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Bevacizumab glioblastoma

Wen-Yu Cheng, Chiung-Chyi Shen, Ming-Tsang Chiao, Yea-Jiuan Liang, Tsuo-Fei Mao, Bai-Shuan Liu, Jun-Peng Chen
INTRODUCTION: A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear. METHODS: In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis...
June 16, 2018: Journal of Neuro-oncology
Benjamin M Ellingson, Lauren E Abrey, Josep Garcia, Olivier Chinot, Wolfgang Wick, Frank Saran, Ryo Nishikawa, Roger Henriksson, Warren P Mason, Robert J Harris, Kevin Leu, Davis C Woodworth, Arnav Mehta, Catalina Raymond, Ararat Chakhoyan, Whitney B Pope, Timothy F Cloughesy
Background: In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed GBM patients treated with chemoradiation with or without bevacizumab (BV). Methods: 798 patients (404 BV and 394 placebo) with newly diagnosed GBM in the AVAglio trial (NCT00943826) had baseline MRI scans available, while 337 BV-treated and 269 placebo-treated patients had >4 MRI scans for response evaluation...
April 20, 2018: Neuro-oncology
D Schiff
No abstract text is available yet for this article.
April 20, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Laura Guarnaccia, Stefania Elena Navone, Elena Trombetta, Chiara Cordiglieri, Alessandro Cherubini, Francesco Maria Crisà, Paolo Rampini, Monica Miozzo, Laura Fontana, Manuela Caroli, Marco Locatelli, Laura Riboni, Rolando Campanella, Giovanni Marfia
Gliomas are the most common brain tumors, with diverse biological behaviour. Glioblastoma (GBM), the most aggressive and with the worst prognosis, is characterized by an intense and aberrant angiogenesis, which distinguishes it from low-grade gliomas (LGGs) and benign expansive lesions, as meningiomas (MNGs). With increasing evidence for the importance of vascularization in tumor biology, we focused on the isolation and characterization of endothelial cells (ECs) from primary GBMs, LGGs and MNGs. Gene expression analysis by Real-Time PCR, immunofluorescence and flow cytometry analysis, tube-like structures formation and vascular permeability assays were performed...
June 8, 2018: Scientific Reports
Claudio Festuccia, Giovanni Luca Gravina, Carmine Giorgio, Andrea Mancini, Cristina Pellegrini, Alessandro Colapietro, Simona Delle Monache, Maria Giovanna Maturo, Roberta Sferra, Paola Chiodelli, Marco Rusnati, Annamaria Cantoni, Riccardo Castelli, Federica Vacondio, Alessio Lodola, Massimiliano Tognolini
Glioblastoma multiforme (GBM) is the most malignant brain tumor, showing high resistance to standard therapeutic approaches that combine surgery, radiotherapy, and chemotherapy. As opposed to healthy tissues, EphA2 has been found highly expressed in specimens of glioblastoma, and increased expression of EphA2 has been shown to correlate with poor survival rates. Accordingly, agents blocking Eph receptor activity could represent a new therapeutic approach. Herein, we demonstrate that UniPR1331, a pan Eph receptor antagonist, possesses significant in vivo anti-angiogenic and anti-vasculogenic properties which lead to a significant anti-tumor activity in xenograft and orthotopic models of GBM...
May 11, 2018: Oncotarget
Christina Schaub, Sied Kebir, Nina Junold, Elke Hattingen, Niklas Schäfer, Joachim P Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Michael Niessen, Frederic Mack, Moritz Stuplich, Theophilos Tzaridis, Oliver Bähr, Rolf-Dieter Kortmann, Uwe Schlegel, Friederike Schmidt-Graf, Veit Rohde, Christian Braun, Mathias Hänel, Michael Sabel, Rüdiger Gerlach, Dietmar Krex, Claus Belka, Hartmut Vatter, Martin Proescholdt, Ulrich Herrlinger, Martin Glas
BACKGROUND: We evaluated patterns of tumor growth in patients with newly diagnosed MGMT-non-methylated glioblastoma who were assigned to undergo radiotherapy in conjunction with bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ) within the randomized phase II GLARIUS trial. METHODS: In 142 patients (94 BEV/IRI, 48 TMZ), we reviewed magnetic resonance imaging scans at baseline and first tumor recurrence. Based on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery images, we assessed tumor growth patterns and tumor invasiveness...
