PMID- 33685189 OWN - NLM STAT- MEDLINE DCOM- 20211021 LR - 20211021 IS - 1802-5307 (Electronic) IS - 0862-495X (Linking) VI - 33 IP - 6 DP - 2020 Winter TI - Practical instructions for testing and targeted therapy in adult patients with solid tumours with NTRK gene fusion in common clinical practice. PG - 414-419 AB - BACKGROUND: Tropomyosin receptor kinase inhibitors (TRKi) have been shown to produce a dramatic and long-lasting effect on tumours harbouring fusions of neurotrophic receptor tyrosine kinase (NTRK) genes. Due to the low incidence of these molecular aberrations in common types of solid adult tumours, the identification of patients eligible for the treatment with TRK inhibitors in routine clinical practice is a major challenge. The current methods for NTRK gene fusion testing include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and several genomic assays using next-generation sequencing (NGS). After considering the characteristics of these tests, we recommend two-step testing for clinical practice in tumours with a low incidence of NTRK gene fusions. In the first step, a fresh or archival formalin fixed paraffin embedded (FFPE) sample is tested using a validated IHC method. If the IHC result is positive, verification using RNA-based should follow, preferably using fresh tissue sample. If fresh tissue bio-psy cannot be obtained, e.g. due to a disproportionate risk or discomfort for the patient, an archival FFPE sample may be used for testing. For tumours with high incidence of NTRK gene fusions, we recommend upfront NGS sequencing. Larotrektinib is currently the only TRK inhibitor registered in the EU. Although entrektinib, another TRK inhibitor, is not yet registered in the EU, it is currently available in the Czech Republic within an Early Access Programme. PURPOSE: The aim of this paper is to provide concise and clear guidance on testing for the presence of NTRK gene fusions and indications for the treatment with TRK inhibitors in the routine clinical oncology practice. FAU - Buchler, Tomas AU - Buchler T FAU - Dundr, Pavel AU - Dundr P FAU - Finek, Jindrich AU - Finek J FAU - Kiss, Igor AU - Kiss I FAU - Matej, Radoslav AU - Matej R FAU - Melichar, Bohuslav AU - Melichar B FAU - Michal, Michal AU - Michal M FAU - Petruzelka, Lubos AU - Petruzelka L LA - eng PT - Journal Article PT - Review TT - Prakticky navod pro testovani a cilenou lečbu dospělych pacientů se solidnimi nadory s genovou fuzi NTRK v běžne klinicke praxi. PL - Czech Republic TA - Klin Onkol JT - Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti JID - 9425213 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Receptor Tyrosine Kinase-like Orphan Receptors) SB - IM MH - Adult MH - Antineoplastic Agents/*therapeutic use MH - Gene Fusion MH - Humans MH - Neoplasms/*drug therapy/*genetics MH - Practice Guidelines as Topic MH - Protein Kinase Inhibitors/*therapeutic use MH - Receptor Tyrosine Kinase-like Orphan Receptors/*genetics OTO - NOTNLM OT - neurotrophic receptor kinase - targeted molecular therapy - entrektinib - larotrektinib - neoplasms EDAT- 2020/01/01 00:00 MHDA- 2023/02/25 06:00 CRDT- 2021/03/09 05:38 PHST- 2021/03/09 05:38 [entrez] PHST- 2020/01/01 00:00 [pubmed] PHST- 2023/02/25 06:00 [medline] AID - 125200 [pii] PST - ppublish SO - Klin Onkol. 2020 Winter;33(6):414-419.