Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma : results from the European Thoracic Oncology Platform Lungscape Project

Blackhall, Fiona H., Peters, Solange, Bubendorf, Lukas, Dafni, Urania, Kerr, Keith M., Hager, Henrik, Soltermann, Alex, O'Byrne, Kenneth J., Dooms, Christoph, Sejda, Aleksandra, Hernandez-Losa, Javier, Marchetti, Antonio, Savic, Spasenija, Tan, Qiang, Thunnissen, Erik, Speel, Ernst-Jan M., Cheney, Richard, Nonaka, Daisuke, de Jong, Jeroen, Martorell, Miguel, Letovanec, Igor, Rosell, Rafael, & Stahel, Rolf A. (2014) Prevalence and clinical outcomes for patients with ALK-positive resected stage I to III adenocarcinoma : results from the European Thoracic Oncology Platform Lungscape Project. Journal of Clinical Oncology, 32(25), pp. 2780-2787.

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PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population.

METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment.

RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS).

CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.

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ID Code: 78363
Item Type: Journal Article
Refereed: Yes
DOI: 10.1200/jco.2013.54.5921
ISSN: 1527-7755
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 by American Society of Clinical Oncology
Deposited On: 03 Nov 2014 22:39
Last Modified: 04 Nov 2014 22:12

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