***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 Morbidity and mortality are high in young children with medulloblastoma who receive craniospinal radiotherapy .  We aim ed to assess whether adjuvant treatment with protracted chemotherapy alone could replace radiotherapy . METHODS We enrolled 79 children aged younger than 5 years who had had surgical resection of medulloblastoma onto a multicentre trial . Patients were treated with combination chemotherapy , which did not include methotrexate , for more than 16 months irrespective of the extent of disease . Early postoperative imaging defined three groups : R0M0 ( no residual disease , no metastasis ) , R1M0 ( radiological residual disease alone ) , and RXM+ ( presence of metastases ) . Patients who did not relapse did not receive radiotherapy . Patients who relapsed or had disease progression received salvage treatment , which consisted of high-dose chemotherapy and stem-cell transplantation followed by local or craniospinal radiotherapy . For children classified as R0M0 , the primary endpoint was 5-year overall survival and the secondary endpoint was 5-year progression-free survival . For children classified as R1M0 or RXM+ , the primary endpoint was best radiological response and the secondary endpoints were 5-year overall survival and 5-year progression-free survival . Analyses were done by intention to treat . FINDINGS Two of 15 patients classified as RXM+ and four of 17 patients classified as R1M0 had a complete radiological response . 5-year progression-free survival was 29 % ( 95 % CI 18 - 44 ) in the R0M0 group , 6 % ( 1 - 27 ) in the R1M0 group , and 13 % ( 4 - 38 ) in the RXM+ group . 5-year overall survival was 73 % ( 59 - 84 ) in the R0M0 group , 41 % ( 22 - 64 ) in the R1M0 group , and 13 % ( 4 - 38 ) in the RXM+ group . In the R0M0 group , 5-year progression-free survival was 41 % ( 26 - 58 ) for the 34 patients who underwent gross total resection compared with 0 % for the 13 patients who had subtotal resection ( relative risk 2.7 [ 1.3 - 5.6 ] , p=0.0065 ) . INTERPRETATION Conventional chemotherapy alone can be used to cure children with non-metastatic medulloblastoma who have gross total resection confirmed by early radiological assessment , but is not sufficient for treatment of those with metastatic or incompletely resected medulloblastoma . Salvage treatment followed by posterior-fossa radiotherapy can effectively treat local relapses or progression This paper describes some of the statistical considerations in the intent-to-treat design and analysis of clinical trials . The pivotal property of a clinical trial is the assignment of treatments to patients at r and om . R and omization alone , however , is not sufficient to provide an unbiased comparison of therapies . An additional requirement is that the set of patients contributing to an analysis provides an unbiased assessment of treatment effects , or that any missing data are ignorable . A sufficient condition to provide an unbiased comparison is to obtain complete data on all r and omized subjects . This can be achieved by an intent-to-treat design wherein all patients are followed until death or the end of the trial , or until the outcome event is reached in a time-to-event trial , irrespective of whether the patient is still receiving or complying with the assigned treatment . The properties of this strategy are contrasted with those of an efficacy subset analysis in which patients and observable patient data are excluded from the analysis on the basis of information obtained postr and omization . I describe the potential bias that can be introduced by such postr and omization exclusions and the pursuant effects on type I error probabilities . Especially in a large study , the inflation in type I error probability can be severe , 0.50 or higher , even when the null hypothesis is true . St and ard statistical methods for the analysis of censored or incomplete observations all require the assumption of missing at r and om to some degree , and none of these methods adjust for the potential bias introduced by post hoc subset selection . Nor is such adjustment possible unless one posits a model that relates the missing observations to other observed information for each subject-models that are inherently untestable . Further , the subset selection bias is confounded with the subset-specific treatment effect , and the two components