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Published in: Journal of Experimental & Clinical Cancer Research 1/2012

Open Access 01-12-2012 | Research

Early perfusion changes in patients with recurrent high-grade brain tumor treated with Bevacizumab: preliminary results by a quantitative evaluation

Authors: Antonello Vidiri, Andrea Pace, Alessandra Fabi, Marta Maschio, Gaetano Marco Latagliata, Vincenzo Anelli, Francesca Piludu, Carmine Maria Carapella, Giuseppe Giovinazzo, Simona Marzi

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

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Abstract

Background

To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up.

Methods

Sixteen patients were enrolled in the present study. For each patient, two PCT examinations, before and after the first dose of bevacizumab, were acquired. Areas of abnormal Cerebral Blood Volume (CBV) were manually defined on the CBV maps, using co-registered T1- weighted images, acquired before treatment, as a guide to the tumor location. Different perfusion metrics were derived from the histogram analysis of the normalized CBV (nCBV) maps; both hyper and hypo-perfused sub-volumes were quantified in the lesion, including tumor necrosis. A two-tailed Wilcoxon test was used to establish the significance of changes in the different perfusion metrics, observed at baseline and during treatment. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated.

Results

Significant reductions in mean and median nCBV were detected throughout the entire patient population, after only a single dose of bevacizumab. The nCBV histogram modifications indicated the normalization effect of bevacizumab on the tumor abnormal vasculature. An improvement in hypoxia after a single dose of bevacizumab was predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up.

