DCE-MRI biomarkers of tumour heterogeneity predict CRC liver metastasis shrinkage following bevacizumab and FOLFOX-6.

Abstract

BACKGROUND:

There is limited evidence that imaging biomarkers can predict subsequent response to therapy. Such prognostic and/or predictive biomarkers would facilitate development of personalised medicine. We hypothesised that pre-treatment measurement of the heterogeneity of tumour vascular enhancement could predict clinical outcome following combination anti-angiogenic and cytotoxic chemotherapy in colorectal cancer (CRC) liver metastases.

METHODS:

Ten patients with 26 CRC liver metastases had two dynamic contrast-enhanced MRI (DCE-MRI) examinations before starting first-line bevacizumab and FOLFOX-6. Pre-treatment biomarkers of tumour microvasculature were computed and a regression analysis was performed against the post-treatment change in tumour volume after five cycles of therapy. The ability of the resulting linear model to predict tumour shrinkage was evaluated using leave-one-out validation. Robustness to inter-visit variation was investigated using data from a second baseline scan.

RESULTS:

In all, 86% of the variance in post-treatment tumour shrinkage was explained by the median extravascular extracellular volume (v(e)), tumour enhancing fraction (E(F)), and microvascular uniformity (assessed with the fractal measure box dimension, d(0)) (R(2)=0.86, P<0.00005). Other variables, including baseline volume were not statistically significant. Median prediction error was 12%. Equivalent results were obtained from the second scan.

CONCLUSION:

Traditional image analyses may over-simplify tumour biology. Measuring microvascular heterogeneity may yield important prognostic and/or predictive biomarkers.

• Authors: J P B O'Connor, C J Rose, A Jackson, Y Watson, S Cheung, F Maders, B J Whitcher, C Roberts, G A Buonaccorsi, G Thompson, A R Clamp, G C Jayson, G J M Parker
• Journal: British journal of cancer (Br J Cancer) Vol. 105 Issue 1 Pg. 139-45 (Jun 28 2011) ISSN: 1532-1827 [Electronic] England
• PMID: 21673686 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• Contrast Media
• Organoplatinum Compounds
• Bevacizumab
• Gadolinium DTPA
• Leucovorin
• Fluorouracil

Topics

• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Biomarkers, Tumor
• Colorectal Neoplasms (diagnosis, drug therapy)
• Contrast Media
• Drug Therapy, Combination
• Female
• Fluorouracil (therapeutic use)
• Gadolinium DTPA
• Humans
• Leucovorin (therapeutic use)
• Liver Neoplasms (diagnosis, drug therapy, secondary)
• Magnetic Resonance Imaging
• Male
• Organoplatinum Compounds (therapeutic use)
• Retrospective Studies
• Survival Rate
• Treatment Outcome