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Published on: August 14, 2019
Do imaging biomarkers relate to outcome in patients treated with VEGF inhibitors?
James P B O'Connor1, Gordon C Jayson
1Centre for Imaging Sciences, University of Manchester, Manchester, United Kingdom. james.o'connor@manchester.ac.uk
Abstract:
The management of solid tumors has been transformed by the advent of VEGF pathway inhibitors. Early clinical evaluation of these drugs has used pharmacodynamic biomarkers derived from advanced imaging such as dynamic MRI, computed tomography (CT), and ultrasound to establish proof of principle. We have reviewed published studies that used these imaging techniques to determine whether the same biomarkers relate to survival in renal, hepatocellular, and brain tumors in patients treated with VEGF inhibitors. Data show that in renal cancer, pretreatment measurements of K(trans) and early pharmacodynamic reduction in tumor enhancement and density have prognostic significance in patients treated with VEGF inhibitors. A weaker, but significant, relationship is seen with subtle early size change (10% in one dimension) and survival. Data from high-grade glioma suggest that pretreatment fractional blood volume and K(trans) were prognostic of overall survival. However, lack of control data with other therapies prevents assessment of the predictive nature of these biomarkers, and such studies are urgently required.
Insights
Advanced imaging biomarkers like K(trans) can predict survival in patients with renal cancer and high-grade glioma treated with vascular endothelial growth factor (VEGF) pathway inhibitors. Early tumor changes show prognostic significance.
Area of Science:
- Oncology
- Radiology
- Pharmacology
Background:
- Vascular endothelial growth factor (VEGF) pathway inhibitors have revolutionized solid tumor management.
- Pharmacodynamic biomarkers from advanced imaging (MRI, CT, ultrasound) were used for early drug evaluation.
- The prognostic value of these imaging biomarkers for patient survival requires further investigation.
Purpose of the Study:
- To review published studies evaluating advanced imaging biomarkers.
- To determine if imaging biomarkers correlate with survival in renal, hepatocellular, and brain tumors treated with VEGF inhibitors.
Main Methods:
- Systematic review of published studies.
- Analysis of pharmacodynamic biomarkers from dynamic MRI, CT, and ultrasound.
- Correlation of biomarkers with patient survival outcomes.
Main Results:
- In renal cancer, pretreatment K(trans) and early reductions in tumor enhancement/density predict survival with VEGF inhibitors.
- Subtle early size changes (10%) also show a significant, albeit weaker, relationship with survival.
- In high-grade glioma, pretreatment fractional blood volume and K(trans) are prognostic for overall survival.
Conclusions:
- Specific advanced imaging biomarkers demonstrate prognostic significance for survival in renal cancer and high-grade glioma patients receiving VEGF inhibitors.
- Further studies with control data are crucial to assess the predictive value of these biomarkers across different therapies.
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