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Bevacizumab glioblastoma

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https://www.readbyqxmd.com/read/29671196/third-line-therapy-in-recurrent-glioblastoma-is-it-another-chance-for-bevacizumab
#1
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
https://www.readbyqxmd.com/read/29666934/quo-vadis-do-immunotherapies-have-a-role-in-glioblastoma
#2
REVIEW
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
https://www.readbyqxmd.com/read/29660022/molecular-ablation-of-tumor-blood-vessels-inhibits-therapeutic-effects-of-radiation-and-bevacizumab
#3
Viveka Nand Yadav, David Altshuler, Padma Kadiyala, Daniel Zamler, Andrea Comba, Henry Appelman, Patrick Dunn, Carl Koschmann, Maria G Castro, Pedro R Löwenstein
Background: Glioblastoma (GBM) is an aggressive and highly vascular tumor with median survival below 2 years. Despite advances in surgery, radiotherapy and chemotherapy survival has improved modestly. To combat glioma vascular proliferation anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) were introduced. Preclinically these agents were effective, yet they did not improve overall survival in Phase III trials. We tested the hypothesis that ganciclovir (GCV)-mediated killing of proliferating endothelial cells expressing HSV1-TK would have direct anti-tumor effects, and whether vessel ablation would affect the anti-tumor activity of anti-VEGF antibodies and radiotherapy...
April 12, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29660006/validation-of-post-operative-residual-contrast-enhancing-tumor-volume-as-an-independent-prognostic-factor-for-overall-survival-in-newly-diagnosed-glioblastoma
#4
Benjamin M Ellingson, Lauren E Abrey, Sarah J Nelson, Timothy J Kaufmann, Josep Garcia, Olivier Chinot, Frank Saran, Ryo Nishikawa, Roger Henriksson, Warren P Mason, Wolfgang Wick, Nicholas Butowski, Keith L Ligon, Elizabeth R Gerstner, Howard Colman, John de Groot, Susan Chang, Ingo Mellinghoff, Robert J Young, Brian M Alexander, Rivka Colen, Jennie W Taylor, Isabel Arrillaga-Romany, Arnav Mehta, Raymond Y Huang, Whitney B Pope, David Reardon, Tracy Batchelor, Michael Prados, Evanthia Galanis, Patrick Y Wen, Timothy F Cloughesy
Background: In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Methods: Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2)...
April 5, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29648580/bevacizumab-plus-hypofractionated-radiotherapy-versus-radiotherapy-alone-in-elderly-patients-with-glioblastoma-the-randomized-open-label-phase-ii-arte-trial
#5
H-G Wirsching, G Tabatabai, U Roelcke, A F Hottinger, F Jörger, A Schmid, L Plasswilm, D Schrimpf, C Mancao, D Capper, K Conen, T Hundsberger, F Caparrotti, R von Moos, C Riklin, J Felsberg, P Roth, D T W Jones, S Pfister, E J Rushing, L Abrey, G Reifenberger, L Held, A von Deimling, A Ochsenbein, M Weller
Background: The addition of bevacizumab to temozolomide-based chemoradiotherapy (TMZ/RT→TMZ) did not prolong overall survival (OS) in patients with newly diagnosed glioblastoma in phase III trials. Elderly and frail patients are underrepresented in clinical trials, but early reports suggested preferential benefit in this population. Patients and Methods: ARTE was a 2:1 randomized, multi-center, open-label, non-comparative phase II trial of hypofractionated RT (40 Gy in 15 fractions) with bevacizumab (10 mg/kg x 14 days) (arm A, N = 50) or without bevacizumab (arm B, N = 25) in patients with newly diagnosed glioblastoma aged ≥65 years...