May 28, 2018: Journal of Cancer Research and Clinical Oncology
Stefania Maraka, Karam Asmaro, Tobias Walbert, Ian Lee
OBJECTIVE: Laser interstitial thermal therapy (LITT) is an image-guided technique that uses high temperature to ablate pathological tissue. Brain tumor patients undergoing LITT may also undergo radiation therapy (RT) either before or after LITT. Both procedures have been reported to increase cerebral edema and thereby the two treatments in close succession may worsen existing edema that can be difficult to control. The purpose of our study was to determine the frequency of increased and/or symptomatic cerebral edema after combined LITT and RT, the radiographic and clinical signs of this cerebral edema, and the treatment required...
May 25, 2018: Lasers in Surgery and Medicine
Ken-Ichiro Matsuda, Kaori Sakurada, Kenji Nemoto, Takamasa Kayama, Yukihiko Sonoda
BACKGROUND: The optimal treatment for elderly patients with glioblastoma has not been established. METHODS: We retrospectively analyzed the safety and efficacy of hypofractionated radiotherapy (45 Gy/15 fr) combined with temozolomide (TMZ) followed by bevacizumab (BEV) salvage treatment in 18 glioblastoma patients aged > 75 years. RESULTS: All of the patients received safe hypofractionated radiotherapy and concomitant TMZ (75 mg/m2 ), and 14 of 18 patients received maintenance TMZ...
May 23, 2018: International Journal of Clinical Oncology
Francesco Pasqualetti, Andrea Pace, Alessandra Gonnelli, Veronica Villani, Martina Cantarella, Durim Delishaj, Caterina Vivaldi, Alessandro Molinari, Sabrina Montrone, Alessia Pellerino, Federica Franchino, Davide Baldaccini, Giuseppe Lombardi, Ivan Lolli, Francesca Catania, Elena Bazzoli, Riccardo Morganti, Alessandra Fabi, Vittorina Zagonel, Guido Bocci, Maria Grazia Fabrini, Roberta Rudà, Riccardo Soffietti, Fabiola Paiar
OBJECTIVES: Bevacizumab is an anti-vascular endothelial growth factor antibody used in the treatment of recurrent glioblastoma (GBM). Despite the large number of studies carried out in patients with recurrent GBM, little is known about the administration of this angiogenesis inhibitor after the failure of the second-line chemotherapy. MATERIALS AND METHODS: In this retrospective multicenter study, on behalf of the Italian Association of Neuro-Oncology, we reported the results obtained in 51 patients with recurrent GBM treated with single-agent bevacizumab after the failure of second-line chemotherapy with fotemustine...
May 18, 2018: American Journal of Clinical Oncology
Megan Mantica, Ashley Pritchard, Frank Lieberman, Jan Drappatz
INTRODUCTION: Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed HGG patients treated with nivolumab in our institution...
May 19, 2018: Journal of Neuro-oncology
Pradeep Goyal, Mary Tenenbaum, Sonali Gupta, Puneet S Kochar, Alok A Bhatt, Manisha Mangla, Yogesh Kumar, Rajiv Mangla
Background: Bevacizumab was approved by the FDA for the treatment of recurrent or progressive glioblastoma (GBM). Imaging responses are typically assessed by gadolinium-enhanced MRI. We sought to determine the significance of qualitative diffusion signature (manifest as variable degree of dark signal) on ADC maps in recurrent gliomas after treatment with bevacizumab. Methods: We performed an institutional review board (IRB) approved retrospective study on patients who underwent MRI of the brain after 8 weeks of receiving bevacizumab for recurrent glioma...
April 2018: Quantitative Imaging in Medicine and Surgery
Silvia Scoccianti, Giulio Francolini, Giulio Alberto Carta, Daniela Greto, Beatrice Detti, Gabriele Simontacchi, Luca Visani, Muhammed Baki, Linda Poggesi, Pierluigi Bonomo, Monica Mangoni, Isacco Desideri, Stefania Pallotta, Lorenzo Livi
The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine. Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects ≤3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12.5 ml: EQD2 < 65 Gy with radiosurgery; >12.5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 ml and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy)...
