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Early stage non-small cell lung cancer patients need brain imaging regardless of symptoms

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Abstract

Background

Japanese Lung Cancer Society and ESMO guideline recommends screening for brain metastasis in all patients with non-small cell lung cancer (NSCLC), while NCCN/ACCP guidelines do not recommend screening patients who are asymptomatic and with clinical stage I NSCLC. However, brain metastasis sometimes occurs in early stage NSCLC patients without any neurological symptoms.

Methods

We retrospectively reviewed medical records of 124 patients admitted to the University of Tokyo Hospital with stage IV NSCLC from January 2012 to April 2016. We analyzed clinical stage, the presence of the central nervous system manifestations and the number of brain metastases.

Results

Forty-six out of 124 cases had brain metastasis at presentation. The brain metastasis group had larger number of female, never smokers and patients with EGFR mutation compared with extracranial metastasis group. Twenty-one of 35 adenocarcinoma cases with brain metastasis had EGFR mutations. Out of 46 brain metastasis patients, 29 patients (63%) were asymptomatic and patients with EGFR mutations were significantly less likely to have neurological symptoms (4/21 vs. 7/14, p = 0.049). Six out of 46 cases with brain metastasis (13%) were clinical T1-2aN0. In clinical T1-2aN0 cases, only one patient had neurological symptoms at presentation.

Conclusion

In clinical T1-2aN0 lung cancer patients with brain metastasis, almost all patients were asymptomatic. Patients with EGFR mutations and brain metastasis were likely to be asymptomatic. Regardless of central nervous system symptoms, routine brain imaging seems warranted in all NSCLC patients, especially in areas where patients have a higher frequency of EGFR mutations.

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References

  1. Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108

    Article  PubMed  Google Scholar 

  2. Stewart BW, Wild CP. (2014) World Cancer Report 2014. Lyon, France: International Agency for Research on Cancer. http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014

  3. Howlader N, Noone AM, Krapcho M, et al. (2017) SEER cancer statistics review (CSR) 1975–2014. Bethesda, MD: National Cancer Institute. https://seer.cancer.gov/csr/1975_2014/

  4. Matsuda A, Matsuda T, Shibata A et al (2014) Cancer incidence and incidence rates in Japan in 2008: a study of 25 population-based cancer registries for the monitoring of cancer incidence in Japan (MCIJ) project. Jpn J Clin Oncol 44(4):388–396

    Article  PubMed  Google Scholar 

  5. Little AG, Gay EG, Gaspar LE et al (2007) National survey of non-small cell lung cancer in the United States: epidemiology, pathology and patterns of care. Lung Cancer 57(3):253–260

    Article  PubMed  Google Scholar 

  6. Sánchez de Cos J, Sojo González MA, Montero MV et al (2009) Non-small cell lung cancer and silent brain metastasis. Survival and prognostic factors. Lung Cancer 63(1):140–145

    Article  PubMed  Google Scholar 

  7. Han G, Bi J, Tan W et al (2016) A retrospective analysis in patients with EGFR-mutant lung adenocarcinoma: is EGFR mutation associated with a higher incidence of brain metastasis? Oncotarget 7(35):56998–57010

    PubMed  PubMed Central  Google Scholar 

  8. Hsu F, De Caluwe A, Anderson D et al (2016) EGFR mutation status on brain metastases from non-small cell lung cancer. Lung Cancer 96:101–107

    Article  PubMed  Google Scholar 

  9. Tanaka K, Kubota K, Kodama T et al (1990) Extrathoracic staging is not necessary for non-small-cell lung cancer with clinical stage T1-2 N0. Ann Thorac Surg 68(3):1039–1042

    Article  Google Scholar 

  10. Cole FH Jr, Thomas JE et al (1994) Cerebral imaging in the asymptomatic preoperative bronchogenic carcinoma patient: is it worthwhile? Ann Thorac Surg 57(4):838–840

    Article  PubMed  Google Scholar 

  11. Ichinose Y, Hara N, Ohta M et al (1989) Preoperative examination to detect distant metastasis is not advocated for asymptomatic patients with stages 1 and 2 non-small cell lung cancer. Preoperative examination for lung cancer. Chest 96(5):1104–1109

