TITLE:
Better Selection Model for EML4-ALK Fusion Gene Test in Patients with Non-Small-Cell Lung Cancer
AUTHORS:
Dekel Shlomi, Amir Onn, Maya Gottfried, Jair Bar, Haim Biran, Maya Ilouze, Addie Dvir, Hovav Nechushtan, Lior Soussan-Gutman, Nir Peled
KEYWORDS:
Lung Cancer; EML4-ALK; Gene Mutation; EGFR; Histology
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.8A,
September
3,
2013
ABSTRACT: Background: In the last decade, the search for
gene mutations in lung cancer has been constantly growing. EGFR, KRAS mutations
and, recently, the EML4-ALK fusion can guide the selection of treatment for patients who carry a
specific mutation. Methods: During 2010-2011, EML4-ALK
fusion test has been performed in Israel, mostly for wild type EGFR
non-squamous NSCLC patients based on fluorescent in-situ hybridization (FISH) technique to detect EML4-ALK
rearrangements. Results: Between January 2010 and December 2011, 3341 patients were diagnosed with lung cancer in Israel. Of the 2997 patients
with NSCLC 687 had squamous cell carcinoma and 2310 had non-squamous NSCLC.
This study focused on available 125 non-squamous NSCLC cases in which analysis for EML4-ALK rearrangement
was available. All were negative for EGFR mutation. Nineteen (15.2%) were found
positive for the fusion, a figure 2 - 10 times higher
compared with previously reported findings. The EML4-ALK fusion was significantly more
prevalent in younger male patients (52.1 vs. 61.3 years, p = 0.049), in whom every additional year
reduced the chance to find the fusion by 7% [CI = 0.93 (0.88 - 0.99), p = 0.03]. Conclusions: A stepwise approach based on
histology and prior EGFR analysis to detect EML4-ALK fusion is highly efficient with a
related increased yield of detection. We recommend testing patients with
non-squamous cell lung carcinoma after ruling out an EGFR mutation. The chance
to find the ALK fusion is significantly greater in younger men.