Clinical characteristics of NSCLC harboring ALK 2p23 translocation at Cleveland Clinic.

Abstract

e18085 Background: The ALK 2p23 translocation, ALK(+), is an important druggable target in 5-7% of non-small cell lung cancer (NSCLC). However, the break-part FISH assay is labor-intensive. Better understanding of the target population’s clinical features and alternative screening tests are desirable to enable cost-effective patient selection for molecular therapy. Methods: NSCLC patients (N=120) seen at the Cleveland Clinic (CC) who had clinical screening ALK 2p23 FISH (Abbott Molecular) were included in this retrospective analysis. Biopsy specimens were also tested using immunohistochemistry (IHC) for ALK overexpression via clone D5F3 (Cell Signaling Tech.) with OptiView ultrasensitive detection (Ventana Medical Sys.). Clinical data were extracted from electronic medical records. Comparison was performed using Fisher’s exact test, Wilcoxon rank sum test or log-rank test. Results: Of the 120 tumors tested, 34 (28.3%) were ALK(+) by FISH, predominantly adenocarcinomas (33/34). 97% of the samples were also tested by ALK-IHC, with a concordance rate of 99%. Comparing to ALK (-) group, ALK(+) patients were younger (median 53 vs 65, p<0.01) and mostly never/light smokers (91% vs 43%, p<0.01). ALK(+) tumors tended to have higher number of metastatic sites at diagnosis, especially for liver metastasis (26.5% vs 10.5%, p=0.04). Interestingly, venous thrombosis (DVT/PE) was also significantly more common in ALK(+) patients (35.3% vs 16.3%, p=0.03). 17 (50%) patients were treated with crizotinib in the ALK(+) group. Two cases with positive screening ALK-IHC helped to identify FISH(+) tumor areas. Of those tumors with EGFR status available (n=103), 6 were EGFR mutation-positive, all being ALK(-). No significant OS difference was seen in ALK(+)/EGFR(-) patients (n=28) compared to ALK(-)/EGFR(-) patients (n=69). Conclusions: ALK 2p23 (+) NSCLC at CC was more commonly seen in younger patients and never/light smokers. They tended to have greater number of metastases, especially in the liver, and significantly higher risk of venous thrombosis. ALK-ultrasensitive IHC using the D5F4 clone helped to identify FISH(+) tumor areas and may be considered a cost-effective screening test demonstrating high concordance with ALK FISH.