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Alexander Drilon, MD

Gregory J. Riely, MD, PhD


NTRK Fusion–Positive NSCLC: Challenges in Detection Methods

By: Vanessa A. Carter, BS
Posted: Friday, June 3, 2022

According to Daniel Kazdal, PhD, of University Hospital Heidelberg, Germany, and colleagues, comprehensive, high-throughput screens to detect genetic fusions are likely to become the standard of care for newly diagnosed non–small cell lung carcinoma (NSCLC). Published in Genes Chromosomes & Cancer, their retrospective review was designed to elucidate the recent challenges concerning the detection of NTRK fusions and the future development of molecules to target this type of lung cancer.

“Different gene fusions are already associated with therapeutic targets in advanced nonsquamous NSCLC, but many other fusions could probably be targeted in the future by new molecules, whatever the tumor stage and the histological subtype,” concluded the study authors. “Therefore, it will certainly be of strong interest to register data concerning all the genomic alterations associated with gene fusions, histological and radiological imaging, the results of immunohistochemistry, liquid biopsies, et cetera.”

Typically, NTRK fusions in NSCLC are often reported in younger patients and more frequently in nonsmokers and White individuals. Although these gene alterations are rare, the status of NTRK fusions must be evaluated in these patients to determine whether they need first-line treatment with entrectinib or larotrectinib. Immunohistochemistry and multiplex digital color-coded barcode technology have both proven successful in detecting these fusions, but RNA next-generation sequencing is notably more efficient for these assessments, the authors commented.

Recently, a comprehensive retrospective analysis of approximately 34,000 patients was performed to detect NTRK fusions. The authors used DNA and RNA sequencing, as well as immunohistochemical approaches, and identified a specificity and sensitivity of 99.9% and 81.1%, respectively. Regarding the immunohistochemistry assay, however, the sensitivity was 87.9% and the specificity was 81.1% in total. Sensitivities among each of the NTRK genes—NTRK1 (96%), NTRK2 (100%), and NTRK3 (79%)—were also not consistent.

Disclosure: For full disclosures of the study authors, visit

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