Genomic aberrations 6p CN-LOH/6p21.3 focal HD and BTG1/ETV6/TP53 mutations (muts) are associated with early disease progression and shorter survival in PCNSL. (A-B) Kaplan-Meier estimates of PFS and OS for the total 78-patient cohort. Median follow-up: 3.5 years (95% confidence interval [CI], 2.6-4.8). Median PFS: 3.5 years (95% CI, 2.8 to NA); 35 progression events. Median OS: 11.2 years (95% CI, 9.8 to NA); 15 deaths. (C-D) PFS and OS of the genetic subgroups in the 78-patient cohort. Kaplan-Meier survival analysis demonstrates that the subgroup with 6p CN-LOH/6p21.3 HD had the earliest progression (n = 16 patients, 12 progressed, median PFS, 0.8 years; 95% CI, 0.2 to NA), followed by the subgroup with BTG1/ETV6/TP53 mut but without 6p CN-LOH/6p21.3 HD (n = 34 patients; 20 progressed; median PFS, 2.8 years; 95% CI, 1.0 to NA). Of patients without such genomic aberrations (none subgroup, n = 28 patients), there were 3 progressions (median PFS not reached). The subgroup of patients with 6p CN-LOH/6p21.3 HD and BTG1/ETV6/TP53 mut had shorter OS than the subgroup without these aberrations: BTG1/ETV6/TP53 (8 deaths; median OS, 9.8 years; 95% CI, 5.7 to NA), 6p CN-LOH/6p21.3 HD (7 deaths; median OS, 11.2 years; 95% CI, 7.3 to NA), and none (0 deaths). Cox proportional hazards regression model (univariate and multivariate) was used to estimate the HR and P value for the association of aberrations at the 4 loci with PFS and OS. Log-rank test was also used to compare survival differences among 3 patient groups and between any 2 patient groups. Of note, in 2-group comparisons, 6p CN-LOH/6p21.3 HD and BTG1/ETV6/TP53 subgroups are not significantly different in PFS (P = .3) and OS (P = .7), but they both have significantly shorter PFS (P = 2.2e−5 and P = 8.4e−5, respectively) and OS (P = .009 and P = .012, respectively) than the none subgroup. The inclusion or exclusion of the 2 patients that did not receive temozolomide had no significant impact on the conclusions drawn from the univariate and multivariate Cox proportional hazards model for PFS and OS.