TY - JOUR
T1 - Voxel-based evidence of perfusion normalization in glioblastoma patients included in a phase I–II trial of radiotherapy/tipifarnib combination
AU - Ken, Soléakhéna
AU - Deviers, Alexandra
AU - Filleron, Thomas
AU - Catalaa, Isabelle
AU - Lotterie, Jean Albert
AU - Khalifa, Jonathan
AU - Lubrano, Vincent
AU - Berry, Isabelle
AU - Péran, Patrice
AU - Celsis, Pierre
AU - Moyal, Elizabeth Cohen Jonathan
AU - Laprie, Anne
PY - 2015/7/19
Y1 - 2015/7/19
N2 - We previously showed that the farnesyl transferase inihibitor, Tipifarnib induced vascularization normalization, oxygenation and radiosensitization in a pre-clinical glioblastoma (GBM) model. The aim of this study was to assess by dynamic-susceptibility-contrast MRI (DSC-MRI) the effect of radiotherapy (RT) and Tipifarnib combination on tumor perfusion in GBM patients. Eighteen patients with newly diagnosed GBM, enrolled in a phase I-II clinical trial associating RT with Tipifarnib, underwent anatomical MR imaging and DSC-MRI before (M0) and two months after treatment (M2). Anatomic volumes of interest (VOIs) were delineated according to contrast-enhanced and hyper-intense signal areas on T1-Gd and T2 images, respectively. Perfusion variations between M0 and M2 were assessed with median relative cerebral blood volume (rCBV) inside these VOIs. Another voxel by voxel analysis of CBV values classified 405,117 tumor voxels into High_, Normal_ and Low_CBVTUMOR according to the distribution of CBV in the contralateral normal tissue. These three categories of CBVTUMOR voxels were color-coded over anatomical MRI. Variations of median rCBV were significantly different for two groups of patients (P 1) and rCBV increased when initial rCBV was 1 presented a significant decrease of High_CBVTUMOR volume (P = 0.015) simultaneously with a significant increase of Normal_CBVTUMOR volume (P = 0.009) after treatment. Group_rCBV_M0 TUMOR volume with an increase of Normal_ and High_CBV TUMOR volume after treatment. Pre and post-treatment CBV measurements with DSC-MRI characterized tumor perfusion evolution in GBM patients treated with RT combined to Tipifarnib; showing variations in favour of tumor perfusion normalization in agreement with our pre-clinical results of vascular normalization.
AB - We previously showed that the farnesyl transferase inihibitor, Tipifarnib induced vascularization normalization, oxygenation and radiosensitization in a pre-clinical glioblastoma (GBM) model. The aim of this study was to assess by dynamic-susceptibility-contrast MRI (DSC-MRI) the effect of radiotherapy (RT) and Tipifarnib combination on tumor perfusion in GBM patients. Eighteen patients with newly diagnosed GBM, enrolled in a phase I-II clinical trial associating RT with Tipifarnib, underwent anatomical MR imaging and DSC-MRI before (M0) and two months after treatment (M2). Anatomic volumes of interest (VOIs) were delineated according to contrast-enhanced and hyper-intense signal areas on T1-Gd and T2 images, respectively. Perfusion variations between M0 and M2 were assessed with median relative cerebral blood volume (rCBV) inside these VOIs. Another voxel by voxel analysis of CBV values classified 405,117 tumor voxels into High_, Normal_ and Low_CBVTUMOR according to the distribution of CBV in the contralateral normal tissue. These three categories of CBVTUMOR voxels were color-coded over anatomical MRI. Variations of median rCBV were significantly different for two groups of patients (P 1) and rCBV increased when initial rCBV was 1 presented a significant decrease of High_CBVTUMOR volume (P = 0.015) simultaneously with a significant increase of Normal_CBVTUMOR volume (P = 0.009) after treatment. Group_rCBV_M0 TUMOR volume with an increase of Normal_ and High_CBV TUMOR volume after treatment. Pre and post-treatment CBV measurements with DSC-MRI characterized tumor perfusion evolution in GBM patients treated with RT combined to Tipifarnib; showing variations in favour of tumor perfusion normalization in agreement with our pre-clinical results of vascular normalization.
KW - Antiangiogenic therapy
KW - Clinical Trial
KW - Dynamic susceptibility-weighted contrast-enhanced MRI
KW - Glioblastoma
KW - Radiotherapy
KW - Tumor Perfusion
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U2 - 10.1007/s11060-015-1860-8
DO - 10.1007/s11060-015-1860-8
M3 - Article
C2 - 26189058
AN - SCOPUS:84942506307
VL - 124
SP - 465
EP - 473
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 3
ER -