Ukihide Tateishi MD, PhD, Abstract Co-Author: Nothing to Disclose

Mototaka Miyake MD, Presenter: Nothing to Disclose

Yoshinori Hirashima, Abstract Co-Author: Nothing to Disclose

Yasuaki Arai MD, Abstract Co-Author: Nothing to Disclose

Kazuro Sugimura MD, PhD, Abstract Co-Author: Research grant, Toshiba Corporation Research grant, Koninklijke Philips Electronics NV Research grant, Mitsubishi Corporation Research grant, Bayer AG Research grant, Eisai Co, Ltd Research grant, DAIICHI SANKYO Group Research Consultant, Shionogi & Co, Ltd

Yasuhide Yamada, Abstract Co-Author: Nothing to Disclose

To confirm the pharmacodynamic parameters obtained from 3-Tesla DCE-MRI as surrogate biomarkers for therapy of bevacizumab (BV) +FOLFIRI (irinotecan, leucovorin, and fluorouracil) in colorectal cancer with liver metastases.

A total of 58 hepatic metastases in 17 patients (median age, 60years) with colorectal carcinoma were enrolled. Treatments of BV plus FOLFIRI were repeated every 2 weeks. DCE-MRI scans were acquired using a 3-Tesla whole-body magnet equipped with dedicated receive-only six-channel dual coil. DCE-MRI was performed before treatment, 7 days after treatment, and every 8 weeks until 12 courses. DCE-MRI images were obtained with VIBE sequence on the transverse plane using 4.45/2.46, 13°FA, section thickness of 5.0 mm, and matrix of 132×320 pixels. Continuous 10-second data acquisition was performed after administration of contrast medium for a total of 3 minutes 20 seconds with 11-12 repeated data sets. The quantitative parameters are measured for a region-of-interest (ROI) defined manually by a reader in tumor and aorta separately. Time intensity curves are generated using the signal enhancement ratio and the baseline tumor T1 relaxation time by a two-compartment pharmacokinetic model. Parameters consisted of Ct (t), Cp (t), Κtrans, Kep, and AUC.

Median follow-up time was 14.3 months (range: 3.0 - 21.5 months), the overall response rate was 47%, and median time-to-progression (TTP) was 12.4 months. Median changes in Ktrans (∆Ktrans), Kep (∆Kep), AUC90 (∆AUC90), and AUC180 (∆AUC180) were 46.8/min, 48.1/min, 18.8mMs, and 16.4nMs, respectively. ΔKtrans, ΔKep, ΔAUC90, and ΔAUC180 were correlated with TTP according to log-rank test. A univariate analysis revealed that ΔKtrans, ΔKep, ΔAUC90, and ΔAUC180 correlated with longer TTP (ΔKtrans: P =0.001, ΔKep: P =0.004, ΔAUC90: P =0.006, ΔAUC180: P <0.0001). Moreover, multivariate analysis showed that ΔKtrans and ΔAUC180 correlated with longer TTP (ΔKtrans: P =0.001, ΔAUC180: P =0.024), ΔKtrans and ΔAUC180 are pharmacodynamic biomarkers of BV combined regimen and that parameter changes may predict higher response and TTP.

DCE-MRI parameters, ∆Ktrans and ∆AUC180 are predictive biomarkers of BV+FOLFIRI in metastatic colorectal cancer with liver metastasis.

Parameters of DCE-MRI are predictive biomarkers for angiogenic activity in tumor.

Tateishi, U, Miyake, M, Hirashima, Y, Arai, Y, Sugimura, K, Yamada, Y, Dynamic Contrast-enhanced MRI as Surrogate Biomarker of Antitumor Effect of Anti-VEGF Antibody Combined Chemotherapy in Colorectal Cancer: A Phase II Study.  Radiological Society of North America 2010 Scientific Assembly and Annual Meeting, November 28 - December 3, 2010 ,Chicago IL. http://archive.rsna.org/2010/9012362.html