***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: In patients with multiple myeloma ( MM ) , risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches . In the present study , we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial . Because of the 2-arm design of the study , we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation ( arm B ) compared with st and ard treatment without bortezomib ( arm A ) . For allanalyzed chromosomal aberrations , progression-free survival ( PFS ) and overall survival ( OS ) were at least equal or superior in the bortezomib arm compared with the st and ard arm . Strikingly , patients with del(17p13 ) benefited the most from the bortezomib-containing treatment : the median PFS in arm A was 12.0 months and in arm B it was 26.2 months ( P = .024 ) ; the 3 year-OS for arm A was 17 % and for arm B it was 69 % ( P = .028 ) . After multivariate analysis , del(17p13 ) was an independent predictor for PFS ( P < .0001 ) and OS ( P < .0001 ) in arm A , whereas no statistically significant effect on PFS ( P = .28 ) or OS ( P = .12 ) was seen in arm B. In conclusion , the adverse impact of del(17p13 ) on PFS and OS could be significantly reduced by bortezomib-based treatment , suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13 ) Adverse prognostic factors in multiple myeloma include advanced age , number of prior therapies , and higher International Staging System ( ISS ) disease stage . In the international , r and omised , phase‐3 Assessment of Proteasome Inhibition for Extending Remissions ( APEX ) study , bortezomib demonstrated significantly longer time to progression ( TTP ) , higher response rates and improved survival compared with high‐dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies . In this APEX subgroup analysis , efficacy of bortezomib and dexamethasone was compared in elderly ( age ≥65 years ) and high‐risk ( > 1 prior line of therapy ; ISS stage II/III ; refractory to prior therapy ) patients . Bortezomib demonstrated substantial clinical activity in these patients . Response rate ( 34–40 % vs. 13–19 % ) , including complete response rate ( 5–8 % vs. 0–1 % ) , was significantly higher with bortezomib versus dexamethasone in all four subgroups . Similarly , median TTP was significantly longer with bortezomib versus dexamethasone , and 1‐year survival probability was significantly higher in all subgroups . As in the total APEX population , rates of grade 3/4 adverse events were higher in bortezomib‐ versus dexamethasone‐treated patients aged ≥65 years and with > 1 prior line , while rates of serious adverse events were similar ; toxicities generally proved manageable . Bortezomib should be considered an appropriate treatment for elderly and high‐risk patients with relapsed multiple myeloma BACKGROUND Thalidomide plus dexamethasone ( TD ) is a st and ard induction therapy for myeloma . We aim ed to assess the efficacy and safety of addition of bortezomib to TD ( VTD ) versus TD alone as induction therapy before , and consolidation therapy after , double autologous stem-cell transplantation in newly diagnosed multiple myeloma . METHODS Patients ( aged 18 - 65 years ) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May , 2006 , and April , 2008 , and data collection continued until June 30 , 2010 . Patients were r and omly allocated ( 1:1 ratio ) by a web-based system to receive three 21-day cycles of thalidomide ( 100 mg daily for the first 14 days and 200 mg daily thereafter ) plus dexamethasone ( 40 mg daily on 8 of the first 12 days , but not consecutively ; total of 320 mg per cycle ) , either alone or with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , and 11 ) . The r and omisation sequence was computer generated by the study coordinating team and was stratified by disease stage . After double autologous stem-cell transplantation , patients received two 35-day cycles of their assigned drug regimen , VTD or TD , as consolidation therapy . The primary endpoint was the rate of complete or near complete response to induction therapy . Analysis was by intention to treat . Patients and treating physicians were not masked to treatment allocation . This study is still underway but is not recruiting participants , and is registered with Clinical Trials.gov , number NCT01134484 , and with EudraCT , number 2005 - 003723 - 39 . FINDINGS 480 patients were enrolled and r and omly assigned to receive VTD ( n=241 patients ) or TD ( n=239 ) . Six patients withdrew consent before start of treatment , and 236 on VTD and 238 on TD were included in the intention-to-treat analysis . After induction therapy , complete or near complete response was achieved in 73 patients ( 31 % , 95 % CI 25·0 - 36·8 ) receiving VTD , and 27 ( 11 % , 7·3 - 15·4 ) on TD ( p<0·0001 ) . Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD ( n=132 , 56 % ) than in those on TD ( n=79 , 33 % ; p<0·0001 ) , with a higher occurrence of peripheral neuropathy in patients on VTD ( n=23 , 10 % ) than in those on TD ( n=5 , 2 % ; p=0·0004 ) . Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD , and in three of five patients on TD . INTERPRETATION VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response , and represents a new st and ard of care for patients with multiple myeloma who are eligible for transplant . FUNDING Seràgnoli Institute of Haematology at the University of Bologna , Bologna , Italy This subgroup analysis of the phase III APEX ( Assessment of Proteasome Inhibition for Extending Remissions ) trial examined whether prior exposure to specific therapies affected the relative efficacy of bortezomib versus dexamethasone in relapsed/refractory myeloma .  Time to progression and overall survival were superior with bortezomib in all subgroups , with no evidence of interaction between any prior therapies and assignment to study therapy . Patients with prior thalidomide exposure had worse outcomes overall , but neither prior thalidomide nor prior autologous stem cell transplantation affected the relative efficacy of bortezomib versus dexamethasone . These results confirm the superiority of bortezomib over dexamethasone , regardless of prior exposure to specific therapies ( clinical trials.gov : NCT00048230 ) OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess  systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review Combinations of bortezomib ( V ) and dexamethasone ( D ) with either lenalidomide ( R ) or cyclophosphamide ( C ) have shown significant efficacy . This r and omized phase 2 trial evaluated VDC , VDR , and VDCR in previously untreated multiple myeloma ( MM ) . Patients received V 1.3 mg/m2 ( days 1 , 4 , 8 , 11 ) and D 40 mg ( days 1 , 8 , 15 ) , with either C 500 mg/m2 ( days 1 , 8) and R 15 mg ( days 1 - 14 ; VDCR ) , R 25 mg ( days 1 - 14 ; VDR ) , C 500 mg/m2 ( days 1 , 8 ; VDC ) or C 500 mg/m2 ( days 1 , 8 , 15 ; VDC-mod ) in 3-week cycles ( maximum 8 cycles ) , followed by maintenance with V 1.3 mg/m2 ( days 1 , 8 , 15 , 22 ) for four 6-week cycles ( all arms)≥very good partial response was seen in 58 % , 51 % , 41 % , and 53 % ( complete response rate of 25 % , 24 % , 22 % , and 47 % ) of patients ( VDCR , VDR , VCD , and VCD-mod , respectively ) ; the corresponding 1-year progression-free survival was 86 % , 83 % , 93 % , and 100 % , respectively . Common adverse events included hematologic toxicities , peripheral neuropathy , fatigue , and gastrointestinal disturbances . All regimens were highly active and well tolerated in previously untreated MM , and , based on this trial , VDR and VCD-mod are preferred for clinical practice and further comparative testing . No substantial advantage was noted with VDCR over the 3-drug combinations . This trial is registered at www . clinical trials.gov ( NCT00507442 ) In a r and omized , phase 3 study , superior complete/near-complete response ( CR/nCR ) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone ( VTD ) versus thalidomide-dexamethasone ( TD ) as induction therapy before , and consolidation after , double autologous stem cell transplantation for newly diagnosed myeloma patients ( intention-to-treat analysis ; VTD , n = 236 ; TD , n = 238 ) . This per- protocol analysis ( VTD , n = 160 ; TD , n = 161 ) specifically assessed the efficacy and safety of consolidation with VTD or TD . Before starting consolidation , CR/nCR rates were not significantly different in the VTD ( 63.1 % ) and TD arms ( 54.7 % ) . After consolidation , CR ( 60.6 % vs 46.6 % ) and CR/nCR ( 73.1 % vs 60.9 % ) rates were significantly higher for VTD-treated versus TD-treated patients . VTD consolidation significantly increased CR and CR/nCR rates , but TD did not ( McNemar test ) . With a median follow-up of 30.4 months from start of consolidation , 3-year progression-free survival was significantly longer for the VTD group ( 60 % vs 48 % for TD ) . Grade 2 or 3 peripheral neuropathy ( 8.1 % vs 2.4 % ) was more frequent with VTD ( grade 3 , 0.6 % ) versus TD consolidation . The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation . VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients r and omly assigned to the VTD arm of the study . The study is registered at www . clinical trials.gov as # NCT01134484 The Intergroupe Francophone du Myelome conducted a r and omized trial to compare bortezomib-dexamethasone ( VD ) as induction before high-dose therapy ( 
    Output:
    
In previously untreated or in relapsed or refractory mm patients , bortezomib-based therapy has improved disease control and , in some patients , overall survival