***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: Efforts to improve local control and survival by increasing the dose of once‐daily radiation therapy beyond 70 Gray ( Gy ) for patients with malignant gliomas have as yet been unsuccessful . Hyperfractionated radiation therapy ( HF ) should allow for delivery of a higher total dose without increasing normal tissue late effects , whereas accelerated hyperfractionated radiation therapy ( AHF ) may minimize tumor re population by shortening overall treatment time . The Radiation Therapy Oncology Group ( RTOG ) conducted a r and omized Phase I/II study of escalating doses of HF and AHF with carmustine ( bis‐chloroethyl nitrosourea [ BCNU ] ) for adults with supratentorial glioblastoma multiforme ( GBM ) or anaplastic astrocytoma ( AA ) . Primary study endpoints were overall survival and acute and chronic treatment‐related toxicity Thirty-two patients prospect ively identified as having poor prognosis high grade glioma , with a MRC prognostic score > 25 , were treated with a short palliative course of radiotherapy . A total dose of 36 Gy in 12 fractions was given to the tumour , including oedema and a 2 cm margin , using parallel pair fields prescribed to the midplane with MV photons .  Twenty-eight patients completed treatment as planned , while four failed to complete treatment because of clinical deterioration or death . The median survival for the whole group was 16 weeks , with seven patients surviving for more than 6 months . Approximately two-thirds of the surviving patients remained at home after the completion of treatment . A matched case-control comparison with data from patients in previous MRC studies who had received a 6-week course of treatment shows that , for this group of patients , survival is similar ( hazard ratio 1.0 ; 95 % confidence interval ( CI ) 0.57 - 1.74 ) . The 95 % CI for the difference in median survival time excludes a reduction of more than 7 weeks with the 36 Gy course . This shortened radiotherapy regimen may therefore be satisfactory for most poor prognosis patients . However , patients with performance status 3 gained little benefit from treatment , and it is suggested that this group should have a trial period of assessment at home prior to a decision on treatment We used " high-dose " metronidazole , an " in vitro " and " in vivo " specific radiosensitizer of hypoxic cells , in a controlled trial to evaluate possible enhancement of radiation effect in patients with supratentorial glioblastomas . Thirty-six patients were stratified according to functional level and r and omly allocated within two weeks of operation to one of two therapeutic groups : Group 1 , radiation alone ; and Group 2 , radiation as in Group 1 but with high-dose metronidazole . We examined survival with the Kaplan-Meier probability plot and non-parametric tests . Patients in Group 2 had a 4 1/2-month delay between relapse and subsequent death ( P = 0.02 ) . This shift of the survival curves suggests a delay in the time of tumor regrowth consistent with the ability of metronidazole to make the hypoxic tumor cells less radioresistant . Nitroimidazole derivatives may be useful radiosensitizers in human solid tumors A r and omised pilot study is reported of d(15)+Be neutrons compared with 4 MV photons in the treatment of patients with astrocytoma . Sixteen patients were treated by photons and 18 by neutrons .  Both treatments were well tolerated by patients . The median survival after photons was 11 months and after neutrons , 7 months . It was demonstrated that four of nine patients treated by neutrons had evidence at autopsy of radiation-induced brain damage . All had residual cancer . No patient treated by photons had signs of radiation-related morbidity . The trial was , therefore , discontinued prematurely 102 patients entered a multicentric r and omized study from May 1978 till December 1980 . After an operative removal of a supratentorial astrocytoma grade 3 or 4 all patients were treated by radiotherapy of the whole brain with 40 Gy , and after a rest of 1 to 2 weeks with a boost dose of 20 Gy to the tumor region . By r and omization the patients got misonidazole ( 400 mg/m2 ) to each of the 30 fractions or a placebo . The overall tolerance was good . A mild transient peripheral neuropathy was seen only in 2 patients . The median of survival time was not significantly different for both groups with 16 months ( grade 3 ) and 10 months ( grade 4 ) . Thus a radiosensitizing effect of misonidazole was not proven 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 The results are reported of a small clinical trial carried out to assess the potential value of the hypoxic cell radiosensitizer misonidazole in the radiation treatment of Grade 3 and 4 supratentorial astrocytomas . A total of 55 patients were r and omly allocated to one of 3 treatment groups . No significant differences were seen between the median survivals of patients in the 2 control radiation groups and that of the third group in which oral misonidazole at a dose of 3 g/m2 preceded each of 4 weekly radiation doses . Possible reasons why no improvement was seen are discussed in detail PURPOSE To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma , where acceleration is used as a means of delivering a shortened course of radical radiotherapy . PATIENTS AND METHODS Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with  accelerated radiotherapy ( 55 Gy in 34 fractions twice daily ) , to planning target volume ( PTV ) defined as enhancing tumour and a 3 cm margin . All had histologically confirmed high grade glioma ( 53 anaplastic astrocytoma , 137 glioblastoma multiforme , 4 gliosarcoma , 5 gemistocytic astrocytoma , 12 high grade astrocytoma not otherwise specified ) . The mean Karnofsky performance status ( KPS ) was 90 and median age was 54 years ( range 19 - 77 ) . RESULTS Of 211 patients entered , 201 were able to complete radiotherapy ; 39 patients ( 19 % ) had deterioration in KPS during radiotherapy and this was transient in 11 . Median survival of 211 patients was 10 months with 1 year , 2 year , and 3 year survival probabilities of 38 % , 14 % , and 8 % respectively . Age and extent of excision were independent prognostic factors for survival . Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference . CONCLUSION Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma . The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity . While acceleration of conventional dose irradiation could be tested in r and omised studies , it is unlikely this approach would result in a clinical ly meaningful survival benefit . Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma . However , it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined , particularly in terms of impact on quality of life , true patient preference , and health economic considerations Elderly patients with malignant glioma have a poorprognosis and the benefit of st and ard radical radiotherapyis equivocal . Twenty-two percent of the adult referralbase with malignant glioma at our centre isof age 70 years or greater . A phaseII study was undertaken to determine if ashorter course of therapy yields a comparable mediansurvival to radical radiotherapy and thus constitutes anappropriate investigational palliative regimen.25 patients were accrued between 1988–1995 , all ofwhom had histologically proven malignant glioma , 23 glioblastomamultiforme and 2 anaplastic astrocytoma . The median agewas 73 ( range 70–78 ) and median Karnofsky PerformanceStatus ( KPS ) was 70 . 40 % had a stereotacticbiopsy only for diagnosis .  Radiotherapy was delivered tolimited fields to a dose of 37.5 Gyin 15 daily fractions over 3 weeks . Anintention-to-treat analysis was undertaken with survival determined from date of initial consultation . The median survival ofthe whole group was 8.0 months ( 95 % CI4.8–9.6 ) . Patients with good performance status ( KPS > 70 ) had a median survival of 10.4 months(95 % CI 9.6–14.7).37.5 Gy in 15 daily fractions appears toyield comparable median survival to that of otherseries of radical radiotherapy . A phase III study of this regimen is recommended in investigating optimalpalliation of elderly malignant glioma patients 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 In Brain Tumor Cooperative Group Study 77 - 02 , eleven institutions r and omized 
    Output:
    
Radiation dose intensification and radiation sensitizer approaches have not demonstrated superior survival rates compared with conventionally fractionated doses of 50 - 60 Gy .
Post-operative external beam radiotherapy is recommended as st and ard therapy for patients with malignant glioma .
For patients older than age 70 , preliminary data suggest that the same survival benefit can be achieved with less morbidity using a shorter course of radiotherapy .