{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:51:00Z","timestamp":1791406260730,"version":"4.3.3"},"reference-count":44,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Uncertainty about the prognostic significance of neurotrophic tropomyosin receptor kinase (\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      ) fusions complicates clinical decisions and interpretation of survival outcomes in oncology care. Drawing on the largest cohort of\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      fusion\u2013positive (\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      +) patients, we establish the prognostic effect of\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      fusions in adults with advanced cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used a large real-world clinicogenomic research database from the United States to emulate a pragmatic randomized trial that determines the causal effect of harboring an\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      gene fusion (\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      +) on survival prognosis for adult patients with advanced solid tumors. We 1:1 matched\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      + patients to patients with no identified\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      genomic alterations (\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      \u2013) using a machine learning matching approach. Excluding patients who received TRK inhibitors, we conducted stratified matching within common tumor groups. We used Kaplan-Meier and Weibull regression survival analyses and estimated the difference in restricted mean survival time (RMST) over 1-, 2-, 3-, and 5-year study periods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 68,145\n                      <jats:italic toggle=\"yes\">NTRK\u2013<\/jats:italic>\n                      patients for matching to 73\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      + patients within seven tumor groups, including colorectal (n = 22), non\u2013small cell lung (n = 13), sarcoma (n = 13), breast (n = 10), head and neck (n = 7), neuroendocrine (n = 4), and prostate (n = 4), and 14\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      + patients representing eight other cancers. The difference in overall survival over 1 year was statistically significant using the Kaplan-Meier estimate (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .008), Weibull regression (hazard ratio, 2.105 [95% CI, 1.207 to 3.673]), and RMST (\u201350 days [95% CI, \u201396 to \u20135];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .029). Differences were also statistically different at 2 years and 3 years. At 5 years, no survival differences were statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In this large real-world target trial emulation,\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      gene fusions were associated with clinically meaningful reductions in overall survival among adults with advanced cancers not treated with TRK inhibitors. These findings clarify the prognostic role of\n                      <jats:italic toggle=\"yes\">NTRK<\/jats:italic>\n                      fusions and inform clinical interpretation of outcomes in routine oncology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00281","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:59:12Z","timestamp":1791403152000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Determining the Causal Effect of Neurotrophic Tropomyosin Receptor Kinase Gene Fusions on Survival Prognosis for Adult Patients With Advanced Cancers"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-8728","authenticated-orcid":true,"given":"Emanuel","family":"Krebs","sequence":"first","affiliation":[{"name":"Regulatory Science Lab, BC Cancer Research Institute, Vancouver, BC, Canada"},{"name":"Academy of Translational Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3285-4115","authenticated-orcid":true,"given":"Nirupama","family":"Tamvada","sequence":"additional","affiliation":[{"name":"Regulatory Science Lab, BC Cancer Research Institute, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-5657","authenticated-orcid":true,"given":"Deirdre","family":"Weymann","sequence":"additional","affiliation":[{"name":"Regulatory Science Lab, BC Cancer Research Institute, Vancouver, BC, Canada"},{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5814-714X","authenticated-orcid":true,"given":"Howard J.","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada"},{"name":"Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7070-4386","authenticated-orcid":true,"given":"Stephen","family":"Chia","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada"},{"name":"Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-3984","authenticated-orcid":true,"given":"Cheryl","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada"},{"name":"Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-0511","authenticated-orcid":true,"given":"Dean A.","family":"Regier","sequence":"additional","affiliation":[{"name":"Regulatory Science Lab, BC Cancer Research Institute, Vancouver, BC, Canada"},{"name":"Academy of Translational Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada"},{"name":"School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-021-00206-y"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0113-0"},{"key":"e_1_3_8_4_2","unstructured":"FDA approves Roche\u2019s RozlytrekTM (entrectinib) for people with ROS1-positive metastatic non-small cell lung cancer and NTRK gene fusion-positive solid 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