{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:25:28Z","timestamp":1790803528258,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>In current clinical practice, invasive methods such as biopsy are commonly used to obtain tumor tissues for epidermal growth factor receptor (EGFR) mutation detection in patients with non-small cell lung cancer (NSCLC). This study aimed to explore the underlying association between various quantitative parameters of CT perfusion imaging (CTPI) and EGFR mutation, thus providing a new auxiliary diagnosis basis for non-invasive prediction of EGFR mutation status in patients with NSCLC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with a confirmed NSCLC diagnosis by surgery or biopsy were prospectively enrolled. All patients underwent pulmonary CTPI within 1\u202fweek before biopsy, as well as EGFR gene detection after biopsy, and were then divided into the EGFR mutation group and the wild-type group. Differences in quantitative parameters between the two groups were analyzed, and significant variables were identified for further construction of the predictive model. The receiver operating characteristic (ROC) curves were constructed, and the area under curve (AUC) was calculated to assess the predictive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 86 patients were included, including 45 women and 41 men. There were 47 cases in the mutation group and 39 cases in the wild-type group. A univariate analysis showed that compared with the wild-type group, blood volume (BV) (5.56\u202f\u00b1\u202f1.51 vs. 3.04\u202f\u00b1\u202f1.07, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), time to peak (TTP) (29.31\u202f\u00b1\u202f5.12 vs. 25.99\u202f\u00b1\u202f5.68, <jats:italic>p<\/jats:italic>\u202f=\u202f0.006), and permeability surface (PS) (18.98\u202f\u00b1\u202f6.79 vs. 11.77\u202f\u00b1\u202f5.56, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001) were all higher in the mutation group. No statistical differences were found in the other five quantitative parameters (<jats:italic>p<\/jats:italic>\u202f&amp;gt;\u202f0.05). A multivariate logistic regression analysis identified BV (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001), TTP (<jats:italic>p<\/jats:italic>\u202f=\u202f0.029), and PS (<jats:italic>p<\/jats:italic>\u202f=\u202f0.014) as independent predictors of EGFR mutation. According to the ROC, the AUC of BV, TTP, and PS were 0.916, 0.739, and 0.788, respectively, and the corresponding cut-off values were 4.69, 23.84, and 12.11, respectively. The AUC of the combined predictive model (BV\u202f+\u202fTTP\u202f+\u202fPS) reached 0.956, which was superior to that of any single parameter (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BV, TTP, and PS were independent predictors of EGFR mutation in patients with NSCLC. The combined CTPI parameter model (BV\u202f+\u202fTTP\u202f+\u202fPS) had the highest predictive performance and could be more reliable than any single parameter in clinical auxiliary diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1660923","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T04:10:34Z","timestamp":1759464634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Non-invasive prediction of EGFR gene mutations in non-small cell lung cancer by multi-parameter CT perfusion imaging"],"prefix":"10.3389","volume":"12","author":[{"given":"Can","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anlvna","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongjian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jncc.2024.01.006","article-title":"Cancer incidence and mortality in China, 2022","volume":"4","author":"Han","year":"2024","journal-title":"J Natl Cancer Cent"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/s1470-2045(23)00444-8","article-title":"Global variations in lung cancer incidence by histological subtype in 2020: a population-based study","volume":"24","author":"Zhang","year":"2023","journal-title":"Lancet Oncol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1433299","DOI":"10.3389\/fimmu.2024.1433299","article-title":"Causal association between immune cells and lung cancer risk: a two-sample bidirectional Mendelian randomization analysis","volume":"15","author":"Xu","year":"2024","journal-title":"Front Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s11523-022-00868-z","article-title":"Prevalence of epidermal growth factor receptor exon 20 insertion mutations in non-small-cell lung Cancer in Europe: a pragmatic literature review and meta-analysis","volume":"17","author":"Van Sanden","year":"2022","journal-title":"Target