Serum biomarkers associated with clinical outcomes fail to predict brain metastases in patients with stage IV non-small cell lung cancers Journal Article


Authors: Li, B. T.; Lou, E.; Hsu, M.; Yu, H. A.; Naidoo, J.; Zauderer, M. G.; Sima, C.; Johnson, M. L.; Daras, M.; Deangelis, L. M.; Fleisher, M.; Kris, M. G.; Azzoli, C. G.
Article Title: Serum biomarkers associated with clinical outcomes fail to predict brain metastases in patients with stage IV non-small cell lung cancers
Abstract: Background Lung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC) may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown. Methods Serum NSE, CYFRA 21-1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pretreatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR) mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray's test. Results A total of 118 patients were enrolled, 31 (26%; 95% CI 0.19-0.35) had brain metastases at baseline and a further 26 (22%; 95% CI 0.15-0.30) developed brain metastases subsequently. Pre-Treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22- 7.34, P = 0.02) by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2), but this was not statistically significant possibly due to small sample size. Conclusions Serum NSE, CYFRA 21-1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time may be applied to independent datasets to identify a patient cohort with a higher biologic propensity for developing brain metastases. Such information may be useful for the study of agents targeting the development of brain metastases. © 2016 Li et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 11
Issue: 1
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2016-01-05
Start Page: e0146063
Language: English
DOI: 10.1371/journal.pone.0146063
PROVIDER: scopus
PMCID: PMC4701719
PUBMED: 26730601
DOI/URL:
Notes: Article -- Export Date: 3 February 2016 -- Source: Scopus
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MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Meier Hsu
    105 Hsu
  3. Helena Alexandra Yu
    94 Yu
  4. Melissa Lynne Johnson
    19 Johnson
  5. Martin Fleisher
    245 Fleisher
  6. Mark Kris
    622 Kris
  7. Mariza Daras
    20 Daras
  8. Jarushka Naidoo
    31 Naidoo
  9. Bob Tingkan Li
    61 Li