Abstract 925: NTRK gene fusion in adults and pediatrics with solid tumors: a record linkage study of expression frequency and patient characteristics using the Auria Biobank in Finland
Authors: Zhang Wei , Perälä Merja , Kallionpää Roosa E. , Pitkänen Niina , Jöhrens Korinna , Schulze-Rath Renate , Schmitz Arndt A , Guo Helen , Zong Jihong 
Published: April 2023

Introduction: Selective tropomyosin receptor kinase (TRK) inhibitors are targeted therapies for patients with solid tumors harboring a neurotrophic-receptor tyrosine kinase (NTRK) gene fusion. Estimates of the frequency of NTRK gene fusions and knowledge about characteristics of affected patients from population-based settings are limited.

Methods: This was a retrospective cohort study using archival tissue samples from patients with histologically-confirmed solid tumors identified from the Auria Biobank in the Turku region of Finland (January 2005-December 2019). We evaluated all solid tumor types in pediatrics, and selected tumor types in adults (colorectal cancer [CRC], non-small cell-lung cancer [NSCLC], sarcoma, and salivary/parotid cancer). Expression of TRK protein was determined by pan-TRK immunohistochemistry (IHC) staining of tumor samples scored by a certified pathologist. NTRK gene fusion including fusion partners was then confirmed by next generation sequencing (NGS). Patients’ demographics, clinical characteristics, and survival status were determined through linkage to hospital electronic health records and the national vital statistics database; patients were followed from 1 year before cancer diagnosis until the end of follow-up/death.

Results: NTRK gene fusion frequency and descriptions of patient and tumor characteristics are shown in the Table. The number of patients confirmed as NTRK positive after NGS as a proportion of those deemed NTRK positive after IHC staining was 80% (8/10) for CRC, 5% (1/21) for NSCLC, 6% (1/18) for salivary/parotid cancer, 0% (0/21) for sarcoma, and 25% (4/16) for pediatric solid tumors.

Conclusions: This study shows that NTRK gene fusions are rare in adult CRC, NSCLC, parotid/salivary tumors, sarcoma, and pediatric solid tumors.

Frequency of NTRK gene fusion in pediatric and select adult solid tumors, and characteristics of NTR NTRK gene fusion-positive NTRK gene fusion subtypes Fusion partners Median age (category) at diagnosis (years) Sex Tumor details Treatment/follow-up status Adults CRC (N=1151) 8 (0.7%) NTRK1 (n=6) NTRK2 (n=1) NTRK3 (n=1) NTRK1: TPM3 (n=3), LMNA (n=1), TPR (n=1), IRF2BP2 (n=1) NTRK2*: FXN (n=1), LPPR1 (n=1) NTRK3: GABRG1 (n=1) *In a single patient with two tumor samples NTRK2 was identified in both samples, but the fusion partner (and other genomic co-alterations) were different between the two samples. 60-69 3 male, 5 female All were grade 2-3 ECOG score 1 (n=4)† MSI: abnormal (n=4), normal (n=1), missing (n=1) †ECOG score was missing for the remaining patients. Chemotherapy: n=3 Radiotherapy: n=1 All alive at end of follow-up (range, 0.3-11.5 years) Sarcoma (N=379) 0 (0.0%) - - - - - - NSCLC (N=288) 1 (0.3%) NTRK3 (n=1) SGCZ (n=1) 60-69 Female Stage IVA, grade II, ECOG score 1 Chemotherapy but not radiotherapy Alive at 0.6 years‘ follow-up Salivary/parotid (N=114) 1 (0.9%) NTRK3 (n=1) ETV6 (n=1) 60-69 Male Salivary cancer, stage 1, T2N0M0 ECOG score was missing No chemotherapy/radiotherapy Alive after 13.9 years‘ follow-up Fibrosarcoma (n=1) Primitive neuroectodermal cancer (n=1) Ewing’s sarcoma (n=1) Papillary thyroid cancer (n=1) Pediatric solid tumors (N=127) 4 (3.1%) NTRK1 (n=1) NTRK2 (n=2) NTRK3 (n=1) NTRK1: TPM3 (n=1) NTRK2: DAB2IP (n=1), LPPR1 (n=1) NTRK3: RAD51B (n=1) NTRK1-TPM3; male, age category‡ 2-11 years, tumor stage unknown, no chemotherapy/radiotherapy. Alive at 15.1 years‘ follow-up. ‡According to US FDA age categories for pediatrics. NTRK2-DAB2IP; male, age category‡ 2-11 years, Grade III tumor, received both chemo- and radiotherapy. Died - survival time 0.9 years. ‡According to US FDA age categories for pediatrics. NTRK2-LPPR1; male, age category‡ 12-18 years, stage IV tumor, received both chemo- and radiotherapy. Died - survival time 1.1 years. ‡According to US FDA age categories for pediatrics. NTRK3-RAD51B; female, age category‡ 12-18 years, tumor stage unknown, no chemotherapy/radiotherapy. Alive at 7.4 years‘ follow-up. ‡According to US FDA age categories for pediatrics.

Citation Format: Wei Zhang, Merja Perälä, Roosa E. Kallionpää, Niina Pitkänen, Korinna Jöhrens, Renate Schulze-Rath, Arndt A Schmitz, Helen Guo, Jihong Zong. NTRK gene fusion in adults and pediatrics with solid tumors: a record linkage study of expression frequency and patient characteristics using the Auria Biobank in Finland [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 925.