A "Vascular Normalization Index" as Potential Mechanistic Biomarker to Predict Survival after a Single Dose of Cediranib in Recurrent Glioblastoma Patients

被引：285

作者：

Sorensen, A. Gregory ^{[1
]}

Batchelor, Tracy T. ^{[2
]}

Zhang, Wei-Ting ^{[1
]}

Chen, Poe-Jou ^{[1
]}

Yeo, Priscilla ^{[1
]}

Wang, Meiyun ^{[1
]}

Jennings, Dominique ^{[1
]}

Wen, Patrick Y. ^{[4
]}

Lahdenranta, Johanna ^{[3
]}

Ancukiewicz, Marek ^{[3
]}

di Tomaso, Emmanuelle ^{[3
]}

Duda, Dan G. ^{[3
]}

Jain, Rakesh K. ^{[3
]}

机构：

[1] Massachusetts Gen Hosp, EL Steele Lab, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA

[4] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 13期

关键词：

ENDOTHELIAL GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; PROGNOSTIC-FACTORS; TUMOR VASCULATURE; KINASE INHIBITOR; GLIOMA; GRADE; ANGIOGENESIS; BEVACIZUMAB; METASTASES;

D O I：

10.1158/0008-5472.CAN-09-0814

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Early imaging or blood biomarkers of tumor response are desperately needed to customize antiangiogenic therapy for cancer patients. Anti-vascular endothelial growth factor (VEGF) therapy can "normalize" brain tumor vasculature by decreasing vessel diameter and permeability, and thinning the abnormally thick basement membrane. We hypothesized that the extent of vascular normalization will be predictive of outcome of anti-VEGF therapy in glioblastoma. We use advanced magnetic resonance imaging methods to monitor vascular parameters and treatment response in 31 recurrent glioblastoma patients enrolled in a phase II trial of cediranib, an oral pan-VEGF receptor tyrosine kinase inhibitor. We evaluated the correlation between clinical outcome and magnetic resonance imaging-measured changes in vascular permeability/flow (i.e., K(trans)) and in microvessel volume, and the change of circulating collagen W levels, all after a single dose of cediranib. Here, we show that evaluation of biomarkers as early as after one day of anti-VEGF therapy with cediranib is predictive of response in patients with recurrent glioblastoma. Changes in K(trans) microvessel volume, and circulating collagen IV correlated with duration of overall survival and/or progression-free survival (P < 0.05). When we combined these three parameters into a "vascular normalization index," we found that it closely associated with overall survival (rho = 0.54; P = 0.004) and progression-free survival (rho = 0.6; P = 0.001). The vascular normalization index described here should be validated in randomized clinical trials. [Cancer Res 2009;69(13):5296-300]

引用

页码：5296 / 5300

页数：5