A non-invasive liquid biopsy may be more effective at detecting clinically relevant mutations in patients with advanced lung cancer than standard biopsies, according to a study published in the journal Clinical Cancer Research.
As the number of targeted therapeutics for non-small cell lung cancer (NSCLC) continues to expand, real-time tumor genotyping is needed to ensure that patients receive care that is optimized for their specific cancer type. Yet, invasive biopsies are difficult to perform and often yield inadequate DNA for next-generation genotyping. Therefore, researchers conducted a study evaluating the feasibility of using cell-free circulating tumor DNA (CTDNA) as a complement or alternative to tissue next-generation sequencing for patients with NSCLC.
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For the study, researchers enrolled 102 patients with advanced NSCLC who had blood samples sent for ctDNA testing as part of their routine care. Overall, they detected 275 alterations in 45 genes and at least one alteration in the ctDNA for 86 of 102 patients (84%), with epidermal growth factor receptor (EGFR) variants being the most common. Additionally, ctDNA tests detected 50 driver and 12 resistance mutations, as well as 22 other genes that could by targeted using experimental therapies, including those in clinical trials.
However, while ctDNA next-generation sequencing was completed for all 102 patients, tissue sequencing was only successful for 50 patients (49%). In these patients, actionable EGFR mutations were detected in 24 tissue and 19 ctDNA samples, yielding a concordance of 79%. The concordance was also higher when blood and tissue samples were collected in quick succession.
From these results, researchers concluded that therapeutically targetable driver and resistance mutations can be detected by ctDNA next-generation sequencing, even when tissue is unavailable, allowing for more accurate diagnosis, improved patient management, and serial sampling to monitor disease progression and treatment resistance. Larger scale studies will be required to validate the use of ctDNA in patients with NSCLC.
Erica L Carpenter, PhD, MBA, University of Pennsylvania, Philadelphia, senior author of the study, lauded thefindings in a press statement released along side the study.
"This represents a bit of a paradigm shift," said Dr Carpenter. "The tissue biopsy sequencing result has been considered the gold standard against which one compares the ctDNA result. Our work suggests that one can act on a ctDNA result, even in the absence of the so-called gold standard, and get a clinical response in these patients. It also offers the advantage of testing without discomfort to the patient and possible risks associated with invasive biopsies."
