Background
Methods
Patients and tumors
Statistics
Results
Patient characteristics
n = 17 patients | |
---|---|
Age (years) | |
Median | 28 |
Range | 18–56 |
Age classes, n (%) | |
≤ 20 years | 2 (11.8) |
21–30 years | 8 (47.1) |
31–40 years | 0 |
41–50 years | 5 (29.4) |
> 50 years | 2 (11.8) |
Gender | |
Female | 3 (17.6) |
Male | 14 (82.4) |
KPS (pre-operative), n (%) | |
90–100 | 10 (58.8) |
70–80 | 6 (35.3) |
< 70 | 0 |
No data | 1 (5.9) |
KPS (start first CT), n (%) | |
90–100 | 3 (17.6) |
70–80 | 13 (76.5) |
< 70 | 0 |
No data | 1 (5.9) |
Tumor localizationc
| |
Supratentorial | 11 (64.7) |
Infratentorial | 6 (35.3) |
Extent of first resection, n (%) | |
Gross total resection | 4 (23.5) |
Subtotal resection | 5 (29.4) |
Partial resection | 5 (29.4) |
Biopsy | 2 (11.8) |
No data | 1 (5.9) |
Histology (initial) | |
Ependymoma WHO grade II | 4 (23.5) |
Anaplastic ependymoma WHO grade III | 13 (76.5) |
Histology (start first CT) | |
Ependymoma WHO grade II | 1 (5.9) |
Anaplastic ependymoma | 14 (82.4) |
Sarcoma/Gliosarcoma | 2 (11.8) |
MGMT promoter methylation status, n (%) | |
Unmethylated | 9 (52.9) |
Methylated | 3 (17.6) |
No data | 5 (29.1) |
First-line therapies beyond surgery, n (%) | |
RT alone | 9 (52.9) |
TMZ/RT → TMZ | 2 (11.8) |
No therapy | 6 (35.3) |
First salvage therapy, n (%) | |
Re-resection | |
alone | 4 (23.5) |
plus RT alone | 2 (11.8) |
plus RT plus TMZ | 2 (11.8) |
plus Bevacizumab | 1 (5.9) |
plus CTa
| 2 (11.8) |
CT aloneb
| 4 (23.5) |
RT alone | 1 (5.9) |
Bevacizumab alone | 1 (5.9) |
First CT, n (%) | |
TMZ | 10 (58.8) |
Procarbazine plus Lomustine plus Vincristine | 3 (17.6) |
Epirubicin plus Ifosfamide | 1 (5.9) |
Carboplatin plus Etoposide | 2 (11.8) |
Carboplatin plus Etoposide plus Vincristine | 1 (5.9) |
Number of surgical interventions | |
1 | 5 (29.4) |
2 | 3 (17.6) |
> 3 | 9 (52.9) |
Survival (from first CT) (all patients n = 17) | |
Median follow-up (months) | 39 |
Median PFS (months) (95% CI) (events) | 10 (3.4–16.6) (15) |
Median OS (months) (95% CI) (events) | 41 (31.6–50.4) (9) |
Survival (from first CT) (n = 15, patients 5 and 9 excludedd) | |
Median follow-up (months) | 39 |
Median PFS (months) (95 % CI) (events) | 6 (1.5–10.5) (14) |
Median OS (months) (95 % CI) (events) | 41 (30.0–52) (8) |
No. | Initial histology | WHO grade |
MGMT status | Localization | Extent of resection | First-line therapy | First salvage therapy | Surgical interventions (n) | Histology at start of CT | First CT | Duration of first CT a
| Best response | DBRa
| PFSa
| OSa
|
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
P1 | E | II | unmethyl. | infratentorial | subtotal | - | RT | 3 | AE | TMZ | 11 | SD | 11 | 17 | 68b
|
IV ventricle | |||||||||||||||
P2 | E | II | unmethyl. | supratentorial | partial | RT | re-resection RT | >3 | AE | PCV | 18 | SD | 4 | 21 | 41 |
parietal | |||||||||||||||
P3 | E | II | unmethyl. | infratentorial | partial | - | re-resection | 2 | AE | TMZ/RT→TMZ | 8 | SD | 29 | 32b
| 32b
|
cerebellar | TMZ/RT→TMZ | ||||||||||||||
