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Bevacizumab glioblastoma

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https://www.readbyqxmd.com/read/28074323/changes-in-cerebral-metabolism-during-ketogenic-diet-in-patients-with-primary-brain-tumors-1-h-mrs-study
#1
Moran Artzi, Gilad Liberman, Nachum Vaisman, Felix Bokstein, Faina Vitinshtein, Orna Aizenstein, Dafna Ben Bashat
Normal brain cells depend on glucose metabolism, yet they have the flexibility to switch to the usage of ketone bodies during caloric restriction. In contrast, tumor cells lack genomic and metabolic flexibility and are largely dependent on glucose. Ketogenic-diet (KD) was suggested as a therapeutic option for malignant brain cancer. This study aimed to detect metabolic brain changes in patients with malignant brain gliomas on KD using proton magnetic-resonance-spectroscopy ((1)H-MRS). Fifty MR scans were performed longitudinally in nine patients: four patients with recurrent glioblastoma (GB) treated with KD in addition to bevacizumab; one patient with gliomatosis-cerebri treated with KD only; and four patients with recurrent GB who did not receive KD...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28057017/the-brain-penetrating-cxcr4-antagonist-prx177561-increases-the-antitumor-effects-of-bevacizumab-and-sunitinib-in-preclinical-models-of-human-glioblastoma
#2
Giovanni Luca Gravina, Andrea Mancini, Francesco Marampon, Alessandro Colapietro, Simona Delle Monache, Roberta Sferra, Flora Vitale, Peter J Richardson, Lee Patient, Stephen Burbidge, Claudio Festuccia
BACKGROUND: Glioblastoma recurrence after treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. It has been demonstrated that anti-VEGF/VEGFR therapies control the invasive phenotype and that relapse occurs through the increased activity of CXCR4. We therefore hypothesized that combining bevacizumab or sunitinib with the novel CXCR4 antagonist, PRX177561, would have superior antitumor activity...
January 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28048647/tu-d-207b-07-radiomic-response-assessment-for-recurrent-glioblastoma-treated-with-bevacizumab-in-the-brain-trial
#3
P Grossmann, V Narayan, R Huang, H Aerts
PURPOSE: To develop radiomic biomarkers for non-invasive response assessment of Bevacizumab (Avastin; Genentech) treatment in recurrent glioblastoma multiforme (GBM). METHODS: We analyzed prospectively acquired data from the BRAIN trial. For 167 patients, we extracted 71 radiomic features each from normalized post-contrast T1-weighted and fluid attenuation inversion recovery (FLAIR) sequences at baseline (pretreatment), and at follow-ups of six and twelve weeks (post-treatment), respectively, where available...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046101/single-cell-mathematical-model-successfully-replicates-key-features-of-gbm-go-or-grow-is-not-necessary
#4
Elizabeth Scribner, Hassan M Fathallah-Shaykh
Glioblastoma (GBM) is a malignant brain tumor that continues to be associated with neurological morbidity and poor survival times. Brain invasion is a fundamental property of malignant glioma cells. The Go-or-Grow (GoG) phenotype proposes that cancer cell motility and proliferation are mutually exclusive. Here, we construct and apply a single glioma cell mathematical model that includes motility and angiogenesis and lacks the GoG phenotype. Simulations replicate key features of GBM including its multilayer structure (i...
2017: PloS One
https://www.readbyqxmd.com/read/28011470/advances-in-experimental-targeted-therapy-and-immunotherapy-for-patients-with-glioblastoma-multiforme
#5
REVIEW
Jiri Polivka, Jiri Polivka, Lubos Holubec, Tereza Kubikova, Vladimir Priban, Ondrej Hes, Kristyna Pivovarcikova, Inka Treskova
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28007759/magnetic-resonance-perfusion-image-features-uncover-an-angiogenic-subgroup-of-glioblastoma-patients-with-poor-survival-and-better-response-to-antiangiogenic-treatment
#6
Tiffany T Liu, Achal S Achrol, Lex A Mitchell, Scott A Rodriguez, Abdullah Feroze, Christine Kim, Navjot Chaudhary, Olivier Gevaert, Josh M Stuart, Griffith R Harsh, Steven D Chang, Daniel L Rubin
BACKGROUND: In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies. METHODS: Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts...
December 22, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28005980/the-prognosis-of-anti-angiogenesis-treatments-combined-with-standard-therapy-for-newly-diagnosed-glioblastoma-a-meta-analysis-of-randomized-controlled-trials
#7
Yuping Li, Mengzhuo Hou, Guangyu Lu, Natalia Ciccone, Xingdong Wang, Hengzhu Zhang
BACKGROUND AND PURPOSE: Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB), the efficacy and safety of BV for patients with newly diagnosed GB remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched electronic databases (PubMed, EMBASE, OVID, etc.) to identify related studies published from January 1966 and August 2016. Eight randomized controlled trials including a total of 2,185 patients with GB were included...
