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Treatment decisions are currently guided by tissue sampling and genetic testing, which are limited by procedural risks, patient tolerance, tumour heterogeneity and mutation evolution. Because co-mutations involving EGFR and other targetable genes can diminish treatment response, identifying\n                    <jats:italic>exclusive<\/jats:italic>\n                    EGFR mutation, defined by the absence of other actionable alterations, represents a clinically favourable scenario for first-line EGFR-TKI therapy. We developed a CT-based radiomics signature, EGFR-RPV, to predict exclusive EGFR mutational status using NSCLC patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009304) from a multi-centre cohort with paired imaging and genomics data, and validated performance in an independent testing set (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200951), alongside transcriptomics enrichment analysis. EGFR-RPV predicted exclusive EGFR mutation with accuracies of 0.77 (95% CI 0.66\u20130.88) and 0.71 (95% CI 0.54\u20130.89) in internal and external testing, respectively, and stratified patient prognosis (hazard ratio 2.15, 95% CI 1.50\u20133.08). FAM190A and CBMO1 were enriched in exclusive EGFR-positive cases, consistent with their roles in cell division regulation and vitamin A biosynthesis, respectively. EGFR-RPV thus offers a non-invasive approach to identify exclusive EGFR mutations, with a potential role in guiding first-line EGFR-TKI use.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-42948-4","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:26:01Z","timestamp":1772817961000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A radio-genomics biomarker for precision epidermal growth factor receptor mutation targeting therapy in non-small cell lung cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"Mitchell","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Copley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristofer","family":"Linton-Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Viola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Cortellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marize","family":"Bahket","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Pinato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Power","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea G.","family":"Rockall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric O.","family":"Aboagye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"42948_CR1","unstructured":"Cancer Research, U. 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