advanced and metastatic NSCLC. However, few efforts have been made to investigate tumor genomic profiling for patients with earlier-stage NSCLC, where surgery acts as a diagnostic and therapeutic tool.

In one study from the United Kingdom, which revealed robust tumor heterogeneity among 100 patients who underwent upfront surgical reception for lung cancer. The heterogeneity was observed by substantial intratumoral subclonal somatic mutations and somatic copy number alterations.

“As more studies use NGS approaches to explore tumor heterogeneity and evolution, there will be an increasing number of opportunities to clinically leverage this growing body of knowledge,” the review authors noted.

Other studies that examined patients who have undergone surgery to resect early-stage disease found that detection of oncogenic alterations that represent potential therapeutic targets are also important for collecting information regarding the potential for recurrence. The investigators said that it is possible that risk models derived from genomic and pathologic features coupled with analysis of circulating tumor DNA (ctDNA) may provide the best risk assessment in patients who have undergone surgery.

NGS can also be used to discern between separate primary lung cancers and intrapulmonary metastases in lung adenocarcinoma, and broad-panel NGS has become the gold standard for differentiating between the two. However, large-panel NGS platforms can be difficult to access, be expensive, and have long turnaround time for results, and thus, not all institutions currently provide NGS testing.

“Moving forward, a comprehensive diagnostic approach that incorporates both histologic subtype and NGS will be essential to discriminate multiple NSCLCs by providing robust confirmation of tumor clonality and identifying actionable mutations,” the investigators noted.

The investigators also outlined that the emergence of new technologies, including machine learning and artificial intelligence, are helping solve some of the challenges that arise with NGS, such as combining the massive amounts of clinical, pathologic, and genomic data into optimal treatment strategies for patients in this population.

“Despite potential future challenges, over the past decade, technological advancements in NGS approaches, reduced costs of sequencing, and newly discovered applications (such as ctDNA) have resulted in considerable progress in tumor biology research and, more importantly, in driving new cancer care treatment paradigms,” wrote the investigators.

Reference

Lengel HB, Connolly JG, Jones GD, et al. The emerging importance of tumor genomics in operable non-small cell lung cancer. Cancers. 2021;13(15):3656. doi:10.3390/cancers13153656