***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells ( αDC1 ) loaded with synthetic peptides for glioma-associated antigen ( GAA ) epitopes and administration of polyinosinic-polycytidylic acid [ poly(I : C ) ] stabilized by lysine and carboxymethylcellulose ( poly-ICLC ) in HLA-A2(+ ) patients with recurrent malignant gliomas . GAAs for these peptides are EphA2 , interleukin (IL)-13 receptor-α2 , YKL-40 , and gp100 . PATIENTS AND METHODS Twenty-two patients ( 13 with glioblastoma multiforme [ GBM ] , five with anaplastic astrocytoma [ AA ] , three with anaplastic oligodendroglioma [ AO ] , and one with anaplastic oligoastrocytoma [ AOA ] ) received at least one vaccination , and 19 patients received at least four vaccinations at two αDC1 dose levels ( 1 × or 3 × 10(7)/dose ) at 2-week intervals intranodally . Patients also received twice weekly intramuscular injections of 20 μg/kg poly-ICLC . Patients who demonstrated positive radiologic response or stable disease without major adverse events  were allowed to receive booster vaccines . T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays . RESULTS The regimen was well-tolerated . The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58 % of patients . Peripheral blood sample s demonstrated significant upregulation of type 1 cytokines and chemokines , including interferon-α and CXCL10 . Nine ( four GBM , two AA , two AO , and one AOA ) achieved progression-free status lasting at least 12 months . One patient with recurrent GBM demonstrated sustained complete response . IL-12 production levels by αDC1 positively correlated with time to progression . CONCLUSION These data support safety , immunogenicity , and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines PURPOSE Glioblastomas are notorious for resistance to therapy , which has been attributed to DNA-repair proficiency , a multitude of deregulated molecular pathways , and , more recently , to the particular biologic behavior of tumor stem-like cells . Here , we aim ed to identify molecular profiles specific for treatment resistance to the current st and ard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide . PATIENTS AND METHODS Gene expression profiles of 80 glioblastomas were interrogated for associations with resistance to therapy . Patients were treated within clinical trials testing the addition of concomitant and adjuvant temozolomide to radiotherapy . RESULTS An expression signature dominated by HOX genes , which comprises Prominin-1 ( CD133 ) , emerged as a predictor for poor survival in patients treated with concomitant chemoradiotherapy  ( n = 42 ; hazard ratio = 2.69 ; 95 % CI , 1.38 to 5.26 ; P = .004 ) . This association could be vali date d in an independent data set . Provocatively , the HOX cluster was reminiscent of a " self-renewal " signature ( P = .008 ; Gene Set Enrichment Analysis ) recently characterized in a mouse leukemia model . The HOX signature and EGFR expression were independent prognostic factors in multivariate analysis , adjusted for the O-6-methylguanine-DNA methyltransferase ( MGMT ) methylation status , a known predictive factor for benefit from temozolomide , and age . Better outcome was associated with gene clusters characterizing features of tumor-host interaction including tumor vascularization and cell adhesion , and innate immune response . CONCLUSION This study provides first clinical evidence for the implication of a " glioma stem cell " or " self-renewal " phenotype in treatment resistance of glioblastoma . Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and respective marker development for individualized treatment and patient selection BACKGROUND Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the st and ard of care for patients with newly diagnosed glioblastoma .  Bevacizumab , a humanized monoclonal antibody against vascular endothelial growth factor A , is currently approved for recurrent glioblastoma . Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known . METHODS In this r and omized , double-blind , placebo-controlled trial , we treated adults who had central ly confirmed glioblastoma with radiotherapy ( 60 Gy ) and daily temozolomide .  Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy . At disease progression , the assigned treatment was revealed , and bevacizumab therapy could be initiated or continued . The trial was design ed to detect a 25 % reduction in the risk of death and a 30 % reduction in the risk of progression or death , the two co primary end points , with the addition of bevacizumab . RESULTS A total of 978 patients were registered , and 637 underwent r and omization . There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group ( median , 15.7 and 16.1 months , respectively ; hazard ratio for death in the bevacizumab group , 1.13 ) . Progression-free survival was longer in the bevacizumab group ( 10.7 months vs. 7.3 months ; hazard ratio for progression or death , 0.79 ) . There were modest increases in rates of hypertension , thromboembolic events , intestinal perforation , and neutropenia in the bevacizumab group . Over time , an increased symptom burden , a worse quality of life , and a decline in neurocognitive function were more frequent in the bevacizumab group . CONCLUSIONS First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma .  Progression-free survival was prolonged but did not reach the prespecified improvement target . