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Updated: Apr 28, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
ALK molecular phenotype in non-small cell lung cancer: CT radiogenomic characterization
Shota Yamamoto1, Ronald L Korn, Rahmi Oklu
1From the Department of Radiological Sciences, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Box 951721, CHS 17-135, Los Angeles, CA 90095-1721 (S.Y., C.M., M.D.K.); Scottsdale Medical Imaging, Scottsdale, Ariz (R.L.K.); Scottsdale Healthcare, Scottsdale, Ariz (R.L.K.); Departments of Vascular Interventional Radiology (R.O.) and Pathology (A.J.I.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass; Department of Radiology, Mayo Clinic, Phoenix, Ariz (M.B.G.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (M.B.G.); Cancer Treatment Centers of America, Goodyear, Ariz (G.J.W.); Translational Genomics Research Institute, Phoenix, Ariz (G.J.W.); and Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea (D.W.K.).
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.
