Table 2.
Randomized controlled trials for elderly patients with GBM
| Study | Age (years) | N | Treatment | Median OS (95% CI) | Hazard Ratio (95% CI) | Note |
|---|---|---|---|---|---|---|
| Surgery | ||||||
| Vuorinen 200328) | >65 | 30 | Biopsy + RT | 85 days | 2.621 (1.035–6.641) | Resection improves survival |
| Resection + RT | 171 days | |||||
| Radiotherapy | ||||||
| Keime-Guibert 200734) | ≥70 | 85 | Resection + best supportive care | 16.9 weeks | 0.47 (0.29–0.76) | ANOCEF trial RT improves survival |
| Resection + RT | 29.1 weeks | |||||
| Roa 200435) | ≥60 | 100 | Std RT (60 Gy/30 Fr) | 5.1 months | 0.89 (0.59–1.36) | Non-inferiority of Hypo-RT |
| Hypo-RT (40 Gy/15 Fr) | 5.6 months | |||||
| Roa 201536) | ≥50 + frail ≥65 | 98 | Std-RT (Hypo-RT) (40 Gy/15 Fr) | 6.4 months (5.1–7.6) | NA | IAEA E33033 trial. Frail: KPS 50–70 |
| Hypo-RT (short-course) (25 Gy/5 Fr) | 7.9 months (9.3–9.6) | |||||
| Guedes de Castro 201737) | ≥65 | 61 | Std-RT (Hypo-RT) (40 Gy/15 Fr) | 6.2 months (5.1–7.6) | NA | Subset analysis of IAEA trial |
| Hypo-RT (short-course) (25 Gy/5 Fr) | 6.8 months (9.3–9.6) | |||||
| Radiation-Chemotherapy | ||||||
| Wick 201222) | >65 | 412 | Std-RT (60 Gy/30 Fr) | 9.6 months | NOA-08 trial Non-inferiority of the dose dense TMZ. MGMT methylation associated with longer OS |
|
| Dose dense TMZ* (100 mg/m2/day, 1-week ) | 8.6 months | 1.09 (0.84–1.42) | ||||
| MGMT unmethylated | 8.2 months | |||||
| MGMT methylated | 11.9 months | 0.62 (0.42–0.91) | ||||
| Malmström 201223) | ≥60 | 342 | Std-RT (60 Gy/30 Fr) | 6.0 months | Nordic trial MGMT promoter methylation status to predict clinical benefit of TMZ but not in RT. More benefit of TMZ monotherapy in GBM aged >70 |
|
| Hypo-RT (34 Gy/10 Fr) | 7.5 months | 0.85 (0.64–1.12) | ||||
| Any radiotherapy | 7.0 months | |||||
| MGMT unmethylated | 8.2 months | 0.97 (0.69–1.38) | ||||
| MGMT methylated | ||||||
| TMZ monotherapy | 8.3 months | 0.7 (0.52–0.93) | ||||
| MGMT unmethylated | 6.8 months | |||||
| MGMT methylated | 9.7 months | 0.56 (0.34–0.93) | ||||
| Perry 201643) | ≥65 | 562 | Hypo-RT alone | 7.6 months | CCTG CE.6 trial. Improvement of OS by addition of TMZ to Hypo-RT for all cases |
|
| MGMT unmethylated | 7.9 months | |||||
| MGMT methylated | 7.7 months | |||||
| Hypo RT + TMZ (3 weeks) | 9.3 months | 0.67 (0.56–0.80) | ||||
| MGMT unmethylated | 10.0 months | 0.75 (0.56–1.01) | ||||
| MGMT methylated | 13.5 months | 0.53 (0.38–0.73) | ||||
GBM: glioblastoma, KPS: Karnofsky Performance Status, MGMT: O6-methylguanine DNA methyltransferase, MGMT unmethylated: absence of MGMT promoter methylation, MGMT methylated: presence of MGMT promoter methylation, OS: overall survival, Std-RT: Standard radiotherapy, Hypo-RT: Hypofractionated radiotherapy, RT: radiotherapy, TMZ: temozolomide.
*
Dose-dense TMZ: 100 mg/m2/day, 1-week on/1-week off regimen.