Value of DCE-MRI and FDG-PET/CT in the prediction of response to preoperative chemotherapy with bevacizumab for colorectal liver metastases

S De Bruyne, N Van Damme, P Smeets, L Ferdinande, W Ceelen, J Mertens, C Van de Wiele, R Troisi, L Libbrecht, S Laurent, K Geboes, M Peeters, S De Bruyne, N Van Damme, P Smeets, L Ferdinande, W Ceelen, J Mertens, C Van de Wiele, R Troisi, L Libbrecht, S Laurent, K Geboes, M Peeters

Abstract

Background: The purpose of this study was to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and (18)F-fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET/CT) for evaluation of response to chemotherapy and bevacizumab and for prediction of progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) with potentially resectable liver lesions.

Methods: A total of 19 mCRC patients were treated with FOLFOX/FOLFIRI and bevacizumab followed by surgery. Dynamic contrast-enhanced magnetic resonance imaging and FDG-PET/CT were performed before treatment and after cycle 5. PET results were quantified by calculating maximum standardised uptake value (SUV(max)) whereas area under the enhancement curve (AUC), initial AUC (iAUC) and the endothelial transfer constant (K(trans)) were used to quantify DCE-MRI. Pathological analysis of the resection specimen was performed, including measurement of microvessel density (MVD) and proliferation index.

Results: Both AUC and iAUC were significantly decreased following bevacizumab therapy (median change of 22% (P=0.002) and 40% (P=0.001) for AUC and iAUC, respectively). Progression-free survival benefit was shown for patients with >40% reduction in K(trans) (P=0.019). In the group of radiological responders, the median baseline SUV(max) was 3.77 (IQR: 2.88-5.60) compared with 7.20 (IQR: 4.67-8.73) in nonresponders (P=0.021). A higher follow-up SUV(max) was correlated with worse PFS (P=0.012). Median MVD was 10.9. Progression-free survival was significantly shorter in patients with an MVD greater than 10, compared with patients with lower MVD (10 months compared with 16 months, P=0.016).

Conclusion: High relative decrease in K(trans), low follow-up SUV(max) and low MVD are favourable prognostic factors for mCRC patients treated with bevacizumab before surgery.

Figures

Figure 1
Figure 1
Flow chart of the study.
Figure 2
Figure 2
(A) Baseline MR image showing a large colorectal metastasis in the right liver lobe. (B) Signal intensity time course in regions of interest placed over the aorta (upper curve), normal liver parenchyma (middle curve) and tumour tissue (lower curve). (C) Parametric map of Ktrans (ml-1/1000) before therapy start. (D) Parametric map of Ktrans after 1 cycle of bevacizumab-containing chemotherapy. A clear effect is seen at the angiogenic tumour rim. The arrow points to the pixel (aorta) used as the arterial input for modelling.
Figure 3
Figure 3
Median values of AUC (A), iAUC (B) and Ktrans (C) at each time point. Two-sided P-values were calculated with the Wilcoxon signed rank test. Significant P-values are reported.
Figure 4
Figure 4
Cumulative progression-free survival rates stratified by ΔKtrans after 1 cycle of chemotherapy (A), ΔKtrans at the end of chemotherapy (B), metabolic CR (C) and MVD (D).
Figure 5
Figure 5
FDG-PET images of a metabolic responder (A) and nonresponder (B) before and after chemotherapy.

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