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

ABSTRACT

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.