Table 1.
Characteristics of the Unadjusted Study Cohort for Glioblastoma WHO Grade 4 From Seven Neuro-oncological Institutions
| Study centers | Center 1 | Center 2 | Center 3 | Center 4 | Center 5 | Center 6 | Center 7 | Total | P-value | |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall | 113 | 314 | 172 | 202 | 106 | 67 | 47 | 1,021 | ||
| Demographics | Age (years) | 60.1 ± 1 | 62.4 ± 1 | 59.5 ± 1 | 62.8 ± 1 | 64.0 ± 1 | 59.4 ± 1 | 55.7 ± 2 | 61.5 ± 0.4 | *.001 |
| M:F ratio | 1:0.7 | 1:0.7 | 1:0.8 | 1:0.6 | 1:0.9 | 1:0.5 | 1:0.8 | 1:0.7 | .642 | |
| Clinical markers | Pre-OP KPS (median, range) | 80 (50–100) | 80 (20–100) | 70 (40–100) | 90 (30–100) | 90 (40–100) | 90 (60–100) | 90 (70–100) | 80 (20–100) | *.001 |
| Post-OP KPS (median, range) | 80 (20–100) | n.a. | 80 (50–100) | 80 (10–100) | 90 (50–100) | 90 (70–100) | 80 (70–100) | 80 (10–100) | *.001 | |
| New postoperative deficit (n, %) | 17 (15.0%) | 54 (17.2%) | 13 (7.6%) | 43 (21.3%) | 10 (9.4%) | 13 (19.4%) | 11 (23.4%) | 161 (15.8%) | *0.001 | |
| IDH status (n, %) | wildtype | 113 (100%) | 314 (100%) | 172 (100%) | 189 (93.6%) | 106 (100%) | 67 (100%) | 47 (100%) | 1,008 (98.7%) | n. appl. |
| mutated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||
| n.a. | 0 | 0 | 0 | 13 (6.4%) | 0 | 0 | 0 | 13 (1.3%) | ||
| MGMT promotor (n, %) | methylated | 56 (49.6%) | 211 (67.2%) | 5 (2.9%) | 95 (47.0%) | 37 (34.9%) | 27 (40.3%) | 33 (70.2%) | 464 (45.5%) | *.001 |
| nonmethylated | 57 (50.4%) | 101 (32.2%) | 4 (2.3%) | 106 (52.5%) | 45 (42.5%) | 35 (52.2%) | 12 (25.5%) | 360 (35.3%) | ||
| n.a. | 0 | 2 (0.6%) | 163 (94.8%) | 1 (0.5%) | 24 (22.6%) | 5 (7.5%) | 2 (4.3%) | 197 (19.3%) | ||
| TERT promotor (n, %) | wildtype | 14 (12.4%) | 17 (5.4%) | 30 (17.4%) | 4 (2.0%) | 0 | 0 | 5 (10.6%) | 70 (6.9%) | *.001 |
| mutated | 98 (86.7%) | 151 (48.1%) | 124 (72.1%) | 3 (1.5%) | 0 | 8 (11.9%) | 12 (25.5%) | 396 (38.8%) | ||
| n.a. | 1 (0.9%) | 146 (46.5%) | 18 (10.5%) | 195 (96.5%) | 106 (100%) | 59 (88.1%) | 30 (63.8%) | 555 (54.4%) | ||
| Localization (n, %) | (sub-)cortical | 88 (77.9%) | 242 (77.1%) | 130 (75.6%) | 133 (65.8%) | 95 (89.6%) | 51 (76.1%) | 33 (70.2%) | 772 (75.6%) | *.001 |
| deep-seated | 13 (11.5%) | 16 (5.1%) | 24 (14.0%) | 49 (24.3%) | 4 (3.8%) | 11 (16.4%) | 9 (19.2%) | 126 (12.3%) | ||
| multifocal | 12 (10.6%) | 54 (17.2%) | 18 (10.5%) | 20 (9.9%) | 7 (6.6%) | 5 (7.5%) | 5 (10.6%) | 121 (11.9%) | ||
| n.a. | 0 | 2 (0.6%) | 0 | 0 | 0 | 0 | 0 | 2 (0.2%) | ||
