Natural history, clinical course and predictors of interval time from initial diagnosis to development of subsequent NSCLC brain metastases

  • Deborah R. Smith
  • Yandong Bian
  • Cheng-Chia Wu
  • Anurag Saraf
  • Cheng-Hung Tai
  • Tavish Nanda
  • Andrew Yaeh
  • Matthew E. Lapa
  • Jacquelyn I. S. Andrews
  • Simon K. Cheng
  • Guy M. McKhann
  • Michael B. Sisti
  • Jeffrey N. Bruce
  • Tony J. C. WangEmail author
Clinical Study



Non-small cell lung cancer (NSCLC) brain metastases are associated with substantial morbidity and mortality. During recent years, accompanying dramatic improvements in systemic disease control, NSCLC brain metastases have emerged as an increasingly relevant clinical problem. However, optimal surveillance practices remain poorly defined. This purpose of this study was to further characterize the natural history, clinical course and risk factors associated with earlier development of subsequent NSCLC brain metastases to better inform clinical practice and help guide survivorship care.


We retrospectively reviewed all institutional NSCLC brain metastasis cases treated with radiotherapy between 1997 and 2015. Exclusion criteria included presence of brain metastases at initial NSCLC diagnosis and incomplete staging information. Interval time to brain metastases and subsequent survival were characterized using Kaplan–Meier and multivariate Cox regression analyses.


Among 105 patients within this cohort, median interval time to development of brain metastases was 16 months. Median interval times were 29, 19, 16 and 13 months for Stage I–IV patients, respectively (P = 0.016). Additional independent predictors for earlier development of NSCLC brain metastases included non-adenocarcinomatous histopathology (HR 3.036, P < 0.001), no prior surgical resection (HR 1.609, P = 0.036) and no prior systemic therapy (HR 3.560, P = 0.004). Median survival following intracranial progression was 16 months. Delayed development of brain metastases was associated with better prognosis (HR 0.970, P < 0.001) but not survival following intracranial disease onset.


Collectively, our results provide valuable insights into the natural history of NSCLC brain metastases. NSCLC stage, histology, prior surgical resection and prior systemic therapy emerged as independent predictors for interval time to brain metastases.


Lung cancer NSCLC Brain metastases Neurooncology Radiation oncology 


Compliance with ethical standards

Conflict of interest

Dr. Wang reports personal fees and non-financial support from AbbVie, non-financial support from Merck, personal fees from AstraZeneca, personal fees from Doximity, personal fees and non-financial support from Novocure, personal fees and non-financial support from Elekta and personal fees from Wolters Kluwer, outside the submitted work.

Supplementary material

11060_2019_3149_MOESM1_ESM.docx (73 kb)
Supplementary material 1 (DOCX 73 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Deborah R. Smith
    • 1
  • Yandong Bian
    • 1
  • Cheng-Chia Wu
    • 1
  • Anurag Saraf
    • 1
  • Cheng-Hung Tai
    • 1
  • Tavish Nanda
    • 1
  • Andrew Yaeh
    • 1
  • Matthew E. Lapa
    • 1
  • Jacquelyn I. S. Andrews
    • 1
  • Simon K. Cheng
    • 1
    • 2
  • Guy M. McKhann
    • 2
    • 3
  • Michael B. Sisti
    • 2
    • 3
  • Jeffrey N. Bruce
    • 2
    • 3
  • Tony J. C. Wang
    • 1
    • 2
    Email author
  1. 1.Department of Radiation OncologyColumbia University Irving Medical CenterNew YorkUSA
  2. 2.Herbert Irving Comprehensive Cancer CenterColumbia University Irving Medical CenterNew YorkUSA
  3. 3.Department of Neurological SurgeryColumbia University Irving Medical CenterNew YorkUSA

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