Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Surrogate Biomarker for Bevacizumab in Colorectal Cancer Liver Metastasis: A Single-Arm, Exploratory Trial

Abstract

PurposeThe purpose of this study is to investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plasma cytokines and angiogenic factors (CAFs) as pharmacodynamic and prognostic biomarkers of bevacizumab monotherapy in colorectal cancer with liver metastasis (CRCLM).Materials and MethodsFrom July 2011 to March 2012, 28 patients with histologically confirmed CRCLM received bevacizumab monotherapy followed by combined FOLFOX therapy. The mean age of the patients was 57 years (range, 30 to 77 years). DCE-MRI (Ktransand IAUC60) was performed at baseline, first follow-up (3 days after bevacizumab monotherapy), and second follow-up (3 days after combined therapy). CAF levels (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], and interleukin-8) were assessed on the same days. Progression-free survival (PFS) time distributions were summarized using the Kaplan-Meier method and compared using log-rank tests.ResultsThe median PFS period was 11.2 months. Ktrans, IAUC60, VEGF, and PlGF values on the first follow-up day were significantly different compared with baseline values. No differences were observed on the second follow-up day. A > 40% decrease in Ktrans from baseline to first follow-up was associated with a longer PFS (hazard ratio, 0.349; 95% confidence interval, 0.133 to 0.912; p=0.032). Changes in CAFs did not show correlation with PFS time.ConclusionDCE-MRI parameters and CAFs are pharmacodynamic biomarkers of bevacizumab for CRCLM. In our study, change in Ktrans at 3 days after bevacizumab monotherapy was a favorable prognostic factor; however, the value of CAFs as a prognostic biomarker was not found.

Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial

“…To our knowledge, no prior published study has analyzed the impact of bevacizumab on circulating proangiogenic biomarkers in sarcoma patients, especially in angiosarcoma patients. A large body of evidence shows that treatment with bevacizumab induces significant changes in circulating biomarkers in different carcinomas (for example, colo-rectal cancers [ 21 , 22 ], hepatocarcinoma [ 23 ], non-small cell lung cancers [ 24 ]), and our observed decrease in circulating VEGF is consistent with bevacizumab’s mechanism of action. Despite the few data on the impact of bevacizumab treatment on circulating PlGF, an increase in PlGF after bevacizumab treatment has been described in the case of non-small cell lung cancer [ 24 ] and colo-rectal cancer [ 25 ].…”

Colorectal cancer: Parametric evaluation of morphological, functional and molecular tomographic imaging

“…Indeed, Hirashima et al[106] observed a significant correlation between a reduction in the Ktrans value 7 days after the start of treatment and a longer time to progression. Subsequently, Kim et al[107] confirmed this finding and found that a reduction of 40% in the Ktrans cut-off value could be used to discriminate responders from nonresponders. De Bruyne et al[108] found that a decrease in Ktrans of more than 40% after bevacizumab chemotherapy in patients with CRLMs was associated with improved PFS.…”

[18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer

“…Preclinical studies indicate that anti-angiogenic therapies cause vascular normalization, [46,47]. Several studies have suggested that changes in K trans may be an early pharmacodynamic biomarker of clinical response to anti-angiogenics [48][49][50]. However, K trans denotes a context-dependent (including degree of tumor perfusion and MRI acquisition setup/equipment) complex combination of tissue blood flow and permeability weighted to varying extents.…”