| dominant hemisphere | 56 (49.6%) | 165 (52.6%) | 80 (46.5%) | 112 (55.5%) | 46 (43.4%) | 40 (59.7%) | 15 (31.9%) | 514 (50.3%) | *.001 | |
| Tumor volumes (mL; mean ± SEM) | Pre-OP CE | 29.4 ± 2 | 39.9 ± 2 | 29.9 ± 2 | 27.7 ± 2 | 35.5 ± 3 | 28.2 ± 3 | 25.5 ± 4 | 32.7 ± 1 | *.001 |
| Pre-OP non-CE | 20.3 ± 1 | 42.6 ± 2 | 107.7 ± 5 | 69.3 ± 4 | 60.0 ± 4 | 49.7 ± 4 | 54.0 ± 6 | 59.2 ± 2 | *.001 | |
| Post-OP CE | 9.1 ± 2 | 1.7 ± 0.2 | 2.8 ± 0.4 | 9.7 ± 1 | 1.1 ± 0.2 | 1.6 ± 1 | 0.2 ± 0.1 | 1.5 ± 0.1 | *.001 | |
| Post-OP non-CE | 8.9 ± 1 | 26.6 ± 2 | 58.9 ± 4 | 58.2 ± 3 | 34.1 ± 3 | 28.0 ± 3 | 26.8 ± 4 | 34.5 ± 1 | *.001 | |
| Adjuvant therapy (n, %) | RT alone | 14 (12.4%) | 8 (2.6%) | 3 (1.7%) | 21 (10.4%) | 11 (10.4%) | 7 (10.5%) | 1 (2.1%) | 65 (6.4%) | *.001 |
| EORTC-26981/22981 | 67 (59.3%) | 247 (78.7%) | 129 (75.0%) | 155 (76.7%) | 74 (69.8%) | 56 (83.6%) | 30 (63.8%) | 758 (74.2%) | ||
| CeTeG | 8 (7.1%) | 0 | 0 | 15 (7.4%) | 0 | 0 | 0 | 23 (2.3%) | ||
| TMZ alone | 15 (13.3%) | 3 (1.0%) | 3 (1.7%) | 0 | 6 (5.7%) | 0 | 2 (4.3%) | 29 (2.8%) | ||
| EORTC-26981/22981 + study drug | 0 | 29 (9.2%) | 25 (14.5%) | 0 | 0 | 0 | 7 (14.9%) | 61 (6.0%) | ||
| none or BSC | 9 (8.0%) | 23 (7.3%) | 12 (7.0%) | 11 (5.5%) | 3 (2.8%) | 3 (4.5%) | 7 (14.9%) | 68 (6.7%) | ||
| n.a. | 0 | 4 (1.3%) | 0 | 0 | 12 (11.3%) | 1 (1.5%) | 0 | 17 (1.7%) | ||
| Outcome | PFS (months; CI) | 8 (6–10) | 10 (9–11) | 6 (5–7) | 6 (5–7) | 8 (8–9) | 10 (9–12) | 11 (9–18) | 8 (8–9) | *.001 |
| OS (months; CI) | 20 (15–29) | 18 (16–20) | 18 (16–20) | 15 (13–18) | 14 (11–16) | 12 (12–15) | 32 (19–45) | 17 (16–18) | *.001 |
Characteristics are given for patients with glioblastoma WHO grade 4 as stratified according to the study center the data were transferred from and are summarized for all patients (total; n = 1,021). Differences between the study centers were analyzed using a 1-way ANOVA (for parametric data) or the Kruskal–Wallis test (for nonparametric data) for continuous variables; and categorical variables were assessed by the χ2 test. Kaplan–Meier estimates and log-rank testing were performed for survival analyses. P-values are given, and asterisks indicate P ≤ .05. BSC, best supportive care; CeTeG, TMZ + CCNU/RT→TMZ + CCNU; CCNU, lomustine; CI, 95% CI.; EORTC-26981/22981, TMZ/RT→TMZ; F, female; KPS, Karnofsky Performance Score; M, male; n.a., not available for review; n. appl., not applicable; PFS, progression-free survival; RT, radiotherapy; TERT, telomerase reverse transcriptase promotor; TMZ, temozolomide.