A 'Vascular Normalization Index' as Potential Mechanistic Biomarker to Predict Survival after a Single Dose of Cediranib in Recurrent Glioblastoma Patients
| Autor: | Emmanuelle di Tomaso, Poe-Jou Chen, Patrick Y. Wen, Dominique Jennings, Johanna Lahdenranta, Dan G. Duda, Tracy T. Batchelor, Rakesh K. Jain, Wei-Ting Zhang, Marek Ancukiewicz, Priscilla Yeo, Meiyun Wang, A. Gregory Sorensen |
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| Rok vydání: | 2009 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Pathology Brain tumor Antineoplastic Agents Vascular permeability Article Disease-Free Survival Cediranib Predictive Value of Tests Internal medicine medicine Humans Microvessel Survival rate Blood Volume Hematologic Tests Brain Neoplasms business.industry Cancer medicine.disease Magnetic Resonance Imaging Survival Rate medicine.anatomical_structure Quinazolines Biomarker (medicine) Collagen Neoplasm Recurrence Local Glioblastoma business Biomarkers Blood vessel medicine.drug |
| Zdroj: | Cancer Research. 69:5296-5300 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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 used 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., Ktrans) and in microvessel volume, and the change of circulating collagen IV 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 Ktrans, 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 (ρ = 0.54; P = 0.004) and progression-free survival (ρ = 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] |
| Databáze: | OpenAIRE |
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