***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND A population -based cohort of children aged 1 - 18 years with acute lymphoblastic leukaemia ( ALL ) was treated with a dexamethasone-based protocol ( Dutch Childhood Oncology Group [ DCOG ] ALL-9 ) . We aim ed to confirm the results of the most effective DCOG ALL protocol for non-high-risk ( NHR ) patients to date ( ALL-6 ) , compare results with ALL-7 and ALL-8 , and study prognostic factors in a non-r and omised setting . METHODS From Jan 1 , 1997 , until Nov 1 , 2004 , patients with ALL were treated according to the ALL-9 protocol in eight Dutch academic centres with their affiliated peripheral hospitals . Patients were stratified into NHR and high risk ( HR ) groups . HR criteria were white-blood-cell count of 50,000 cells per microL or more , T-cell phenotype , mediastinal mass , CNS or testicular involvement , and Philadelphia chromosome or MLL rearrangement ; patients who did not fulfil these criteria were deemed to be NHR . The NHR group was treated with a three-drug induction ( dexamethasone , vincristine , and asparaginase ) for 6 weeks , medium-dose methotrexate for 3 weeks , then maintenance therapy . HR patients received a four-drug induction ( as for the NHR patients plus daunorubicin ) for 6 weeks , high-dose methotrexate for 8 weeks , and two intensification courses before receiving maintenance therapy . Triple intrathecal medication was given 13 times in NHR patients , 15 times in HR patients ( 17 times for patients with initial CNS involvement ) . No patient received cranial irradiation . Maintenance therapy was given until 109 weeks for all patients and consisted of mercaptopurine and methotrexate for 5 weeks , alternated with dexamethasone and vincristine for 2 weeks . Kaplan-Meier analysis was done on an intention-to-treat basis with event-free survival as the primary endpoint . This trial is registered at trialregister.nl , number NTR460/SNWLK-ALL-9 . FINDINGS 859 patients were recruited to the study .  Complete remission was achieved in 592 ( 98.5 % ) of the 601 patients in the NHR group and 250 ( 96.9 % ) of the 258 in the HR group . Five patients in the NHR group and four in the HR group died during induction . Median follow-up for patients alive was 72.2 ( range 4.8 - 132.7 ) months as of August , 2008 . 5-year event-free survival was 81 % ( SE 1 % ) in all patients : 84 % ( 2 % ) in NHR patients , and 72 % ( 3 % ) in HR patients . Isolated CNS relapses occurred in 22 ( 2.6 % ) of 842 patients . In a multivariate analysis , DNA index was the strongest predictor of outcome ( < 1.16 vs > or=1.16 ; relative risk 0.42 , 95 % CI 0.22 - 0.78 ) , followed by age ( 1 - 9 vs > or=10 years ; 2.23 , 1.60 - 3.11 ) and white-blood-cell count ( < 50,000 vs > or=50,000 cells per microL ; 1.60 , 1.13 - 2.26 ) . INTERPRETATION The overall results of the dexamethasone-based DCOG ALL-9 protocol are better than those of our previous Berlin-Frankfurt-Münster-based protocol s ALL-7 and ALL-8 . The results for  NHR patients were achieved with high cumulative doses of dexamethasone and vincristine , but without the use of anthracyclines , etoposide , cyclophosphamide , or cranial irradiation , therefore minimising the risk of side-effects . FUNDING Dutch Health Insurers Minimal residual disease ( MRD ) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia ( ALL ) .  Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse . Between 2005 and 2008 , we conducted a prospect i ve study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non‐ex vivo T depleted myeloablative transplantation . Immunoglobulin (Ig)H/T‐cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high‐risk paediatric ALL enrolled . There were no significant demographic differences except remission status ( first or second complete remission ) between the 95 children with MRD < 10−3 and the 27 with MRD ≥10−3 . Multivariate analysis identified sex match and MRD as being significantly associated with 5‐year survival . MRD ≥10−3 compromised the 5‐year cumulative incidence of relapse ( 43·6 vs. 16·7 % ) . Complete remission status and stem cell source did not modify the relationship between MRD and prognosis . Thus , pre‐transplant MRD is still a major predictor of outcome for ALL . The MRD‐guided strategy result ed in survival for 72·3 % of patients with MRD<10−3 and 40·4 % of those with MRD ≥10−3 BACKGROUND Minimal residual disease ( MRD ) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia ( ALL ) during remission . We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification . METHODS Between Oct 1 , 2003 and June 30 , 2011 , consecutive children and young adults ( aged 1 - 25 years ) with ALL from the UK and Irel and were recruited . Eligible patients were categorised into clinical st and ard , intermediate , and high risk groups on the basis of a combination of National Cancer Institute ( NCI ) criteria , cytogenetics , and early response to induction therapy , which was assessed by bone marrow blast counts taken at days 8 ( NCI high-risk patients ) and 15 ( NCI st and ard-risk patients ) after induction began . Clinical st and ard-risk and intermediate-risk patients were assessed for MRD . Those classified as MRD low risk ( undetectable MRD at the end of induction [ day 29 ] or detectable MRD at day 29 that became undetectable by week 11 ) were r and omly assigned to receive one or two delayed intensification courses . Patients had received induction , consolidation , and interim maintenance therapy before they began delayed intensification . Delayed intensification consisted of pegylated asparaginase on day 4 ; vincristine , dexamethasone ( alternate weeks ) , and doxorubicin for 3 weeks ; and 4 weeks of cyclophosphamide and cytarabine . Computer r and omisation was done with stratification by MRD result and