You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era.
Abstract 1:
PURPOSE The International Prognostic Index ( IPI ) is widely used for risk stratification of patients with aggressive B-cell lymphoma . The introduction of rituximab has markedly improved outcome , and R-CHOP ( rituximab + cyclophosphamide , doxorubicin , vincristine , prednisone ) has become the st and ard treatment for CD20(+ ) diffuse large B-cell lymphoma . To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP , we analyzed the prognostic relevance of IPI in three prospect i ve clinical trials . PATIENTS AND METHODS In total , 1,062 patients treated with rituximab were included ( MabThera International Trial [ MInT ] , 380 patients ; dose-escalated regimen of cyclophosphamide , doxorubicin , vincristine , etoposide , and prednisone ( MegaCHOEP ) trial , 72 patients ; CHOP + rituximab for patients older than age 60 years [ RICOVER-60 ] trial , 610 patients ) . A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free , progression-free , and overall survival . RESULTS IPI score was significant for all three end points . Rituximab significantly improved treatment outcome within each IPI group result ing in a quenching of the Kaplan-Meier estimators . However , IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid . The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP . CONCLUSION The effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy . These results demonstrate that the IPI is still valid in the R-CHOP era


Title 2:
Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era.
Abstract 2:
BACKGROUND The introduction of rituximab ( R ) to conventional CHOP chemotherapy for newly diagnosed diffuse large B-cell lymphoma ( DLBCL ) led to an unequivocal improvement in survival , establishing RCHOP as the st and ard of care . Still , nearly 40 % of DLBCL patients will eventually die of relapsed disease . Efforts to improve outcomes by addition of new biologic agents ( X ) to the RCHOP backbone are underway . In this era of R(X)CHOP , it is imperative to develop prognostic and predictive markers , not only to identify patients who will suffer a particularly aggressive course , but also to accurately select patients for clinical trials from which they will most benefit . DESIGN The following review was undertaken to describe prognostic factors in DLBCL , with emphasis on markers that are accurate , relatively available , and clinical ly applicable in 2014 . RESULTS The International Prognostic Index retains its validity in the era of RCHOP , although with limited ability to predict those with < 50 % chance of long-term survival . Gene expression profiling has provided novel insights into the biology of DLBCL and led to the development of immunohistochemistry ( IHC ) algorithms that are in routine practice . Identification of a ' double-hit ' ( DH ) lymphoma by fluorescent in situ hybridization with aberrations involving MYC and /or BCL2 and BCL6 genes has important implication s due to its extremely dismal prognosis with RCHOP . Other markers such as the absolute lymphocyte count ( ALC ) , serum immunoglobulin free light chains , vitamin D levels , serum cytokines/chemokines , and imaging with positron emission tomography ( PET ) have all shown promise as future predictive/prognostic tests . CONCLUSIONS The future for new treatment options in DLBCL is promising with current clinical trials testing novel targeted agents such as bortezomib , lenalidomide , and ibrutinib as the ' X ' in R(X)CHOP . Predictive factors are required to select and r and omize patients appropriately for these trials . We envision the day when ' X ' will be chosen based on the biological characteristics of the tumor


Title 3:
Outcomes of MYC‐associated lymphomas after R‐CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704
Abstract 3:
Double hit lymphoma ( DHL ) and double protein‐expressing ( MYC , BCL2 ) lymphomas ( DPL ) fare poorly with R‐CHOP ( rituximab + cyclophosphamide , doxorubicin , vincristine , prednisolone ) ; consolidative autologous stem cell transplant ( ASCT ) may improve outcomes . S9704 , a phase III r and omized study of CHOP + /−R with or without ASCT enabled evaluation of intensive consolidation . Immunohistochemistry ( IHC ) identified 27 of 198 patients ( 13·6 % ) with MYC overexpression ; 20 ( 74 % ) harboured concurrent BCL2 overexpression . Four had DHL and 16 had DPL only . With median 127 months follow‐up , there is a trend favouring outcomes after ASCT in DPL and MYC protein overexpressing patients , whereas all DHL patients have died irrespective of ASCT


