***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: A controlled , prospect i ve , r and omized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) and /or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma . A total of 303 patients were r and omized into this study , of whom 222 ( 73 % ) were within the Valid Study Group ( VSG ) , having met the protocol criteria of neuropathology , corticosteroid control , and therapeutic approach . Patients were divided into four r and om groups , and received BCNU ( 80 mg/sq m/day on 3 successive days every 6 to 8 weeks ) , and /or radiotherapy ( 5000 to 6000 rads to the whole brain through bilateral opposing ports ) , or best conventional care but no chemotherapy or radiotherapy . Analysis was performed on all patients who received any amount of therapy ( VSG ) and on the Adequately Treated Group ( ATG ) , who had received 5000 or more rads radiotherapy , two or more courses of chemotherapy , and had a minimum survival of 8 or more weeks ( the interval that would have been required to have received either the radiotherapy or chemotherapy ) . Median survival of patients in the VSG was , best conventional care : 14 weeks ( ATG : 17.0 weeks ) ; BCNU : 18.5 weeks ( ATG : 25.0 weeks ) ; radiotherapy : 35 weeks ( ATG : 37.5 weeks ) ; and BCNU plus radiotherapy : 34.5 weeks ( ATG : 40.5 weeks ) . All therapeutic modalities showed some statistical superiority compared to best conventional care . There was no significant difference between the four groups in relation to age distribution , sex , location of tumor , diagnosis , tumor characteristics , signs or symptoms , or the amount of corticosteroid used . An analysis of prognostic factors indicates that the initial performance status ( Karnofsky rating ) , age , the use of only a surgical biopsy , parietal location , the presence of seizures , or the involvement of cranial nerves II , III , IV , and VI are all of significance . Toxicity included acceptable , reversible thrombocytopenia and leukopenia OBJECTIVES The optimal treatment for patients with glioblastoma with unfavorable prognostic factors , such as old age and low performance status , remains controversial . We conducted a prospect i ve study to assess the effect of temozolomide and short-course radiation versus short-course radiation alone in the treatment of poor-prognosis patients with newly diagnosed glioblastoma . PATIENTS AND METHODS Forty-five patients with a newly diagnosed glioblastoma , older than 70 years or aged 50 - 70 years and with a Karnofsky performance score < or=70 were enrolled in this prospect i ve study . Twenty-three patients were treated with an abbreviated course of radiotherapy ( 30 Gy in 6 fractions over 2 weeks ) and 22 patients with the same radiotherapy schedule plus adjuvant temozolomide at the dose of 150 - 200 mg/m(2 ) for 5 days every 28-day cycle . The primary end point was overall survival . Secondary end points included progression-free survival and toxicity . RESULTS Median overall survival was 7.3 months in the radiotherapy group and 9.4 months in the radiotherapy plus temozolomide group ( P = 0.003 ) , with respective 6-month overall survivals of 78 % and 95 % , respectively . Median progression-free survival was 4.4 months in the radiotherapy group and 5.5 months in the radiotherapy plus temozolomide group ( P = 0.01 ) , and respective 6-month progression-free survival rates were 22 % and 45 % . In multivariate analysis , Karnofsky performance score was the only significant independent predictive factor of survival ( P = 0.03 ) . Adverse effects of radiotherapy were mainly represented by neurotoxicity ( 24 % ) , which resolved in most cases with the use of steroids . Grade 3 - 4 hematologic toxicity occurred in 36 % of patients treated with temozolomide . CONCLUSIONS The addition of temozolomide to short-term radiotherapy result ed in a statistically significant survival benefit with minimal additional toxicity in poor-prognosis patients with newly diagnosed glioblastoma . Future studies need to define the best combined regimens of radiotherapy and temozolomide on survival and quality of life in this subgroup of patients 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 To report toxicity and overall survival ( OS ) in patients with newly diagnosed glioblastoma multiforme ( GBM ) treated with hypofractionated intensity-modulated radiotherapy ( hypo-IMRT ) with concurrent and adjuvant temozolomide ( TMZ ) . METHODS AND MATERIAL S Patients with newly diagnosed GBM after biopsy or resection and with adequate performance status and organ or bone marrow function were eligible for this study . Patients received postoperative hypo-IMRT to the surgical cavity and residual tumor seen on T1-weighted brain MRI with a 5-mm margin to a total dose of 60 Gy in 10 fractions ( 6 Gy/fraction ) and to the T2 abnormality on T2-weighted MRI with 5-mm margin to 30 Gy in 10 fractions ( 3 Gy/fraction ) . Concurrent TMZ was given at 75 mg/m(2)/day for 28 consecutive days . Adjuvant TMZ was given at 150 to 200 mg/m(2)/day for 5 days every 28 days . Toxicities were defined using Common Terminology Criteria for Adverse Events version 3.0 .  RESULTS Twenty-four patients were treated , consisting of 14 men , 10 women ; a median age of 60.5 years old ( range , 27 - 77 years ) ; and a median Karnofsky performance score of 80 ( range , 60 - 90 ) . All patients received hypo-IMRT and concurrent TMZ according to protocol , except for 2 patients who received only 14 days of concurrent TMZ . The median number of adjuvant TMZ cycles was 6.5 ( range , 0 - 14).With a median follow-up of 14.8 months ( range , 2.7 - 34.2 months ) for all patients and a minimum follow-up of 20.6 months for living patients , no instances of grade 3 or higher nonhematologic toxicity were observed . The median OS was 16.6 months ( range , 4.1 - 35.9 months ) . Six patients underwent repeated surgery for suspected tumor recurrence ; necrosis was found in 50 % to 100 % of the resected specimens . CONCLUSION In selected GBM patients , 60 Gy hypo-IMRT delivered in 6-Gy fractions over 2 weeks with concurrent and adjuvant TMZ is safe . OS in this small cohort of patients was comparable to that treated with current st and ard of care therapy 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 PURPOSE Surgery remains the st and ard treatment for glioma , followed by radiotherapy ( RT ) with or without chemotherapy . Despite multidisciplinary approaches , the median survival time for patients with glioblastoma multiform ( GBM ) remains at less than 1 year from initial diagnosis . Temozolomide ( TMZ ) , an oral alkylating agent , has shown promising activity in the treatment of malignant gliomas . We conducted a multicenter r and omized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM . PATIENTS AND METHODS One hundred thirty patients with pathologically confirmed , newly diagnosed GBM were r and omly assigned ( 110 assessable patients ) to receive either TMZ 75 mg/m(2)/d orally , concomitantly with RT ( 60 Gy in 30 fractions ; group A , n = 57 ) , followed by six cycles of TMZ ( 150 mg/m(2 ) on days 1 through 5 and 15 to 19 every 28 days ) , or RT alone ( 60 Gy in 30 fractions ; group B , n = 53 ) . RESULTS Median time to progression was 10.8 months in group A and 5.2 months in group B ( P = .0001 ) . One-year progression-free survival rate was 36.6 % in group A and 7.7 % in group B. Median overall survival ( OS ) time was also significantly better in group A versus group B ( 13.4 v 7.7 months , respectively ; P < .0001 ) , as was the 1-year OS at 56.3 % 
    Output:
    
Radiotherapy/TMZ provides better survival outcomes than radiotherapy alone in treating GBM