Real-world challenges in undertaking NTRK fusion testing in non-small cell lung cancer.

Background: We performed a retrospective analysis to determine the incidence of neurotrophic tropomyosin-receptor kinase ( NTRK) fusion in non-small cell lung cancer (NSCLC).
Methods: Archival NSCLC tissues between 2018-2020 were screened by immunohistochemistry (IHC) with IHC-positive cases undergoing confirmatory molecular analysis. Correlative clinicopathologic parameters were collected.
Results: Of 289 samples analyzed, 10 (3.5%) cases had NTRK expression on IHC. The median age of patients with NTRK-positivity on IHC was 74.9 (range, 44-88) years and 70% had a smoking history. The cohort included seven adenocarcinomas and one each squamous cell carcinoma, large-cell neuroendocrine and not otherwise specified histologies. PDL1 expression was ≤50% in five cases. Concurrent EGFR mutations were detected in three cases, with two cases also showing a PIK3CA E542K mutation and MET amplification, respectively. Due to insufficient tumor material, RNA-sequencing was undertaken in only one IHC-positive case, with the other nine cases analyzed by Fluorescent in-situ Hybridisation. A NTRK fusion, EML4-NTRK3 gene fusion was detected in one patient, a frequency of 0.35%.
Conclusions: NTRK fusions in NSCLC are rare. This study highlights real world diagnostic challenges regarding NTRK testing, such as requirements of adequate tumor tissue and appropriate testing methodologies.
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-113/coif). SP served on the advisory board of Astra Zeneca, received speaking honoraria from Astra Zeneca, Roche and MSD, and received research funding from Roche outside the submitted work. The other authors have no conflicts of interest to declare.
(2023 Journal of Thoracic Disease. All rights reserved.)