***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: BACKGROUND Both the epidermal growth factor receptor and vascular endothelial growth factor pathways are frequently overexpressed in glioblastoma multiforme . This study combined bevacizumab , a vascular endothelial growth factor inhibitor , and erlotinib , an epidermal growth factor receptor inhibitor , with st and ard radiation and temozolomide ( TMZ ) , with the goal of improving overall survival ( OS ) . METHODS Treatment consisted of fractionated radiotherapy to 60 Gy , with daily TMZ at 75 mg/m²/d and erlotinib 150 - 200 mg/d ( or 500 - 600 mg/d for patients on enzyme-inducing antiepileptic drugs ) . Bevacizumab was given at 10 mg/kg every 2 weeks , starting ≥4 weeks after surgery . After radiotherapy , adjuvant TMZ was given at 200 mg/m²/d × 5d per 28-day cycle , with unchanged erlotinib and bevacizumab doses . Treatment continued until progression or for 12 months . Efficacy was compared against an institutional historical control . A sample of 55 patients was calculated to provide 85 % power to detect a hazard ratio of 0.67 for OS . RESULTS Fifty-nine patients were enrolled for efficacy analysis after a 15-patient safety lead-in . For the efficacy group , median age was 54 years ; median KPS was 90 . Gross total and subtotal resections were achieved in 33 % and 53 % , respectively . The most frequent related grade 3/4 adverse effects were lymphopenia , thrombocytopenia , neutropenia , diarrhea , weight loss , and fatigue . One patient died of disseminated aspergillosis . Median OS was 19.8 months ( vs 18 mo for HC , P = .33 ) and median progression-free survival was 13.5 months ( vs 8.6 mo for HC , P = .03 ) . CONCLUSIONS The combination of bevacizumab , erlotinib , TMZ , and radiotherapy appears to be well tolerated and improved progression-free survival but did not reach the primary endpoint of improved OS 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 . ) BACKGROUND Prognosis of unresectable glioblastoma ( GB ) remains poor , despite temozolomide (TMZ)-based chemoradiation . Activity of bevacizumab ( BEV ) and irinotecan ( IRI ) has been reported in recurrent disease . We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB . PATIENTS AND METHODS Patients with unresectable GB , age 18 - 70 , IK ≥50 were eligible . The experimental arm ( BEV/IRI ) consisted of neo-adjuvant intravenous BEV , 10 mg/kg , and IRI , 125 mg/m(2 ) , every 2 weeks for four cycles before radiotherapy ( RT ) ( 60 Gy ) , concomitant oral TMZ , 75 mg/m(2)/day , and BEV , 10 mg/kg every 2 weeks . Adjuvant BEV and IRI were given every 2 weeks for 6 months . The control arm consisted of concomitant oral TMZ , 75 mg/m(2)/day during RT , and 150 - 200 mg/m(2 ) for 5 days every 28 days for 6 months . The use of BEV was allowed at progression in the control arm . RESULTS Patients ( 120 ) were included from April 2009 to January 2011 . The working hypothesis was that treatment would increase the progression-free survival at 6 month ( PFS-6 ) from 50 % to 66 % . The primary objective was not achieved , and only 30 out of 60 patients were alive without progression at 6 months ( 50.0 % [ IC95 % ( 36.8 ; 63.1 ) ] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules . PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm . The median overall survival was not different between the two arms ( 11.1 months ) . Main toxicities were three fatal intracranial bleedings , three bile duct or digestive perforations/infections ( 1 fatal ) , and six thrombotic episodes in the BEV/IRI arm , whereas there was one intracranial bleeding , two bile duct or digestive perforations/infections ( 1 fatal ) , and one thrombotic episode in the control arm . CONCLUSIONS Neo-adjuvant and adjuvant BEV/IRI , combined with TMZ-radiation , is not recommended for further evaluation in the first-line treatment of unresectable GB . CLINICAL TRIAL REGISTRATION Clinical trial registered under EUDRACT number 2008 - 002775 - 28 ( NCT01022918 ) BACKGROUND High- grade gliomas ( HGGs ) are among the most prothrombotic of malignancies . METHODS We performed a prospect i ve study to investigate 11 potential biomarkers for prediction of venous thromboembolism ( VTE ) in newly diagnosed HGG patients who had undergone a neurosurgical intervention .  