Title 4:
MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma.
Abstract 4:
MYC rearrangements occur in 5 % to 10 % of diffuse large B-cell lymphomas ( DLBCL ) and confer an increased risk to cyclophosphamide , hydroxydaunorubicin , oncovin , and prednisone ( CHOP ) and rituximab (R)-CHOP treated patients . We investigated the prognostic relevance of MYC- , BCL2- and BCL6-rearrangements and protein expression in a prospect i ve r and omized trial . Paraffin-embedded tumor sample s from 442 de novo DLBCL treated within the RICOVER study of the German High- Grade Non-Hodgkin Lymphoma Study Group ( DSHNHL ) were investigated using immunohistochemistry and fluorescence in situ hybridization ( FISH ) to detect protein expression and breaks of MYC , BCL2 , and BCL6 . Rearrangements of MYC , BCL2 , and BCL6 were detected in 8.8 % , 13.5 % , and 28.7 % , respectively . Protein overexpression of MYC ( > 40 % ) was encountered in 31.8 % of tumors ; 79.6 % and 82.8 % of tumors expressed BCL2 and BCL6 , respectively . MYC translocations , MYChigh , BCL2high , and BCL6low protein expressions were associated with inferior survival . In multivariate Cox regression modeling , protein expression patterns of MYC , BCL2 and BCL6 , and MYC rearrangements were predictive of outcome and provided prognostic information independent of the International Prognostic Index ( IPI ) for overall survival and event-free survival . A combined immunohistochemical or FISH/immunohistochemical score predicts outcome in DLBCL patients independent of the IPI and identifies a subset of 15 % of patients with dismal prognosis in the high-risk IPI group following treatment with R-CHOP . Registered at http://www.cancer.gov/ clinical trials : RICOVER trial of the DSHNHL is NCT 00052936


Title 5:
MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations.
Abstract 5:
In large B-cell lymphoma ( LBCL ) MYC- and MYC/BCL2 double-hit ( DH ) translocations have been associated with inferior survival . We hypothesised that the negative prognostic impact of MYC translocation was determined by an immunoglobulin MYC translocation partner gene ( IG-MYC ) , as opposed to a non-immunoglobulin partner gene ( nonIG-MYC ) . In a prospect i ve , unselected cohort of 237 LBCL patients MYC and BCL2 translocations were identified by fluorescent in situ hybridisation ( FISH ) with split probes . MYC translocation partner gene was identified by IGH/MYC fusion probes and /or kappa/lambda split probes . Clinical data were collected from patient files . MYC translocation was identified in 28/225 patients .  IG-MYC translocation partner gene was identified in 12/24 patients .  DH translocation was identified in 23/228 patients .  IG-MYC translocation partner gene was identified in 9/19 DH patients . Neither MYC-nor DH translocation showed correlation with survival . However , MYC translocation with IG-MYC translocation partner gene was associated with worse OS compared with both MYC translocation with nonIG-MYC translocation partner gene ( P = 0.02 ) as well as absence of MYC translocation ( P = 0.03 ) . In patients with DH a similar , however , stronger correlation was seen ( P = 0.003 and P = 0.0004 respectively ) . MYC - or DH translocation with nonIG-MYC translocation partner gene was not associated with worse overall survival ( P = 0.2 and P = 0.3 respectively ) . Most patients received Rituximab ( 86 % ) and CHOP/CHOP-like chemotherapy regimes ( 81 % ) . We suggest that prognostic stratification of LBCL patients by MYC and /or DH translocations should include identification of MYC translocation partner gene because approximately half of the cases harbour nonIG-MYC translocation partner genes with no or minor influence on survival
The current analysis indicated that MYC and /or BCL2 protein overexpression , and particularly co-overexpression was related to short overall survival  in R-CHOP treated DLBCL patients , showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment