Imaging biomarkers from multiparametric magnetic resonance imaging are associated with survival outcomes in patients with brain metastases from breast cancer
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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, K trans , k ep , v e ), 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 ΔK trans (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, ΔK trans 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.
• 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.
KeywordsBreast 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
Eastern Cooperative Oncology Group
Human epidermal growth factor receptor 2
Initial area under curve for the first 60 s
Volume transfer constant
(maximal signal – baseline signal)/baseline signal
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.
Written informed consent was obtained from all subjects (patients) in this study
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).
• diagnostic or prognostic study
• performed at one institution
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