Abstract:
:Targeting tumor angiogenesis is a potential therapeutic strategy for glioblastoma because of its high vascularization. Tivozanib is an oral pan-VEGF receptor tyrosine kinase inhibitor that hits a central pathway in glioblastoma angiogenesis. We conducted a phase II study to test the effectiveness of tivozanib in patients with recurrent glioblastoma. Ten adult patients were enrolled and treated with tivozanib 1.5 mg daily, 3 weeks on/1 week off in 28-day cycles. Brain MRI and blood biomarkers of angiogenesis were performed at baseline, within 24-72 h of treatment initiation, and monthly thereafter. Dynamic contrast enhanced MRI, dynamic susceptibility contrast MRI, and vessel architecture imaging were used to assess vascular effects. Resting state MRI was used to assess brain connectivity. Best RANO criteria responses were: 1 complete response, 1 partial response, 4 stable diseases, and 4 progressive disease (PD). Two patients were taken off study for toxicity and 8 patients were taken off study for PD. Median progression-free survival was 2.3 months and median overall survival was 8.1 months. Baseline abnormal tumor vascular permeability, blood flow, tissue oxygenation and plasma sVEGFR2 significantly decreased and plasma PlGF and VEGF increased after treatment, suggesting an anti-angiogenic effect of tivozanib. However, there were no clear structural changes in vasculature as vessel caliber and enhancing tumor volume did not significantly change. Despite functional changes in tumor vasculature, tivozanib had limited anti-tumor activity, highlighting the limitations of anti-VEGF monotherapy. Future studies in glioblastoma should leverage the anti-vascular activity of agents targeting VEGF to enhance the activity of other therapies.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Kalpathy-Cramer J,Chandra V,Da X,Ou Y,Emblem KE,Muzikansky A,Cai X,Douw L,Evans JG,Dietrich J,Chi AS,Wen PY,Stufflebeam S,Rosen B,Duda DG,Jain RK,Batchelor TT,Gerstner ERdoi
10.1007/s11060-016-2332-5subject
Has Abstractpub_date
2017-02-01 00:00:00pages
603-610issue
3eissn
0167-594Xissn
1573-7373pii
10.1007/s11060-016-2332-5journal_volume
131pub_type
杂志文章abstract::Astrocytic neoplasms are genetically heterogeneous; however a low frequency of genomic changes has been found in juvenile pilocytic astrocytoma (PA) in molecular studies. Concerning pleomorphic xanthoastrocytomas (PXA), recent studies have given heterogeneous results for chromosomal alterations. We studied the subtelo...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9763-6
更新日期:2009-06-01 00:00:00
abstract::Primary germinomas in the spinal cord are very rare with only 15 cases published previously. In this case a 22-year-old woman with urinary incontinence, lumbago, and bilateral leg pain and weakness was found to have a solid tumor in the conus medullaris between the L1 and L2 vertebral bodies. Serum HCG was elevated wi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-3092-9
更新日期:2006-01-01 00:00:00
abstract::Two distinct mechanisms, vasculogenesis and angiogenesis implement the formation of the vascular network in the embryo. Vasculogenesis gives rise to the heart and the first primitive vascular plexus inside the embryo and in its surrounding membranes, as the yolk sac circulation. Angiogenesis is responsible for the rem...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/a:1006493130855
更新日期:2000-10-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases collected in Sweden and ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0504-2
更新日期:2011-09-01 00:00:00
abstract::Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1854-6
更新日期:2015-09-01 00:00:00
abstract::Stereotactic radiosurgery is a frequently performed procedure for patients with benign intracranial tumors. Benign tumors are good candidates for radiosurgery because they are generally non-invasive, are well visualized by magnetic resonance imaging, and their slow rate of proliferation makes conventional radiation do...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-009-9831-6
更新日期:2009-05-01 00:00:00
abstract:PURPOSE:Intracranial glioblastomas with simultaneous spinal lesions prior to chemoradiation therapy or craniotomy, defined as initial spinal metastasis, are not well understood. Herein, we investigated intracranial glioblastoma and demonstrated the importance of spinal screening using gadolinium enhanced spinal magneti...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-03036-4
更新日期:2019-01-01 00:00:00
abstract::Glioblastoma (GBM) is the most common adult CNS malignancy but its impact on quality of life (QOL) is poorly understood. In other patient populations, illness intrusiveness (the extent to which disease and treatment disrupts valued activities and interests) is associated with low subjective well-being, after controlli...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1943-6
更新日期:2016-01-01 00:00:00
abstract::Comparison between myelography (MY) and magnetic resonance imaging (MRI) was carried out in 36 patients with clinical suspicion of spinal cord or root compression due to metastatic disease in the spinal canal. In 3 patients metastatic lesions were visualized on MY but not on MRI, while there were no cases with a negat...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00172475
更新日期:1992-07-01 00:00:00
abstract::Embryonal tumors are an aggressive subtype of high-grade, pediatric central nervous system (CNS) tumors often with dismal survival rates. The 5-year survival for highest-risk embryonal tumors may be as low as 10 %. We report feasibility and efficacy from our experience using intravenous (IV) cyclophosphamide concurren...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-0969-2
更新日期:2012-11-01 00:00:00
abstract::Thymidine analogs (TAs) are synthetic nucleosides that incorporate into newly synthesized DNA. Halogenated pyrimidines (HPs), such as bromodeoxyuridine (BrdU), are a class of TAs that can be detected with antibodies and are commonly used for birthdating individual cells and for assessing the proliferative index of cel...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-011-0621-6
更新日期:2011-12-01 00:00:00
abstract::The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity levels, prevalence and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1821-2
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Based on limited literature, an at risk group of patients for development of neoplastic meningitis (NM) are those with resected cerebellar parenchymal metastases. OBJECTIVE:Characterize the incidence of NM in patients with cerebellar metastases treated with either surgical resection or radiotherapy. PATIEN...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9594-5