2016: PloS One
https://www.readbyqxmd.com/read/28001091/treatment-options-for-recurrent-high-grade-gliomas
#8
Harjus S Birk, Seunggu J Han, Nicholas A Butowski
High-grade gliomas are aggressive brain tumors encompassing Grade III and IV classifications. Of these, glioblastoma (GB) is the most malignant with a high rate of recurrence after initial resection. Although standard treatment does exist for newly diagnosed GBs, therapeutic strategies for recurrent GB are less solidified. However, mounting evidence describes the role of re-resection, bevacizumab, chemotherapy, targeted molecular therapies, immunotherapeutic approaches and radiotherapy in recurrent GB management...
January 2017: CNS Oncology
https://www.readbyqxmd.com/read/27942839/immune-modulation-associated-with-vascular-endothelial-growth-factor-vegf-blockade-in-patients-with-glioblastoma
#9
Alissa A Thomas, Jan L Fisher, Thomas H Hampton, Brock C Christensen, Gregory J Tsongalis, Gilbert J Rahme, Chery A Whipple, Sandra E Steel, Melissa C Davis, Arti B Gaur, Lionel D Lewis, Marc S Ernstoff, Camilo E Fadul
BACKGROUND: Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV)...
December 9, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27940247/sdf-1-blockade-enhances-anti-vegf-therapy-of-glioblastoma-and-can-be-monitored-by-mri
#10
Lei Deng, Jason H Stafford, Shie-Chau Liu, Sophia B Chernikova, Milton Merchant, Lawrence Recht, J Martin Brown
Despite the approval of antiangiogenic therapy for glioblastoma multiforme (GBM) patients, survival benefits are still limited. One of the resistance mechanisms for antiangiogenic therapy is the induction of hypoxia and subsequent recruitment of macrophages by stromal-derived factor (SDF)-1α (CXCL-12). In this study, we tested whether olaptesed pegol (OLA-PEG, NOX-A12), a novel SDF-1α inhibitor, could reverse the recruitment of macrophages and potentiate the antitumor effect of anti-vascular endothelial growth factor (VEGF) therapy...
December 7, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27918718/randomized-double-blind-placebo-controlled-multicenter-phase-ii-study-of-onartuzumab-plus-bevacizumab-versus-placebo-plus-bevacizumab-in-patients-with-recurrent-glioblastoma-efficacy-safety-and-hepatocyte-growth-factor-and-o-6-methylguanine-dna-methyltransferase
#11
Timothy Cloughesy, Gaetano Finocchiaro, Cristóbal Belda-Iniesta, Lawrence Recht, Alba A Brandes, Estela Pineda, Tom Mikkelsen, Olivier L Chinot, Carmen Balana, David R Macdonald, Manfred Westphal, Kirsten Hopkins, Michael Weller, Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, David S Shames
Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression...
January 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27918194/first-report-of-tumor-treating-fields-use-in-combination-with-bevacizumab-in-a-pediatric-patient-a-case-report
#12
Daniel O'Connell, Violet Shen, William Loudon, Daniela A Bota
We report the first case of a pediatric patient with glioblastoma (GBM; WHO grade IV astrocytoma) successfully treated with tumor treating fields (TTF). The patient was diagnosed with GBM when 13 years of age and progressed through surgical resection, radiotherapy and chemotherapy. Discrete tumor growth visualized on MRI with stable neurological examination was monitored for 6 months with subsequent stable disease observed radiographically and clinically for 7 months while adherent to Optune(®) (TTF). TTF thereby played a role in forestalling recurrent GBM growth in this young woman for 7 months without significant adverse effects...
December 5, 2016: CNS Oncology
https://www.readbyqxmd.com/read/27903792/clinical-effectiveness-of-bevacizumab-in-patients-with-recurrent-brain-tumours-a-population-based-evaluation
#13
REVIEW
Mário L de Lemos, Adeline Markarian, Esther Chan, Kimberly Schaff, Susan Walisser
BACKGROUND: Bevacizumab is an antiangiogenic agent active in patients with recurrent malignant gliomas. However, evidence for its clinical efficacy is relatively limited so that bevacizumab is approved for this indication in Canada and the United States, but not in the European Union. We reviewed the effectiveness of bevacizumab in patients with recurrent brain tumour using a large population database. METHODS: This was a retrospective, multicentre, study conducted at the BC Cancer Agency, a public cancer care organisation for the residents of the Canadian province of British Columbia...
November 30, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27896520/early-perfusion-mri-predicts-survival-outcome-in-patients-with-recurrent-glioblastoma-treated-with-bevacizumab-and-carboplatin
#14
Iwan E Bennett, Kathryn M Field, Christopher M Hovens, Bradford A Moffat, Mark A Rosenthal, Katharine Drummond, Andrew H Kaye, Andrew P Morokoff
Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes...