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00884741 . ) The objective of the study was to investigate the predictive value of various clinical , biochemical , and histopathological parameters , with special emphasis on the expression of the retinoblastoma protein ( pRB ) , on the radiation response in bladder cancer . In order to obtain a truly objective response measure , patients receiving preoperative radiotherapy followed by cystectomy  were studied . Pretreatment tumour sample s and clinical data from 108 consecutive patients were collected . End points were complete response ( CR ) to radiotherapy , relapse-free survival time and overall survival time . Expression of pRB was assessed by immunohistochemical staining as present or absent . Complete response to radiotherapy  was obtained in 42 of 106 evaluable patients ( 40 % ) . Predictive for CR to radiotherapy , in univariate analysis , was transurethral resection ( as opposed to biopsy ) , B-haemoglobin , no upper urinary retention , and loss of pRB staining . Loss of pRB staining was the strongest independent predictor of radiation response in multivariate logistic regression analysis and absence of upper urinary retention was the only other significant factor . Loss of pRB was the only parameter showing statistically significant , independent association with relapse-free survival , whereas B-haemoglobin was also independently associated with overall survival . Loss of pRB expression seems to indicate a phenotype displaying enhanced radiosensivity and may be of benefit by denoting patients who would selectively benefit from a treatment schedule containing radiotherapy BACKGROUND In 2004 , a r and omised phase III trial by the European Organisation for Research and Treatment of Cancer ( EORTC ) and National Cancer Institute of Canada Clinical Trials Group ( NCIC ) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy .  We report the final results with a median follow-up of more than 5 years . METHODS Adult patients with newly diagnosed glioblastoma were r and omly assigned to receive either st and ard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide . The methylation status of the methyl-guanine methyl transferase gene , MGMT , was determined retrospectively from the tumour tissue of 206 patients . The primary endpoint was overall survival . Analyses were by intention to treat . This trial is registered with Clinical trials.gov , number NCT00006353 . FINDINGS Between Aug 17 , 2000 , and March 22 , 2002 , 573 patients were assigned to treatment . 278 ( 97 % ) of 286 patients in the radiotherapy alone group and 254 ( 89 % ) of 287 in the combined-treatment group died during 5 years of follow-up . Overall survival was 27.2 % ( 95 % CI 22.2 - 32.5 ) at 2 years , 16.0 % ( 12.0 - 20.6 ) at 3 years , 12.1 % ( 8.5 - 16.4 ) at 4 years , and 9.8 % ( 6.4 - 14.0 ) at 5 years with temozolomide , versus 10.9 % ( 7.6 - 14.8 ) , 4.4 % ( 2.4 - 7.2 ) , 3.0 % ( 1.4 - 5.7 ) , and 1.9 % ( 0.6 - 4.4 ) with radiotherapy alone ( hazard ratio 0.6 , 95 % CI 0.5 - 0.7 ; p<0.0001 ) . A benefit of combined therapy was recorded in all clinical prognostic subgroups , including patients aged 60 - 70 years . Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy . INTERPRETATION Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up . A few patients in favourable prognostic categories survive longer than 5 years . MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide . FUNDING EORTC , NCIC , Nélia and Amadeo Barletta Foundation , Schering-Plough BACKGROUND Epigenetic silencing of the MGMT ( O6-methylguanine-DNA methyltransferase ) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents .  METHODS We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a r and omized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide .  The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis . RESULTS The MGMT promoter was methylated in 45 percent of 206 assessable cases . Irrespective of treatment , MGMT promoter methylation was an independent favorable prognostic factor ( P<0.001 by the log-rank test ; hazard ratio , 0.45 ; 95 percent confidence interval , 0.32 to 0.61 ) . Among patients whose tumor contained a methylated MGMT promoter , a survival benefit was observed in patients treated with temozolomide and radiotherapy ; their median survival was 21.7 months ( 95 percent confidence interval , 17.4 to 30.4 ) , as compared with 15.3 months ( 95 percent confidence interval , 13.0 to 20.9 ) among those who were assigned to only radiotherapy ( P=0.007 by the log-rank test ) . In the absence of methylation of the MGMT promoter , there was a smaller and statistically insignificant difference in survival between the treatment groups . CONCLUSIONS Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide , whereas those who did not have a methylated MGMT promoter did not have such a benefit BACKGROUND The epidermal growth factor receptor variant III deletion mutation , EGFRvIII , is expressed in ∼30 % of primary glioblastoma and linked to poor long-term survival . Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin . In previous phase II trials ( ACTIVATE/ACT II ) , rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival . This multicenter , single-arm phase II clinical trial ( ACT III ) was performed to confirm these results . METHODS Rindopepimut and st and ard adjuvant temozolomide chemotherapy were admin 
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O-6-methylguanine-DNA methyltransferase status predicts a more favourable response to treatment and is thus a predictive marker .
Based on genomic aberrations , Verhaak et al have suggested a division of GBM into three subgroups , namely , proneural , classical and mesenchymal , which could be meaningful in the clinic and could help guide and differentiate treatment decisions according to the specific subgroup .