Abstract
Background
To assess the impact of location versus number of extra-pulmonary metastatic sites (EPMS) on survival in stage IV non-small cell lung cancer (NSCLC).
Methods and materials
Retrospective analysis was conducted on patients diagnosed during 1999–2013 with stage IV, M1b (AJCC 7th edition) NSCLC using the large, institutional Glans-Look Database, which contains patient demographic, clinical, pathological, treatment, and outcome information. We assessed the impact of location and number of EPMS and identified correlates of overall survival using the Kaplan–Meier method and Cox regression.
Results
We identified a total of 2065 NSCLC patients with EPMS. Median age was 67 (IQR 58–75) years, 52% were men, and 78% were current or former smokers. 60% had one EPMS, and 40% had two or more EPMS. Among those with only one EPMS, most frequent organ involvement included bone (40%), brain (32%), and liver (13%). Median overall survival (mOS) was worst in those with liver metastasis and best in those with adrenal metastasis (2.0 vs. 5.2 months, p = 0.015). However, outcomes based on site of organ involvement were not significantly different in multivariable analysis. Compared to patients with one EPMS, individuals with two or more EPMS experienced worse outcomes (mOS ≤ 2.9 vs. 3.9 months, p < 0.001), and were associated with worse prognosis in Cox regression analysis (HR 1.5, 95% CI 1.3–1.7, p < 0.001).
Conclusions
Number rather than location of EPMS is a prognostic factor in patients with stage IV M1b NSCLC. This information is relevant for accurate prognostication, stratification of participants in future clinical trials, and timely and appropriate advanced care planning.
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References
Canadian Cancer Statistics 2017. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Toronto: Canadian Cancer Society; 2017. http://www.cancer.ca/Canadian-CancerStatistics-2017-EN.pdf. Accessed 28 Aug 2017.
Niu F, Zhou Q, Yang J, et al. Distribution and prognosis of uncommon metastases from non-small cell lung cancer. BMC Cancer. 2016;16:149. https://doi.org/10.1186/s12885-016-2169-5.
Riihimaki M, Hemminki A, Fallah M, et al. Metastatic sites and survival in lung cancer. Lung Cancer. 2014;86(1):78–84. https://doi.org/10.1016/j.lungcan.2014.07.020.
Kawano D, Takeo S, Katusura M, Tsukamoto S, Masuyama E, Nakaji Y. Surgical treatment of stage IV non-small cell lung cancer. Int Cardiovasc Thorac Surg. 2012;14(2):167–70. https://doi.org/10.1093/icvts/ivr036.
Socinski MA, Evans T, Gettinger S, et al. Treatment of stage IV non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of chest physicians evidence-based clinical practice guidelines. Chest. 2013;143(suppl 5):e341S–358S. https://doi.org/10.1378/chest.12-236.
Ramalingam SB, Belani C. Systemic chemotherapy for advanced non-small cell lung cancer. Recent advanced and future directions. Oncologist. 2008;13(suppl 1):5–13. https://doi.org/10.1634/theoncologist.13-S1-5.
Non-small cell. lung cancer survival rates, by stage. American Cancer Society. http://cancer.org/cancer/lungcancer-non-smallcell/detailedhuide/non-small-cell-lung-cancer-survival-rates. Published May 16, 2016. Accessed 28 Aug 2017.
Dias M, Coutinho D, Linhas R, et al. Non-small lung cancer: are M1a and M1b the same Stage? Eur Respir J. 2015; 46(suppl 59): PA4288. https://doi.org/10.1183/13993003.congress-2015.PA4288.
Tamura T, Kurishsima K, Nakazawa K, et al. Specific organ metastases and survival in mNSCLC. Mol Clin Oncol. 2015; 3(1):217 https://doi.org/10.3892/mco.2014.410.
Hendriks LE, Derks JL, Postmus PE, et al. Single organ metastatic disease and local disease status, prognostic factors for overall survival in stage IV non-small cell lung cancer: results from a population-based study. Eur J Cancer. 2015;51:2534–44.
R: A language and environment for statistical computing [computer program]. Version 3.3.0. Vienna, Austria. R Foundation for Statistical Computing, R Core Team; 2016. https://www.R-project.org.
Ko JJ, Tudor R, Li H, et al. Reasons for lack of referral to medical oncology for systemic therapy in stage IV non-small-cell lung cancer: comparison of 2003–2006 with 2010–2011. Curr Oncol. 2017. https://doi.org/10.3747/co.24.3691.
Pikin O, Ryabov A, Glushko V, et al. Does surgery have real benefit in resectable oligometastatic NSCLC? J Thorac Oncol. 2017;12(1):s779.
