European Radiology

, Volume 28, Issue 11, pp 4860–4870 | Cite as

Imaging biomarkers from multiparametric magnetic resonance imaging are associated with survival outcomes in patients with brain metastases from breast cancer

  • Bang-Bin Chen
  • Yen-Shen Lu
  • Chih-Wei Yu
  • Ching-Hung Lin
  • Tom Wei-Wu Chen
  • Shwu-Yuan Wei
  • Ann-Lii Cheng
  • Tiffany Ting-Fang ShihEmail author



The aim of this study is to investigate the correlation of survival outcomes with imaging biomarkers from multiparametric magnetic resonance imaging (MRI) in patients with brain metastases from breast cancer (BMBC).


This study was approved by the institutional review board. Twenty-two patients with BMBC who underwent treatment involving bevacizumab on day 1, etoposide on days 2-4, and cisplatin on day 2 in 21-day cycles were prospectively enrolled for a phase II study. Three brain MRIs were performed: before the treatment, on day 1, and on day 21. Eight imaging biomarkers were derived from dynamic contrast-enhanced MRI (Peak, IAUC60, Ktrans, kep, ve), diffusion-weighted imaging [apparent diffusion coefficient (ADC)], and MR spectroscopy (choline/N-acetylaspartate and choline/creatine ratios). The relative changes (Δ) in these biomarkers were correlated with the central nervous system (CNS)-specific progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier and Cox proportional hazard models.


There were no significant differences in the survival outcomes as per the changes in the biomarkers on day 1. On day 21, those with a low ΔKtrans (p = 0.024) or ΔADC (p = 0.053) reduction had shorter CNS-specific PFS; further, those with a low ΔPeak (p = 0.012) or ΔIAUC60 (p = 0.04) reduction had shorter OS compared with those with high reductions. In multivariate analyses, ΔKtrans and ΔPeak were independent prognostic factors for CNS-specific PFS and OS, respectively, after controlling for age, size, hormone receptors, and performance status.


Multiparametric MRI may help predict the survival outcomes in patients with BMBC.

Key Points

• Decreased angiogenesis after chemotherapy on day 21 indicated good survival outcome.

• ΔK trans was an independent prognostic factors for CNS-specific PFS.

• ΔPeak was an independent prognostic factors for OS.

• Multiparametric MRI helps clinicians to assess patients with BMBC.

• High-risk patients may benefit from more intensive follow-up or treatment strategies.


Breast cancer Neovascularization, pathologic Survival analysis Diffusion magnetic resonance imaging Magnetic resonance spectroscopy 



Proton magnetic resonance spectroscopy


Apparent diffusion coefficient




Central nerve system




Dynamic contrast-enhanced magnetic resonance imaging


Diffusion-weighted imaging


Eastern Cooperative Oncology Group


Estrogen receptor


Human epidermal growth factor receptor 2


Initial area under curve for the first 60 s


Reflux constant


Volume transfer constant




Overall survival


(maximal signal – baseline signal)/baseline signal


Progression-free survival


Progesterone receptor


Region of interest


Extravascular extracellular volume fraction



This study has received funding by the National Taiwan University (NTU-ICRP-103R7557 to Y.S.L.), Ministry of Science and Technology, Taiwan (MOST 103-2314-B-002-170-MY3 to Y.S.L.)

Compliance with ethical standards


The scientific guarantor of this publication is Tiffany Ting-Fang Shih.

Conflict of interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Fu-Chang Hu, Sc.D., kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

All study subjects or cohorts have been previously reported.

This study is based on our previous works (Clin Cancer Res. 2015 Apr 15;21(8):1851-8; BMC Cancer. 2016 Jul 13;16:466. NCT01281696).


• prospective

• diagnostic or prognostic study

• performed at one institution


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Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Bang-Bin Chen
    • 1
    • 2
  • Yen-Shen Lu
    • 3
    • 4
  • Chih-Wei Yu
    • 1
    • 2
  • Ching-Hung Lin
    • 3
    • 4
  • Tom Wei-Wu Chen
    • 3
    • 4
  • Shwu-Yuan Wei
    • 1
  • Ann-Lii Cheng
    • 3
    • 4
  • Tiffany Ting-Fang Shih
    • 1
    • 2
    Email author
  1. 1.Department of RadiologyCollege of Medicine, National Taiwan UniversityTaipeiTaiwan
  2. 2.Department of Medical ImagingNational Taiwan University HospitalTaipeiTaiwan
  3. 3.Department of OncologyNational Taiwan University HospitalTaipeiTaiwan
  4. 4.Department of Internal MedicineCollege of Medicine, National Taiwan UniversityTaipeiTaiwan

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