***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: 2098 Background : The prognosis for newly-diagnosed GBM remains poor . Adding temozolomide to radiation therapy improved the median event-free survival ( EFS ) to 6.9 months and median overall survival to 14.6 months . The five year survival remains < 10 % . GBM 's have abundant neo-vascularization and the highest level of vascular endothelial growth factor ( VEGF ) . Bevacizumab is an antibody to VEGF and is the most active agent for recurrent GBM . Hypoxia inducing factor-1 α ( HIF-1 α ) is an important regulator of VEGF , and topotecan may inhibit HIF-1 α . We performed a phase II trial in newly diagnosed GBM patients , adding bevacizumab and topotecan to st and ard therapy . METHODS Eighty newly diagnosed GBM patients were enrolled after their craniotomy between December 2009 and December 2010 . Patients received st and ard radiation therapy and temozolomide at 75 mg/m2/d beginning between 2 - 6 weeks post-craniotomy . Bevacizumab , 10 mg/kg every 14 days was added a minimum of 4 weeks post-op . Two weeks after radiation therapy was completed , 12 monthly cycles of temozolomide at 150 - 200 mg/m2/d days 1 - 5 , oral topotecan at 1.5 mg/m2/day days 2 - 6 for patients not on an enzyme inducing anti-epileptic drug ( EIAED ) and 2.0 mg/m2/day days 2 - 6 for patients on an EIAED bevacizumab at 10 mg/kg on days 1 and 15 . RESULTS Adding bevacizumab and topotecan to st and ard therapy result ed in a 6-month EFS of 90 % . The median overall survival has not been reached , but 96 % of the patients are alive at 8 months . The regimen was tolerable , 96 % completed radiation therapy . Eight patients came off due to  toxicity  , there were 2 CNS hemorrhages , 2 grade 4 thrombocytopenias , 1 pulmonary embolus , 1 colon perforation , 1 craniotomy bone flap infection , and 1 CMV pneumonitis . There were 2 toxic deaths , 1 from CMV pneumonits and 1 from CNS hemorrhage . There are 10 progressions . A comprehensive analysis of tumor biomarkers is underway . CONCLUSIONS Adding bevacizumab to temozolomide and radiation followed by temozolomide , bevacizumab and oral topotecan  is tolerable . The 6-month EFS is encouraging . R and omized phase III trials of the addition of bevacizumab to the treatments of newly diagnosed GBM patients are essential PURPOSE This open-label , prospect i ve , multicenter single-arm phase II study combined bevacizumab ( BV ) with radiation therapy ( RT ) and temozolomide ( TMZ ) for the treatment of newly diagnosed glioblastoma ( GBM ) . The objectives were to determine the efficacy of this treatment combination and the associated toxicity . PATIENTS AND METHODS Seventy patients with newly diagnosed GBM were enrolled between August 2006 and November 2008 . Patients received st and ard RT starting within 3 to 6 weeks after surgery with concurrent administration of daily TMZ and biweekly BV . After completion of RT , patients resumed TMZ for 5 days every 4 weeks and continued biweekly BV . MGMT promoter methylation was assessed on patient tumor tissue . A University of California , Los Angeles/Kaiser Permanente Los Angeles ( KPLA ) control cohort of newly diagnosed patients treated with first-line RT and TMZ who had mostly received BV at recurrence was derived for comparison . RESULTS The overall survival ( OS ) and progression-free survival ( PFS ) were 19.6 and 13.6 months , respectively , compared to 21.1 and 7.6 months in the University of California , Los Angeles/KPLA control cohort , and 14.6 and 6.9 months in the European Organisation for Research and Treatment of Cancer-National Cancer Institute of Canada cohort . Correlation of MGMT promoter methylation and improved OS and PFS was retained in the study group . Comparative subset analysis showed that poor prognosis patients ( recursive partitioning analysis class V/VI ) may derive an early benefit from the use of first-line BV . Toxicity attributable to RT/TMZ was similar , and additional toxicities were consistent with those reported in other BV trials . CONCLUSION Patients treated with  BV and TMZ  during and after RT showed improved PFS without improved OS compared to the University of California , Los Angeles/KPLA control group . Additional studies are warranted to determine if BV administered first-line improves survival compared to BV at recurrence Purpose : Response Evaluation Criteria  in Solid Tumors ( RECIST ) evaluation does not take into account the pretreatment tumor kinetics and may provide incomplete information about experimental drug activity . Tumor growth rate ( TGR ) allows for a dynamic and quantitative assessment of the tumor kinetics . How TGR varies along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown . Experimental Design : Medical records from all patients ( N = 253 ) prospect ively treated in 20 phase I trials were analyzed .  