Figure 2.
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.

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.

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