are not identifiable without additional untestable assumptions . Methods for sensitivity analysis to assess the impact of bias in the efficacy subset analysis are described . It is generally believed that the efficacy subset analysis has greater power than the intent-to-treat analysis . However , even when the efficacy subset analysis is assumed to be unbiased , or have a true type I error probability equal to the desired level alpha , situations are described where the intent-to-treat analysis in fact has greater power than the efficacy subset analysis . The intent-to-treat design , wherein all possible patients continue to be followed , is especially powerful when an effective treatment arrests progression of disease during its administration . Thus , a patient benefits long after the patient becomes noncompliant or the treatment is terminated . In such cases , a l and mark analysis using the observations from the last patient evaluation is likely to prove more powerful than life-table or longitudinal analyses . Examples are described PURPOSE AND EXPERIMENTAL DESIGN Cerebellar primitive neuroectodermal tumors/medulloblastomas ( PNET/MB ) are the most common malignant brain tumors in childhood . To identify PNET/MB biological prognostic factors that define a patient group with a sufficiently good prognosis to permit a reduction in treatment intensity , we determined the expression levels of MYC mRNA in fresh frozen tumor sample s from 26 PNET/MB patients using semiquantitative reverse transcription-PCR . RESULTS MYC mRNA expression levels in primary PNET/MB showed a wide range with a 22-fold difference between the highest and lowest values and did not correlate with MYC gene amplification . MYC mRNA expression was an independent significant prognostic factor for progression-free survival outcome and was more predictive than st and ard clinical factors . The combination of low MYC mRNA expression and high TrkC mRNA expression identified a good outcome group of PNET/MB patients ( n = 7 ) with 100 % progression-free survival after a median follow-up time of 55 months ( range , 15 - 91 months ) . Three of these seven good outcome patients survived without radiotherapy . CONCLUSIONS Low MYC mRNA expression is a powerful independent predictor of favorable clinical outcome in PNET/MB . Assessment of MYC mRNA levels is feasible and may be incorporated in prospect i ve PNET/MB clinical trials to aid in treatment planning for patients with PNET/MB on confirmation of our results in larger studies PURPOSE To identify biologic prognostic factors in childhood primitive neuroectodermal tumors ( PNET ) , including medulloblastoma , that accurately define patient groups with sufficiently good prognosis to permit a reduction in treatment intensity . PATIENTS AND METHODS We determined expression levels of the neurotrophin receptor TrkC mRNA in formalin-fixed tumor sample s from 87 well characterized PNET patients using in situ hybridization . Comparison of TrkC mRNA expression levels with clinical and other laboratory variables was performed using univariate and multivariate Cox regression analysis . RESULTS High TrkC mRNA expression was found to be associated more with higher 5-year cumulative survival rate than was low TrkC mRNA expression ( 89 % v 46 % , respectively ) . When compared with established clinical prognostic factors and laboratory variables of potential prognostic significance , TrkC mRNA expression , by univariate analysis , was found to be the single most powerful predictor of outcome ( hazards ratio , 4.81 ; P < .00005 ) , exceeding all clinical prognostic factors . In multivariate analysis , the hazards ratio remained significant ( P < .00005 ) . CONCLUSION High TrkC mRNA expression in PNET is a powerful independent predictor of favorable clinical outcome . Assessment of TrkC mRNA levels may aid in treatment planning for patients with PNETs and should be incorporated prospect ively into PNET clinical trials PURPOSE To analyze the impact of radiotherapy ( RT ) parameters on outcome in a r and omized study of  pre-RT chemotherapy for M0-M1 medulloblastoma . METHODS AND MATERIAL S Patients were r and omized to RT alone or RT preceded by chemotherapy with vincristine , etoposide , carboplatin , and cyclophosphamide . RT consisted of craniospinal RT , 35 Gy in 21 fractions , followed by a posterior fossa ( PF ) boost of 20 Gy in 12 fractions . The accuracy of cribriform