***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: One hundred and three patients with hemispheric supratentorial glioblastoma multiforme were studied . All patients were operated on and a histologic diagnosis of glioblastoma multiforme was made . Patients were r and omly placed in one of three treatment schedules within 3 weeks of surgery : Group A : combined radiation therapy and drug ( CCNU ) therapy ( 26 cases ) ; Group B : CCNU given orally every 6–8 weeks ( 27 cases ) ; Group C : st and ard radiation therapy alone ( 50 cases ) . All patients were periodically controlled by clinical and instrumental ( EEG , scan , EMG , CAT ) evaluations ; laboratory data examinations were also frequently performed . The treatment results have been evaluated according to length of survival , social quality of life , and positive or negative response to chemotherapy . In our opinion the clinical findings are interesting but the statistical results are somewhat negative , especially when the groups of patients are not homogeneous The Radiation Therapy Oncology Group ( RTOG ) and the Eastern Cooperative Oncology Group ( ECOG ) conducted a phase III trial in patients with malignant gliomas to evaluate 4 treatment arms : 1 ) 60 Gy to the whole brain ; 2 ) 60 Gy plus 10-Gy boost ; 3 ) 60 Gy plus carmustine ( BCNU ) ; and 4 ) 60 Gy plus semustine plus dacarbazine .  Between September 1974 and March 1979 , 626 patients with malignant gliomas were treated on protocol RTOG 7401/ECOG 1374 . Each institution chose a subset of the treatments to which the patients would be r and omized . Patients were stratified according to subset and r and omized to the 4 treatment arms . There were no differences in survival among treatment arms . For patients greater than 60 years of age , the addition of chemotherapy to radiation therapy did not improve survival . For patients aged 40 - 60 years , there was a statistically significant increase in overall survival when BCNU was added to 60 Gy ( P less than .01 ) , with an increase in 2-year survival from 8 % to 23 % . This beneficial effect of BCNU is apparent in both histological groups ( astrocytoma with atypical or anaplastic foci and glioblastoma multiforme ) . Although few confirmatory autopsies are available , long-term survival in patients with astrocytomas with atypical and anaplastic foci who were treated with 60 Gy plus BCNU ( 5-yr survival , 22 % ) suggests no significant late CNS toxicity , compared to 60 Gy alone ( 5-yr survival , 15 % ) . This is confirmed by comparable neurological function in long-term survivors 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 An attempt was made to evaluate the potential advantages of chemotherapy in the treatment of 62 patients with glioblastoma . Twenty-four of the 62 patients received adjuvant nitrosourea chemotherapy with carmustine ( BCNU ) , lomustine ( CCNU ) , or semustine ( methyl CCCNU ) in addition to surgery and radiotherapy . Thirty-three of the 62 patients were involved in a controlled , prospect i ve , r and omly allocated study . Quality or quantity of survival was not prolonged in patients who received chemotherapy . Age greater than 64 years , a severe postoperative neurological deficit , or the onset of symptoms less than 12 months prior to surgery were associated with a worse prognosis . The valid evaluation of the effect of a form of treatment on survival in patients with glioblastoma is contingent on the regorous avoidance of preselected factors that may predispose the treated group to a more favorable prognosis This prospect i ve and r and omized trial reports the effects of three chemotherapeutic regimens on three different clinical parameters in adults with supratentorial malignant brain gliomas : 1 ) duration of the interval between surgery and relapse ( the " free interval " ) ; 2 ) total survival time ; and 3 ) rate and length of objective remissions . All patients were irradiated with 5500 to 6000 rads after neurosurgery aim ed at an optimum removal . The administration of VM-26 , 60 mg/sq m on Day 1 , plus CCNU , 130 mg/sq m on Day 2 , repeated every 6 weeks , had no significant effect on the length of the free interval between surgery and relapse . Thus , the median duration of this period was 39 weeks in the group of 61 patients who received adjuvant chemotherapy and 30 weeks in 55 controls without treatment .  Neither was the total survival time prolonged by the administration of early chemotherapy . The best prognostic factor for the duration of the free interval and survival was age : patients under 50 years old survived statistically significantly longer . The rate of the objective remission , defined as a clear-cut clinical improvement persisting 6 weeks after complete discontinuation of steroids , was measured after tumor relapse . In patients who were not previously treated with chemotherapy , CCNU alone or VM-26 plus CCNU produced objective remissions in only 15 % of treated patients . Out of 17 cases treated previously by VM-26 plus CCNU , none responded to procarbazine after relapse Forty-one consecutive patients with supratentorial primary brain tumors ( 38 Grade III and IV astrocytomas , one giant-cell astrocytoma , and two cases with insufficient tissue for diagnosis ) were r and omly allocated within 2 weeks of surgery to one of three therapeutic groups . Group 1 ( 15 patients ) received radiation therapy totaling 4000 to 4500 rads in 4 to 5 weeks . Group 2 ( 13 patients ) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea CCNU ) 130 mg/sq m orally every 6 weeks . Group 3 ( 13 patients ) received radiation therapy plus CCNU as for Groups 1 