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Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer†
Article first published online: 26 JAN 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 18, pages 4502–4511, 15 September 2012
How to Cite
Doebele, R. C., Lu, X., Sumey, C., Maxson, D. A., Weickhardt, A. J., Oton, A. B., Bunn, P. A., Barón, A. E., Franklin, W. A., Aisner, D. L., Varella-Garcia, M. and Camidge, D. R. (2012), Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer. Cancer, 118: 4502–4511. doi: 10.1002/cncr.27409
- Issue published online: 5 SEP 2012
- Article first published online: 26 JAN 2012
- Manuscript Accepted: 13 SEP 2011
- Manuscript Revised: 9 SEP 2011
- Manuscript Received: 11 AUG 2011
- nonsmall cell lung cancer;
- epidermal growth factor receptor;
- anaplastic lymphoma kinase tyrosine kinase receptor;
- Kirsten rat sarcoma viral oncogene
The discovery of distinct subsets of nonsmall cell lung cancer (NSCLC) characterized by activation of driver oncogenes has greatly affected personalized therapy. It is hypothesized that the dominant oncogene in NSCLC would be associated with distinct patterns of metastatic spread in NSCLC at the time of diagnosis.
A total of 209 consecutive patients with stage IV nonsquamous NSCLC with an EGFR (epidermal growth factor receptor) mutation (N = 39), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation (N = 49), ALK (anaplastic lymphoma receptor tyrosine kinase) gene rearrangement (N = 41), or wild-type for all 3 (triple negative, N = 80) were included. The percentage of patients with metastatic disease at a given site was compared between each molecular cohort (EGFR, KRAS, or ALK) and the triple negative cohort.
ALK gene rearrangement was significantly associated with pericardial disease (odds ratio [OR] = 4.61; 95% confidence interval [CI] = 1.30, 16.37; P = .02) and pleural disease (OR = 4.80; 95% CI = 2.10, 10.97; P < .001). Patients with ALK gene rearrangements (OR = 5.50; 95% CI = 1.76, 17.18; P = .003) and patients with EGFR mutations (OR = 5.17; 95% CI = 1.63, 16.43; P = .006) were predisposed to liver metastasis compared to the triple negative cohort. No molecular cohort had a predisposition to pulmonary nodules, or adrenal, bone, or brain metastasis compared to the triple negative cohort. The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001).
The results support the hypothesis that the dominant molecular oncogenes in NSCLC are associated with different biological behaviors manifesting as distinct patterns of metastatic spread at the time of diagnosis. Cancer 2012. © 2012 American Cancer Society.