Oncol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"102080","DOI":"10.1016\/j.canep.2021.102080","article-title":"Uncommon EGFR mutations in non-small-cell lung cancer: a systematic literature review of prevalence and clinical outcomes","volume":"76","author":"John","year":"2022","journal-title":"Cancer Epidemiol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.3389\/fgene.2019.01008","article-title":"Genomic profiling of driver gene mutations in Chinese patients with non-small cell lung Cancer","volume":"10","author":"Meng","year":"2019","journal-title":"Front Genet"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40364-022-00444-7","article-title":"Emerging precision neoadjuvant systemic therapy for patients with resectable non-small cell lung cancer: current status and perspectives","volume":"11","author":"Godoy","year":"2023","journal-title":"Biomark Res"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e14635","DOI":"10.1200\/JCO.2024.42.16_suppl.e14635","article-title":"Comparison of pembrolizumab plus chemotherapy versus concurrent or sequential radiochemotherapy in patients with driver mutation-lacking lung adenocarcinoma presenting with recurrent laryngeal nerve invasion leading to hoarseness","volume":"42","author":"Lu","year":"2024","journal-title":"J Clin Oncol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.jtho.2017.12.001","article-title":"Updated molecular testing guideline for the selection of lung Cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology","volume":"13","author":"Lindeman","year":"2018","journal-title":"J Thorac Oncol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1200\/jco.2017.76.7293","article-title":"Molecular testing guideline for the selection of patients with lung Cancer for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists\/International Association for the Study of Lung Cancer\/Association for Molecular Pathology Clinical Practice Guideline Update","volume":"36","author":"Kalemkerian","year":"2018","journal-title":"J Clin Oncol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.jtho.2021.09.017","article-title":"Introduction to 2021 WHO classification of thoracic tumors","volume":"17","author":"Tsao","year":"2022","journal-title":"J Thorac Oncol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e0257294","DOI":"10.1371\/journal.pone.0257294","article-title":"Size-specific dose estimates of adult, chest computed tomography examinations: comparison of Chinese and updated 2017 American College of Radiology diagnostic reference levels based on the water-equivalent diameter","volume":"16","author":"Hu","year":"2021","journal-title":"PLoS One"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e001492","DOI":"10.1136\/bmjresp-2022-001492","article-title":"Differential clinicopathological features, treatments and outcomes in patients with exon 19 deletion and exon 21 L858R EGFR mutation-positive adenocarcinoma non-small-cell lung cancer","volume":"10","author":"Batra","year":"2023","journal-title":"BMJ Open Respir Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.cllc.2021.06.001","article-title":"Comparative efficacy and safety of TKIs alone or in combination with antiangiogenic agents in advanced EGFR-mutated NSCLC as the first-line treatment: a systematic review and Meta-analysis","volume":"23","author":"Zhang","year":"2022","journal-title":"Clin Lung Cancer"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.jtho.2024.03.016","article-title":"Unveiling the landscape of uncommon EGFR mutations in NSCLC-A systematic review","volume":"19","author":"Borgeaud","year":"2024","journal-title":"J Thorac Oncol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"107123","DOI":"10.1016\/j.phrs.2024.107123","article-title":"PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: clinical challenges and opportunities","volume":"202","author":"Liu","year":"2024","journal-title":"Pharmacol Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1056\/NEJMoa1913662","article-title":"Overall survival with Osimertinib in untreated, EGFR-mutated advanced NSCLC","volume":"382","author":"Ramalingam","year":"2020","journal-title":"N Engl J Med"},{"key":"ref19","first-page":"1473","article-title":"Protein expression and significance of VEGF, EGFR and MMP-9 in non-small cell lung carcinomas","volume":"12","author":"Jin","year":"2011","journal-title":"Asian Pac J Cancer Prev"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"11006","DOI":"10.4238\/2015.September.21.13","article-title":"Correlation of EGFR gene amplification with invasion and metastasis of non-small cell lung cancer","volume":"14","author":"Jia","year":"2015","journal-title":"Genet