Conclusions

These preliminary results show that a quantification of changes in necrotic intra-tumoral regions could be proposed as a potential imaging biomarker of tumor response to anti-VEGF therapies.
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Literature
1.
go back to reference Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R: A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001, 95: 190-198. 10.3171/jns.2001.95.2.0190.CrossRefPubMed Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R: A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001, 95: 190-198. 10.3171/jns.2001.95.2.0190.CrossRefPubMed
2.
go back to reference Stupp R, Mason WP, van den Bent MJ, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005, 352: 987-996. 10.1056/NEJMoa043330.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005, 352: 987-996. 10.1056/NEJMoa043330.CrossRefPubMed
3.
go back to reference Park JK, Hodges T, Arko L, Shen M, Dello Iacono D, McNabb A, Olsen Bailey N, Kreisl TN, Iwamoto FM, Sul J, Auh S, Park GE, Fine HA, Black PM: Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol. 2010, 28: 3838-3843. 10.1200/JCO.2010.30.0582.PubMedCentralCrossRefPubMed Park JK, Hodges T, Arko L, Shen M, Dello Iacono D, McNabb A, Olsen Bailey N, Kreisl TN, Iwamoto FM, Sul J, Auh S, Park GE, Fine HA, Black PM: Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol. 2010, 28: 3838-3843. 10.1200/JCO.2010.30.0582.PubMedCentralCrossRefPubMed
4.
go back to reference Jain RK: Antiangiogenic therapy for cancer: current and emerging concepts. Oncology. 2005, 19: 7-16. ReviewPubMed Jain RK: Antiangiogenic therapy for cancer: current and emerging concepts. Oncology. 2005, 19: 7-16. ReviewPubMed
5.
go back to reference Vredenburgh JJ, Desjardins A, Herndon JE, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS: Bevacizumab plus irinotecan in recurrent glioblastoma multi- forme. J Clin Oncol. 2007, 25: 4722-4729. 10.1200/JCO.2007.12.2440.CrossRefPubMed Vredenburgh JJ, Desjardins A, Herndon JE, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS: Bevacizumab plus irinotecan in recurrent glioblastoma multi- forme. J Clin Oncol. 2007, 25: 4722-4729. 10.1200/JCO.2007.12.2440.CrossRefPubMed
6.
go back to reference Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA: Phase II trial of single- agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009, 27: 740-745. 10.1200/JCO.2008.16.3055.PubMedCentralCrossRefPubMed Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA: Phase II trial of single- agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009, 27: 740-745. 10.1200/JCO.2008.16.3055.PubMedCentralCrossRefPubMed
7.
go back to reference Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM: Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010, 28: 1963-1972. 10.1200/JCO.2009.26.3541.CrossRefPubMed Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM: Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010, 28: 1963-1972. 10.1200/JCO.2009.26.3541.CrossRefPubMed
8.
go back to reference Goh V, Ng QS, Miles K: Computed Tomography Perfusion Imaging for Therapeutic Assessment: Has It Come of Age as a Biomarker in Oncology?. Invest Radiol. 2011, 47: 2-4.CrossRef Goh V, Ng QS, Miles K: Computed Tomography Perfusion Imaging for Therapeutic Assessment: Has It Come of Age as a Biomarker in Oncology?. Invest Radiol. 2011, 47: 2-4.CrossRef
9.
go back to reference Ng CS, Charnsangavej C, Wei W, Yao JC: Perfusion CT findings in patients with metastatic carcinoid tumors undergoing bevacizumab and interferon therapy. AJR Am J Roentgenol. 2011, 196: 569-576. 10.2214/AJR.10.4455.CrossRefPubMed Ng CS, Charnsangavej C, Wei W, Yao JC: Perfusion CT findings in patients with metastatic carcinoid tumors undergoing bevacizumab and interferon therapy. AJR Am J Roentgenol. 2011, 196: 569-576. 10.2214/AJR.10.4455.CrossRefPubMed
10.
go back to reference Sorensen AG, Batchelor TT, Zhang WT, Chen PJ, Yeo P, Wang M, Jennings D, Wen PY, Lahdenranta J, Ancukiewicz M, di Tomaso E, Duda DG, Jain RK: A "vascular normalization index" as potential mechanistic biomarker to predict survival after a single dose of cediranibin recurrent glioblastoma patients. Cancer Res. 2009, 69: 5296-5300. 10.1158/0008-5472.CAN-09-0814.PubMedCentralCrossRefPubMed Sorensen AG, Batchelor TT, Zhang WT, Chen PJ, Yeo P, Wang M, Jennings D, Wen PY, Lahdenranta J, Ancukiewicz M, di Tomaso E, Duda DG, Jain RK: A "vascular normalization index" as potential mechanistic biomarker to predict survival after a single dose of cediranibin recurrent glioblastoma patients. Cancer Res. 2009, 69: 5296-5300. 10.1158/0008-5472.CAN-09-0814.PubMedCentralCrossRefPubMed
11.
go back to reference Sawlani RN, Raizer J, Horowitz SW, Shin W, Grimm SA, Chandler JP, Levy R, Getch C, Carroll TJ: Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging-pilot study. Radiology. 2010, 55: 622-628.CrossRef Sawlani RN, Raizer J, Horowitz SW, Shin W, Grimm SA, Chandler JP, Levy R, Getch C, Carroll TJ: Glioblastoma: a method for predicting response to antiangiogenic chemotherapy by using MR perfusion imaging-pilot study. Radiology. 2010, 55: 622-628.CrossRef
12.
go back to reference Fellah S, Girard N, Chinot O, Cozzone PJ, Callot V: Early evaluation of tumoral response to antiangiogenic therapy by arterial spin labeling perfusion magnetic resonance imaging and susceptibility weighted imaging in a patient with recurrent glioblastoma receiving bevacizumab. J Clin Oncol. 2011, 10 (29): 308-311.CrossRef Fellah S, Girard N, Chinot O, Cozzone PJ, Callot V: Early evaluation of tumoral response to antiangiogenic therapy by arterial spin labeling perfusion magnetic resonance imaging and susceptibility weighted imaging in a patient with recurrent glioblastoma receiving bevacizumab. J Clin Oncol. 2011, 10 (29): 308-311.CrossRef
