***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: 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 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 Optimal adjuvant management of adult low- grade gliomas is controversial . Recently described tumor classification based on molecular subtype has the potential to individualize adjuvant therapy but has not yet been evaluated as part of a prospect i ve trial . Methods Patients aged 18 or older with newly diagnosed World Health Organization grade II low- grade gliomas and gross residual disease after surgical resection were enrolled in the study . Patients received monthly cycles of temozolomide for up to 1 year or until disease progression . For patients with available tissue , molecular subtype was assessed based upon 1p/19q codeletion and isocitrate dehydrogenase-1 R132H mutation status . The primary outcome was radiographic response rate ; secondary outcomes included progression-free survival ( PFS ) and overall survival ( OS ) . Results One hundred twenty patients were enrolled with median follow-up of 7.5 years . Overall response rate was 6 % , with median PFS and OS of 4.2 and 9.7 years , respectively . Molecular subtype was associated with rate of disease progression during treatment ( P<.001 ) , PFS ( P=.007 ) , and OS ( P<.001 ) . Patients with 1p/19q codeletion demonstrated a 0 % risk of progression during treatment . In an exploratory analysis , pretreatment lesion volume was associated with both PFS ( P<.001 ) and OS ( P<.001 ) . Conclusions While our study failed to meet the primary endpoint for objective radiographic response , patients with high-risk low- grade glioma receiving adjuvant temozolomide demonstrated a high rate of radiographic stability and favorable survival outcomes while meaningfully delaying radiotherapy . Patients with 1p/19q codeletion are potential c and i date s for omission of adjuvant radiotherapy , but further work is needed to directly compare chemotherapy with combined modality therapy PURPOSE Radiation Therapy Oncology Group ( RTOG ) 0424 was a phase 2 study of a high-risk low- grade glioma ( LGG ) population who were treated with temozolomide ( TMZ ) and radiation therapy ( RT ) , and outcomes were compared to those of historical controls . This study was design ed to detect a 43 % increase in median survival time ( MST ) from 40.5 to 57.9 months and a 20 % improvement in 3-year overall survival ( OS ) rate from 54 % to 65 % at a 10 % significance level ( 1-sided ) and 96 % power . METHODS AND MATERIAL S Patients with LGGs with 3 or more risk factors for recurrence ( age ≥40 years , astrocytoma histology , bihemispherical tumor , preoperative tumor diameter of ≥6 cm , or a preoperative neurological function status of > 1 ) were treated with RT ( 54 Gy in 30 fractions ) and concurrent and adjuvant TMZ . RESULTS From 2005 to 2009 , 129 evaluable patients ( 75 males and 54 females ) were accrued . Median age was 49 years ; 91 % had a Zubrod score of 0 or 1 ; and 69 % , 25 % , and 6 % of patients had 3 , 4 , and 5 risk factors , respectively . Patients had median and minimum follow-up examinations of 4.1 years and 3 years , respectively . The 3-year OS rate was 73.1 % ( 95 % confidence interval : 65.3%-80.8 % ) , which was significantly improved compared to that of prespecified historical control values ( P<.001 ) . Median survival time has not yet been reached . Three-year progression-free survival was 59.2 % . Grade s 3 and 4 adverse events occurred in 43 % and 10 % of patients , respectively . One patient died of herpes encephalitis . CONCLUSIONS The 3-year OS rate of 73.1 % for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls ( P<.001 ) and the study -hypothesized rate of 65 % PURPOSE Cerebral low- grade gliomas ( LGG ) in adults are mostly composed of astrocytomas , oligodendrogliomas , and mixed oligoastrocytomas . There is at present no consensus in the policy of treatment of these tumors . We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric r and omized trials conducted by the European Organization for Research and Treatment of Cancer ( EORTC ) . The dose-response study is the subject of this article . METHODS AND MATERIAL S For the dose-response trial , 379 adult patients with cerebral LGGs were r and omized central ly at the EORTC Data Center to receive irradiation postoperatively ( or postbiopsy ) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality -controlled radiation therapy . All known parameters with possible influences on prognosis were prospect ively recorded . Conventional treatment techniques were recommended . RESULTS With 343 ( 91 % ) eligible and evaluable patients followed up for at least 50 months with a median of 74 months , there is no significant difference in terms of survival ( 58 % for the low-dose arm and 59 % for the high-dose arm ) or the progression free survival ( 47 % and 50 % ) between the two arms of the trial . However , this prospect i ve trial has revealed some important facets about the prognostic parameters : The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors ( p < 0.0001 ) on multivariate analysis . Other prognostic factors , most of which are known , have now been quantified and confirmed in this prospect i ve study . CONCLUSION The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup , but objective prognostic parameters are recognized . The tumor size or T parameter as used in this study appears to be a very important factor PURPOSE To compare survival and toxicity in adult patients treated with low-dose ( 50.4 Gy/28 fractions ) versus high-dose ( 64.8 Gy/36 fractions ) localized radiation therapy ( RT ) for supratentorial low- grade astrocytoma , oligodendroglioma , and mixed oligoastrocytoma . PATIENTS AND METHODS From 1986 to 1994 , 203 eligible/analyzable 
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Adjuvant therapy with PCV result ed in prolonged PFS and OS in patients with newly diagnosed high-risk LGG .
This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation .
Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV .
In patients with LGG with an unfavorable natural history , such as with intact 1p/19q and wild-type IDH1 , RT/TMZ plus adjuvant TMZ may be the best option .
Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV