Background
Methods
Patient selection
Radiotherapy
MGMT methylation analysis
Statistical analyses
Results
Patient characteristics and treatment
Treatment | |||||
---|---|---|---|---|---|
Total | Stupp | HFRT + TMZ | HFRT |
p
| |
Number of patients | 104 | 33 (32%) | 37 (35%) | 34 (33%) | |
Gender | 0.65 | ||||
Male
| 53 (51%) | 19 (58%) | 18 (49%) | 16 (47%) | |
Female
| 51 (49%) | 14 (42%) | 19 (51%) | 18 (53%) | |
Age | <0.01* | ||||
Median (years)
| 75 [70–88] | 73 [70–81] | 75 [70–80] | 79 [70–88] | |
< 75.5 years
| 55 (53%) | 24 (73%) | 20 (54%) | 11 (32%) | |
≥ 75.5 years
| 49 (47%) | 9 (27%) | 17 (46%) | 23 (68%) | |
KPS | <0.01* | ||||
Median | 70 [30–100] | 80 [50–100] | 70 [30–100] | 60 [40–90] | |
KPS < 70
| 40 (38%) | 5 (15%) | 13 (35%) | 22 (65%) | |
KPS ≥ 70
| 64 (62%) | 28 (85%) | 24 (65%) | 12 (35%) | |
Type of suregery | 0.09 | ||||
Resection (complete/ partial)
| 5 / 9 (5% / 9%) | 2 / 6 (6% / 18%) | 1 / 2 (3% / 5%) | 2 / 1 (6% / 3%) | |
Biopsy
| 90 (86%) | 25 (76%) | 34 (92%) | 31 (91%) | |
MGMT status | 0.58 | ||||
Methylated
| 33 (45%) | 11 (41%) | 12 (43%) | 10 (56%) | |
Unmethylated
| 40 (55%) | 16 (59%) | 16 (57%) | 8 (44%) | |
Unknown
| 31 | 6 | 9 | 16 | |
RPA Class | <0.001* | ||||
I-II
| 14 (14%) | 8 (24%) | 3 (8%) | 3 (9%) | |
III
| 52 (50%) | 20 (61%) | 22 (59%) | 10 (29%) | |
IV
| 38 (36%) | 5 (15%) | 12 (32%) | 21 (62%) | |
Adjuvant Temozolomide | 28 (27%) | 18 (55%) | 10 (10%) | 0 (0%) | <0.0001* |
Treatment at recurrence | 12 (12%) | 7 (21%) | 3 (8%) | 2 (6%) | 0.1 |
Overall survival and prognostic factors
Median survival (months) | 12 months survival (%) | Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|---|---|
HR [95%CI] |
p
| HR [95%CI] |
p
| |||
Age | ||||||
< 75.5 years
| 5.6 | 18.6 | ||||
≥ 75.5 years
| 5.1 | 17.8 | 1.03 [0.69–1.53] | 0.88 | 0.76 [0.49–1.20] | 0.25 # $
|
KPS | ||||||
< 70
| 3.2 | 7.5 | ||||
≥ 70
| 7.8 | 25 | 0.52 [0.34–0.77] | < 0.01 | 0.70 [0.45–1.09] | 0.11 #
|
Gender | ||||||
Female
| 4.5 | 15.7 | ||||
Male
| 6.1 | 20.7 | 0.70 [0.47–1.05] | 0.08 | 0.71 [0.47–1.08] | 0.10 # $
|
MGMT status | ||||||
Methylated
| 5.9 | 12.1 | ||||
Unmethylated
| 4.8 | 17.5 | 1.14 [0.72–1.82] | 0.57 | ||
Type of surgery | ||||||
Biopsy
| 4.8 | 50 | ||||
Resection
| 13.5 | 13 | 0.43 [0.24–0.77] | < 0.05 | 0.47 [0.26–0.86] | < 0.05 #
|
RPA class | ||||||
I-II
| 13.5 | 50 | ||||
III
| 5.5 | 15.4 | 1.95 [1.07–3.57] | < 0.05 * | 2.15 [1.17–3.95] | < 0.05 $ * |
IV
| 3.1 | 7.9 | 3.08 [1.65–5.76] | < 0.001 * | 2.87 [1.53–5.41] | < 0.01 $ * |
Type of treatment | ||||||
HFRT + TMZ
| 5.5 | 18.9 | ||||
Stupp
| 9.6 | 24.2 | 0.74 [0.46–1.20] | 0.22¤
| ||
HFRT
| 3.9 | 8.8 | ||||
HFRT + TMZ or Stupp
| 5.9 | 22.9 | 0.6 [0.40–0.92] | < 0.05§
| 0.54 [0.33–0.88] | < 0.05 # $ §
|
Discussion
Major interest | Reference | Year | Design | Number of patients | Age | KPS | Treatment | Median survival in months (p) | Notes |
---|---|---|---|---|---|---|---|---|---|
