RT Journal Article
T1 Efficient Identification of Patients With NTRK Fusions Using a Supervised Tumor-Agnostic Approach
A1 Hernandez, S.
A1 Conde Gallego, Esther
A1 Molero, A.
A1 Suarez-Gauthier, A.
A1 Martinez, R.
A1 Alonso, M.
A1 Plaza Hernández, José Carlos
A1 Camacho, C.
A1 Chantada, D.
A1 Juaneda-Magdalena, L.
A1 Garcia-Toro, E.
A1 Saiz-Lopez, P.
A1 Rojo, F.
A1 Abad, M.
A1 Boni, V.
A1 Del Carmen, S.
A1 Regojo, R.M.
A1 Sanchez-Frias, M.E.
A1 Teixido, C.
A1 Paz-Ares Rodríguez, Luis Gonzaga
A1 López-Ríos Moreno, Fernando
AB The neurotrophic tropomyosin receptor kinase (NTRK) family gene rearrangements have been recently incorporated as predictive biomarkers in a "tumor-agnostic" manner. However, the identification of these patients is extremely challenging because the overall frequency of NTRK fusions is below 1%. Academic groups and professional organizations have released recommendations on the algorithms to detect NTRK fusions. The European Society for Medical Oncology proposal encourages the use of next-generation sequencing (NGS) if available, or alternatively immunohistochemistry (IHC) could be used for screening with NGS confirmation of all positive IHC results. Other academic groups have included histologic and genomic information in the testing algorithm. OBJECTIVE.—: To apply some of these triaging strategies for a more efficient identification of NTRK fusions within a single institution, so pathologists can gain practical insight on how to start looking for NTRK fusions. DESIGN.—: A multiparametric strategy combining histologic (secretory carcinomas of the breast and salivary gland; papillary thyroid carcinomas; infantile fibrosarcoma) and genomic (driver-negative non-small cell lung carcinomas, microsatellite instability-high colorectal adenocarcinomas, and wild-type gastrointestinal stromal tumors) triaging was put forward. RESULTS.—: Samples from 323 tumors were stained with the VENTANA pan-TRK EPR17341 Assay as a screening method. All positive IHC cases were simultaneously studied by 2 NGS tests, Oncomine Comprehensive Assay v3 and FoundationOne CDx. With this approach, the detection rate of NTRK fusions was 20 times higher (5.57%) by only screening 323 patients than the largest cohort in the literature (0.30%) comprising several hundred thousand patients. CONCLUSIONS.—: Based on our findings, we propose a multiparametric strategy (ie, "supervised tumor-agnostic approach") when pathologists start searching for NTRK fusions.
PB College of American Pathologists
YR 2024
FD 2024-03-01
LK https://hdl.handle.net/20.500.14352/118194
UL https://hdl.handle.net/20.500.14352/118194
LA eng
NO Hernandez, S., Conde, E., Molero, A., Suarez-Gauthier, A., Martinez, R., Alonso, M., Plaza, C., Camacho, C., Chantada, D., Juaneda-Magdalena, L., Garcia-Toro, E., Saiz-Lopez, P., Rojo, F., Abad, M., Boni, V., Del Carmen, S., Regojo, R. M., Sanchez-Frias, M. E., Teixido, C., … Lopez-Rios, F. (2024). Efficient identification of patients with ntrk fusions using a supervised tumor-agnostic approach. Archives of Pathology & Laboratory Medicine, 148(3), 318-326. https://doi.org/10.5858/arpa.2022-0443-OA
DS Docta Complutense
RD 11 abr 2025