Authors’ contributions U.G. Mueller-Lisse and A. Tufman contributed equally. U.G. Mueller-Lisse: study idea, literature search, study design, data analysis, data interpretation, manuscript writing; A. Tufman: study design, literature search, data interpretation, manuscript writing, manuscript editing; H.A. Zimmermann: data analysis; C. Reiners: literature search, data collection, data interpretation; S. Reu data analysis, data interpretation; M.F. Reiser: data collection, data interpretation; R.M. Huber: study idea, study design, data interpretation, manuscript editing.
Authors’ agreement The authors declare that they approved of the version to be published; and agree to be accountable for all aspects of the work, in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Treatment of advanced EML4-ALK-translocation-positive non-small-cell lung cancer (NSCLC) with an ALK tyrosine kinase inhibitor (TKI) is now standard of care. Since EML4-ALK gene fusion is rare in NSCLC and testing depletes both tissue samples and health care funds, deciding who to screen is critical. CT features associated with EML4-ALK-positive cases may help prioritize individual patients for ALK testing in settings where biopsy size or health care factors make ubiquitous testing difficult.
We used well-described computed tomography (CT) lung tumor features to distinguish EML4-ALK-translocation-positive from ALK-negative European patients with advanced NSCLC. CT scans were evaluated for lung tumor location (either central or peripheral versus combined), growth pattern (focal versus diffuse), array (single versus multiple lesions), delineation (infiltrative versus circumscribed), composition (solid only versus nonsolid parts), site-specific blood vessel appearance (normal versus altered), and air inclusions (present versus absent). Two-tailed statistical tests (Fisher exact/Student-T) were used to compare ALK-positive and ALK-negative tumors. The analyses took potential confounders into account including patient age, gender, previous NSCLC therapy, UICC stage, and smoking status.
Ten of 39 adult European Caucasian patients (age 57 ± 10 years, 17 female) were ALK positive. Diffuse tumor growth (ALK positive 9, ALK negative 7/5, p < 0.0005/p < 0.0001, agreement 95%), multiple lung lesion arrays (ALK positive 9, ALK negative 6, p < 0.0002, agreement 82%), and combined central/peripheral tumor location (ALK positive 9, ALK negative 12/7, p < 0.01/p < 0.0005, agreement 82%) each were associated with ALK-positive cases.
Diffuse tumor growth, multiple lung lesion arrays, and combined central/peripheral tumor location are CT features that may prove useful in prioritizing NSCLC samples for ALK testing in this setting.