Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial

被引:16
作者
Beije, N. [1 ,2 ]
Kraan, J. [1 ,2 ]
Taal, W. [3 ]
van der Holt, B. [4 ]
Oosterkamp, H. M. [5 ]
Walenkamp, A. M. [6 ]
Beerepoot, L. [7 ]
Hanse, M. [8 ]
van Linde, M. E. [9 ]
Otten, A. [10 ]
Vernhout, R. M. [4 ]
de Vos, F. Y. F. [11 ]
Gratama, J. W. [1 ,2 ]
Sleijfer, S. [1 ,2 ]
van den Bent, M. J. [3 ]
机构
[1] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Med Oncol, NL-3015 CN Rotterdam, Netherlands
[2] Canc Genom Netherlands, NL-3015 CN Rotterdam, Netherlands
[3] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Neurooncol, NL-3075 EA Rotterdam, Netherlands
[4] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Clin Trial Ctr, NL-3015 CE Rotterdam, Netherlands
[5] Med Ctr Haaglanden, Dept Med Oncol, NL-2512 VA The Hague, Netherlands
[6] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, NL-9713 GZ Groningen, Netherlands
[7] St Elizabeth Hosp, Dept Oncol, NL-5022 GC Tilburg, Netherlands
[8] Catharina Hosp, Dept Neurol, NL-5623 EJ Eindhoven, Netherlands
[9] Vrije Univ Amsterdam Med Ctr, Dept Oncol, NL-1081 HV Amsterdam, Netherlands
[10] Isala Klin, Dept Neurol, NL-8025 AB Zwolle, Netherlands
[11] Univ Med Ctr Utrecht, Dept Med Oncol, NL-3584 CX Utrecht, Netherlands
关键词
circulating endothelial cells; glioblastoma; angiogenesis; endothelial damage; bevacizumab; lomustine; BELOB; CLINICAL-VALUE; GLIOMAS; ANGIOGENESIS; VARIABILITY;
D O I
10.1038/bjc.2015.191
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma. Methods: In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated. Results: The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log(10)CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log(10)CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS. Conclusion: CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.
引用
收藏
页码:226 / 231
页数:6
相关论文
共 23 条
[1]   Clinical value of circulating endothelial cells and circulating tumor cells in metastatic breast cancer patients treated first line with bevacizumab and chemotherapy [J].
Bidard, F. -C. ;
Mathiot, C. ;
Degeorges, A. ;
Etienne-Grimaldi, M. -C. ;
Delva, R. ;
Pivot, X. ;
Veyret, C. ;
Bergougnoux, L. ;
de Cremoux, P. ;
Milano, G. ;
Pierga, J. -Y. .
ANNALS OF ONCOLOGY, 2010, 21 (09) :1765-1771
[2]   Circulating endothelial cells - Biomarker of vascular disease [J].
Blann, AD ;
Woywodt, A ;
Bertolini, F ;
Bull, TM ;
Buyon, JP ;
Clancy, RM ;
Haubitz, M ;
Hebbel, RP ;
Lip, GYH ;
Mancuso, P ;
Sampol, J ;
Solovey, A ;
Dignat-George, F .
THROMBOSIS AND HAEMOSTASIS, 2005, 93 (02) :228-235
[3]  
Chinot OL, 2014, NEW ENGL J MED, V370, P709, DOI 10.1056/NEJMoa1308345
[4]   Prognostic Value of CD109+Circulating Endothelial Cells in Recurrent Glioblastomas Treated with Bevacizumab and Irinotecan [J].
Cuppini, Lucia ;
Calleri, Angelica ;
Bruzzone, Maria Grazia ;
Prodi, Elena ;
Anghileri, Elena ;
Pellegatta, Serena ;
Mancuso, Patrizia ;
Porrati, Paola ;
Di Stefano, Anna Luisa ;
Ceroni, Mauro ;
Bertolini, Francesco ;
Finocchiaro, Gaetano ;
Eoli, Marica .
PLOS ONE, 2013, 8 (09)
[5]   Revacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy [J].
Dickson, Paxton V. ;
Hamner, John B. ;
Sims, Thomas L. ;
Fraga, Charles H. ;
Ng, Catherine Y. C. ;
Rajasekeran, Surender ;
Hagedorn, Nikolaus L. ;
McCarville, M. Beth ;
Stewart, Clinton F. ;
Davidoff, Andrew M. .
CLINICAL CANCER RESEARCH, 2007, 13 (13) :3942-3950
[6]   Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma [J].
Friedman, Henry S. ;
Prados, Michael D. ;
Wen, Patrick Y. ;
Mikkelsen, Tom ;
Schiff, David ;
Abrey, Lauren E. ;
Yung, W. K. Alfred ;
Paleologos, Nina ;
Nicholas, Martin K. ;
Jensen, Randy ;
Vredenburgh, James ;
Huang, Jane ;
Zheng, Maoxia ;
Cloughesy, Timothy .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (28) :4733-4740
[7]   A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma [J].
Gilbert, Mark R. ;
Dignam, James J. ;
Armstrong, Terri S. ;
Wefel, Jeffrey S. ;
Blumenthal, Deborah T. ;
Vogelbaum, Michael A. ;
Colman, Howard ;
Chakravarti, Arnab ;
Pugh, Stephanie ;
Won, Minhee ;
Jeraj, Robert ;
Brown, Paul D. ;
Jaeckle, Kurt A. ;
Schiff, David ;
Stieber, Volker W. ;
Brachman, David G. ;
Werner-Wasik, Maria ;
Tremont-Lukats, Ivo W. ;
Sulman, Erik P. ;
Aldape, Kenneth D. ;
Curran, Walter J., Jr. ;
Mehta, Minesh P. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (08) :699-708
[8]   Inter-observer variability in the measurement of diffuse intrinsic pontine gliomas [J].
Hayward, Robert M. ;
Patronas, Nicolas ;
Baker, Eva H. ;
Vezina, Gilbert ;
Albert, Paul S. ;
Warren, Katherine E. .
JOURNAL OF NEURO-ONCOLOGY, 2008, 90 (01) :57-61
[9]   Angiogenesis in brain tumours [J].
Jain, Rakesh K. ;
Di Tomaso, Emmanuelle ;
Duda, Dan G. ;
Loeffler, Jay S. ;
Sorensen, A. Gregory ;
Batchelor, Tracy T. .
NATURE REVIEWS NEUROSCIENCE, 2007, 8 (08) :610-622
[10]   Endothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells [J].
Kraan, J. ;
van den Broek, P. ;
Verhoef, C. ;
Grunhagen, D. J. ;
Taal, W. ;
Gratama, J. W. ;
Sleijfer, S. .
BRITISH JOURNAL OF CANCER, 2014, 111 (01) :149-156