JOURNAL of
ONCOLOGICAL
SCIENCES

ORIGINAL RESEARCH ARTICLE

The relationship between EGFR mutation and metastasis pattern in lung adenocarcinoma
Received Date : 19 Jun 2019
Accepted Date : 06 Aug 2019
Doi: 10.1016/j.jons.2019.08.002 - Article's Language: EN
J Oncol Sci 5 (2019) 65-69
This is an open access article under the CC BY-NC-ND license
ABSTRACT
Aim: The metastatic pattern of non-small cell lung cancer (NSCLC) has been described in several studies. Frequent metastatic sites are lung, liver, bone, surrenal, and brain. Hypotheses were speculated to explain the tendency of specific sites. Over-expression of EGFR alters the biology and tumoral behavior. The mutations of EGFR mainly occur in exon 19, and 21and could lead the way through the tumor growth and metastasis. We try to elucidate the relationship between EGFR mutation and metastatic pattern. Material and Method: In this retrospective nested case-control study, one hundred and five patients diagnosed with lung adenocarcinoma included who had EGFR mutation status and imaging studies at the time of diagnosis. Results: The metastatic pattern was not different between EGFR mutant and wild type patients. There was no statistical difference in terms of survival between EGFR mutant and wild type patients (p ¼ 0.25). The OS according to the organ metastasis between EGFR mutant and wild type group was not significant except liver. The EGFR mutant patients with liver metastasis had better survival compared with wild type patients (p ¼ 0.04). Also, the multiplicity and solidarity of the metastatic tumors were compared in metastatic organs. There was no significant difference between groups. The subsequent EGFR mutation type was not related to the metastatic pattern. Conclusion: The incidence of the metastatic sites was not different between EGFR mutant and wild type patients in our study. In contrast to the literature, liver metastasis found to be related to improved OS.
KAYNAKLAR
  1. Viadana E. K-L A. Patterns of metastases in adenocarcinomas of man. An autopsy study of 4,728 cases. J Med. 1975;6(1):1e14.
  2. Hess KR, Varadhachary GR, Taylor SH, et al. Metastatic patterns in adenocarcinoma. Cancer. 2006. https://doi.org/10.1002/cncr.21778. [Crossref]  [PubMed] 
  3. Paget S. THE DISTRIBUTION OF SECONDARY GROWTHS IN CANCER OF THE BREAST. Lancet. 1889. https://doi.org/10.1016/S0140-6736(00)49915-0. [Crossref] 
  4. Neoplastic Diseases. A treatise on tumours. By James Ewing, A.M., M.D., Sc.D., professor of pathology at cornell university medical college, N.Y.; pathologist to the memorial hospital. Third edition. Royal 8vo. Pp. 1127, with 546 illustrations. 1928. Phil. BJS. 1928;16(61):174e175. https://doi.org/10.1002/ bjs.1800166126. [Crossref] 
  5. Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol. 2011. https://doi.org/10.1038/nrclinonc.2011.44. [Crossref]  [PubMed] 
  6. Fujino S, Enokibori T, Tezuka N, et al. A comparison of epidermal growth factor receptor levels and other prognostic parameters in non-small cell lung cancer. Eur J Cancer A. 1996. https://doi.org/10.1016/S0959-8049(96)00243-2. [Crossref] 
  7. Douillard JY, Shepherd FA, Hirsh V, et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol. 2010. https:// doi.org/10.1200/JCO.2009.24.3030. [Crossref]  [PubMed] 
  8. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of nonesmall-cell lung cancer to gefitinib. N Engl J Med. 2004. https://doi.org/10.1056/NEJMoa040938. [Crossref]  [PubMed] 
  9. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non - small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011. https:// doi.org/10.1200/JCO.2010.33.4235. [Crossref]  [PubMed] 
  10. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatinepaclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361(10):947e957. https:// doi.org/10.1056/NEJMoa0810699. [Crossref]  [PubMed] 
  11. Johnson ML, Sima CS, Chaft J, et al. Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinomas. Cancer. 2013. https://doi.org/10.1002/cncr.27730. [Crossref]  [PubMed]  [PMC] 
  12. Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res. 2007. https://doi.org/10.1158/1078-0432.CCR-06-2478. [Crossref]  [PubMed] 
  13. Eichler AF, Kahle KT, Wang DL, et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol. 2010. https://doi.org/10.1093/neuonc/noq076. [Crossref]  [PubMed]  [PMC] 
  14. Lee YJ, Choi HJ, Kim SK, et al. Frequent central nervous system failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors in Korean patients with nonsmall-cell lung cancer. Cancer. 2010. https://doi.org/10.1002/cncr.24877. [Crossref]  [PubMed] 
  15. Matsumoto S, Takahashi K, Iwakawa R, et al. Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer. 2006. https://doi.org/10.1002/ ijc.21940.