Mol Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"i10","DOI":"10.1093\/annonc\/mdx703","article-title":"Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors","volume":"29","author":"Westover","year":"2018","journal-title":"Ann Oncol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1146\/annurev-pathol-011110-130206","article-title":"EGFR mutations and lung cancer","volume":"6","author":"da Cunha","year":"2011","journal-title":"Annu Rev Pathol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"188645","DOI":"10.1016\/j.bbcan.2021.188645","article-title":"Challenge and countermeasures for EGFR targeted therapy in non-small cell lung cancer","volume":"1877","author":"Tian","year":"2022","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.jtho.2020.10.006","article-title":"Dual EGFR-VEGF pathway inhibition: a promising strategy for patients with EGFR-mutant NSCLC","volume":"16","author":"Le","year":"2021","journal-title":"J Thorac Oncol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1002\/cncr.21366","article-title":"Clinical significance of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma","volume":"104","author":"Kojima","year":"2005","journal-title":"Cancer"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3845","DOI":"10.7150\/ijbs.70958","article-title":"VEGF\/VEGFR-targeted therapy and immunotherapy in non-small cell lung Cancer: targeting the tumor microenvironment","volume":"18","author":"Zhao","year":"2022","journal-title":"Int J Biol Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12880-021-00692-3","article-title":"Pulmonary lesions: correlative study of dynamic triple-phase enhanced CT perfusion imaging with tumor angiogenesis and vascular endothelial growth factor expression","volume":"21","author":"Zou","year":"2021","journal-title":"BMC Med Imaging"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12876-024-03257-0","article-title":"Predictive value of preoperative CT enhancement rate and CT perfusion parameters in colorectal cancer","volume":"24","author":"Li","year":"2024","journal-title":"BMC Gastroenterol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1111\/1759-7714.14105","article-title":"Evaluation of dual-energy and perfusion CT parameters for diagnosing solitary pulmonary nodules","volume":"12","author":"Zhu","year":"2021","journal-title":"Thorac Cancer"},{"key":"ref30","first-page":"13516","article-title":"Diagnostic and prognostic value of CT perfusion parameters in patients with advanced NSCLC after chemotherapy","volume":"13","author":"Lin","year":"2021","journal-title":"Am J Transl Res"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1245\/s10434-024-16806-4","article-title":"Significance of tumor microvasculature in the tumor microenvironment in adenocarcinoma with EGFR common mutations","volume":"32","author":"Matsudo","year":"2025","journal-title":"Ann Surg Oncol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"690254","DOI":"10.3389\/fonc.2021.690254","article-title":"Comparison of spectral and perfusion computed tomography imaging in the differential diagnosis of peripheral lung Cancer and focal organizing pneumonia","volume":"11","author":"Deng","year":"2021","journal-title":"Front Oncol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1148\/radiol.2021204642","article-title":"US contrast agent arrival time difference ratio for benign versus malignant subpleural pulmonary lesions","volume":"301","author":"Bi","year":"2021","journal-title":"Radiology"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2754","DOI":"10.21037\/qims-24-1261","article-title":"Differentiation of inflammatory pseudotumors and malignant pulmonary nodules using the time-to-peak in first-pass dual-input volume computed tomography-perfusion","volume":"15","author":"Guo","year":"2025","journal-title":"Quant Imaging Med Surg"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e894","DOI":"10.1016\/j.ejrad.2013.08.023","article-title":"Dynamic volume perfusion CT in patients with lung cancer: baseline perfusion characteristics of different histological subtypes","volume":"82","author":"Shi","year":"2013","journal-title":"Eur J Radiol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1660923\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T04:10:34Z","timestamp":1759464634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1660923\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":35,"alternative-id":["10.3389\/fmed.2025.1660923"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1660923","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]},"article-number":"1660923"}}