***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 A prospect i ve , open-label phase II study was conducted to determine whether donepezil , a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer 's type dementia , improved cognitive functioning , mood , and quality of life ( QOL ) in irradiated brain tumor patients . PATIENTS AND METHODS Thirty-four patients received donepezil 5 mg/d for 6 weeks , then 10 mg/d for 18 weeks , followed by a washout period of 6 weeks off drug . Outcomes were assessed at baseline , 12 , 24 ( end of treatment ) , and 30 weeks ( end of wash-out ) . All tests were administered by a trained research nurse . RESULTS Of 35 patients who initiated the study , 24 patients ( mean age , 45 years ) remained on study for 24 weeks and completed all outcome assessment s. All 24 patients had a primary brain tumor , mostly low- grade glioma . Scores significantly improved between baseline ( pretreatment ) and week 24 on measures of attention/concentration , verbal memory , and figural memory and a trend for verbal fluency ( all P < .05 ) . Confused mood also improved from baseline to 24 weeks ( P = .004 ) , with a trend for fatigue and anger ( all P < .05 ) . Health-related QOL improved significantly from baseline to 24 weeks , particularly , for brain specific concerns with a trend for improvement in emotional and social functioning ( all P < .05 ) . CONCLUSION Cognitive functioning , mood , and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil .  Toxicities were minimal . We are planning a double blinded , placebo-controlled , phase III trial of donepezil to confirm these favorable results From 1990 to 1994 , patients with newly diagnosed malignant gliomas were enrolled and r and omized between hyperfractionated radiation ( HFX ) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily . All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1–3 q8 weeks for 1 year . Patients were stratified by age , KPS , and histology . The primary endpoint was overall survival ( OS ) , with secondary endpoints including progression-free survival ( PFS ) and toxicity . Out of the 712 patients accrued , 694 ( 97.5 % ) were analyzable cases ( 350 HFX , 344 st and ard arm ) . There was no significant difference between the arms on overall acute or late treatment-related toxicity . No statistically significant effect for HFX , as compared to st and ard therapy , was found on either OS , with a median survival time ( MST ) of 11.3 versus 13.1 months ( p = 0.20 ) or PFS , with a median PFS time of 5.7 versus 6.9 months ( p = 0.18 ) . The treatment effect on OS remained insignificant based on the multivariate analysis ( hazard ratio 1.16 ; p = 0.0682 ) . When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme ( MST : 10.3 vs. 11.2 months ; p = 0.34 ) , anaplastic astrocytoma ( MST : 69.8 vs. 50.0 months ; p = 0.91 ) or anaplastic oligodendroglioma ( MST : 92.1 vs. 66.5 months ; p = 0.33 ) . Though this trial provided many invaluable secondary analyses , there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients Background Outcome of low- grade glioma ( LGG , WHO grade II ) is highly variable reflecting molecular heterogeneity of the disease . We compared two different single modality treatment strategies : st and ard radiotherapy ( RT ) versus primary temozolomide ( TMZ ) chemotherapy with the aim of tailoring treatment and identifying predictive molecular factors . Methods 477 patients ( 2005 – 2012 , median FU 48 months ) with a low- grade glioma ( astrocytoma , oligoastrocytoma , oligodendroglioma , WHO grade II ) with at least one high-risk feature ( age > 40 years , progressive disease , tumor > 5 cm or crossing the midline , neurological symptoms ( e.g. focal or mental deficits , increased intracranial pressure or intractable seizures ) ) were , after stratification by chromosome 1p-status , r and omized to either conformal RT ( 50.4 Gy/28 fractions ) or dose-dense TMZ ( 75 mg/m2 daily × 21 days , q28 days , max . 12 cycles ) . R and om treatment allocation was performed online using a minimization technique . A planned analysis was performed after 246 progression events . All analyses are intent to treat . Primary clinical endpoint was progression-free survival ( PFS ) , correlative analyses included molecular markers ( 1p/19q co-deletion , MGMT methylation status , IDH1 + 2 mutations ) . The trial has been registered at the European Trials Registry ( EudraCT 2004 - 002714 - 11 ) and at Clinical Trials.gov ( NCT00182819 ) . Findings Four hundred seventy-seven patients were r and omized . Severe hematological toxicity occurred in 14 % of TMZ-treated patients , infections in 3 % of TMZ-treated patients , and 1 % of RT-treated patients . Moderate to severe fatigue was recorded in 3 % of patients in the RT group and 7 % in the TMZ group . At a median follow-up of 48 months ( IQR:31–56 ) , median PFS was 39 months ( IQR:16–46 ) in the TMZ arm and 46 months ( IQR:19–48 ) in the RT group ( hazard ratio 1.16 , 95 % CI , 0.9–1.5 ; p=0.22 ) . Median OS has not been reached . Exploratory analyses identified treatment-dependent variation in outcome of molecular LGG subgroups ( n=318 ) . Interpretation There was no significant difference in outcome of the overall patient population treated with either radiotherapy alone or TMZ chemotherapy alone . Further data maturation is needed for overall survival analyses and evaluation of the full predictive impact of the molecular subtypes for individualized treatment choices . Funding Merck & Co , Swiss-Bridge Award 2011 , Swiss Cancer League We characterized health-related quality of life ( HRQoL ) , cognitive , and functional status in newly diagnosed glioblastoma ( GBM ) patients receiving Tumor treating fields ( TTFields ) with temozolomide ( TMZ ) versus