    Article  PubMed  CAS  Google Scholar 

  12. Yohena T, Yoshino I, Kitajima M et al (2004) Necessity of preoperative screening for brain metastasis in non-small cell lung cancer patients without lymph node metastasis. Ann Thorac Cardiovasc Surg. 10(6):347–349

    PubMed  Google Scholar 

  13. Balekian AA, Fisher JM, Gould MK (2016) Brain imaging for staging of patients with clinical stage IA non-small cell lung cancer in the national lung screening trial adherence with recommendations from the choosing wisely campaign. Chest 149(4):943–950

    Article  PubMed  Google Scholar 

  14. Silvestri GA, Gonzalez AV, Jantz MA et al (2013) Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143(5 Suppl):e211S–e250S

    Article  PubMed  Google Scholar 

  15. Ettinger DS, Wood DE, Aisner DL et al (2017) Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 15(4):504–535

    Article  PubMed  Google Scholar 

  16. Ferrigno D, Buccheri G (1994) Cranial computed tomography as a part of the initial staging procedures for patients with non-small-cell lung cancer. Chest 106(4):1025–1029

    Article  PubMed  CAS  Google Scholar 

  17. Shi AA, Digumarthy SR, Temel JS et al (2006) Does initial staging or tumor histology better identify asymptomatic brain metastases in patients with non-small cell lung cancer? J Thorac Oncol. 1(3):205–210

    Article  PubMed  Google Scholar 

  18. Lung Cancer Guideline based on EBM (2016) Japan Lung Cancer Society, Kanehara Shuppan. https://www.haigan.gr.jp/modules/guideline/index.php?content_id=3

  19. Novello S, Barlesi F, Califano R et al (2016) Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 27(suppl 5):v1–v27

    Article  PubMed  CAS  Google Scholar 

  20. Shin DY, Na II, Kim CH et al (2014) EGFR mutation and brain metastasis in pulmonary adenocarcinomas. J Thorac Oncol. 9(2):195–199

    Article  PubMed  CAS  Google Scholar 

  21. Midha A, Dearden S, McCormack R (2015) EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 5(9):2892–2911

    PubMed  PubMed Central  Google Scholar 

  22. Mitsudomi T, Yatabe Y (2007) Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer. Cancer Sci 98(12):1817–1824

    Article  PubMed  CAS  Google Scholar 

  23. Matsumoto S, Takahashi K, Iwakawa R et al (2006) Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 119(6):1491–1494

    Article  PubMed  CAS  Google Scholar 

  24. Salvatierra A, Baamonde C et al (1990) Extrathoracic staging of bronchogenic carcinoma. Chest 97(5):1052–1058

    Article  PubMed  CAS  Google Scholar 

  25. Kormas P, Bradshaw JR, Jeyasingham K (1992) Preoperative computed tomography of the brain in non-small cell bronchogenic carcinoma. Thorax 47(2):106–108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Suzuki K, Koike T, Asakawa T et al (2011) A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical IA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol. 6(4):751–756

    Article  PubMed  Google Scholar 

  27. Asamura H, Hishida T, Suzuki K et al (2013) Radiographically determined noninvasive adenocarcinoma of the lung: survival outcomes of Japan Clinical Oncology Group 0201. J Thorac Cardiovasc Surg 146(1):24–30

    Article  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

HK have full access to the data and takes responsibility for its integrity and have final responsibility for the decision to submit for publication. TA and HK are responsible for the study concept and design. TA, HK, MS, YA, YG, JN and TN are responsible for acquisition of data, analysis and interpretation of data. TA and HK are responsible for drafting of the manuscript. TA, HK, MS, YA, YG, JN and TN are responsible for critical revision of the manuscript.

Corresponding author

Correspondence to Hidenori Kage.

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No author has any conflict of interest.

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Ando, T., Kage, H., Saito, M. et al. Early stage non-small cell lung cancer patients need brain imaging regardless of symptoms. Int J Clin Oncol 23, 641–646 (2018). https://doi.org/10.1007/s10147-018-1254-y

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  • DOI: https://doi.org/10.1007/s10147-018-1254-y

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