November 28, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27849336/durability-of-single-dose-intra-arterial-bevacizumab-after-blood-brain-barrier-disruption-for-recurrent-glioblastoma
#15
Shamik Chakraborty, Christopher G Filippi, Jan-Karl Burkhardt, Sherese Fralin, Ashley Ray, Tamika Wong, Rafael Ortiz, David J Langer, John A Boockvar
BACKGROUND: Bevacizumab (BV) has been used to treat recurrent glioblastoma with a progression free survival of approximately 3-3.5 months. Typically, it is administered intravenously every 2-3 weeks at dosages ranging from 5-15 mg/kg. Serious side effects include GI tract perforations, hematologic disorders, intracranial hemorrhage, and malignant hypertension. We hypothesized that selective intracranial intra-arterial infusion (SIACI) of BV following blood/brain barrier disruption (BBBD) with mannitol may allow for reduced dosage, lower toxicity, and equivalent or superior progression free survival (PFS)...
November 2016: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/27816996/alisertib-demonstrates-significant-antitumor-activity-in-bevacizumab-resistant-patient-derived-orthotopic-models-of-glioblastoma
#16
C Kurokawa, H Geekiyanage, C Allen, I Iankov, M Schroeder, B Carlson, K Bakken, J Sarkaria, J A Ecsedy, A D'Assoro, B Friday, E Galanis
Aurora A kinase (AURKA), a member of the serine/threonine kinase family, plays a critical role in cell division, and it is widely overexpressed in a variety of tumors including glioblastoma (GBM). Alisertib (MLN8237) is an orally administered selective AURKA inhibitor with potent antiproliferative activity, currently undergoing clinical testing in different tumor types. In vitro evaluation of alisertib against the primary GBM lines, GBM6, GBM10, GBM12 and GBM39 showed significant antitumor activity with IC50s ranging between 30 and 95 nM...
November 5, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27815391/quantitative-fluorescence-microscopy-measures-vascular-pore-size-in-primary-and-metastatic-brain-tumors
#17
Rajendar K Mittapalli, Chris E Adkins, Kaci A Bohn, Afroz S Mohammad, Julie A Lockman, Paul R Lockman
Tumors residing in the central nervous system (CNS) compromise the blood-brain barrier (BBB) via increased vascular permeability, with the magnitude of changes dependent on the tumor type and location. Current studies determine penetrability of a cancer therapeutic by administering progressively larger molecules until cutoff is observed where little to no tumor accumulation occurs. However, decades-old experimental work and mathematical modeling document methods to calculate both the size of the vascular opening (pore) with solute permeability values...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27803607/progression-pattern-and-adverse-events-with-bevacizumab-in-glioblastoma
#18
A Mamo, A Baig, M Azam, Y S Rho, S Sahebjam, T Muanza, S Owen, K Petrecca, M C Guiot, J Al-Shami, R Sharma, P Kavan
BACKGROUND: The use of bevacizumab in the management of glioblastoma multiforme (gbm) remains controversial. In Canada, bevacizumab is approved for the treatment of recurrent gbm. We describe a pattern of progression across treatment lines in gbm. METHODS: During 2008-2014, 64 patients diagnosed with gbm were treated with bevacizumab at McGill University hospitals. Of those patients, 30 (46.9%) received bevacizumab in the first line (B1L), and 34 (53.1%) received it in the second line and beyond (B2L+)...
October 2016: Current Oncology
https://www.readbyqxmd.com/read/27803067/large-scale-radiomic-profiling-of-recurrent-glioblastoma-identifies-an-imaging-predictor-for-stratifying-anti-angiogenic-treatment-response
#19
Philipp Kickingereder, Michael Götz, John Muschelli, Antje Wick, Ulf Neuberger, Russell T Shinohara, Martin Sill, Martha Nowosielski, Heinz-Peter Schlemmer, Alexander Radbruch, Wolfgang Wick, Martin Bendszus, Klaus H Maier-Hein, David Bonekamp
PURPOSE: Antiangiogenic treatment with bevacizumab, a mAb to the VEGF, is the single most widely used therapeutic agent for patients with recurrent glioblastoma. A major challenge is that there are currently no validated biomarkers that can predict treatment outcome. Here we analyze the potential of radiomics, an emerging field of research that aims to utilize the full potential of medical imaging. EXPERIMENTAL DESIGN: A total of 4,842 quantitative MRI features were automatically extracted and analyzed from the multiparametric tumor of 172 patients (allocated to a discovery and validation set with a 2:1 ratio) with recurrent glioblastoma prior to bevacizumab treatment...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27777151/management-of-patients-with-primary-intramedullary-spinal-cord-glioblastoma
#20
Bedjan Behmanesh, Matthias Setzer, Juergen Konczalla, Patrick Harter, Johanna Quick-Weller, Lioba Imoehl, Kea Franz, Florian Gessler, Volker Seifert, Gerhard Marquardt
BACKGROUND: Primary intramedullary spinal cord glioblastoma are very rare tumors of the spinal cord. They imply a very poor prognosis since complete surgical resection is not possible due to the infiltrative growth of these tumors. The aim of this study is to present our data achieved with an aggressive multimodality treatment. METHODS: We retrospectively reviewed our clinical database. All patients with histologically proven intramedullary spinal cord glioblastoma treated in our department were included in this study...
October 21, 2016: World Neurosurgery
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