TMZ alone in a planned interim analysis of a r and omized phase III trial [ NCT00916409 ] , which showed significant improvement in progression-free and overall survival with TTFields/TMZ . After radiotherapy with concomitant TMZ , newly diagnosed GBM patients were r and omized ( 2:1 ) to TTFields/TMZ ( n = 210 ) or TMZ ( n = 105 ) . Interim analysis was performed in 315 patients with ≥18 months of follow-up . HRQoL , a secondary endpoint , was evaluated in per- protocol patient population and expressed as change from baseline ( CFB ) at 3 , 6 , and 9 months for each subscale in the EORTC QLQ-C30/BN20 . Karnofsky performance scores ( KPS ) and Mini-Mental State Examination scores ( MMSE ) were assessed . CFB in HRQoL was balanced in treatment groups at the 12-month time point . Initially , HRQoL improved in patients treated with TTFields/TMZ ( CFB3 : 24 % and CFB6 : 13 % ) versus TMZ ( CFB3 : −7 % and CFB6 : −17 % ) , though this difference was no longer evident at the 9-month point . General scales , including physical and social functioning , showed no difference at 9 and 12 months . TTFields/TMZ group reported higher concerns of “ itchy skin ” . KPS over 12 months was just below 90 in both groups . Cognitive status ( MMSE ) was stable over time . HRQoL , KPS , and MMSE were balanced in both groups over time . There was no preliminary evidence that HRQoL , cognitive , and functional status is adversely affected by the continuous use of TTFields BACKGROUND Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low- grade glioma has been shown to have no significant effect on progression-free survival . If these treatments have a different effect on health-related quality of life ( HRQOL ) , it might affect the choice of therapy . We postulated that temozolomide compromises HRQOL and global cognitive functioning to a lesser extent than does radiotherapy . METHODS We did a prospect i ve , phase 3 , r and omised controlled trial at 78 medical centres and large hospitals in 19 countries . We enrolled adult patients ( aged ≥18 years ) with histologically confirmed diffuse ( WHO grade II ) astrocytoma , oligodendroglioma , or mixed oligoastrocytoma , with a WHO performance status of 2 or lower , without previous chemotherapy or radiotherapy , who needed active treatment other than surgery . We r and omly assigned eligible patients ( 1:1 ) using a minimisation technique , stratified by WHO performance status ( 0 - 1 vs 2 ) , age ( < 40 years vs ≥40 years ) , presence of contrast enhancement on MRI , chromosome 1p status ( deleted vs non-deleted vs indeterminate ) , and the treating medical centre , to receive either radiotherapy ( 50·4 Gy in 28 fractions of 1·8 Gy for 5 days per week up to 6·5 weeks ) or temozolomide chemotherapy ( 75 mg/m2 daily , for 21 of 28 days [ one cycle ] for 12 cycles ) . The primary endpoint was progression-free survival ( results published separately ) ; here , we report the results for two key secondary endpoints : HRQOL ( assessed using the European Organisation for Research and Treatment of Cancer 's [ EORTC ] QLQ-C30 [ version 3 ] and the EORTC Brain Cancer Module [ QLQ-BN20 ] ) and global cognitive functioning ( assessed using the Mini-Mental State Examination [ MMSE ] ) . We did analyses on the intention-to-treat population . This study is closed and is registered at EudraCT , number 2004 - 002714 - 11 , and at Clinical Trials.gov , number NCT00182819 . FINDINGS Between Dec 6 , 2005 , and Dec 21 , 2012 , we r and omly assigned 477 eligible patients  to either radiotherapy ( n=240 ) or temozolomide chemotherapy ( n=237 ) . The difference in HRQOL between the two treatment groups was not significant during the 36 months ' follow-up ( mean between group difference [ averaged over all timepoints ] 0·06 , 95 % CI -4·64 to 4·75 , p=0·98 ) . At baseline , 32 ( 13 % ) of 239 patients who received radiotherapy and 32 ( 14 % ) of 236 patients who received temozolomide chemotherapy  had impaired cognitive function , according to the MMSE scores . After r and omisation , five ( 8 % ) of 63 patients who received radiotherapy and three ( 6 % ) of 54 patients who received temozolomide chemotherapy and who could be followed up for 36 months had impaired cognitive function , according to the MMSE scores . No significant difference was recorded between the groups for the change in MMSE scores during the 36 months of follow-up . INTERPRETATION The effect of temozolomide chemotherapy or radiotherapy  on HRQOL or global cognitive functioning did not differ in patients with low- grade glioma . These results do not support the choice of temozolomide alone over radiotherapy alone in patients with high-risk low- grade glioma . FUNDING Merck Sharp & Dohme-Merck & Co , National Cancer Institute , Swiss Cancer League , National Institute for Health Research , Cancer Research UK , Canadian Cancer Society Research Institute , National Health and Medical Research Council , European Organisation for Research and Treatment of Cancer Cancer Research Fund Background The addition of bevacizumab to temozolomide-based chemoradiotherapy ( TMZ/RT → TMZ ) did not prolong overall survival ( OS ) in patients with newly diagnosed glioblastoma in phase III trials . Elderly and frail patients are underrepresented in clinical trials , but early reports suggested preferential benefit in this population . Patients and methods ARTE was a 2 : 1 r and omized , multi-center , open-label , non-comparative phase II trial of hypofractionated RT ( 40 Gy in 15 fractions ) with bevacizumab ( 10 mg/kg × 14 days ) ( arm A , N = 50 ) or without bevacizumab ( arm 
    Output:
    
Radiotherapy for gliomas with a good prognosis may increase the risk of neurocognitive side effects in the long term ; however the magnitude of the risk is uncertain .