R A Manneh Kopp1, J M Sepúlveda-Sánchez1,2, Y Ruano3, O Toldos3, A Pérez Núñez4, D Cantero3, A Hilario5, A Ramos5, G de Velasco1, P Sánchez-Gómez6, A Hernández-Laín7,8. 1. Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain. 2. Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain. 3. Department of Pathology (Neuropathology), Hospital Universitario 12 de Octubre, 28041, Madrid, Spain. 4. Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain. 5. Departments Radiology (A.H., A.R.), Hospital Universitario 12 de Octubre, Madrid, Spain. 6. Neuro-Oncology Unit, Health Institute Carlos III-UFIEC, Madrid, Spain. 7. Department of Pathology (Neuropathology), Hospital Universitario 12 de Octubre, 28041, Madrid, Spain. aurelio.hlain@salud.madrid.org. 8. Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain. aurelio.hlain@salud.madrid.org.
Abstract
BACKGROUND: Some phase 2 trials had reported encouraging progression-free survival with Bevacizumab in monotherapy or combined with chemotherapy in glioblastoma. However, phase 3 trials showed a significant improvement in progression free survival without a benefit in overall survival. To date, there are no predictive biomarker of response for Bevacizumab in glioblastoma. METHODS: We used Immunochemical analysis on tumor samples and pretreatment and post-treatment perfusion-MRI to try to identify possible predictive angiogenesis-related biomarkers of response and survival in patients with glioblastoma treated with bevacizumab in the first recurrence. We analyzed histological parameters: vascular proliferation, mitotic number and Ki-67 index; molecular factors: MGMT promoter methylation, EGFR amplification and EGFR variant III; immunohistochemical: MET, Midkine, HIF1, VEGFA, VEGF-R2, CD44, Olig2, microvascular area and microvascular density; and radiological: rCBV. RESULTS: In the statistical analysis, no significant correlation of any histological, molecular, microvascular or radiological parameters could be demonstrated with the response rate, PFS or OS with bevacizumab treatment. CONCLUSION: Unfortunately, in this histopathological, molecular, immunohistochemical and neuroradiological study we did not find any predictive biomarker of response or survival benefit for Bevacizumab in glioblastoma.
BACKGROUND: Some phase 2 trials had reported encouraging progression-free survival with Bevacizumab in monotherapy or combined with chemotherapy in glioblastoma. However, phase 3 trials showed a significant improvement in progression free survival without a benefit in overall survival. To date, there are no predictive biomarker of response for Bevacizumab in glioblastoma. METHODS: We used Immunochemical analysis on tumor samples and pretreatment and post-treatment perfusion-MRI to try to identify possible predictive angiogenesis-related biomarkers of response and survival in patients with glioblastoma treated with bevacizumab in the first recurrence. We analyzed histological parameters: vascular proliferation, mitotic number and Ki-67 index; molecular factors: MGMT promoter methylation, EGFR amplification and EGFR variant III; immunohistochemical: MET, Midkine, HIF1, VEGFA, VEGF-R2, CD44, Olig2, microvascular area and microvascular density; and radiological: rCBV. RESULTS: In the statistical analysis, no significant correlation of any histological, molecular, microvascular or radiological parameters could be demonstrated with the response rate, PFS or OS with bevacizumab treatment. CONCLUSION: Unfortunately, in this histopathological, molecular, immunohistochemical and neuroradiological study we did not find any predictive biomarker of response or survival benefit for Bevacizumab in glioblastoma.
Entities:
Keywords:
Bevacizumab; Biomarkers; Glioblastoma; Microvacular density; Microvascular area
Authors: A Hilario; J M Sepulveda; A Perez-Nuñez; E Salvador; J M Millan; A Hernandez-Lain; V Rodriguez-Gonzalez; A Lagares; A Ramos Journal: AJNR Am J Neuroradiol Date: 2014-01-23 Impact factor: 3.825
Authors: A Hilario; A Ramos; A Perez-Nuñez; E Salvador; J M Millan; A Lagares; J M Sepulveda; P Gonzalez-Leon; A Hernandez-Lain; J R Ricoy Journal: AJNR Am J Neuroradiol Date: 2011-12-29 Impact factor: 3.825
Authors: W A Palmisano; K K Divine; G Saccomanno; F D Gilliland; S B Baylin; J G Herman; S A Belinsky Journal: Cancer Res Date: 2000-11-01 Impact factor: 12.701
Authors: Kathleen M Schmainda; Melissa Prah; Jennifer Connelly; Scott D Rand; Raymond G Hoffman; Wade Mueller; Mark G Malkin Journal: Neuro Oncol Date: 2014-01-15 Impact factor: 12.300
Authors: Mark R Gilbert; James J Dignam; Terri S Armstrong; Jeffrey S Wefel; Deborah T Blumenthal; Michael A Vogelbaum; Howard Colman; Arnab Chakravarti; Stephanie Pugh; Minhee Won; Robert Jeraj; Paul D Brown; Kurt A Jaeckle; David Schiff; Volker W Stieber; David G Brachman; Maria Werner-Wasik; Ivo W Tremont-Lukats; Erik P Sulman; Kenneth D Aldape; Walter J Curran; Minesh P Mehta Journal: N Engl J Med Date: 2014-02-20 Impact factor: 91.245
Authors: Rakesh K Jain; Emmanuelle di Tomaso; Dan G Duda; Jay S Loeffler; A Gregory Sorensen; Tracy T Batchelor Journal: Nat Rev Neurosci Date: 2007-08 Impact factor: 34.870
Authors: Ken Chang; Biqi Zhang; Xiaotao Guo; Min Zong; Rifaquat Rahman; David Sanchez; Nicolette Winder; David A Reardon; Binsheng Zhao; Patrick Y Wen; Raymond Y Huang Journal: Neuro Oncol Date: 2016-05-04 Impact factor: 12.300
Authors: D A Reardon; A Desjardins; J J Vredenburgh; S Gururangan; J H Sampson; S Sathornsumetee; R E McLendon; J E Herndon; J E Marcello; J Norfleet; A H Friedman; D D Bigner; H S Friedman Journal: Br J Cancer Date: 2009-11-17 Impact factor: 7.640
Authors: Maurizio Martini; Ivana de Pascalis; Quintino Giorgio D'Alessandris; Vincenzo Fiorentino; Francesco Pierconti; Hany El-Sayed Marei; Lucia Ricci-Vitiani; Roberto Pallini; Luigi Maria Larocca Journal: BMC Cancer Date: 2018-05-10 Impact factor: 4.430
Authors: Bruno Carvalho; José Manuel Lopes; Roberto Silva; Joana Peixoto; Dina Leitão; Paula Soares; Ana Catarina Fernandes; Paulo Linhares; Rui Vaz; Jorge Lima Journal: Sci Rep Date: 2021-03-16 Impact factor: 4.379