To optimize the molecular workup of patients with metastatic non-small cell lung cancer (NSCLC) using DNA and RNA next-generation sequencing (NGS), smoking status may need to be considered, according to a study published in the Journal of Thoracic Oncology.

The study was conducted using samples collected between March 2018 and January 2019 from 390 patients with NSCLC who had not yet started treatment. Samples were analyzed either in parallel — that is, DNA NGS and RNA NGS were done in addition to immunohistochemical staining for ALK, ROS1, and PD-L1 — or sequentially — that is, RNA NGS was only done if DNA NGS did not show one of the following pathogenic driver mutations:  KRAS, BRAF, EGFR, ERBB2 (including ERBB2 amplification), or MET exon 14 skipping.

A total of 192 patients had their samples analyzed in parallel and 198 sequentially. Among the patients who had their samples analyzed sequentially, 53% had to be analyzed using RNA NGS because no pathogenic driver mutation was identified by DNA NGS.

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Overall, additional analysis with RNA NGS affected treatment options for 5% of patients and the utility of RNA NGS appeared to depend on smoking status: a fusion or exon skipping event was detected by RNA NGS in 32% of never-smokers and 4% of former and current smokers (P =.00).

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The study also showed that the sequential and parallel approach had the same median turnaround time of 9 days, but if additional RNA NGS was needed, that time increased to 15 days.

The study authors concluded that “switching to a sequential approach drastically reduced the amount of unnecessary diagnostics steps and the accompanying costs,” and that a parallel approach should be used for never-smokers because RNA NGS has a “much higher” yield.

Disclosure: Some of the authors disclosed financial relationships with pharmaceutical or medical device companies. For a full list of disclosures, please refer to the original study.


Cohen D, Hondelink LM, Solleveld-Westerink N, et al. Optimizing mutation and fusion detection in non-small cell lung cancer by sequential DNA and RNA sequencing [published online January 31, 2020]. J Thorac Oncol. doi: 10.1016/j.jtho.2020.01.019