brainstem | |||||||||||||||
IV ventricle | |||||||||||||||
P4 | E | II | unmethyl. | supratentorial | partial | - | re-resection | 3 | E | TMZ | 6 | SD | 2 | 5 | 5 |
III ventricle | |||||||||||||||
P5 | AE | III | n.d. | supratentorial | gross total | RT | re-resection | 2 | sarcoma | epirubicin | 5 | CR | 106 | 131b
| 131b
|
parietal | ifosfamide | ||||||||||||||
temporal | |||||||||||||||
occipital | |||||||||||||||
P6 | AE | III | unmethyl. | infratentorial | subtotal | RT | carboplatin | 1 | AE | carboplatin | 5 | PR | 7 | 11 | 16b
|
IV ventricle | etoposide | etoposide | |||||||||||||
P7 | AE | III | n.d. | supratentorial | partial | - | re-resection | >3 | AE | carboplatin | 1 | PD | - | 2 | 44b
|
parietal | etoposide | ||||||||||||||
vincristine | |||||||||||||||
cyclo-phosphamide | |||||||||||||||
P8 | AE | III | unmethyl. | infratentorial | gross | - | re-resection | >3 | AE | TMZ | 17 | SD | 21 | 25 | 80b
|
IV ventricle | total | RT | |||||||||||||
P9 | AE | III | n.d. | supratentorial | biopsy | RT | re-resection | 3 | gliosarcoma | TMZ | 9 | SD | 7 | 10 | 23 |
frontal | TMZ | ||||||||||||||
temporal | |||||||||||||||
P10 | AE | III | n.d. | infratentorial | gross | RT | TMZ | 1 | AE | TMZ | 5 | SD | 31 | 33 | 101b
|
cerebellar | total | ||||||||||||||
P11 | AE | III | unmethyl. | supratentorial | subtotal | RT | TMZ | 1 | AE | TMZ | 9 | SD | 9 | 10 | 13 |
III ventricle | |||||||||||||||
P12 | AE | III | n.d. | supratentorial | subtotal | TMZ/RT → TMZ | re-resection | >3 | AE | TMZ/RT → TMZ | 5 | SD | 4 | 5 | 48 |
parietal | bevacizumab | ||||||||||||||
P13 | AE | III | unmethyl. | supratentorial | gross total | RT | re-resection | 3 | AE | PCV | 8 | SD | 1 | 5 | 40 |
parietal | PCV | ||||||||||||||
P14 | AE | III | unmethyl. | supratentorial | biopsy | - | re-resection | 2 | AE | TMZ | 1 | PD | - | 2 | 2 |
temporal | RT | ||||||||||||||
III ventricle | TMZ | ||||||||||||||
P15 | AE | III | methyl. | infratentorial | partial | RT | re-resection | 3 | AE | carboplatin | n.d. | PD | - | 4 | 29b
|
cerebellar | etoposide | ||||||||||||||
brainstem | |||||||||||||||
IV ventricle | |||||||||||||||
P16 | AE | III | methyl. | supratentorial | n.d. | RT | PCV | 1 | AE | PCV | 3 | SD | 2 | 6 | 39 |
temporal | |||||||||||||||
P17 | AE | III | methyl. | supratentorial | subtotal | TMZ/RT → TMZ | bevacizumab | 1 | AE | TMZ/RT → TMZ | 1 | PD | - | 1 | 6 |
parietal |
Benefit from chemotherapy
MGMT promoter methylation and survival in intracranial ependymoma
Association of age, tumor localization, gender, KPS and MGMT promoter methylation status with survival
Variable | Number of patients (events) | Median OS (months) (95 % CI) |
p value (log-rank) |
p value (cox regression) | Hazard Ratio (95 % CI) |
---|---|---|---|---|---|
Agea
| |||||
< 40 years | 9 (5) | 48 (28.5–67.5) | 1 | ||
≥ 40 years | 8 (4) | 41 (13.8–68.14) | 0.587 | 0.589 | 1.45 (0.37–5.64) |
Tumor localizationa
| |||||
Infratentorial | 6 (0) | undefined | 1 | ||