TGR  was computed during the pretreatment period ( reference ) and the experimental period . Associations between TGR , st and ard prognostic scores [ Royal Marsden Hospital ( RMH ) score ] , and outcome [ progression-free survival ( PFS ) and overall survival ( OS ) ] were computed ( multivariate analysis ) . Results : We observed a reduction of TGR between the reference versus experimental periods ( 38 % vs. 4.4 % ; P < 0.00001 ) . Although most patients were classified as stable disease ( 65 % ) or progressive disease ( 25 % ) by RECIST at the first evaluation , 82 % and 65 % of them exhibited a decrease in TGR , respectively . In a multivariate analysis , only the decrease of TGR was associated with PFS ( P = 0.004 ) , whereas the RMH score was the only variable associated with OS ( P = 0.0008 ) . Only the investigated regimens delivered were associated with a decrease of TGR ( P < 0.00001 , multivariate analysis ) . Computing TGR profiles across different clinical trials reveals specific patterns of antitumor activity . Conclusions : Exploring TGR in phase I patients is simple and provides clinical ly relevant information : ( i ) an early and subtle assessment of signs of antitumor activity ; ( ii ) independent association with PFS ; and ( iii ) it reveals drug-specific profiles , suggesting potential utility for guiding the further development of the investigational drugs . Clin Cancer Res ; 20(1 ) ; 246–52 . © 2013 AACR 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 . ) Purpose : To determine if the addition of bevacizumab to radiation therapy and temozolomide , followed by bevacizumab , temozolomide , and irinotecan , for newly diagnosed glioblastoma patients is safe and effective . Experimental Design : A total of 75 patients with newly diagnosed glioblastoma were enrolled in the phase II trial that investigated the addition of bevacizumab to st and ard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide . The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy . Two weeks after radiation therapy , the patients began 6 to 12 cycles of 5-day temozolomide with bevacizumab and irinotecan every 14 days . The primary endpoint was the proportion of patients alive 16 months after informed consent . Results : The therapy had moderate toxicity . Three patients , one of whom had a grade 2 central nervous system hemorrhage , came off study during radiation therapy . Seventy patients started the postradiation therapy , and 16 ( 23 % ) terminated this adjuvant therapy early because of toxicity . The median overall survival was 21.2 months ( 95 % CI : 17.2–25.4 ) , and 65 % of the patients were alive at 16 months ( 95 % CI : 53.4–74.9 ) . The median progression-free survival was 14.2 months ( 95 % CI : 12–16 ) . Conclusion : The addition of bevacizumab to st and ard radiation therapy and temozolomide , followed by bevacizumab , irinotecan , and temozolomide , for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls . The results from phase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established . Clin Cancer Res ; 17(12 ) ; 4119–24 . © 2011 AACR PURPOSE To evaluate the efficacy of adding bevacizumab , a vascular endothelial growth factor ( VEGF ) inhibitor , and everolimus , a mammalian target of rapamycin ( mTOR inhibitor ) , to st and ard radiation therapy/temozolomide in the first-line treatment of patients with glioblastoma . PATIENTS AND METHODS Following surgical resection or biopsy , patients with newly diagnosed glioblastoma received st and ard radiation therapy/temozolomide plus bevacizumab 10 mg/kg intravenously ( IV ) every 2 weeks . Four weeks after the completion of radiation therapy , patients began oral everolimus 10 mg daily , and continued bevacizumab every 2 weeks ; therapy continued until tumor progression or unacceptable toxicity . RESULTS Sixty-eight patients were treated , 82 % of whom had previously undergone partial or complete surgical resection . Sixty-four patients completed combined modality therapy , and 57 patients began maintenance therapy with bevacizumab/everolimus . Thirty-one of 51 patients ( 61 % ) with measurable tumor had objective responses . After a median follow-up of 17 months , the median progression-free survival ( PFS ) was 11.3 months ( 95 % confidence interval [ CI ] , 9.3 - 13.1 months ) ; median overall survival was 13.9 months . Toxicity was consistent with the known toxicity profile of bevacizumab ;  grade 3/4 toxicities during maintenance therapy related to everolimus included fatigue ( 27 % ) , pneumonitis ( 7 % ) , and stomatitis ( 5 % ) . CONCLUSIONS The use of bevacizumab and everolimus as part of first-line combined modality therapy for glioblastoma was feasible and efficacious . The PFS compared favorably to previous reports with st and ard radiation therapy/temozolomide therapy , and is similar to results achieved in other phase II trials in which bevacizumab was added to fist-line treatment . O 
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No significant difference was observed in PFS and OS .
The use of MTT with RT compared to st and ard therapy  increased SAE while yielded comparable survival in glioblastoma multiforme patients