Glioblastoma

Question 1

What trial defines the current SOC in GBM?

Answer 1

Stupp, EORTC 26899 (Lancet 2009), PRT
Ages 18-70, PS 0-2
RT alone vs chemoRT with concurrent and adjuvant TMZ
75 mg/m2 daily, 150-200 mg/m2 d1-5 q4wks x 6c
MS 12.1 vs 14.6 months
2-yr OS 11% vs 27%

Question 2

Is there a benefit to using Tumor Treating Fields?

Answer 2

Stupp (JAMA 2015), PRT
Stupp regimen then randomzied to adjuvant TMZ or adjuvant TMZ+TTF
OS improved 20.5 vs 15.6 months
PFS improved 7 vs 4 months

Question 3

Elderly patients: RT or supportive care?

Answer 3

Keime-Guibert, France (NEJM 2007), PRT
Age 70 and older, KPS 70 and higher
Randomized RT 50.4Gy/28fx vs best supportive care after biopsy/resection.
No difference in QOL or cognition.
MS improved with RT 29 vs 17 weeks
RT improves OS in elderly pts with GBM (if good PS).

Question 4

Hypofrac for elderly/poor PS patients?

Answer 4

Roa, Canadian (JCO 2004), PRT
Patients 60 and older
Randomized 60Gy/30fx vs 40 Gy/15 fx (no chemo)
No difference in OS (MS 5.1 vs 5.6 months)
26% stopped long course vs 10% in short course arm

Roa, IAEA (JCO 2015), PRT
Elderly&Frail pts (age 50 & older & KPS 50-70 or age 65 & older with KPS 50 & higher)
R 25Gy/5fx vs 40Gy/15fx (no chemo)
Same OS, PFS, and QOL outcomes

Question 5

TMZ alone in elderly patients?

Answer 5

Wick, NOA-08 (Lancet 2012), PRT
Age >65 and KPS 60 & higher
R TMZ alone (100 mg/m2 7 days on/off for as long as tolerated) vs (RT alone 60 Gy/30fx)
OS similar (8.6 vs 9.6 months)
Pts w/ MGMT promoter methylation had better OS.
MGMT pts had improved EFS with TMZ.
Pts w/o methylation had improved EFS with RT.

Malmstrom, Nordic Trial (Lancet 2012), PRT
Age >60
R TMZ alone (200 mg/m2 d1-5 of 28 day cycle up to 6c) vs RT alone 60Gy/30fx vs RT alone 34Gy/10fx.
MS improved for TMZ alone (8 mo) compared to standard RT (6 mo) but not vs hypofrac RT (7.5 mo).
Pts >70yo, improved OS in both TMZ and hypofrac RT arms.
Use of TMZ alone or hypofrac RT should be SOC in elderly population, especially if >70.

Question 6

Add TMZ to short-course RT?

Answer 6

Perry, EORTC 26062 (NEJM 2017), PRT
Age 60 & older
40Gy/15fx, R to no chemo vs 3 wks concurrent TMZ & monthly adjuvant TMZ up to 12c.
MS improved with RT+TMZ (9.3 vs 7.6 mo).
MGMT methylated patients benefitted most (OS 13.5 vs 7.7 mo).