April 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29618055/malignancy-index-using-intraoperative-flow-cytometry-is-a-valuable-prognostic-factor-for-glioblastoma-treated-with-radiotherapy-and-concomitant-temozolomide
#6
Taiichi Saito, Yoshihiro Muragaki, Takahiro Shioyama, Takashi Komori, Takashi Maruyama, Masayuki Nitta, Takayuki Yasuda, Junji Hosono, Saori Okamoto, Takakazu Kawamata
BACKGROUND: Intraoperative prediction of radiochemosensitivity is desirable for improving the clinical management of glioblastoma (GBM) patients. We have previously developed an original technique for intraoperative flow cytometry (iFC) and defined a malignancy index (MI). OBJECTIVE: To determine whether MI correlates with prognosis in GBM patients who underwent the standard treatment protocol of radiotherapy and temozolomide administration. METHODS: The current study included 102 patients with GBM that had been newly diagnosed from 2010 to 2015 who underwent our iFC analysis and received the standard treatment protocol...
March 30, 2018: Neurosurgery
https://www.readbyqxmd.com/read/29618054/influence-of-residual-disease-following-surgical-resection-in-newly-diagnosed-glioblastoma-on-clinical-neurocognitive-and-patient-reported-outcomes
#7
William A Hall, Stephanie L Pugh, Jeffrey S Wefel, Terri S Armstrong, Mark R Gilbert, David G Brachman, Maria Werner-Wasik, Merideth M Wendland, Paul D Brown, Samuel T Chao, Kevin S Roof, H Ian Robins, Minesh P Mehta, Walter J Curran, Benjamin Movsas
BACKGROUND: The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE: To examine these uncertainties. METHODS: NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection...
March 30, 2018: Neurosurgery
https://www.readbyqxmd.com/read/29617713/bevacizumab-may-improve-quality-of-life-but-not-overall-survival-in-glioblastoma-an-epidemiological-study
#8
D Gramatzki, P Roth, E J Rushing, J Weller, N Andratschke, S Hofer, D Korol, L Regli, A Pangalu, M Pless, J Oberle, R Bernays, H Moch, S Rohrmann, M Weller
Background: The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the US and Switzerland, but not the European Union, in 2009. Here we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level. Patients and methods: The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010-2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log rank test and Cox proportional hazards models...
March 30, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29590461/prognostic-value-of-contrast-enhancement-and-flair-for-survival-in-newly-diagnosed-glioblastoma-treated-with-and-without-bevacizumab-results-from-acrin-6686
#9
Jerrold L Boxerman, Zheng Zhang, Yair Safriel, Jeffrey M Rogg, Ronald L Wolf, Suyash Mohan, Helga Marques, A Gregory Sorensen, Mark R Gilbert, Daniel P Barboriak
Background: ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and FLAIR-hyperintense tumor assessed by central reading prognosticate overall survival (OS). Methods: 284 patients (171 men; median age 57 years, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 weeks post- chemoradiation initiation)...
March 26, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29574193/nonclinical-assessments-of-the-potential-biosimilar-pf-06439535-and-bevacizumab
#10
Marjorie A Peraza, Karen E Rule, Michael H I Shiue, Gregory L Finch, Stéphane Thibault, Paul R Brown, David W Clarke, Michael W Leach
Bevacizumab, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), is approved for treatment of metastatic colorectal cancer, nonsquamous non-small-cell lung cancer, metastatic kidney cancer, and glioblastoma. To support clinical development of the potential bevacizumab biosimilar PF-06439535, nonclinical studies evaluated structural, functional, toxicological, and toxicokinetic similarity to bevacizumab sourced from the European Union (bevacizumab-EU) and United States (bevacizumab-US)...
March 21, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29573206/identification-of-transcriptome-signature-for-predicting-clinical-response-to-bevacizumab-in-recurrent-glioblastoma
#11
Seung Won Choi, Hyemi Shin, Jason K Sa, Hee Jin Cho, Harim Koo, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam
Glioblastomas are among the most fatal brain tumors. Although no effective treatment option is available for recurrent glioblastomas (GBMs), a subset of patients evidently derived clinical benefit from bevacizumab, a monoclonal antibody against vascular endothelial growth factor. We retrospectively reviewed patients with recurrent GBM who received bevacizumab to identify biomarkers for predicting clinical response to bevacizumab. Following defined criteria, the patients were categorized into two clinical response groups, and their genetic and transcriptomic results were compared...