Newton PK, Mason J, Bethel K, et al. Spreaders and sponges define metastasis in lung cancer: a Markov chain Monte Carlo mathematical model. Cancer Res. 2013;73(9):2760–9. https://doi.org/10.1158/0008-5472.CAN-12-4488.
Bates J, Milano M. Prognostic significance of sites of extrathoracic metastasis in patients with non-small cell lung cancer. J Thorac Dis. 2017;9(7):1903–10. http://jtd.amegroups.com/article/view/14548.
Eberhardt WEE, Mitchell A, Crowley, et al. The IASLC lung cancer staging project: proposals for the revision of the m descriptors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2015;10(11):1515–22. https://doi.org/10.1097/JTO/000000000000673.
Wood SL, Pernemalm M, Crosbie PA, Whetton AD. The role of tumor micro-environment in lung cancer metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev. 2014;40:558–66. https://doi.org/10.1016/j.ctrv.2013.10.001.
Owen S, Souhami L. The management of brain metastases in non-small cell lung cancer. Front Oncol. 2014. https://doi.org/10.3389/fonc.2014.00248.
Chen YM, Fang YT, Lai CH, et al. A survival scoring system for non-small cell lung cancer patients with de novo bone metastases. PLoS ONE. 2016;11(12):e0167923. https://doi.org/10.1371/journal.pone.0167923.
Joss RA, Burki K, Dalwuen P, et al. Combination chemotherapy with mitomycin, vindestine and cisplatin or non-small cell lung cancer. Association of antitumor activity with initial tumour burden and treatment center. Cancer. 1990;65:2426–34.
Oh Y, Taylor S, Bekele BM, et al. Number of metastatic sites is a strong predictor of survival in patients with nonsmall cell lung cancer with or without brain metastases. Cancer. 2009;115:2930–8.
Alexander BM, Othus M, Caglar HB, et al. Tumor volume is a prognostic factor in non-small-cell lung cancer treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;79:1381–7.
Park JH, Kim TM, Keam B, et al. Tumor burden is predictive of survival in patients with non-small-cell lung cancer and with activating epidermal growth factor receptor mutations who receive getfitinib. Clin Lung Cancer. 2013;14(4):383–9. https://doi.org/10.1016/j.cllc.2012.10.007.
Goldie JH, Colman AJ. The genetic origin of drug resistance in neoplasms: implications for systemic therapy. Cancer Res. 1984;44:3643–53.
Foo J, Michor F. Evolution of resistance to targeted anti-cancer therapies during continuous and pulsed administration strategies. PloS Comput Biol. 2009;5:e1000557.
Chang YP, Chen YM, Lai CH, et al. The impact of de novo liver metastasis on clinical outcome in patients with advanced non-small-cell lung cancer. PloS ONE. 2017;12(6):e0178676. https://doi.org/10.1371/journal.pone.0178676.
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;12(11):1193–9. https://doi.org/10.1093/neuonc/noq076.
Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008;372(9652):1809–18. https://doi.org/10.1016/S0140-6736(08)61758-4.
Ishii H, Azuma K, Yamada K, Kinoshita T, Imamura Y, Hoshino T. Predictive factors in patients with EGFR mutation-negative non-small cell lung cancer treated with erlotinib. Oncol Lett. 2014;8:2699–704. https://doi.org/10.3892/ol.2014.2548.
Lee DS, Kang JH, Lee CG, et al. Predicting survival in patients with advanced non-squamous non-small cell lung cancer: validating the extent of metastasis. Cancer Res Treat. 2013;45(2):85–102. https://doi.org/10.4143/crt.2013.45.2.95.
Iyengar P, Lau S, Donington JS, Suh RD. Local therapy for limited metastatic non-small cell lung cancer: what are the options and is there a benefit? Presentation at: ASCO Annual Meeting; June 6, 2016; Chicago.
Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small cell lung cancer. N Engl J Med. 2010;363(8):733–42. https://doi.org/10.1056/NEJMoa1000678.
Pirl WF, Greer JA, Traeger L, et al. Depression and survival in metastatic non-small cell lung cancer: effects of early palliative care. J Clin Oncol. 2012;30(12):1310–5. https://doi.org/10.1200/jco.2011.28.3166.
Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. Ca Cancer J Clin. 2017;67:93–9. https://doi.org/10.3322/caac.21388.
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Gibson, A.J.W., Li, H., D’Silva, A. et al. Impact of number versus location of metastases on survival in stage IV M1b non-small cell lung cancer. Med Oncol 35, 117 (2018). https://doi.org/10.1007/s12032-018-1182-8
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DOI: https://doi.org/10.1007/s12032-018-1182-8