***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 Subgroup analyses in r and omized trials examine whether effects of interventions differ between subgroups of study population s according to characteristics of patients or interventions . However , findings from subgroup analyses may be misleading , potentially result ing in suboptimal clinical and health decision making . Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered . The objectives of this study are : 1 ) to describe the reporting of subgroup analyses and cl aims of subgroup effects in r and omized controlled trials , 2 ) to assess study characteristics associated with reporting of subgroup analyses and with cl aims of subgroup effects , and 3 ) to examine the analysis , and interpretation of subgroup effects for each study 's primary outcome . Methods We will conduct a systematic review of 464 r and omized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine . We will r and omly select journal articles , stratified in a 1:1 ratio by higher impact versus lower impact journals . According to 2007 ISI total citations , we consider the New Engl and Journal of Medicine , JAMA , Lancet , Annals of Internal Medicine , and BMJ as higher impact journals . Teams of two review ers will independently screen full texts of reports for eligibility , and abstract data , using st and ardized , pilot-tested extraction forms . We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with cl aims of subgroup effects for the primary and any other outcomes . Discussion A clear underst and ing of subgroup analyses , as currently conducted and reported in published r and omized controlled trials , will reveal both strengths and weaknesses of this practice . Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses , and cl aim and interpretation of subgroup effects in r and omized trials We evaluated the role of rituximab ( R ) both in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma ( FL ) . A total of 465 patients were r and omized to induction with 6 cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) ( every 3 weeks ) or R-CHOP ( R : 375 mg/m(2 ) intravenously , day 1 ) . Those in complete remission ( CR ) or partial remission ( PR ) were r and omized to maintenance with R ( 375 mg/m(2 ) intravenously once every 3 months for a maximum of 2 years ) or observation . R-CHOP induction yielded an increased overall response rate ( CHOP , 72.3 % ; R-CHOP , 85.1 % ; P < .001 ) and CR rate ( CHOP , 15.6 % ; R-CHOP , 29.5 % ; P < .001 ) . Median progression-free survival ( PFS ) from first r and omization was 20.2 months after CHOP versus 33.1 months after R-CHOP ( hazard ratio [ HR ] , 0.65 ; P < .001 ) . Rituximab maintenance yielded a median PFS from second r and omization of 51.5 months versus 14.9 months with observation ( HR , 0.40 ; P < .001 ) . Improved PFS was found both after induction with CHOP ( HR , 0.30 ; P < .001 ) and R-CHOP ( HR , 0.54 ; P = .004 ) . R maintenance also improved overall survival from second r and omization : 85 % at 3 years versus 77 % with observation ( HR , 0.52 ; P = .011 ) . This is the first trial showing that in relapsed/resistant FL rituximab maintenance considerably improves PFS not only after CHOP but also after R-CHOP induction In this r and omized multicenter study of 136 patients , 6 courses of CHOP ( cyclo-phosphamide/doxorubicin/vincristine/prednisone ) followed by rituximab ( CHOP-R ) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting ( R-HDS ) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma ( FL ) after the introduction of monoclonal antibodies . The analysis was intention to treat with event-free survival ( EFS ) as the primary endpoint . Complete remission ( CR ) was 62 % with CHOP-R and 85 % with R-HDS ( P < .001 ) . At a median follow-up ( MFU ) of 51 months , the 4-year EFS was 28 % and 61 % , respectively ( P < .001 ) , with no difference in overall survival ( OS ) . Molecular remission ( MR ) was achieved in 44 % of CHOP-R and 80 % of R-HDS patients ( P < .001 ) , and was the strongest independent outcome predictor . Patients relapsing after CHOP-R underwent salvage R-HDS in 71 % of cases . Salvage R-HDS had an 85 % CR rate and a 68 % 3-year EFS ( MFU , 30 months ) . We conclude that ( 1 ) achieving MR is critical for effective disease control , regardless of which treatment is used ; ( 2 ) R-HDS ensures superior disease control and molecular outcome than CHOP-R , but no OS improvement ; and ( 3 ) CHOP-R failures have a good outcome after salvage R-HDS , suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS-like treatments . This trial was registered at www . clinical trials.gov as no. NCT00435955 Conventional chemotherapy has failed to substantially prolong survival for patients with advanced follicular lymphoma . To improve outcomes , the German Low- Grade Lymphoma Study Group ( GLSG ) initiated a r and omized trial to compare the effect of potentially curative myeloablative radiochemotherapy followed by autologous stem cell transplantation ( ASCT ) with interferon-alpha ( IFN-alpha ) maintenance therapy in first remission . Three hundred seven patients ( younger than 60 years ) with follicular lymphoma were recruited into the trial from 130 institutions . After 2 cycles of cyclophosphamide-doxorubicin-vincristine-prednisone ( CHOP ) or mitoxantrone-chlorambucil-prednisone ( MCP ) induction chemotherapy , patients were r and omly assigned to either the ASCT or the IFN-alpha group . The respective therapy was started when patients achieved complete or partial remission after induction chemotherapy .  