March 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29524243/toward-a-noninvasive-estimate-of-interstitial-fluid-pressure-by-dynamic-contrast-enhanced-mri-in-a-rat-model-of-cerebral-tumor
#12
Rasha Elmghirbi, Tavarekere N Nagaraja, Stephen L Brown, Kelly A Keenan, Swayamprava Panda, Glauber Cabral, Hassan Bagher-Ebadian, George W Divine, Ian Y Lee, James R Ewing
PURPOSE: This study demonstrates a DCE-MRI estimate of tumor interstitial fluid pressure (TIFP) and hydraulic conductivity in a rat model of glioblastoma, with validation against an invasive wick-in-needle (WIN) technique. An elevated TIFP is considered a mark of aggressiveness, and a decreased TIFP a predictor of response to therapy. METHODS: The DCE-MRI studies were conducted in 36 athymic rats (controls and posttreatment animals) with implanted U251 cerebral tumors, and with TIFP measured using a WIN method...
March 9, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29507697/differential-scanning-calorimetry-of-plasma-in-glioblastoma-toward-a-new-prognostic-monitoring-tool
#13
Philipp O Tsvetkov, Emeline Tabouret, Andrei Y Roman, Sylvie Romain, Céline Bequet, Olga Ishimbaeva, Stéphane Honoré, Dominique Figarella-Branger, Olivier Chinot, François Devred
Glioblastoma is the most frequent and aggressive primary brain tumor in adults. Recently, a growing number of studies have shown that denaturation profile of plasma samples obtained by differential scanning calorimetry (DSC) can represent a signature of a disease. In this study, we analyzed for the first time the DSC denaturation profiles of the plasma from patients with recurrent glioblastoma (n=17). Comparison to the one of healthy individuals (n=10) and to already described profiles in others cancer showed clear differences suggesting that this DSC profile may constitute a signature of glioblastoma...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29507055/anti-tumor-activity-of-dlx1008-an-anti-vegfa-antibody-fragment-with-low-picomolar-affinity-in-human-glioma-models
#14
Emese Szabo, Douglas J Phillips, Miriam Droste, Andrea Marti, Titus Kretzschmar, Abdijapar Shamshiev, Michael Weller
Angiogenesis mediated by vascular endothelial growth factor (VEGF) is a hallmark of glioblastoma. Based on response rate and improved progression-free survival (PFS), although not overall survival (OS), the 149 kDa anti-VEGF-A IgG antibody bevacizumab (Avastin® ) has been approved in the US and Japan for recurrent glioblastoma and in Japan for newly diagnosed glioblastoma. However, it is not approved in the EU. Here we characterize the biological activity of DLX1008, a 26 kDa anti-VEGF-A single chain antibody fragment (scFv) which shows 30-fold stronger affinity to human VEGF-A than bevacizumab...
March 5, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29476996/advantages-and-disadvantages-of-combined-chemotherapy-with-carmustine-wafer-and-bevacizumab-in-patients-with-newly-diagnosed-glioblastoma-a-single-institutional-experience
#15
Yukinori Akiyama, Yuusuke Kimura, Rei Enatsu, Takeshi Mikami, Masahiko Wanibuchi, Nobuhiro Mikuni
OBJECTIVE: To retrospectively determine the safety and efficacy of combined chemotherapy with carmustine (BCNU) wafer, bevacizumab, and temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma (GBM). METHODS: A total of 54 consecutive newly diagnosed GBMs were resected at our institution between 2010 and 2016. Twenty-nine patients underwent BCNU wafer implantation into the resection cavity followed by standard radiochemotherapy with with temozolomide (TMZ, Stupp regimen) plus additional bevacizumab treatment between 2013 and 2016...
February 21, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29473980/low-dose-t1w-dce-mri-for-early-time-points-perfusion-measurement-in-patients-with-intracranial-tumors-a-pilot-study-applying-the-microsphere-model-to-measure-absolute-cerebral-blood-flow
#16
Ka-Loh Li, Daniel Lewis, Alan Jackson, Sha Zhao, Xiaoping Zhu
BACKGROUND: Previous studies have measured cerebral blood flow (CBF) with DSC-MRI using an "early time points" (ET) method based on microsphere theory. PURPOSE: To develop and assess a new ET method for absolute CBF estimation using low-dose high-temporal (LDHT) T1W-DCE-MRI. STUDY TYPE: Retrospective cohort study. SUBJECTS: Seven patients with sporadic vestibular schwannoma (VS) who underwent test-retest imaging; one patient with glioblastoma multiforme (GBM) imaged pretreatment; and 12 neurofibromatosis type 2 (NF2) patients undergoing bevacizumab treatment, imaged pre- and 90 days posttreatment...