and 2 . When the disease progressed , patients in Groups 1 and 2 were crossed over to receive CCNU and irradiation respectively . The median survival time in these groups was 188 , 259 , and 252 days , and the mean survival 263 , 262 , and 329 days . The median time from diagnosis to crossover ( Groups 1 and 2 ) or to progression ( Group 3 ) was 163 , 99 , and 220 days , and the mean time was 172 , 108 , and 231 days . There was no statistically significant difference between the means or medians in any of these situations From September , 1972 to December , 1976 , 102 consecutive patients operated on for glioblastoma multiforme were r and omized , after total or subtotal tumor resection , to receive irradiation alone , irradiation plus BCNU or irradiation plus CCNU . BCNU and CCNU adjuvant chemotherapy was repeated every 6 - -8 weeks as long as the patients remained in complete remission . Patients were comparable for median age , type of surgery , and histological grade III and IV .  Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups . The percent of optimal dose administered was 96 % for BCNU and 93 % for CCNU . In the group treated with radiotherapy alone ( 32 cases ) the median survival was 10.5 months , while in the groups treated with BCNU ( 34 cases ) and CCNU ( 36 cases ) the median survival was 12 and 16 months , respectively . Both relapse-free ( P = 0.05 ) and total survival ( P = 0.03 ) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery . Present results show that in resectable glioblastoma multiforme , a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy . The cure rate was not improved BACKGROUND A r and omised controlled trial of radiotherapy alone versus radiotherapy with concomitant and adjuvant temozolomide for patients with glioblastoma showed that survival was higher for patients assigned combination treatment compared with those assigned st and ard radiotherapy alone . This paper reports the health-related quality of life ( HRQOL ) of the patients in this trial . METHODS 573 patients with newly diagnosed glioblastoma were r and omly allocated either radiotherapy alone or radiotherapy and temozolomide . The primary endpoint was survival , and HRQOL was a secondary endpoint . We assessed HRQOL at baseline and at every 3 months during treatment until progression using the European Organisation for Research and Treatment of Cancer ( EORTC ) quality of life question naire core-30 ( QLQ-C30 ) and the EORTC brain cancer module ( EORTC BN-20 ) . We calculated changes from baseline score for seven predefined HRQOL measures ( fatigue , overall health , social function , emotional function , future uncertainty , insomnia , and communication deficit ) and differences between groups for these measures at every time point . The significance of , and proportions of patients with , improved HRQOL scores -- defined as a change of 10 points or more -- were recorded . This trial is registered on the US National Cancer Institute website http://www.cancer.gov/ search /New Clinical Trials , NCT00006353 . FINDINGS Baseline question naires were available for 490 ( 86 % ) patients . Baseline HRQOL scores did not differ between groups . At first follow-up , groups differed only in social functioning , favouring the radiotherapy-only group ( mean score 79.0 [ SD 3.2 ] for patients assigned radiotherapy vs 67.4 [ 2.7 ] for those assigned radiotherapy and temozolomide ; difference between groups 11.6 points [ 95 % CI 3.5 - 19.7 ] , p=0.0052 ) . Over subsequent assessment s , HRQOL was much the same between treatment groups . INTERPRETATION Addition of temozolomide during and after radiotherapy for patients with newly diagnosed glioblastoma significantly improved survival without a negative effect on HRQOL The authors report 63 patients with biopsy-proved malignant ( Grade s 3 and 4 ) astrocytomas who were r and omly placed in one of three treatment schedules within 2 weeks of surgery . One group ( 22 patients ) received radiation therapy alone ; the second group ( 22 patients ) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea ( CCNU ) orally at intervals of 8 weeks ; and the third group ( 19 patients ) received combined radiation and drug therapy .  Patients who received radiation therapy , with or without the drug , had a significantly longer survival than did those who received the drug alone . There was no difference in survival between the two groups who received radiation . The nitrosourea derivative CCNU does not seem to be an effective agent in the therapy of primary malignant brain tumors Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor . We conducted a prospect ively r and omized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas . Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time ( 67 vs 35 weeks ) than did patients receiving only irradiation . The major toxic effect of dianhydrogalactitol  is hematologic suppression of a cumulative nature .  Dianhydrogal 
    Output:
    
CONCLUSION Concomitant temozolomide during radiotherapy and post-radiation adjuvant temozolomide is recommended for all patients ages 18 - 70 with newly diagnosed glioblastoma multiforme who are fit for radical therapy ( ECOG 0 - 1 ) .
Temozolomide may be considered in other situations ( i.e. , ECOG 2 , biopsy only , age > 70 , intermediate grade glioma ) , but there is no high-level evidence to support this decision .
Moreover , there are few data on long-term toxicities or quality of life with temozolomide .
Adjuvant chemotherapy may be an option for younger patients with anaplastic ( grade 3 ) astrocytoma and patients with pure or mixed oligodendroglioma .