Figure 1.

Study algorithm. On the left, the discovery cohort is represented; 224 diffuse large B-cell lymphoma (DLBCL) patients enrolled in the DLCL04 (n= 130) and R-HDS0305 (n= 94) trials with available formalin-fixed, paraffin embedded (FFPE) tissue were initially considered in this analysis. Targeted gene expression profiling (TGEP) success rate was 92.4% (n=207), with 17 cases not yelding enough highquality mRNA to undergo successful GEP assessment. Only cases originally diagnosed as DLBCL non-otherwise specified (NOS) were considered. Therefore 21 cases classified in different DLBCL categories were excluded; 99 NOS-DLBCL FFPE patient samples from the DLCL04 trial and 87 samples from the R-HDS0305 trial were finally included in this study. On the right, the three validation cohorts: a cohort of 928 patients from Sha and coworkers²⁷ (469 treated with R-CHOP; 459 with RBCHOP), a public gene expression dataset (Affymetrix Human Genome U133 Plus 2.0 Array), GSE10846, (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10846), including 233 patients treated with R-CHOP regimen (Lenz et al. 2008)³⁶; an additional validation cohort including 102 consecutive DLBCL NOS cases with available FFPE tissue, treated with R-CHOP/R-CHOP-like regimens. RB-CHOP: R-CHOP plus bortezomib.