***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 Recently , the RTOG and ECOG concluded a joint r and omized study on malignant gliomas that was in progress for the past five years . A total of 626 patients entered this protocol . Sixty‐seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial . The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone . The four options were : ( 1 ) control radiation ; 6000 rad/6–7 weeks to whole brain ; ( 2 ) a higher radiation dose ; Control dose plus a booster dose of 1000 rad/1–2 weeks to the tumor ; ( 3 ) control radiation dose plus BCNU ( 80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks ) ; ( 4 ) Control radiation dose plus combination methyl‐CCNU ( 125 mg/m2/day orally X 1 and repeat methyl‐CCNU every 8 weeks ) , and DTIC ( 150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks ) . All pertinent patient characteristics were studied and several important prognostic factors have been identified . Notably , age , histologic type ( Astrocytoma with anaplastic foci , versus glioblastoma multiforme ) , initial performance status , time since first symptoms and presence or absence of seizure . At this time , it appeared that there was no treatment option which was significantly better than the control . The study identified that age was the most important prognostic factor . Patients who were younger than age 40 years had an 18‐month survival of 64 % , patients who were age 40–60 years had an 18‐month survival of 20 % , and patients who were older than age 60 had an 18‐month survival of 8 % . The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan .  Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma . In further evaluation of any beneficial effect of chemotherapy , it was identified that only among the 40–60‐year‐old groups , BCNU treated patients appeared to have significantly increased survival than patients in the control groups ( P = 0.01 , one‐sided ) . Similarly , methyl‐CCNU + DTIC was suggestively better than the control ( P = 0.08 , one‐sided ) . The higher radiation dose , 7000 rad/8–9 weeks appeared to give no significantly better survival over the control dose option . Both BCNU and methyl‐CCNU + DTIC  produced some toxicity . The combination of methyl‐CCNU + DTIC was more toxic  than BCNU , producing severe or worse thrombocytopenia in 23 % of the patients as compared to 6 % on BCNU A total of 474 adult patients with malignant glioma ( astrocytoma ) grade 3 or 4 were r and omised into an MRC study ( BR2 ) comparing 45 Gy ( in 20 fractions over 4 weeks ) with 60 Gy ( in 30 fractions over 6 weeks ) of radiotherapy given post-operatively . Using 2:1 r and omisation , 318 patients were allocated the 60 Gy course and 156 the 45 Gy course . Adjuvant chemotherapy was not given . The results show that a 60 Gy course produces a modest lengthening of progression-free and overall survival . They suggest a statistically significant prolongation of median survival from 9 months in the 45 Gy group to 12 months in the 60 Gy group ( hazard ratio = 0.75 , chi 2 = 7.36 , d.f . = 1 , P = 0.007 ) . Over 80 % of patients reported no morbidity from the radiotherapy , and there was no evidence of increased short-term morbidity in the higher dose group . Late morbidity was not assessed . A prognostic index defined in a previous MRC study was vali date d in this new cohort . It identifies a group of patients ( 20 % of the total ) with a 2 year survival rate of 28 % ( 95 % confidence interval 19 % to 38 % ) . It was apparent that the survival advantage to the higher dose was maintained even in the poorest prognostic groups defined by this index 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 A prospect i ve , r and omized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas . All patients were irradiated with 6,000 rads after possibly radical removal of tumors . CCNU administration in the doses of 100 mg/sq m of body surface every 6 - 8 weeks following surgery proved to have no significant effect on the survival of patients . The median survival time in patients receiving radiation therapy alone was 61 + /- 7 weeks , while in those receiving additional chemotherapy was 56 + /- 4 weeks . Tumor histological malignancy and patients age were found to be the only important prognostic factors , irrespective of the treatment modality 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 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 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 .  Dianhydrogalactitol may play an important role ( in conjunction with radiation therapy ) in the initial treatment of patients with supratentorial glioma . Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma Within 3 weeks of 
    Output:
    
There was no evidence that the effect of chemotherapy  differed in any group of patients defined by age , sex , histology , performance status , or extent of resection .