更新日期:2008-08-01 00:00:00
abstract::A better understanding of the relationship between glioblastomas molecular subtypes and radio-chemotherapy is needed for the development of individualized strategies. In this study, we aimed to assess whether non-homologous end-joining (NHEJ) protein expression is associated and could predict responses to treatment of...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2367-7
更新日期:2017-04-01 00:00:00
abstract::There is general agreement that most chemotherapy agents achieve only relatively low concentrations in the normal central nervous system, that the blood-brain barrier is variably disrupted in malignant brain tumors, and that the concentration of chemotherapy drugs in the brain adjacent to tumor is intermediate between...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/BF01052723
更新日期:1994-01-01 00:00:00
abstract::We describe a 61-year-old man with a multiple neurologic complication of Merkel cell carcinoma, a rare skin cancer. An enhancing brain mass, and cytologically proven leptomeningeal disease produced a succession of symptoms including seizures, bilateral radiculopathies, myoclonus, a cauda equina syndrome and altered me...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF01052924
更新日期:1994-01-01 00:00:00
abstract::Malignant primary spinal cord gliomas (PSCGs) are rare, and the optimal treatment for these lesions remains controversial. We report herein treatment outcomes of six malignant PSCGs managed with temozolomide (TMZ)-based multidisciplinary treatment. TMZ was administered concomitantly with fractionated radiotherapy for ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-010-0249-y
更新日期:2011-01-01 00:00:00
abstract::To investigate the underlying intratumoral diversity of molecular profiles in glioblastomas, a proteomic approach was introduced to compare samples from regions of different histological grade. Using two-dimensional gel electrophoresis (2DE) with matrix-assisted laser-desorption/ionization time-of-flight mass spectrom...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-009-9805-8
更新日期:2009-08-01 00:00:00
abstract::We have investigated the anti-tumor activity of ex vivo activated and expanded T cells which had been sensitized in vivo to one of two different syngeneic rat glioma cell lines; D74 or RT-2. Rats were sensitized by inoculation of irradiated tumor cells into each hind foot pad. After 10 days, the tumor-draining lymph n...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005771717409
更新日期:1997-03-01 00:00:00
abstract:PURPOSE:Because raised matrix metalloprotease (MMP) levels are associated with glioma invasion and angiogenesis, we tested the efficacy of marimastat (MT) an orally active drug that can reduce MMP levels, in patients with gliomas. PATIENTS AND METHODS:A total of 162 patients with intracranial glioblastoma multiforme o...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s11060-005-9098-5
更新日期:2006-07-01 00:00:00
abstract::To study the clinical characteristics, treatment approach and outcome of pleomorphic xanthoastrocytoma (PXA), patients were identified using the National Cancer Intitute's Surveillance, Epidemiology, and End Results (SEER) database. A total of 214 patients were identified with PXA using the November 2010 submission. P...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-0939-8
更新日期:2012-10-01 00:00:00
abstract::There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors o...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005729329526
更新日期:1997-01-01 00:00:00
abstract::We examined the mechanism of action of nitrosoureas as represented by 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) with respect to p53 and the G2M cell cycle checkpoint using two glioblastoma cell lines: U251MG and U373MG, with mutated p53. At log-phase cell growth, fresh medium con...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1016342013616
更新日期:2002-08-01 00:00:00
abstract:PURPOSE:Prediction of clinical outcomes in patients with primary central nervous system lymphoma (PCNSL) is important for optimization of treatment planning. Quantitative imaging biomarkers for PCNSL have not yet been established. This study evaluated the prognostic value of pretreatment dynamic contrast-enhanced MRI a...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2960-z
更新日期:2018-11-01 00:00:00
abstract::We report a case of association of a brain tumor with multiple colorectal polyposis and offer an analysis of the relevant literature with a view to revising the classification of the syndrome in relation to familial multiple polyposis and Gardner's syndrome. Differences emerged, depending on the brain tumor type, whic...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF01058460
更新日期:1995-01-01 00:00:00
abstract::The completion of the Human Genome Project resulted in discovery of many unknown novel genes. This feat paved the way for the future development of novel therapeutics for the treatment of human disease based on novel biological functions and pathways. Towards this aim, we undertook a bioinformatics analysis of in-hous...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0314-6
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly defi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03565-x
更新日期:2020-07-01 00:00:00
abstract::Malignant rhabdoid tumors (MRT) are aggressive neoplasms generally of the infant kidney, although a few extrarenal, central nervous system-located, were reported. We describe two cases of such tumors arising intracerebrally in patients aged 16 and 31 years, hence older than the usually reported, with survival times of...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1022135518846
更新日期:2003-01-01 00:00:00
abstract::Majority of the cerebellopontine angle (CPA) tumors are acoustic neuromas, while bulk of the non-acoustic tumors are formed by meningiomas and epidermoid cysts. Primary paraganglioma is a rare tumor in this location, with only two such cases having been reported in the literature, till date. Recently, a case has been ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-004-5952-0
更新日期:2005-08-01 00:00:00
abstract:PURPOSE:Preclinical studies have suggested promising activity for the combination of disulfiram and copper (DSF/Cu) against glioblastoma (GBM) including re-sensitization to temozolomide (TMZ). A previous phase I study demonstrated the safety of combining DSF/Cu with adjuvant TMZ for newly diagnosed GBM. This phase II s...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11060-019-03125-y
更新日期:2019-05-01 00:00:00