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

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

Research output: Contribution to journalArticle

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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 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
JournalRadiology
Volume272
Issue number2
DOIs
StatePublished - 2014

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Non-Small Cell Lung Carcinoma
Phenotype
Disease-Free Survival
Neoplasms
Biomarkers
anaplastic lymphoma kinase
Health Insurance Portability and Accountability Act
Research Ethics Committees
Pleural Effusion
Lymphoma
Phosphotransferases
Retrospective Studies
Therapeutics

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

ALK molecular phenotype in non-small cell lung cancer : CT radiogenomic characterization. / Yamamoto, Shota; Korn, Ronald L.; Oklu, Rahmi; Migdal, Christopher; Gotway, Michael; Weiss, Glen J.; Iafrate, A. John; Kim, Dong Wan; Kuo, Michael D.

In: Radiology, Vol. 272, No. 2, 2014, p. 568-576.

Research output: Contribution to journalArticle

Yamamoto, S, Korn, RL, Oklu, R, Migdal, C, Gotway, M, Weiss, GJ, Iafrate, AJ, Kim, DW & Kuo, MD 2014, 'ALK molecular phenotype in non-small cell lung cancer: CT radiogenomic characterization', Radiology, vol. 272, no. 2, pp. 568-576. https://doi.org/10.1148/radiol.14140789
Yamamoto, Shota ; Korn, Ronald L. ; Oklu, Rahmi ; Migdal, Christopher ; Gotway, Michael ; Weiss, Glen J. ; Iafrate, A. John ; Kim, Dong Wan ; Kuo, Michael D. / ALK molecular phenotype in non-small cell lung cancer : CT radiogenomic characterization. In: Radiology. 2014 ; Vol. 272, No. 2. pp. 568-576.
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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 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.",
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T1 - ALK molecular phenotype in non-small cell lung cancer

T2 - CT radiogenomic characterization

AU - Yamamoto, Shota

AU - Korn, Ronald L.

AU - Oklu, Rahmi

AU - Migdal, Christopher

AU - Gotway, Michael

AU - Weiss, Glen J.

AU - Iafrate, A. John

AU - Kim, Dong Wan

AU - Kuo, Michael D.

PY - 2014

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N2 - 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.

AB - 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.

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