  16. Omuro AMP, Kris MG, Miller VA, et al. High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer. 2005. https://doi.org/10.1002/cncr.21033. [Crossref]  [PubMed] 
  17. Welsh JW, Komaki R, Amini A, et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from nonsmall- cell lung cancer. J Clin Oncol. 2013. https://doi.org/10.1200/ JCO.2011.40.1174.
  18. Hsu F, De Caluwe A, Anderson D, Nichol A, Toriumi T, Ho C. Patterns of spread and prognostic implications of lung cancer metastasis in an era of driver mutations. Curr Oncol. 2017;24(4):228e233. https://doi.org/10.3747/co.24.3496. [Crossref]  [PubMed]  [PMC] 
  19. Laack E, Simon R, Regier M, et al. Miliary never-smoking adenocarcinoma of the lung: strong association with epidermal growth factor receptor exon 19 deletion. J Thorac Oncol. 2011. https://doi.org/10.1097/JTO.0b013e3181fb7cf1. [Crossref]  [PubMed] 
  20. Sekine A, Kato T, Hagiwara E, et al. Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: distinguishing influence of exon 19 deletion on radiographic features. Lung Cancer. 2012. https://doi.org/10.1016/ j.lungcan.2011.12.017.
  21. Poonia S, Berge EM, Aisner DL, Damek D, Doebele RC. EGFR exon 19 deletion mutations and systemic/central nervous system miliary metastasis: clinical correlations and response to therapy. Clin Lung Cancer. 2014;15(5):387e389. https://doi.org/10.1016/j.cllc.2014.04.005. [Crossref]  [PubMed]  [PMC] 
  22. Hendriks LEL, Smit EF, Vosse BAH, et al. EGFR mutated non-small cell lung cancer patients: more prone to development of bone and brain metastases? Lung Cancer. 2014. https://doi.org/10.1016/j.lungcan.2014.01.006. [Crossref]  [PubMed] 
  23. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatinepaclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009. https://doi.org/10.1056/ NEJMoa0810699. [Crossref]  [PubMed] 
  24. Koivunen JP, Mermel C, Zejnullahu K, et al. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008. https://doi.org/ 10.1158/1078-0432.CCR-08-0168. [Crossref]  [PubMed]  [PMC] 
  25. Ulivi P, Chiadini E, Dazzi C, et al. Nonsquamous, non-small-cell lung cancer patients who carry a double mutation of EGFR, EML4-ALK or KRAS: frequency, clinical-pathological characteristics, and response to therapy. Clin Lung Cancer. 2016. https://doi.org/10.1016/j.cllc.2015.11.004. [Crossref]  [PubMed] 
  26. Mordant P, Arame A, De Dominicis F, et al. Which metastasis management allows long-term survival of synchronous solitary M1b non-small cell lung cancer? Eur J Cardiothorac Surg. 2012. https://doi.org/10.1093/ejcts/ezr042. [Crossref]  [PubMed] 
  27. Wu KL, Tsai MJ, Yang CJ, et al. Liver metastasis predicts poorer prognosis in stage IV lung adenocarcinoma patients receiving first-line gefitinib. Lung Cancer. 2015. https://doi.org/10.1016/j.lungcan.2015.02.012. [Crossref]  [PubMed] 
  28. Kuchuk M, Kuchuk I, Sabri E, Hutton B, Clemons M, Wheatley-Price P. The incidence and clinical impact of bone metastases in non-small cell lung cancer. Lung Cancer. 2015. https://doi.org/10.1016/j.lungcan.2015.04.007. [Crossref]  [PubMed] 
  29. Tsuya A, Kurata T, Tamura K, Fukuoka M. Skeletal metastases in non-small cell lung cancer: a retrospective study. Lung Cancer. 2007. https://doi.org/10.1016/ j.lungcan.2007.03.013.
  30. Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001. https://doi.org/10.1053/ ctrv.2000.0210.
  31. Reungwetwattana T, Nakagawa K, Cho BC, et al. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. August 2018. https://doi.org/10.1200/JCO.2018.78.3118. JCO2018783118. [Crossref]  [PubMed]