***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: Despite similar morphological aspects , anaplastic oligodendroglial tumors ( AOTs ) form a heterogeneous clinical subgroup of gliomas . The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas . To identify new genomic regions associated with prognosis , 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization . The data were processed using a binary tree method . Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis ( p < 0.0001 ) . Type I tumors ( 25 % ) were characterized by : ( 1 ) an EGFR amplification , ( 2 ) a poor prognosis , ( 3 ) a higher rate of necrosis , and ( 4 ) an older age of patients . Type II tumors ( 21.7 % ) had : ( 1 ) loss of prognostic BACs located on 1p tightly associated with 19q deletion , ( 2 ) a longer survival , ( 3 ) an oligodendroglioma phenotype , and ( 4 ) a frontal location in brain . Type III AOTs ( 11.7 % ) exhibited : ( 1 ) a deletion of prognostic BACs located on 21q , and ( 2 ) a short survival . Finally , type IV tumors ( 41.7 % ) had different genomic patterns and prognosis than type I , II and III AOTs . Multivariate analysis showed that genomic type provides additional prognostic data to clinical , imaging and pathological features . Similar results were obtained in the cohort of 45 central ly review ed – vali date d cases of AOTs . Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs PURPOSE This is one of a few studies that have explored the value of baseline symptoms and  health-related quality of life ( HRQOL )  in predicting survival in patients with brain cancer . PATIENTS AND METHODS Baseline  HRQOL scores ( from the European Organisation for Research and Treatment of Cancer [ EORTC ] Quality of Life Question naire C30 and the EORTC Brain Cancer Module ) were examined in 247 patients with anaplastic oligodendrogliomas to determine the relationship with overall survival by using Cox proportional hazards regression models .  Refined techniques as the bootstrap resampling procedure and the computation of C indexes and R2 coefficients were used to explore the stability of the models as well as better assess the potential benefit of using HRQOL to predict survival in clinical practice and research . RESULTS Classical analysis controlled for major clinical prognostic factors selected emotional functioning ( P = .0016 ) , communication deficit ( P = .0261 ) , future uncertainty ( P = .0481 ) , and weakness of legs ( P = .0001 ) as statistically significant prognostic factors of survival . However , several issues question the validity of these findings and no single model was found to be preferable over all others . C indexes , which estimate the probability of a model to correctly predict which patient among a r and omly chosen pair of patients will survive longer , and R2 coefficients , which measure the proportion of variability explained by the model , did not exhibit major improvement when adding selected or all HRQOL scores to clinical factors . CONCLUSION While classical techniques lead to positive results , more refined analyses suggest that baseline HRQOL scores add relatively little to clinical factors to predict survival . These results may have implication s for future use of HRQOL as a prognostic factor for patients with cancer PURPOSE O6-methylguanine-methyltransferase ( MGMT ) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy ( RT ) . It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine , lomustine , and vincristine ( PCV ) chemotherapy in patients with anaplastic oligodendroglial tumors ( AOT ) . PATIENTS AND METHODS In the European Organisation for the Research and Treatment of Cancer study 26951 , 368 patients with AOT were r and omly assigned to either RT alone or to RT followed by adjuvant PCV . From 165 patients of this study , formalin-fixed , paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis . This was investigated with methylation specific multiplex ligation-dependent probe amplification . RESULTS In 152 cases , an MGMT result was obtained , in 121 ( 80 % ) cases MGMT promoter methylation was observed . Methylation strongly correlated with combined loss of chromosome 1p and 19q loss ( P = .00043 ) . In multivariate analysis , MGMT promoter methylation , 1p/19q codeletion , tumor necrosis , and extent of resection were independent prognostic factors . The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival . In tumors diagnosed at central pathology review as glioblastoma , no prognostic effect of MGMT promoter methylation was observed . CONCLUSION In this study , on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy . The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The increased chemosensitivity of oligodendroglial tumors has been associated with loss of heterozygosity ( LOH ) on chromosomes 1p and 19q . Other clinical and molecular factors have also been identified as being prognostic and predictive for treatment outcome . Seventy-seven patients with anaplastic oligodendroglioma ( AO ) or anaplastic oligoastrocytoma ( AOA ) , treated in Beijing Tiantan Hospital from 2006 through 2008 , were review ed . LOH 1p , LOH 19q , IDH1 mutation , O(6)-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation , and protein expression level of MGMT , P53 , EGFR , and Ki-67 were evaluated . Age at diagnosis , LOH 1p and 19q , IDH1 mutation , P53 expression level , reoperation when progression , and adjuvant chemotherapy  were statistically significant factors for overall survival ( OS ) in univariate analysis . Further multivariate analysis showed that age at diagnosis ( P = .010 ) , LOH 1p and 19q ( P = .016 ) , IDH1 mutation ( P = .011 ) , and reoperation after progression ( P = .048 ) were independent predictors for longer survival in these patients . Nonr and om associations were found between LOH 1p and LOH 19q , MGMT promoter methylation and LOH 1p or 19q , IDH1 mutation and LOH 1p and 19q , IDH1 mutation and MGMT promoter methylation , whereas mutual exclusion was found between MGMT promoter methylation and MGMT expression level . The present study confirmed that age at diagnosis , LOH 1p and 19q , IDH1 mutation , and reoperation after progression were independent significant prognostic factors for patients with anaplastic oligodendroglial tumors . Inter-relationship between LOH 1p , LOH 19q , IDH1 mutation , MGMT promoter methylation , and MGMT expression level were also revealed . Future clinical trials for AO and AOA should consider the molecular alterations of patients PURPOSE The st and ard of care for anaplastic gliomas is surgery followed by radiotherapy . The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas . PATIENTS AND METHODS Patients ( N = 318 ) were r and omly assigned 2:1:1 ( A : B1:B2 ) to receive conventional radiotherapy ( arm A ) ; procarbazine , lomustine ( CCNU ) , and vincristine ( PCV ; arm B1 ) ; or temozolomide ( arm B2 ) at diagnosis . At occurrence of unacceptable toxicity or disease progression , patients in arm A were treated with PCV or temozolomide ( 1:1 r and om assignment ) , whereas patients in arms B1 or B2 received radiotherapy . The primary end point was time to treatment failure ( TTF ) , defined as progression after radiotherapy and one chemotherapy in either sequence . RESULTS Patient characteristics in the intention-to-treat population ( n = 274 ) were balanced between arms . All histologic diagnoses were central ly confirmed . Median TTF ( hazard ratio [ HR ] = 1.2 ; 95 % CI , 0.8 to 1.8 ) , progression-free survival ( PFS ; HR = 1.0 ; 95 % CI , 0.7 to 1.3 , and overall survival ( HR = 1.2 ; 95 % CI , 0.8 to 1.9 ) were similar for arms A and B1/B2 . Extent of resection was an important prognosticator . Anaplastic oligodendrogliomas and oligoastrocytomas share the same , better prognosis than anaplastic astrocytomas . Hypermethylation of the O(6)-methylguanine DNA-methyltransferase ( MGMT ) promoter ( HR = 0.59 ; 95 % CI , 0.36 to 1.0 ) , mutations of the isocitrate dehydrogenase ( IDH1 ) gene ( HR = 0.48 ; 95 % CI , 0.29 to 0.77 ) , and oligodendroglial histology ( HR = 0.33 ; 95 % CI , 0.2 to 0.55 ) reduced the risk of progression . Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm . CONCLUSION Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas . IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas , with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation Purpose : Recent studies have shown the prognostic significance of IDH1 mutations in glioma . It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy . We determined the effect of IDH1 mutations on progression-free survival and overall survival ( OS ) , and its correlation with other clinical and molecular features in the prospect i ve r and omized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine , 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea , and vincristine ( PCV ) in anaplastic oligodendroglioma . Experimental Design : IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments . MGMT promoter methylation was assessed using methylation-specific multiplex ligation – dependant probe amplification based on methylation-sensitive restriction analysis . Loss of chromosomes 1p , 19q , 10 , and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization . Results : From 159 patients , sufficient material was available for IDH1 analysis . In 151 and 118 of these patients , respectively , the 1p/19q status and the MGMT promoter methylation status were known . In 73 cases ( 46 % ) , an IDH1 mutation was found and only one IDH2 mutation was identified . The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation , and inversely correlated with loss of chromosome 10 , EGFR amplification , polysomy of chromosome 7 , and the presence of necrosis . IDH1 mutations were found to be prognostic in the radiotherapy- and the radiotherapy/PCV-treated patients , for both progression-free survival and OS . With Cox proportional hazard modeling for OS with stepwise selection , IDH1 mutations and 1p/19q codeletion but not MGMT promoter methylation were independent prognostic factors . Conclusion : In this homogeneously treated group of anaplastic oligodendroglioma patients , the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy .  IDH1 mutations were strongly associated with 1p/19q codeletion 
    Output:
    
AUTHORS ' CONCLUSIONS Early PCV , either before or after RT , appears to improve OS of participants with AO or AOA .
Use of biomarkers including codeletion of chromosomes 1p and 19q with or without IDH-1 or -2 mutation identify a subset of people with increased sensitivity to combined PCV and RT .
However , PCV was associated with significant grade 3 and 4 toxicities , and whether temozolomide can be substituted for this remains unclear