***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: 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 BACKGROUND It is controversial if distant recurrence of glioblastoma is more common after temozolomide ( TMZ ) concurrent with radiotherapy ( RT ) . Optimal therapy for patients with recurrent disease after RT/TMZ  is unclear . Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival . METHODS We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003 - 2007 . Statistical analyses included Kaplan-Meier method for survival , and multivariate Cox proportional hazards model for the effect of salvage treatment on survival . RESULTS 58 patients ( 86.6 % ) recurred locally ; 9 patients ( 13.4 % ) had a distant non-contiguous focus of new disease . Median survival(MS ) was 17 months ; median time-to-progression(TTP ) 6.8 months . The local and distant groups had comparable prognostic factors . There was no difference in MS(p=0.35 ) or TTP(p=0.95 ) by location of recurrence . At relapse , 26 patients ( 38.8 % ) received continuous , dose-intense TMZ , 24(35.8 % ) other therapy(4.5 % RT ; 20.9 % lomustine+/-procarbazine ; 4.5 % etoposide ; 1.5 % conventional TMZ ; 4.5 % TMZ then lomustine ) , and 17(25.4 % ) were untreated . Dose-intense TMZ was associated with prolonged MS compared to all other patients ( 21.5 months vs. 12.4 months , p=0.019 , HR=3.86 , 95%CI : 1.81 - 8.22 ) and similar to MS with other chemotherapy regimens(18.8 months , p=0.40 , HR=1.30 , 95 % CI : 0.65 - 2.61 ) . CONCLUSION The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local . Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma .  Overall survival is similar to other conventional salvage regimens ; however TMZ may be better tolerated . This study is limited by its retrospective nature and potential selection bias . Prospect i ve controlled studies are needed PURPOSE In patients with newly diagnosed glioblastoma multiforme , to determine whether cisplatin plus carmustine ( BCNU ) administered before and concurrently with radiation therapy ( RT ) improves survival compared with BCNU and RT and whether survival using accelerated RT ( ART ) is equivalent to survival using st and ard RT ( SRT ) . PATIENTS AND METHODS After surgery , patients were stratified by age , performance score , extent of surgical resection , and histology ( glioblastoma v gliosarcoma ) and then r and omly assigned to arm A ( BCNU plus SRT ) , arm B ( BCNU plus ART ) , arm C ( cisplatin plus BCNU plus SRT ) , or arm D ( cisplatin plus BCNU plus ART ) . RESULTS Four hundred fifty-one patients were r and omly assigned , and 401 were eligible .  Frequent toxicities included myelosuppression , vomiting , sensory neuropathy , and ototoxicity and were worse with cisplatin . There was no difference in toxicity between SRT and ART .  Median survival times and 2-year survival rates for patients who received BCNU plus RT ( arms A and B ) compared with cisplatin , BCNU , and RT ( arms C and D ) were 10.1 v 11.5 months , respectively , and 11.5 % v 13.7 % , respectively ( P = .19 ) . Median survival times and 2-year survival rates for patients who received SRT ( arms A and C ) compared with ART ( arms B and D ) were 11.2 v 10.5 months , respectively , and 13.8 % v 11.4 % , respectively ( P = .33 ) . CONCLUSION Cisplatin administered concurrently with BCNU and RT result ed in more toxicity but provided no significant improvement in survival .  SRT and ART produced similar toxicity and survival In Brain Tumor Cooperative Group Study 77 - 02 , eleven institutions r and omized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery : conventional radiotherapy ( 6000 cGy in 30 - 35 fractions ) + BCNU , conventional radiotherapy + streptozotocin , hyperfractionated ( twice daily ) radiotherapy ( 6600 cGy in 60 fractions ) + BCNU , and conventional radiotherapy with misonidazole followed by BCNU . Data were analyzed for the total r and omized population and for the 557 patients ( 86 % with glioblastoma multiforme ) who met protocol eligibility specifications ( including confirmed histopathology on central review ) .  Median survival was approximately 10 months following r and omization . Overall there was no statistically significant difference in survival among the four groups . Among non-glioblastoma patients , the misonidazole group appeared to have poor survival . Peripheral neuropathy was a dose-limiting toxicity with misonidazole . It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma 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 study of 108 patients with cerebral malignant gliomas was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie Memorial Center in Kraków . 44 patients with histologically proven glioblastoma multiforme and 64 patients with anaplastic astrocytoma received postoperative radiotherapy . Patients were r and omized to two treatment arms : Conventionally Fractionated Radiotherapy ( CFR ) and Hypofractionated Radiotherapy ( HF ) . In the CFR group , the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks , then a 10 Gy ‘ boost ’ in 5 fractions in 5 days was delivered to the site of the primary lesion . In the HF group , there were 3 courses of irradiation separated by a one month interval . In each of the two first series the patients received 20 Gy in 5 fractions in 5 days to the whole brain , and in the third course , 10 Gy ‘ boost ’ in 5 days was delivered as in the CFR regimen . The tolerance to treatment has been found to be good in both groups . The 2-year actuarial survival rate for patients with anaplastic astrocytoma was 22 % for CFR and 18 % for HF . Patients with glioblastoma multiforme treated with HF had a better prognosis in comparison to the CFR group with the two-year actuarial survival rates being 23 % and 10 % , respectively . This difference is statistically significant at the 0.05 level Summary Purpose : To assess the effect of cisplatin ( CDDP ) plus concurrent radiation therapy on hearing loss . Methods : 451 patients with glioblastoma multiforme ( GBM ) were r and omly assigned after surgery to : Arm A : Carmustine ( BCNU ) + st and ard radiation therapy ( SRT ) ; Arm B : BCNU + accelerated radiation therapy ( ART : 160 cGy twice daily for 15 days ) ; Arm C : CDDP + BCNU + SRT ; or Arm D : CDDP + BCNU + ART . Patients on arms C and D received  audiograms  at baseline , and prior to the start of 
    Output:
    
Although these trials may not have completely reported adverse effects , they did not note any significant toxicity attributable to radiation .
Attrition , performance , detection and reporting bias for the outcome of overall survival was low .
There was unclear attrition , performance , detection and reporting bias relating to the outcomes of adverse effects , progression free survival and quality of life .
AUTHORS ' CONCLUSIONS Postoperative conventional daily radiotherapy improves survival for adults with good performance status and HGG as compared to no postoperative radiotherapy .
Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy , particularly for individuals aged 60 and older with glioblastoma .
There is insufficient data regarding hyperfractionation versus conventionally fractionated radiation ( without chemotherapy ) and for accelerated radiation versus conventionally fractionated radiation ( without chemotherapy).There are HGG subsets who have poor prognosis even with treatment ( e.g. glioblastoma histology , older age and poor performance status ) .
No r and omised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these poor prognosis patients