***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 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 patients were r and omized : 101 to low-dose RT , 102 to high-dose RT . Almost half were younger than 40 years , and 95 % had grade 2 tumors . Histologic subtype was astrocytoma ( or mixed oligo-astrocytoma with astrocytoma dominant ) in 32 % of patients and oligodendroglioma ( or oligoastrocytoma with oligodendroglioma dominant ) in 68 % . Tumor diameter was less than 5 cm in 35 % of patients , and 41 % of tumors showed some degree of contrast enhancement . Extent of resection was gross total in 14 % of patients , subtotal in 35 % , and biopsy only in 51 % . RESULTS At the time of the present analysis , 83 patients ( 41 % ) are dead , and median follow-up is 6.43 years in the 120 who are still alive . Survival at 2 and 5 years is nonsignificantly better with low-dose RT ; survival at 2 and 5 years was 94 % and 72 % , respectively , with low-dose RT and 85 % and 64 % , respectively , with high-dose RT ( log rank P = .48 ) . Multivariate analysis identified histologic subtype , tumor size , and age as the most significant prognostic factors . Survival is significantly better in patients who are younger than 40 years and in patients who have oligodendroglioma or oligo-dominant histology . Grade 3 to 5 radiation neurotoxicity ( necrosis ) was observed in seven patients , with one fatality in each treatment arm . The 2-year actuarial incidence of grade 3 to 5 radiation necrosis was 2.5 % with low-dose RT and 5 % with high-dose RT . CONCLUSION This phase III prospect i ve r and omized trial of low- versus high-dose radiation therapy for adults with supratentorial low- grade astrocytoma , oligodendroglioma , and oligoastrocytoma found somewhat lower survival and slightly higher incidence of radiation necrosis in the high-dose RT arm . The most important prognostic factors for survival are histologic subtype , tumor size , and age . The study design of the ongoing intergroup trial in this population will be discussed Diffuse infiltrative low grade gliomas ( LGG ) account for approximately 15 % of all gliomas . The prognosis of LGG differs between high-risk and low-risk patients notwithst and ing varying definitions of what constitutes a high-risk patient . Maximal safe resection optimally is the initial treatment . Surgery that achieves a large volume resection improves both progression-free and overall survival . Based on results of three r and omized clinical trials ( RCT ) , radiotherapy ( RT ) may be deferred in patients with low-risk LGG ( defined as age < 40 years and having undergone a complete resection ) , although combined chemoradiotherapy has never been prospect ively evaluated in the low-risk population . The recent RTOG 9802 RCT established a new st and ard of care in high-risk patients ( defined as age > 40 years or incomplete resection ) by demonstrating a nearly twofold improvement in overall survival with the addition of PCV ( procarbazine , CCNU , vincristine ) chemotherapy following RT as compared to RT alone . Chemotherapy alone as a treatment of LGG may result in less toxicity than RT ; however , this has only been prospect ively studied once ( EORTC 22033 ) in high-risk patients . A challenge remains to define when an aggressive treatment improves survival without impacting quality of life ( QoL ) or neurocognitive function and when an effective treatment can be delayed in order to preserve QoL without impacting survival . Current WHO histopathological classification is poorly predictive of outcome in patients with LGG . The integration of molecular biomarkers with histology will lead to an improved classification that more accurately reflects underlying tumor biology , prognosis , and hopefully best therapy PURPOSE There is no consensus on the treatment strategy for adult patients with cerebral low- grade glioma . The diagnosis and primary treatment are usually undertaken by surgery . Some investigators doubt the efficacy of postoperative radiotherapy ( RT ) , whereas others advise routine postoperative RT . We report the primary results of a multicenter r and omized trial on this controversy . METHODS AND MATERIAL S From 24 European centers , 311 adult patients with low- grade glioma were r and omized central ly after surgery from March 1986 through September 1997 , between the two arms of the trial . The irradiated group received 54 Gy in 6 weeks . The other patients did not receive any treatment after surgery until the tumor showed progression , defined as clinical -neurologic deterioration and evidence of progressive tumor on imaging . RESULTS Of 290 eligible and assessable patients ( 93 % ) , the irradiated group showed a significant ( log-rank p = 0.02 ) improvement in time to progression but not in overall survival , with a median follow-up of 5 years . The 5-year estimate was , respectively , 63 % vs. 66 % ( overall survival ) and 44 % vs. 37 % ( time to progression ) for the treated and control arms . Different treatment modalities , including RT , were undertaken for the 85 controls when a progressive tumor was noted . CONCLUSION Early postoperative conventional RT such as that used for this protocol appears to improve the time to progression or progression-free survival , but not overall survival , for patients with low- grade glioma Glioblastomas ( GBM ) may originate de novo ( primary ) , or following transformation from a lower grade glioma ( secondary ) , and it has been postulated that these tumors may have different biological behaviors . We performed a correlative analysis involving 204 patients with glioma treated prospect ively on NCCTG clinical trials . Central pathology review of tumor tissues taken at the time of initial diagnosis and at recurrence were performed in all patients . Tumors progressed from low ( WHO grade 2 ) to high ( grade 3–4 ) at recurrence in 45 % low grade oligodendroglioma patients , in 70 % with low grade oligoastrocytoma , and 74 % with low grade astrocytoma ( P = 0.031 ) . Median overall survival ( OS ) from initial diagnosis varied by histology : oligodendroglioma , 8.8 years ; ( 95 % CI 5.7–10.2 ) ; oligoastrocytoma , 4.4 years ( 95 % CI 3.5–5.6 ) ; astrocytoma grade 2 3.1 years ( astrocytoma grade 2–4 , 2.1 years ) ( 95 % CI 1.7–2.5 , P < 0.001 ) . Mean time to recurrence ( TTR ) also varied between patients with de novo GBM , those secondary GBM , and those that remained non-GBM at recurrence ( 1.1 ± 1.1 vs. 2.9 ± 1.8 vs. 4.0 ± 2.9 years , respectively , P < 0.001 ) . Median OS from time of recurrence also varied between these three categories ( 0.7 years , 95 % CI : 0.5–1.1 vs. 0.6 years , CI : 0.5–1.0 vs. 1.4 years , 95 % CI : 1.1–2.0 , respectively ) ( P < 0.001 ) . At time of relapse , transformation to higher grade is frequent in low grade pure and mixed astrocytomas , but is observed in less than half of those with low grade oligodendroglioma . From time of recurrence , OS was not significantly different for those with primary versus secondary GBM , and it may thus be reasonable include patients with secondary GBM in clinical therapeutic trials for recurrent disease BACKGROUND Pilocytic astrocytoma is a rare tumor in adults . This report is of a prospect i ve clinical trial with long-term follow-up . METHODS Between 1986 and 1994 , 20 eligible 
    Output:
    
This study found that early postoperative radiotherapy is associated with an increase in time to progression compared to observation ( and delayed radiotherapy upon disease progression ) for people with LGG but does not significantly improve overall survival ( OS ) .
People in both cohorts who were free from tumour progression showed no differences in cognitive deficit , focal deficit , performance status , and headache after one year .
Early radiation therapy was associated with the following adverse effects : skin reactions , otitis media , mild headache , nausea , and vomiting .
People with LGG who undergo early radiotherapy  showed an increase in time to progression compared with people who were observed and had radiotherapy at the time of progression .
There was no significant difference in overall survival between people who had  early  versus  delayed radiotherapy ; however , this finding may be due to the effectiveness of rescue therapy with radiation in the control arm .
People who underwent early radiation had better seizure control at one year than people who underwent delayed radiation .
There were no cases of radiation-induced malignant transformation of LGG .