13.
go back to reference Saraswathy S, Crawford FW, Lamborn KR, Pirzkall A, Chang S, Cha S, Nelson SJ: Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy. J Neurooncol. 2009, 91: 69-81. 10.1007/s11060-008-9685-3.PubMedCentralCrossRefPubMed Saraswathy S, Crawford FW, Lamborn KR, Pirzkall A, Chang S, Cha S, Nelson SJ: Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy. J Neurooncol. 2009, 91: 69-81. 10.1007/s11060-008-9685-3.PubMedCentralCrossRefPubMed
14.
go back to reference Nowosielski M, Recheis W, Goebel G, Güler O, Tinkhauser G, Kostron H, Schocke M, Gotwald T, Stockhammer G, Hutterer M: ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma. Neuroradiology. 2011, 53: 291-302. 10.1007/s00234-010-0808-0.PubMedCentralCrossRefPubMed Nowosielski M, Recheis W, Goebel G, Güler O, Tinkhauser G, Kostron H, Schocke M, Gotwald T, Stockhammer G, Hutterer M: ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma. Neuroradiology. 2011, 53: 291-302. 10.1007/s00234-010-0808-0.PubMedCentralCrossRefPubMed
15.
go back to reference Hattingen E, Jurcoane A, Bähr O, Rieger J, Magerkurth J, Anti S, Steinbach JP, Pilatus U: Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in recurrent glioblastomas: a 31P/1H MRSI and quantitative magnetic resonance imaging study. Neuro Oncol. 2011, 13: 1349-1363. 10.1093/neuonc/nor132.PubMedCentralCrossRefPubMed Hattingen E, Jurcoane A, Bähr O, Rieger J, Magerkurth J, Anti S, Steinbach JP, Pilatus U: Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in recurrent glioblastomas: a 31P/1H MRSI and quantitative magnetic resonance imaging study. Neuro Oncol. 2011, 13: 1349-1363. 10.1093/neuonc/nor132.PubMedCentralCrossRefPubMed
16.
go back to reference Ellingson BM, Cloughesy TF, Lai A, Nghiemphu PL, Mischel PS, Pope WB: Quantitative volumetric analysis of conventional MRI response in recurrent glioblastoma treated with bevacizumab. Neuro Oncol. 2011, 13: 401-409. 10.1093/neuonc/noq206.PubMedCentralCrossRefPubMed Ellingson BM, Cloughesy TF, Lai A, Nghiemphu PL, Mischel PS, Pope WB: Quantitative volumetric analysis of conventional MRI response in recurrent glioblastoma treated with bevacizumab. Neuro Oncol. 2011, 13: 401-409. 10.1093/neuonc/noq206.PubMedCentralCrossRefPubMed
17.
go back to reference Pieper S, Lorensen B, Schroeder W, Kikinis R, The NA-MIC Kit: TK, VTK, pipelines, grids and 3D slicer as an open platform for the medical image computing community. Proceedings of the 3rd IEEE International Symposium on Biomedical Imaging: Nano to Macro. 2006, : 698-701. Pieper S, Lorensen B, Schroeder W, Kikinis R, The NA-MIC Kit: TK, VTK, pipelines, grids and 3D slicer as an open platform for the medical image computing community. Proceedings of the 3rd IEEE International Symposium on Biomedical Imaging: Nano to Macro. 2006, : 698-701.
18.
go back to reference Masunaga S, Liu Y, Tanaka H, Sakurai Y, Suzuki M, Kondo N, Maruhashi A, Ono K: Reducing intratumor acute hypoxia through bevacizumabtreatment, referring to the response of quiescent tumor cells and metastatic potential. Br J Radiol. 2011, 84: 1131-1138. 10.1259/bjr/38457938.PubMedCentralCrossRefPubMed Masunaga S, Liu Y, Tanaka H, Sakurai Y, Suzuki M, Kondo N, Maruhashi A, Ono K: Reducing intratumor acute hypoxia through bevacizumabtreatment, referring to the response of quiescent tumor cells and metastatic potential. Br J Radiol. 2011, 84: 1131-1138. 10.1259/bjr/38457938.PubMedCentralCrossRefPubMed
19.
go back to reference Yopp AC, Schwartz LH, Kemeny N, Gultekin DH, Gönen M, Bamboat Z, Shia J, Haviland D, D'Angelica MI, Fong Y, DeMatteo RP, Allen PJ, Jarnagin WR: Antiangiogenic therapy for primary liver cancer: correlation of changes in dynamic contrast-enhanced magnetic resonance imaging with tissue hypoxia markers and clinical response. Ann Surg Oncol. 2011, 18: 2192-2199. 10.1245/s10434-011-1570-1.PubMedCentralCrossRefPubMed Yopp AC, Schwartz LH, Kemeny N, Gultekin DH, Gönen M, Bamboat Z, Shia J, Haviland D, D'Angelica MI, Fong Y, DeMatteo RP, Allen PJ, Jarnagin WR: Antiangiogenic therapy for primary liver cancer: correlation of changes in dynamic contrast-enhanced magnetic resonance imaging with tissue hypoxia markers and clinical response. Ann Surg Oncol. 2011, 18: 2192-2199. 10.1245/s10434-011-1570-1.PubMedCentralCrossRefPubMed
20.
go back to reference Keunen O, Johansson M, Oudin A, Sanzey M, Rahim SA, Fack F, Thorsen F, Taxt T, Bartos M, Jirik R, Miletic H, Wang J, Stieber D, Stuhr L, Moen I, Rygh CB, Bjerkvig R, Niclou SP: Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci. 2011, 108: 3749-3754. 10.1073/pnas.1014480108.PubMedCentralCrossRefPubMed Keunen O, Johansson M, Oudin A, Sanzey M, Rahim SA, Fack F, Thorsen F, Taxt T, Bartos M, Jirik R, Miletic H, Wang J, Stieber D, Stuhr L, Moen I, Rygh CB, Bjerkvig R, Niclou SP: Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci. 2011, 108: 3749-3754. 10.1073/pnas.1014480108.PubMedCentralCrossRefPubMed
Metadata
Title
Early perfusion changes in patients with recurrent high-grade brain tumor treated with Bevacizumab: preliminary results by a quantitative evaluation
Authors
Antonello Vidiri
Andrea Pace
Alessandra Fabi
Marta Maschio
Gaetano Marco Latagliata
Vincenzo Anelli
Francesca Piludu
Carmine Maria Carapella
Giuseppe Giovinazzo
Simona Marzi
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-31-33

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