Shota Yamamoto1, Ronald L Korn, Rahmi Oklu, Christopher Migdal, Michael B Gotway, Glen J Weiss, A John Iafrate, Dong-Wan Kim, Michael D Kuo. 1. From 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.).
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.
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-ALKtumors and can potentially identify patients with a shorter durable response to crizotinib.
Authors: Alda L Tam; Howard J Lim; Ignacio I Wistuba; Anobel Tamrazi; Michael D Kuo; Etay Ziv; Stephen Wong; Albert J Shih; Robert J Webster; Gregory S Fischer; Sunitha Nagrath; Suzanne E Davis; Sarah B White; Kamran Ahrar Journal: J Vasc Interv Radiol Date: 2015-11-25 Impact factor: 3.464
Authors: Bruno Hochhegger; Matheus Zanon; Stephan Altmayer; Gabriel S Pacini; Fernanda Balbinot; Martina Z Francisco; Ruhana Dalla Costa; Guilherme Watte; Marcel Koenigkam Santos; Marcelo C Barros; Diana Penha; Klaus Irion; Edson Marchiori Journal: Lung Date: 2018-10-09 Impact factor: 2.584
Authors: Emmanuel Rios Velazquez; Chintan Parmar; Ying Liu; Thibaud P Coroller; Gisele Cruz; Olya Stringfield; Zhaoxiang Ye; Mike Makrigiorgos; Fiona Fennessy; Raymond H Mak; Robert Gillies; John Quackenbush; Hugo J W L Aerts Journal: Cancer Res Date: 2017-05-31 Impact factor: 12.701