fossa , skull base , and PF field placement was assessed . RESULTS Between 1992 and 2000 , 217 patients were r and omized , of whom 179 were eligible for analysis . At a median follow-up of 5.4 years , the 3- and 5-year overall survival rate was 79.5 % and 70.7 % , respectively . The 3- and 5-year event-free survival ( EFS ) rate was 71.6 % and 67.0 % , respectively . EFS was significantly better for the chemotherapy plus RT group ( 3-year EFS rate 78.5 % vs. 64.8 % , p = 0.0366 ) . Overall survival and EFS were significantly better for patients completing RT within 50 days compared with those taking > 50 days to complete RT ( 3-year overall survival rate 84.1 % vs. 70.9 % , p = 0.0356 , 3-year EFS rate 78.5 % vs. 53.7 % , p = 0.0092 ) . Multivariate analysis identified the use of chemotherapy ( p = 0.0248 ) and RT duration ( p = 0.0100 ) as predictive of better EFS . Planning films were review ed for 131 ( 74.4 % ) of 176 patients . Sixty-five ( 49.6 % ) had no targeting deviations and 58 ( 44.3 % ) had one or more deviations . PF recurrence occurred in 11 ( 34.4 % ) of 32 with a PF targeting deviation compared with 13 ( 16.3 % ) of 80 without ( p = 0.043 ) . No statistically significant impact of other targeting deviations on recurrence risk or EFS were found . CONCLUSION The results of this study have confirmed the importance of the duration of RT for medulloblastoma . Also , attention to detail when planning RT is important , as illustrated in the case of PF field placement BACKGROUND Current treatment for medulloblastoma , which includes postoperative radiotherapy and 1 year of chemotherapy , does not cure many children with high-risk disease . We aim ed to investigate the effectiveness of risk-adapted radiotherapy followed by a shortened period of dose-intense chemotherapy in children with medulloblastoma . METHODS After resection , patients were classified as having average-risk medulloblastoma ( < or = 1.5 cm2 residual tumour and no metastatic disease ) or high-risk medulloblastoma ( > 1.5 cm2 residual disease or metastatic disease localised to neuraxis ) medulloblastoma . All patients received risk-adapted craniospinal radiotherapy ( 23.4 Gy for average-risk disease and 36.0 - 39.6 Gy for high-risk disease ) followed by four cycles of cyclophosphamide-based , dose-intensive chemotherapy . Patients were assessed regularly for disease status and treatment side-effects . The primary endpoint was 5-year event-free survival ; we also measured overall survival . This study is registered with Clinical Trials.gov , number NCT00003211 . FINDINGS Of 134 children with medulloblastoma who underwent treatment ( 86 average-risk , 48 high-risk ) , 119 ( 89 % ) completed the planned protocol . No treatment-related deaths occurred . 5-year overall survival was 85 % ( 95 % CI 75 - 94 ) in patients in the average-risk group and 70 % ( 54 - 84 ) in those in the high-risk group ( p=0.04 ) ; 5-year event-free survival was 83 % ( 73 - 93 ) and 70 % ( 55 - 85 ) , respectively ( p=0.046 ) . For the 116 patients whose histology was review ed central ly , histological subtype correlated with 5-year event-free survival ( p=0.04 ) : 84 % ( 74 - 95 ) for classic histology , 77 % ( 49 - 100 ) for desmoplastic tumours , and 57 % ( 33 - 80 ) for large-cell anaplastic tumours . INTERPRETATION Risk-adapted radiotherapy followed by a shortened schedule of dose-intensive chemotherapy can be used to improve the outcome of patients with high-risk medulloblastoma This international , prospect i ve , r and omised therapeutic study is based on previous , separate studies of the two societies . The study asks two principal questions : ( 1 ) Is it possible to improve the results of therapy by inserting , between surgery and post-operative irradiation , an intensive course of chemotherapy consisting of vincristine , procarbazine and methotrexate , followed by citrovorum factor rescue ? ( 2 ) In “ low risk ” patients ( i.e. those with macroscopically “ complete ” resection and absence of met 
    Output:
    
Based on the evidence identified in this systematic review , a benefit of chemotherapy can not be excluded , but at this moment we are unable to draw a definitive conclusion regarding treatment with or without chemotherapy .
This systematic review only allowed a conclusion on the concept of treatment , not on the best strategy regarding specific chemotherapeutic agents and radiation dose .