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

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.

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).

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.
© RSNA, 2014

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Yamamoto S., Korn R.L., Oklu, R., Migdal C., Gotway M.B., Weiss G.J., Iafrate J., Kim D.W. and Kuo MD. “ALK Molecular Phenotype in Non–Small Cell Lung Cancer. CT Radiogenomic Characterization Radiol., Ahead of Print, 10.1148/radiol.14140789, (2014).