GBM Flashcards
What is the pathognomonic finding for GBM?
(presence of this = diagnosis)
Pseudopalisading necrosis
What is the median survival of GBM?
14 months
What is the treatment paradigm for GBM?
Maximal safe resection with neurological preservation, followed by adjuvant chemoRT as per the Stupp trial
What is the epidemiology of GBM?
Most common primary malignant brain tumour in adults (80%)
Median age at dx 64
M:F 1.5:1
White ethnicity > others
What are the diagnostic criteria for a GBM as per WHO 2021 classification?
adult patient
diffuse astrocytic tumour
IDH-wildtype
and at least one of the following:
- necrosis
- microvascular proliferation
- TERT promoter mutation
- EGFR gene amplification
- combined gain of whole chromosome 7 and loss of chromosome 10 [+7/-10]
What is the MEAN criteria?
Pathology criteria for dx of glioma
More = higher grade
high Mitotic index
Endothelial proliferation
nuclear Atypia
Necrosis
Previously GBM was diagnosed if 3 of these were present
What is the ChemoRT aspect of GBM treatment?
RT 60Gy/30# with concurrent Temozolamide (75mg/m^2) daily on RT, and then 150-200mg/m2 adjuvantly for days 1-5 of 28 day cycle for 6 months (shorter if not tolerated)
What is the IDH mutation status of GBM as per 2021 WHO classification?
Glioblastoma is defined as a diffuse astrocytic tumour in adults that is IDH-wild type (ie. not mutated).
Grade 4 astrocytoma IDH mutated is a separate entity
What proportion of GBMs are de novo vs secondary arising from an existing lower grade tumour?
90% vs 10%
What are the three histological variants of GBM as per WHO 2021 classification?
giant cell glioblastoma
gliosarcoma
epithelioid glioblastoma
What genetic syndromes are associated with increased risk of GBM?
vast majority of GBM are sporadic
Assoc. with:
NF1
Li fraumeni syndrome
Turcot syndrome
Ollier disease
Maffucci syndrome
What parts of the brain does GBM have a predilection for arising in?
Subcortical white matter
Deep grey matter of cerebral hemispheres, esp temporal lobe
Supratentorial white matter is most common location
But can arise anywhere in brain
What is a multifocal GBM compared to a multicentric GBM
Multifocal glioblastomas are tumours which have multiple discrete areas of contrast-enhancing tumour embedded with, or connected by, T2/FLAIR signal abnormality. Multifocal glioblastomas are considered to be part of the one tumour.
vs Multicentric: multiple discrete areas of contrast-enhancing tumour without connecting T2/FLAIR signal abnormality. They are considered to represent separate synchronous tumours.
What proportion of GBMs are multifocal?
20%
Do multifocal have a better or worse prognosis than regular GBM?
Worse prognosis
Macroscopic appearance of GBM
Location
Size
Shape
Colour
Edges
Presence/absence of special features e.g. haemorrhage
Glioblastomas are typically poorly marginated, diffusely infiltrating, necrotic masses localised to the cerebral hemispheres.
Supratentorial white matter most common location.
Considerable regional variation in appearance within the tumour is characteristic:
- may be firm or gelatinous.
- Some areas are firm and white
- some are soft and yellow (secondary to necrosis)
- some are cystic with local haemorrhage.
- significant variability in size from only a few centimetres to lesions that replace a hemisphere.
- Infiltration beyond the visible tumour margin is always present.
Microscopic appearance of GBM
- Pleomorphic astrocytes with marked atypia and numerous mitoses are seen.
- Varied patterns sometimes within one tumour seen
- Necrosis and microvascular proliferation are hallmarks of glioblastomas.
- Multinucleated giant cells (if dominant feature»_space; giant cell GBM)
IHC of GBM
GFAP: positive but of variable intensity
S100: positive
nestin: positive
p53 protein: positive if TP53 mutated
EGFR: positive in 40-98% of cases
IDH-1 R132H: negative (by definition, otherwise not an IDH-wildtype glioblastoma, but rather an astrocytoma, IDH-mutant WHO CNS grade 4)
H3 K27M mutation: negative (if positive then diffuse midline glioma H3 K27-altered)
Genetic changes seen in GBM
EGFR gene amplification
TERT promoter mutations
combined gain of whole chromosome 7, loss of chromosome 10 [+7/-10]
alterations of the CDK4/6–RB1 cell-cycle pathway: 80% due to deletions of CDKN2A
How does the epidemiology go epithelioid GBM differ from usual GBM?
Epithelioid more common in young adults and young children
What are microscopic features of epithelioid GBM?
These tumours are heterogeneous with large epithelioid cells that have abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Rhabdoid cells are also sometimes encountered
What are the options for treating GBM?
60Gy/30# with concurrent TMZ
40.05Gy/15# with concurrent TMZ
34GY/10#
25Gy/5#
TMZ mono therapy
Best supportive care
Is there benefit to radiotherapy alone in GBM?
Yes-
Laperriere et al. conducted a systematic review which included 6 randomised controlled trials comparing conventional radiation therapy with no radiation therapy.
Patient groups included grade 3 and 4 gliomas. Doses ranged from 50-60 Gy
Survival benefit with post op radiotherapy RR = 0.81, 95% CI:0.74-0.88, p <0.00001
What is the evidence supporting use of 60GY/30# with concurrent TMZ followed by adjuvant TMZ in GBM?
Stupp trial
- Between 2000 and 2002, 286 patients were randomised to receive radiation therapy alone (60 Gy in 30 fractions) and 287 patients were randomised to receive radiation therapy (60 Gy in 30 fractions) and continuous daily TMZ (75 mg per square meter of body surface area per day, 7 days per week from the first to the last day of radiation therapy) followed by six cycles of adjuvant TMZ (150 to 200 mg per square meter for 5 days during each 28 day cycle).
- After a median follow up of 28 months, the median survival was 14.6 months in the radiation therapy plus TMZ group versus 12.1 months in the radiation therapy alone group (HR = 0.63, 95% CI:0.52-0.75, p <0.001).
- The 2-year overall survival was 26.5% in the radiation therapy plus TMZ group versus 10.4% in the radiation therapy alone group.
- 2-year progression free survival was 11.2% in the radiation therapy plus TMZ group and 1.8% in the radiation therapy alone group.
- The updated 5-year results showed 5-year survival of 9.8% versus 1.9%
