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ALK Molecular Phenotype in Non-Small Cell Lung Cancer: CT Radiogenomic Characterization

Cited 80 time in Web of Science Cited 84 time in Scopus
Authors
Yamamoto, Shota; Korn, Ronald L.; Oklu, Rahmi; Migdal, Christopher; Gotway, Michael B.; Weiss, Glen J.; Iafrate, A. John; Kim, Dong-Wan; Kuo, Michael D.
Issue Date
2014-08
Citation
Radiology, Vol.272 No.2, pp.568-576
Abstract
Purpose: To present a radiogenomic computed tomographic (CT) characterization of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) (ALK+). Materials and Methods: In this HIPAA-compliant institutional review board-approved retrospective study, CT studies, ALK status, and clinical-pathologic data in 172 patients with NSCLC from three institutions were analyzed. A screen of 24 CT image traits was performed in a training set of 59 patients, followed by random forest variable selection incorporating 24 CT traits plus six clinical-pathologic covariates to identify a radiogenomic predictor of ALK+ status. This predictor was then validated in an independent cohort (n = 113). Test-for-accuracy and subset analyses were performed. A similar analysis was performed to identify a biomarker associated with shorter progression-free survival (PFS) after therapy with the ALK inhibitor crizotinib. Results: ALK+ status was associated with central tumor location, absence of pleural tail, and large pleural effusion. An ALK+ radiogenomic CT status biomarker consisting of these three imaging traits with patient age of younger than 60 years showed strong discriminatory power for ALK+ status, with a sensitivity of 83.3% (15 of 18), a specificity of 77.9% (74 of 95), and an accuracy of 78.8% (89 of 113) in independent testing. The discriminatory power was particularly strong in patients with operable disease (stage IIIA or lower), with a sensitivity of 100.0% (five of five), a specificity of 88.1% (37 of 42), and an accuracy of 89.4% (42 of 47). Tumors with a disorganized vessel pattern had a shorter PFS with crizotinib therapy than tumors without this trait (11.4 vs 20.2 months, P =.041). Conclusion: ALK+ NSCLC has distinct characteristics at CT imaging that, when combined with clinical covariates, discriminate ALK+ from non-ALK tumors and can potentially identify patients with a shorter durable response to crizotinib.
ISSN
0033-8419
URI
http://hdl.handle.net/10371/165414
DOI
https://doi.org/10.1148/radiol.14140789
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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