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

Abstract

Background:The purpose of this study was to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-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 (SUVmax) whereas area under the enhancement curve (AUC), initial AUC (iAUC) and the endothelial transfer constant (Ktrans) 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 Ktrans (P=0.019). In the group of radiological responders, the median baseline SUVmax 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 SUVmax 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 Ktrans, low follow-up SUVmax and low MVD are favourable prognostic factors for mCRC patients treated with bevacizumab before surgery.

Update on the Role of Imaging in Management of Metastatic Colorectal Cancer

“…A high baseline K trans has been shown to correlate with better outcome with cytotoxic agents in CRC (52). In a study by De Bruyne et al (53), a decrease in K trans of more than 40% after bevacizumab-containing chemotherapy was associated with better progression-free survival, although this has not been corroborated in other studies. DW imaging can also help detect small lesions (<10 mm) that are not detectable with other modalities (54).…”

Do Imaging Biomarkers Relate to Outcome in Patients Treated with VEGF Inhibitors?

“…For example, in 4 studies of primary rectal cancer and mCRC treated with bevacizumab and cytotoxic therapy, pretreatment and early acute pharmacodynamic changes in tumor F, K trans , and BV did not relate to extent of tumor regression or RECIST response (62)(63)(64)(65). This finding could be interpreted as proof that imaging biomarkers do not relate to outcome in this setting.…”

Prognostication and response assessment in liver and pancreatic tumors: The new imaging

“…De Bruyne et al [127] 19 DCE-MRI AUC decrease CRC metastases Bevacizumab Vriens et al [129] 23 DCE-MRI K trans decrease CRC metastases Cytotoxic therapy Coenegrachts et al [130] 10 DCE-MRI Kep increase CRC metastases Bevacizumab + FOLFIRI Deckers et al [126] 20 DWI ADC decrease CRC metastases Chemotherapy Niwa et al [133] 63 DWI ADC decrease PDAC Gemcitabine Cuneo et al [134] 12 DWI ADC increase PDAC Chemoradiation Yao et al [135] 39 pCT BF decrease PanNET Bevacizumab ± everolimus Miyazaki et al [132] [115,116] .…”

“…Many studies have been conducted with DCE-MRI, probably as a consequence of the standardization of DCE-MRI-derived endpoints. De Bruyne et al [127] reported that bevacizumab therapy could decrease DCE-MRI-derived AUC in patients with CRC liver metastases. Vriens et al [128] reported a large reduction in DCE-MRI-derived perfusion parameters and glucose metabolic rate at 18 F-FDG PET/CT in CRC metastases treated with bevacizumab.…”