Abstract 132P
Background
Selective tropomyosin receptor kinase (TRK) inhibitors, indicated for patients with solid tumors harboring a gene fusion involving one of the three neurotrophic TRK genes (NTRK1-3), are now approved in US and Europe. However, systematic estimates of NTRK gene fusion frequency and knowledge on its disease characteristics in each tumor entity are limited. This study aims to characterize biobank samples with linkage to electronic health records (EHR) to describe: 1. NTRK gene fusion frequency amongst papillary thyroid carcinoma (PTC) cohort; 2. patient demographics, natural history of disease, and clinical journey.
Methods
A retrospective cohort (n=389) of histologically-confirmed PTC patients, diagnosed between 1993-2018, with research-consented archival formalin-fixed paraffin-embedded tumor samples were obtained from Auria Biobank. All samples were stained for pan-TRK protein expression by immunohistochemistry (IHC) antibody clone EPR17341 and by next generation sequencing (NGS) using Illumina TruSight170 kit. Due to data completeness, genomic data of a subcohort (n=234) diagnosed between 2005-2017 were linked to the Turku University Hospital EHR to describe clinical characteristics. Observation period began 1 year prior to diagnosis till end of follow-up/death.
Results
1.54% (6/389) patients were identified with NTRK3 gene fusions and partners of EML4, RBPMS, and ETV6. Of the 6 patients, 1 expressed BRAF V600E, and 2 additional patients presented RB1 deletion and NSG2-KIF5B gene fusion respectively. The overall subcohort is 26% male, mean age at diagnosis of 53 years, and mean Charlson Comorbidity Index score at diagnosis of 2.6. At end of follow-up, 86% are alive. Of the 3/234 patients harboring NTRK gene fusion, 2 are male, mean age at diagnosis was 33 years, early stage at diagnosis (I=1, II= 2), and no comorbidities were present at diagnosis. All 3 patients received only radioiodine ablation and are currently alive with mean observation period of 8.63 years.
Conclusions
This study confirms the rarity of NTRK gene fusions in PTC, the ability of IHC and NGS to identify these patients, and the capability to link genomic data with EHR to describe clinical characteristics.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Bayer AG.
Funding
Bayer AG.
Disclosure
W. Zhang: Full/Part-time employment: Bayer US LLC. R. Schulze-Rath: Full/Part-time employment: Bayer AG. B. Farahmand: Full/Part-time employment: Bayer AB. S. Bender: Full/Part-time employment: Bayer AG. A. Schmitz: Full/Part-time employment: Bayer AG. J. Zong: Full/Part-time employment: Bayer US LLC. All other authors have declared no conflicts of interest.