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

Eur Radiol. 2018 Nov;28(11):4860-4870. doi: 10.1007/s00330-018-5448-5. Epub 2018 May 16.

Abstract

Objectives: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Breast cancer; Diffusion magnetic resonance imaging; Magnetic resonance spectroscopy; Neovascularization, pathologic; Survival analysis.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / pathology*
  • Choline / analysis
  • Creatinine / analysis
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging / methods*
  • Magnetic Resonance Spectroscopy
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Aspartic Acid
  • N-acetylaspartate
  • Creatinine
  • Choline