February 23, 2018: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/29472310/temozolomide-plus-bevacizumab-in-elderly-patients-with-newly-diagnosed-glioblastoma-and-poor-performance-status-an-anocef-phase-ii-trial-atag
#17
Germán Reyes-Botero, Stéphanie Cartalat-Carel, Olivier L Chinot, Maryline Barrie, Luc Taillandier, Patrick Beauchesne, Isabelle Catry-Thomas, Jérôme Barrière, Jean-Sebastien Guillamo, Michel Fabbro, Didier Frappaz, Alexandra Benouaich-Amiel, Emilie Le Rhun, Chantal Campello, Isabelle Tennevet, François Ghiringhelli, Marie-Laure Tanguy, Karima Mokhtari, Jérôme Honnorat, Jean-Yves Delattre
LESSONS LEARNED: Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study. BACKGROUND: The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established...
February 22, 2018: Oncologist
https://www.readbyqxmd.com/read/29467925/plasma-ykl-40-as-a-biomarker-for-bevacizumab-efficacy-in-patients-with-newly-diagnosed-glioblastoma-in-the-phase-3-randomized-avaglio-trial
#18
Mogens K Boisen, Camilla B Holst, Nicola Consalvo, Olivier L Chinot, Julia S Johansen
YKL-40 is a glycoprotein with pro-angiogenic functions. We hypothesized that patients with newly diagnosed glioblastoma and low baseline plasma YKL-40 levels derive greater benefit from first-line bevacizumab. Plasma samples were collected from 563 patients in the randomized, phase 3 AVAglio trial who received bevacizumab or placebo plus radiotherapy/temozolomide. Raw plasma YKL-40 concentrations were converted to age-corrected percentiles of normal healthy YKL-40 levels and divided into quartiles (Q). The impact of baseline plasma YKL-40 level on survival was investigated using Cox regression analyses...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434840/autophagy-activation-promotes-bevacizumab-resistance-in-glioblastoma-by-suppressing-akt-mtor-signaling-pathway
#19
He Huang, Jian Song, Zheng Liu, Li Pan, Guozheng Xu
Glioblastomas are the most common primary and malignant brain tumors. The standard therapy includes surgery and radiotherapy plus chemotherapy, with additional bevacizumab to block the angiogenesis in tumors. However, the ever-growing tolerance of glioblastomas to chemotherapeutic drugs impairs the clinical outputs of tumor treatment. The present study investigated the tolerance of glioblastomas to bevacizumab. Although bevacizumab resulted in direct anti-proliferation and pro-apoptosis effects on glioblastoma cells via downregulating the anti-apoptotic proteins and upregulating the pro-apoptotic proteins, tolerance was also encountered that was mainly caused by autophagy induction in tumor cells...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29427211/treatment-with-5-azacitidine-delay-growth-of-glioblastoma-xenografts-a-potential-new-treatment-approach-for-glioblastomas
#20
Tobias Kratzsch, Susanne Antje Kuhn, Andreas Joedicke, Uwe Karsten Hanisch, Peter Vajkoczy, Jens Hoffmann, Iduna Fichtner
PURPOSE: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. The epigenetically active ribonucleoside analog 5-azacitidine is a new therapy option that changes tumor cell chromatin, which is frequently modified by methylation and deacetylation in malignant gliomas. METHODS: In vitro, we analyzed cell viability, cell apoptosis, and migration of human GBM cells. In vivo, we established subcutaneous and intracerebral GBM mouse models originating from U87MG, U373MG, and primary GBM cells as well as one patient-derived xenograft...
February 9, 2018: Journal of Cancer Research and Clinical Oncology
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