ALK molecular phenotype in non-small cell lung cancer: CT radiogenomic characterization

Shota Yamamoto, Ronald L. Korn, Rahmi Oklu, Christopher Migdal, Michael B. Gotway, Glen J. Weiss, A. John Iafrate, Dong Wan Kim, Michael D. Kuo

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83 Scopus citations


Purpose: To present a radiogenomic computed tomographic (CT) characterization of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) (ALK+). Materials and In this HIPAA-compliant institutional review board-approved Methods: 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.

Original languageEnglish (US)
Pages (from-to)568-576
Number of pages9
Issue number2
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Yamamoto, S., Korn, R. L., Oklu, R., Migdal, C., Gotway, M. B., Weiss, G. J., Iafrate, A. J., Kim, D. W., & Kuo, M. D. (2014). ALK molecular phenotype in non-small cell lung cancer: CT radiogenomic characterization. Radiology, 272(2), 568-576.