In addition , we tested 2 VTE risk assessment models ( RAMs ) . The strongest predictors of VTE , which were identified by statistical forward selection , were used for the first RAM . The parameters used for the second RAM were both predictive of VTE and available in routine clinical practice . RESULTS One hundred forty-one HGG patients were included in this study , and 24 ( 17 % ) of them developed VTE during follow-up . An association with the risk of future VTE was found for the following parameters : leukocyte count , platelet count , sP-selectin , prothrombin-fragment 1 + 2 , FVIII activity , and D-dimer . The first RAM included low platelet count ( < 25th percentile of the study population ) and elevated sP-selectin ( ≥75th percentile ) . The cumulative VTE probability after 12 months was 9.7 % for score 0 ( n = 76 ) , 18.9 % for score 1 ( n = 59 ) , and 83.3 % for score 2 ( n = 6 ) . The second RAM included low platelet count ( < 25th percentile ) , elevated leukocyte count , and elevated D-dimer ( ≥75th percentile ) . The probability of VTE was 3.3 % for score 0 ( n = 63 ) , 23.0 % for score 1 ( n = 53 ) , and 37.7 % for score 2 ( n = 22 ) or score 3 ( n = 3 ) . CONCLUSIONS We identified biomarkers suitable for assessing the VTE risk in newly diagnosed HGG patients . The application of 2 RAMs allowed identification of patients at high risk of developing VTE . We could also define patients at low risk of VTE , who would most probably not benefit from extended primary thromboprophylaxis PURPOSE To determine the safety of the addition of bevacizumab to st and ard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme ( GBM ) . METHODS AND MATERIAL S A total of 125 patients with newly diagnosed GBM were enrolled in the study , and received st and ard radiation therapy and daily temozolomide .  All patients underwent a craniotomy and were at least 2 weeks postoperative .  Radiation therapy was administered in 1.8-Gy fractions , with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy , followed by a boost of 9 to 14.4 Gy , to a total dose of 59.4 Gy . Patients received temozolomide at 75 mg/m(2 ) daily throughout the course of radiation therapy . Bevacizumab was given at 10 mg/kg intravenously every 14 days , beginning a minimum of 4 weeks postoperatively . RESULTS Of the 125 patients , 120 ( 96 % ) completed the protocol -specified radiation therapy . Five patients had to stop the protocol therapy , 2 patients with pulmonary emboli , and 1 patient each with a Grade 2 central nervous system hemorrhage , Grade 4 pancytopenia , and wound dehiscence requiring surgical intervention . All 5 patients ultimately finished the radiation therapy . After radiation therapy , 3 patients had progressive disease , 2 had severe fatigue and decreased performance status , 1 patient had a colonic perforation , and 1 had a rectal fissure ; these 7 patients therefore did not proceed with the protocol -specified adjuvant temozolomide , bevacizumab , and irinotecan . However , 113 patients ( 90 % ) were able to continue on study . CONCLUSIONS The addition of bevacizumab to st and ard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM PURPOSE Venous thromboembolism ( VTE ) is a well-recognized complication of cancer . Laboratory parameters might be useful to assess the VTE risk in patients with cancer . The aim of this study was to investigate D-dimer and prothrombin fragment 1 + 2 ( F 1 + 2 ) , which reflect activation of blood coagulation and fibrinolysis , for prediction of cancer-associated VTE . PATIENTS AND METHODS In a prospect i ve , observational , cohort study of 821 patients with newly diagnosed cancer or progression of disease who did not recently receive chemotherapy , radiotherapy , or surgery  were enrolled and followed for a median of 501 days ( interquartile range , 255 to 731 days ) . The malignancies in these patients were as follows : breast ( n = 132 ) , lung ( n = 119 ) , stomach ( n = 35 ) , lower gastrointestinal tract ( n = 106 ) , pancreas ( n = 46 ) , kidney ( n = 22 ) , and prostate ( n = 101 ) cancers ; high- grade glioma ( n = 102 ) ; malignant lymphoma ( n = 94 ) ; multiple myeloma ( n = 17 ) ; and other tumor types ( n = 47 ) . The study end point was occurrence of objective ly confirmed symptomatic or fatal VTE . RESULTS VTE occurred in 62 patients ( 7.6 % ) . The cutoff level for elevated D-dimer and elevated F 1 + 2 was set at the 75th percentile of the total study population . In multivariable analysis that included elevated D-dimer , elevated F 1 + 2 , age , sex , surgery , chemotherapy , and radiotherapy , the hazard ratios ( HRs ) of VTE in patients with elevated D-dimer ( HR , 1.8 ; 95 % CI , 1.0 to 3.2 ; P = .048 ) and elevated F 1 + 2 ( HR , 2.0 
    Output:
    
As there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism , anticoagulation may be advisable in certain newly diagnosed adult GBM patients who display a history of thromboembolism and /or more serious risk factors for thromboembolic events