Most common Brain tumor in adults
GBM
Median survival
~ 14 months
Treatment paradigm
- Maximum safe resection
- Adjuvant CRT
Basic RT dose
60Gy in 30 fractions
RT Doses
Epidemiology
- Median age 64 years
- Male gender (1.5:1)
- 10,000 cases a year
Anatomy
Mostly supra tentorial
white matter tracts
Pathology
Glial cells of CNS
Mean criteria
M: Mitotic index
E: Endothilial proliferation
A: Nuclear atypia
N: Necrosis
Molecular diagnosis
Molecular diagnosis
MGMT Methylation
MGMT is located on 10q26
MGMT methylated is GBM
Molecular diagnosis
IDH Mutation
IDH wild type is GBM
It is an independent prognostic factor
* IDH Mutant: 27.4 months
* IDH Wild type: 14 months
Other molecular genes to look for
- ATRX lost
- CDKN2A/B deleted
- TERT mutation
- EGFR amplified
- H3.3G34R/V wild type or mutant: if mutant then diffuse hemispheric glioma
- H3K27M: mutant: Diffuse midline glioma
Clinical presentation
Headache
cognitive changes
seizures
motor weakness
Work up
H&P
neuro examination
fundoscopic examination
Basic Labs
Imaging
Imaging
MRI Brain with and without contrast
* Heterogenous enhancement
* central necrosis
* edema
* T1 hypointense
* T2 hyperintense
Prognostic factors
- Age
- extent of resection
- MGMT status
- IDH status
Surgery
Maximum safe resection
Get MRI 24-48 hours post surgery
Chemotherapy
TMZ
- 75 mg/m2 daily concurrently including weekends
- 150-200 mg/m2 adjuvantly days 1-5 for 6-12 months
- ADR: constipation, thrombocytopenia, neutropenia
- Give prophylaxis for pneumocystis pneumonia, Trimethoprim/sulfamethoxazole
Adjuvant RT
Improves OS
60Gy in 30 fractions
40Gy in 15 fractions
Stupp trial
OS and PFS improved with CRT when compared to RT alone
* MS: 12 months vs 15 months
* 5 yr OS: 1.9 % vs 9.8%
* MGMT: 15.3 months vs 21.7 months
MGMT methylation
Improved survival
11.8 months to 15.3 months
WBRT
for palliative pts
multifocal disease
low KPS
Median OS ~ 7 months