balancing for sex , age , and white blood cell count at diagnosis by method of minimisation . Patients , clinicians , and data analysts were not masked to treatment allocation . The primary outcome was event-free survival ( EFS ) , which was defined as time to relapse , secondary tumour , or death . Our aim was to rule out a 7 % reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses . Analyses were by intention to treat . This trial is registered , number IS RCT N07355119 . FINDINGS Of 3207 patients registered in the trial overall , 521 MRD low-risk patients were r and omly assigned to receive one ( n=260 ) or two ( n=261 ) delayed intensification courses . Median follow-up of these patients was 57 months ( IQR 42 - 72 ) . We recorded no significant difference in EFS between the group given one delayed intensification ( 94·4 % at 5 years , 95 % CI 91·1 - 97·7 ) and that given two delayed intensifications ( 95·5 % , 92·8 - 98·2 ; unadjusted odds ratio 1·00 , 95 % CI 0·43 - 2·31 ; two-sided p=0·99 ) . The difference in 5-year EFS between the two groups was 1·1 % ( 95 % CI -5·6 to 2·5 ) . 11 patients ( actuarial relapse at 5 years 5·6 % , 95 % CI 2·3 - 8·9 ) given one delayed intensification and six ( 2·4 % , 0·2 - 4·6 ) given two delayed intensifications relapsed ( p=0·23 ) . Three patients ( 1·2 % , 0 - 2·6 ) given two delayed intensifications died of treatment-related causes compared with none in the group given one delayed intensification ( p=0·08 ) . We recorded no significant difference between groups for serious adverse events and grade 3 or 4 toxic effects ; however , the second delayed intensification course was associated with one ( < 1 % ) treatment-related death , and 74 episodes of grade 3 or 4 toxic effects in 45 patients ( 17 % ) . INTERPRETATION Treatment reduction is feasible for children and young adults with ALL who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD by the end of induction therapy . FUNDING Medical Research Council and Leukaemia and Lymphoma Research Summary Background Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades , the outcome of those who relapse has remained static . We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens . Methods This open-label r and omised trial was undertaken in 22 centres in the UK and Irel and and nine in Australia and New Zeal and . Patients aged 1–18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-risk , intermediate-risk , and st and ard-risk groups on the basis of duration of first complete remission , site of relapse , and immunophenotype . All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed r and omisation . Neither patients nor those giving interventions were masked . After three blocks of therapy , all high-risk group patients and those from the intermediate group with postinduction high minimal residual disease ( ≥10−4 cells ) received an allogenic stem-cell transplant . St and ard-risk and intermediate-risk patients with postinduction low minimal residual disease ( < 10−4 cells ) continued chemotherapy . The primary outcome was progression-free survival and the method of analysis was intention-to-treat . R and omisation was stopped in December , 2007 because of differences in progression-free and overall survival between the two groups . This trial is registered , reference number ISCRTN45724312 . Findings Of 239 registered patients , 216 were r and omly assigned to either idarubicin ( 109 analysed ) or mitoxantrone ( 103 analysed ) . Estimated 3-year progression-free survival was 35·9 % ( 95 % CI 25·9–45·9 ) in the idarubicin group versus 64·6 % ( 54·2–73·2 ) in the mitoxantrone group ( p=0·0004 ) , and 3-year overall survival was 45·2 % ( 34·5–55·3 ) versus 69·0 % ( 58·5–77·3 ; p=0·004 ) . Differences in progression-free survival between groups were mainly related to a decrease in disease events ( progression , second relapse , disease-related deaths ; HR 0·56 , 0·34–0·92 , p=0·007 ) rather than an increase in adverse treatment effects ( treatment death , second malignancy ; HR 0·52 , 0·24–1·11 , p=0·11 ) . Interpretation As compared with idarubicin , mitoxantrone conferred a significant benefit in progression-free and overall survival  in children with relapsed acute lymphobastic leukaemia , a potentially useful clinical finding that warrants further investigation . Funding Cancer Research UK , Leukaemia and Lymphoma Research , Cancer Council NSW , and Sporting Chance Cancer Foundation Objective . To obtain estimates of direct health care costs for prostate cancer ( PC ) from diagnosis to death to inform state transition models . Methods . A stratified r and om sample of PC patients residing in 3 geographically diverse regions of Ontario , Canada , and diagnosed in 1993–1994 , 1997–1998 , and 2001–2002 , was selected from the Ontario Cancer Registry . We retrieved patients ’ pathology reports to identify referring physicians and contacted surviving patients and next of kin of deceased patients for informed consent . We review ed clinic charts to obtain data required to allocate each patient ’s observation time to 11 PC-specific health states . We linked these data to health care administrative data bases to calculate re source use and costs ( Canadian dollars , 2008 ) per health state . A multivariable mixed-effects model determined predictors of costs . Results . The final sample numbered 829 patients . In the regression model , total direct costs increased with age , comorbidity , and Gleason score ( all P < 0.0001 ) . Radical prostatectomy was the most costly primary treatment health state ( $ 46 
    Output:
    
Compared with no testing , MRD testing by flow cytometry in newly diagnosed patients with precursor B-cell ALL represents good value for money at commonly used willingness-to-pay thresholds of $ 50,000/QALY and $ 100,000/QALY