Surgery | Vuorien et al.[30] | 2003 | Prospective | 23 | ≥ 65 | > 60 | Biopsy + RT | 2.8 | Longer survival after resection while time to neurological deterioration did not differ. |
Resection + RT | 5.7 (< 0.05) | ||||||||
Radio-therapy | Roa et al.[6] | 2004 | Prospective | 100 | ≥ 60 | ≥ 50 | RT | 5.1 | Half overall treatment time for HFRT with no difference in survival. |
HFRT | 5.6 (ns) | ||||||||
Keime-Guibert et al. [5] | 2010 | Prospective | 81 | ≥ 70 | ≥ 70 | Supportive care | 3.9 | No negative effect of RT on quality of life. | |
RT | 6.7 (< 0.01) | ||||||||
Radio-therapy + TMZ | Minniti et al. [34] | 2009 | Prospective | 43 | ≥ 70 | ≥ 60 | HFRT + TMZ | 9.3 | Grade 3–4 hematologic toxicity occurred in 28% of patients. no negative effect on quality of life. |
Minniti et al. [33] | 2012 | Prospective | 71 | >70 | > 60 | HFRT + TMZ and TMZ | 12.4 | Grade 3–4 hematologic toxicity occurred in15% of patients. | |
Minniti et al. [31] | 2015 | Retrospecitve | 127 | ≥ 65 | ≥ 60 | RT + TMZ and TMZ | 12 | No difference in overall survival or progression free survival between standard RT and HFRT | |
HFRT + TMZ and TMZ | 12.5 (ns)
| ||||||||
Lombardi et al. [11] | 2015 | Retrospecitve | 237 | ≥65 | ECOG PS 0–2 | HFRT + TMZ | 13.8 | Potential advantage of standard RT over HFRT for “moderate” elderly patients with good clinical status and extensive surgery | |
RT + TMZ | 19.4 (p = 0.02)
| ||||||||
Perry et al.[14] | 2017 | Prospective | 562 | ≥65 | ECOG PS 0–2 | HFRT | 7.6 | The addition of TMZ (concomitant and adjuvant) to HFRT resulted in longer overall survival than HFRT alone | |
HFRT + TMZ and TMZ | 9.3 (p < 0.001)
| ||||||||
Present study | 2017 | Retrospective | 104 | ≥ 70 | ≥ 30 | HFRT | 3.9 (p < 0.05)*
| Potential benefit of combining TMZ with RT in an unselected cohort, irrespective of MGMT promoter status. | |
HFRT + TMZ | 5.5 | ||||||||
RT + TMZ | 9.6 (ns)**
| ||||||||
HFRT alone | Guedes de Castro et al. [32] | 2017 | Prospective | 61 | ≥ 65 | ≥ 50 | HFRT 40Gy in 15 fractions | 6.2 | HFRT of 25Gy in 5 fractions seemed acceptable especially for elderly patients with a poor performance status or contraindication to chemotherapy. |
HFRT 25Gy in 5 fractions | 9.1 | ||||||||
TMZ alone | Wick et al. [8] | 2012 | Prospective | 371 | > 65 | ≥ 60 | Dose-dense TMZ alone | 8.0 | MGMT methylation is a predictive marker of TMZ alone efficacy. |
RT | 9.6 (ns) | ||||||||
Malmström et al. [7] | 2012 | Prospective | 291 | ≥ 60 | OMS 0–2 | TMZ alone | 8 | No benefit of RT over HFRT. MGMT methylation is a predictive marker of TMZ alone efficacy. | |
HFRT | 7.5 | ||||||||
RT | 6 | ||||||||
Poor perfor-mance status | Gállego Pérez-Larraya et al. [35] | 2011 | Prospective | 70 | ≥ 70 | <70 | TMZ alone | 5.8 | KPS improvement in 30% of patients by 10 or more points. |
Reyes-Botero et al. [36] | 2013 | Prospective | 66 | ≥ 70 | <70 | TMZ + Bevacizumab | 5.5 | Lower safety of the combination of TMZ with bevacizumab, no survival benefit |