{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:46:47Z","timestamp":1777434407006,"version":"3.51.4"},"reference-count":107,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T00:00:00Z","timestamp":1610150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (&lt;5%), and at a higher frequency (&gt;80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring NTRK gene fusions. In Phase I\/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma\/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an NTRK gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered.<\/jats:p>","DOI":"10.3390\/curroncol28010038","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T04:55:31Z","timestamp":1611032131000},"page":"346-366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients"],"prefix":"10.3390","volume":"28","author":[{"given":"S\u00e9bastien","family":"Perreault","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Division of Child Neurology CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rose","family":"Chami","sequence":"additional","affiliation":[{"name":"Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J.","family":"Deyell","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia Children\u2019s Hospital and Research Institute, Vancouver, BC V6H 3N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"El Demellawy","sequence":"additional","affiliation":[{"name":"Pathology Department, Children\u2019s Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8716-7924","authenticated-orcid":false,"given":"Benjamin","family":"Ellezam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nada","family":"Jabado","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology, MUHC, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-1108","authenticated-orcid":false,"given":"Daniel A.","family":"Morgenstern","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aru","family":"Narendran","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Oncology and, Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poul H. B.","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"},{"name":"Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7088-8146","authenticated-orcid":false,"given":"Jonathan D.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8514-9861","authenticated-orcid":false,"given":"Stephen","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1158\/2159-8290.CD-14-0765","article-title":"TRKing Down an Old Oncogene in a New Era of Targeted Therapy","volume":"5","author":"Vaishnavi","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_2","first-page":"539","article-title":"Oncogenes in Solid Human Tumours","volume":"300","author":"Pulciani","year":"1982","journal-title":"Nat. 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