June 2018: Critical Reviews in Oncology/hematology
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
BACKGROUND: Vascular endothelial growth factor (VEGF) isoforms, particularly the diffusible VEGF-121, could play a major role in the response of recurrent glioblastoma (GB) to anti-angiogenetic treatment with bevacizumab. We hypothesized that circulating VEGF-121 may reduce the amount of bevacizumab available to target the heavier isoforms of VEGF, which are the most clinically relevant. METHODS: We assessed the plasma level of VEGF-121 in a brain xenograft model, in human healthy controls, and in patients suffering from recurrent GB before and after bevacizumab treatment...
May 10, 2018: BMC Cancer
Michael W Ruff, Adip G Bhargav, Aditya Raghunathan
Extraneural glioblastoma metastases are exceedingly rare, though previously described in the literature. Activating mutations in the BRAF kinase gene (V600E) are present in a minority of glioblastoma patients. Here, we describe a case of systemic metastases of a clonal subpopulation of BRAF V600E mutated glioblastoma in a patient previously treated with surgery, radiation, temozolomide and bevacizumab. The patient presented with a subacute cervical myelopathy during adjuvant treatment. He underwent emergent surgical decompression of an epidural spine metastasis...
May 9, 2018: Brain Tumor Pathology
Timo A Auer, Hanns-Christian Breit, Federico Marini, Mirjam Renovanz, Marc A Brockmann, Yasemin Tanyildizi
No abstract text is available yet for this article.
May 4, 2018: Journal of Neuroradiology. Journal de Neuroradiologie
Claire Provost, Aurélie Prignon, Laura Rozenblum-Beddok, Quentin Bruyer, Sylvie Dumont, Fatiha Merabtene, Valérie Nataf, Cédric Bouteiller, Jean-Noël Talbot
The aim of this study was to evaluate two RGD radiotracers radiolabelled with fluorine-18 or gallium-68, in detecting angiogenesis in grafted human tumours and monitoring their treatment with the anti-angiogenic agent bevacizumab. Sixteen mice bearing an U87MG tumour in one flank and a contralateral A549 tumour were treated with intravenous injections of bevacizumab twice a week for 3 weeks. PET images with 18 F-RGD-K5 and 68 Ga-RGD were acquired before treatment (baseline), after three bevacizumab injections (t1) and after seven bevacizumab injections (t2)...
April 10, 2018: Oncotarget
Antonio Omuro, Kathryn Beal, Katharine McNeill, Robert J Young, Alissa Thomas, Xuling Lin, Robert Terziev, Thomas J Kaley, Lisa M DeAngelis, Mariza Daras, Igor T Gavrilovic, Ingo Mellinghoff, Eli L Diamond, Andrew McKeown, Malbora Manne, Andrew Caterfino, Krishna Patel, Linda Bavisotto, Greg Gorman, Michael Lamson, Philip Gutin, Viviane Tabar, Debyani Chakravarty, Timothy A Chan, Cameron W Brennan, Elizabeth Garrett-Mayer, Rashida A Karmali, Elena Pentsova
Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m2 once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m2 5 days during each 28-day cycle)...
June 10, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Rahul A Sastry, Ganesh M Shankar, Elizabeth R Gerstner, William T Curry
Despite updated management of glioblastoma (GB), progression is virtually inevitable. Previous data suggest a survival benefit from resection at progression; however, relatively few studies have evaluated the role of surgery in the context of contemporary GB treatment and widespread use of bevacizumab and chemotherapy. As such, the purpose of this study is to evaluate outcomes following surgical resection in patients with progressive GB since 2008. The records of all patients who underwent biopsy or resection of GB between January 1, 2008, and December 31, 2015, were retrospectively reviewed to identify 368 patients with progressive GB...
July 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Enrico Franceschi, Giuseppe Lamberti, Alexandro Paccapelo, Monica Di Battista, Giovenzio Genestreti, Santino Minichillo, Antonella Mura, Stefania Bartolini, Raffaele Agati, Alba A Brandes
BACKGROUND: Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. METHODS: We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. RESULTS: Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected...
April 18, 2018: Journal of Neuro-oncology
Sylvia C Kurz, Patrick Y Wen
PURPOSE OF REVIEW: More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies. RECENT FINDINGS: The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma...
April 18, 2018: Current Treatment Options in Neurology
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