Supratentorial | 11 (9) | 39 (9.87–68.13) | 0.011 (*) | 0.163 | 50.8 (0.20–12662.82) |
Gender | |||||
Female | 3 (2) | 41 (0–97.01) | 1 | ||
Male | 14 (7) | 48 (35.84–60.16) | 0.888 | 0.888 | 0.89 (0.18–4.34) |
KPSa
| |||||
100–80 | 11 (6) | 48 (14.47–81.54) | 1 | ||
< 80 | 5 (3) | 41 (11.96–70.04) | 0.872 | 0.872 | 1.12 (0.28–4.52) |
MGMT promoter methylation | |||||
not methylated | 9 (5) | 40 (9.3–70.7) | 1 | ||
methylated | 3 (2) | 39 (undefined) | 0.433 | 0.443 | 2.02 (0.34–12.2) |
Discussion
First author, year [Ref] | Trial design | Patient diagnosis, n | Tumor localization | Treatment regimen, n | Response rates, n | Median PFS, after start CT | Median OS, after start CT |
---|---|---|---|---|---|---|---|
present study | Retrospective | newly diagnosed and recurrent WHO grade II and III ependymoma, 17 | supratentorial or infratentorial | TMZ-based CT: 10 | CR: 1 | 10 months | 41 months |
platinum-based CT: 3 | PR: 1 | ||||||
PCV: 3 | SD: 11 | ||||||
epirubicin/ifosfamide: 1 (no prior CT) | PD: 4 | ||||||
Gilbert et al., 2014 [16] | Prospective | recurrent WHO grade II ependymoma, 24 and grade III,18 ependymoma | intracranial and/or spinal | TMZ plus lapatinib | WHO grade II | WHO-grade II: 45 weeks | - |
PR: 2 | WHO-grade III: 25.3 weeks | ||||||
SD/PD: no data | |||||||
WHO grade III | |||||||
CR: 1 | |||||||
PR: 1 | |||||||
SD/PD: no data | |||||||
Chamberlain and Johnston, 2009 [15] | Retrospective | recurrent WHO grade II ependymoma, 25 | supratentorial | TMZ (after platinum-based CT) | PR: 1 | 2 months | 3 months |
SD: 9 | |||||||
PD: 15 | |||||||
Green et al., 2009 [26] | Retrospective | recurrent WHO grade II and III ependymoma, 8 | supratentorial or infratentorial | bevacizumab (after platinum-based CT or TMZ) | PR: 6 | 6.4 months | 9.4 months |
SD: 1 | |||||||
PD: 1 | |||||||
Brandes et al., 2005 [17] | Retrospective | recurrent WHO grade II and III ependymoma, 28 | intracranial | cisplatin-based CT: 13 (no prior CT) | CR: 2 | 9.9 months | 31 months |
PR: 2 | |||||||
SD: 7 | |||||||
PD: 2 | |||||||
versus | versus | versus | versus | ||||
CT without cisplatin: 15 (no prior CT) | PR: 2 | 10.9 months | 40.7 months | ||||
SD: 11 | |||||||
PD: 2 | |||||||
Soffietti et al., 2005 [14] | Prospective | recurrent WHO grade II and III ependymoma, 11 | intracranial | TMZ (some after nitrosourea or platinum-based CT) | CR: 2 | CR: 9–48+ months | - |
PR: 3 | PR: 4–15+ months | ||||||
SD: 5 | SD: 7–44+ months | ||||||
PD: 1 | |||||||
Lombardi et al., 2013 [13] | case report | recurrent anaplastic ependymoma | supratentorial | TMZ plus cisplatin (after platinum-based CT alone and TMZ alone) | PR | 9 months | 11 months |
Freyschlag et al., 2011 [12] | case report | recurrent anaplastic ependymoma | supratentorial | TMZ | no evidence of radiographic progression | 5+ months | - |
Rojas-Marcos et al., 2003 [25] | case report | recurrent anaplastic ependymoma | infratentorial (initial) and supratentorial (at recurrence) | tamoxifen plus isotretinoin (after TMZ, platinum-based CT, CCNU) | CR | 17 months | - |