Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis
Yoshinori Hirashima
Department of Medical Oncology Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, Japan
Search for more papers by this authorCorresponding Author
Yasuhide Yamada
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanSearch for more papers by this authorUkihide Tateishi
Department of Radiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan
Search for more papers by this authorKen Kato
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorMototaka Miyake
Diagnostic Radiology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorYosuke Horita
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKohei Akiyoshi
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorAtsuo Takashima
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorNatsuko Okita
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorDaisuke Takahari
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorTakako Nakajima
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorTetsuya Hamaguchi
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorYasuhiro Shimada
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKuniaki Shirao
Department of Medical Oncology Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, Japan
Search for more papers by this authorYoshinori Hirashima
Department of Medical Oncology Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, Japan
Search for more papers by this authorCorresponding Author
Yasuhide Yamada
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, JapanSearch for more papers by this authorUkihide Tateishi
Department of Radiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan
Search for more papers by this authorKen Kato
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorMototaka Miyake
Diagnostic Radiology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorYosuke Horita
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKohei Akiyoshi
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorAtsuo Takashima
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorNatsuko Okita
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorDaisuke Takahari
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorTakako Nakajima
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorTetsuya Hamaguchi
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorYasuhiro Shimada
Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorKuniaki Shirao
Department of Medical Oncology Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, Japan
Search for more papers by this authorAbstract
Bevacizumab (BV) is an antivascular endothelial growth factor antibody. When administered with other chemotherapeutic drugs, BV-combined regimens prolong survival of colorectal cancer patients. We conducted a phase II trial to confirm the pharmacokinetic parameters from 3-Tesla dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as surrogate biomarkers of BV + FOLFIRI regimen efficacy in colorectal cancer with liver metastases. DCE-MRI was performed before treatment, on the seventh day after first treatment and every 8 weeks thereafter using a 3-Tesla MRI system. DCE-MRI parameters-area under the contrast concentration versus time curve at 90 and 180 s (AUC90 and AUC180, respectively) after contrast injection, and volume transfer constant of contrast agents (Ktrans and Kep) were calculated from liver metastases. Fifty-eight liver metastases were analyzed. Univariate analysis revealed that a decrease in Ktrans ratios (ΔKtrans), Kep ratios (ΔKep), AUC90 ratios (ΔAUC90) and AUC180 ratios (ΔAUC180) correlated with higher response (all p < 0.0001) and longer time to progression (TTP) (ΔKtrans: p = 0.001; ΔKep: p = 0.004; ΔAUC90: p = 0.006; ΔAUC180: p < 0.0001). Multivariate analysis showed that ΔAUC180 was correlated with higher response (p = 0.009), and ΔKtrans and ΔAUC180 were correlated with longer TTP (ΔKtrans: p = 0.001; ΔAUC180: p = 0.024). ΔKtrans and ΔAUC180 are pharmacodynamic biomarkers of the blood perfusion of BV + FOLFIRI. Our data suggest that ΔKtrans and ΔKep can predict response to chemotherapy at 1 week. Changes in 3-Tesla DCE-MRI parameters confirmed the potential of these biomarkers of blood perfusion as surrogate predictors of response and TTP.
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