Two hundred forty patients with follicular lymphoma are evaluable for the comparison of ASCT and IFN-alpha . In patients who underwent ASCT , the 5-year progression-free survival ( PFS ) rate was 64.7 % , and in the IFN-alpha arm it was 33.3 % ( P < .0001 ) . As expected , acute toxicity was higher in the ASCT group , but early mortality was below 2.5 % in both study arms . In this r and omized , multicenter trial , high-dose radiochemotherapy followed by ASCT significantly improved PFS compared with IFN-alpha in patients with follicular lymphoma when applied as consolidation in first remission . Longer follow-up is necessary to determine the effect of ASCT on overall survival The combination of cyclophosphamide , vincristine , and prednisone ( CVP ) is one of several st and ard treatment options for advanced follicular lymphoma . This , like similar chemotherapeutic regimens , induces response rates of 60 % to 80 % , with a median response duration of under 2 years . Rituximab , a chimeric monoclonal antibody against CD20 , is active in follicular lymphoma , both as monotherapy and in combination with chemotherapy . Previously untreated patients with stages III to IV follicular lymphoma were r and omly assigned to receive either 8 cycles of CVP plus rituximab ( R-CVP ; n = 162 ) or CVP ( n = 159 ) .  Overall and complete response rates were 81 % and 41 % in the R-CVP arm versus 57 % and 10 % in the CVP arm , respectively ( P < .0001 ) . At a median follow-up of 30 months , patients treated with R-CVP had a very significantly prolonged time to progression ( median 32 months versus 15 months for CVP ; P < .0001 ) . Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months in the CVP arm ( P < .0001 ) . Rituximab did not add significantly to the toxicity of CVP . The addition of rituximab to the CVP regimen significantly improves the clinical outcome in patients with previously untreated advanced follicular lymphoma , without increased toxicity Doxorubicin-based immunochemotherapy , with interferon , has been shown to improve survival in patients with advanced follicular lymphoma .  High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy . In a r and omized study using a purged autologous stem-cell support , we compared these 2 approaches in patients with advanced follicular lymphoma . Newly diagnosed advanced follicular lymphoma patients ( 172 patients ) were r and omly assigned either to an immunochemotherapy regimen ( cyclophosphamide , doxorubicin , teniposide , prednisone , and interferon ) or to a high-dose therapy followed by purged autologous stem-cell transplantation . Compared with the patients who received chemotherapy and interferon , patients treated with high-dose therapy had a higher response rate ( 69 % vs 81 % , P = .045 ) and a longer median event-free survival ( not reached vs 45 months ) . This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation . The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy . Autologous stem-cell transplantation can not be considered as the st and ard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden PURPOSE To compare the long-term outcome of patients with previously untreated follicular lymphoma ( FL ) needing therapy , after treatment with cyclophosphamide , vincristine and prednisone ( CVP ) versus CVP plus rituximab ( R-CVP )  and to evaluate the predictive value of known prognostic factors after treatment with R-CVP . PATIENTS AND METHODS Patients with previously untreated CD20-positive stage III/IV FL were r and omly assigned to eight cycles of R-CVP ( n = 159 ) or CVP alone ( n = 162 ) . The median follow-up period was 53 months . RESULTS The primary end point-time to treatment failure ( TTF ) , which included patients without a response after four cycles as an event-was significantly prolonged in patients receiving R-CVP versus CVP ( P < .0001 ) . Improvements in all other end points , including overall and complete response rates ( P < .0001 ) , time to progression ( TTP ; P < .0001 ) , response duration ( P < .0001 ) , time to next antilymphoma treatment ( P < .0001 ) , and overall survival ( OS ; P = .029 ; 4-year OS : 83 % v 77 % ; ) were achieved with R-CVP versus CVP alone . Univariate analyses demonstrated an improvement in TTP with R-CVP versus CVP irrespective of the Follicular Lymphoma International Prognostic Index ( FLIPI ) subgroup , the International Prognostic Index ( IPI ) subgroup , baseline histology , and the presence or absence of B symptoms or bulky disease . By multivariate analysis , FLIPI retains a strong predictive power for TTP in the presence of the trial treatment effect . CONCLUSION Analysis of all outcome measures , including OS , confirm the benefit of adding R to CVP in the front-line treatment of FL One hundred and eleven patients with low‐ grade histology non‐Hodgkin 's lymphoma achieving a restaged complete response to one of three induction therapies on Eastern Cooperative Oncology Group ( ECOG ) protocol EST 2474 were r and omized to receive either maintenance treatment with BCNU , cyclophosphamide , vincristine , and prednisone ( BCVP ) given every 6 weeks for an additional 18 months or no further therapy  . Overall toxicity was moderate . The median progression‐free survival ( PFS ) on maintenance therapy was 3.2 years versus 2.0 years for those observed without treatment ( P = 0.02 ) . Progression‐free survival was significantly shorter for patients with nodular and diffuse pattern ( ND ) , histiocytic or mixed histology compared with pure nodular lymphocytic , or poorly differentiated counterpart ( P = 0.0007 ) , thus confirming the prognostic significance of histologic subtypes . However , the overall survival of patients was not improved by maintenance treatment , suggesting that therapy upon relapse was an equally effective alternative clinical strategy As a part of an ongoing prospect i ve controlled trial , the Southwest Oncology Group compared the results of treatment of advanced non‐Hodgkin 's lymphoma with two CHOP regimens ( cyclophosphamide , adriamycin , vincristine and prednisone with either low‐dose bleomycin or BCG 
    Output:
    
Available evidence suggests that high-dose therapy and ASCT as part of FL initial treatment does not improve overall survival .