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Flashcards in Neuro-oncology Deck (22):
1

How is best outcome obtained?

Maximal safe resection is performed,
Surgical morbidity minimized
Adequate representative tumor tissue

2

What decisions re: aggressiveness of surgery for primary brain lesions depend on?

Age and PS
Proximity to “eloquent” areas of brain
Feasibility of decreasing mass effect with aggressive surgery
Resectability of tumor (including number and location of lesions)
Time since last surgery in patients with recurrent disease

3

What sort of tumor is Temozolomide recommended for?

MGMT-promotor methylated tumor
MGMT = Methylguanine methyl-transferase

4

What surgical options are there?

Stereotactic biopsy
Open biopsy
Subtotal resection (STR)
Complete resection = Gross total resection (GTR)

5

How common is seizure

81% of low-grade gliomas

more frequently a/w oligodendrogliomas

6

What is the most common non-infiltrative astrocytoma?

Pilocytic astrocytoma

circumscribed, often resectable, rarely transform

7

What are the low-risk features for low grade gliomas?

40yo or less
Gross total resection performed

8

What are the features of Anapaestic oligodendrogiomas

They are relatively rare. Usually in frontal lobes
Characterized by:
- High cellularity
- Nuclear pleomorphism
- Frequent mitosis
- Endothelial proliferation
- Necrosis

Can be mixed up with GBM
Characteristic allelic loss of chr 1p and 19q

9

What are implanted wafers ?

Administers Carmustine using a biodegradable polymer (wafer) placed intra-operatively into the surgical cavity.

Has demonstrated significant improvement in survival with HG gliomas (30 w vs 20 w, adj HR 0.67)

Phase III placebo-controlled study in n=32
BCNU polymer used in combination with RT

Larger Phase III with n=240 newly Dx malignant glioma
Med survival 12m to 14m.

Carmustine can potentially interact with other agents, resulting in increased toxicity

Implantation of the wafer may preclude future participation of clinical trials of adjuvant therapy

10

Tell me about MGMT

MGMT = O-6-methylguanine-DNA-methyltransferase

DNA repair enzyme, can cause resistance to DNA-alkylating drugs

Oligodendrogliomas frequently exhibit MGMT hypermethylation and low expression levels
In the Temozolomide arm of both the Nordic and German trials, patients with MGMT promoter methylation had longer survival than those without (10m vs 7m, HR 0.7)

11

What are the side-effects of Bevacizumab

Hypertension
Impaired wound healing
Colonic Perforation
Thromboembolism

12

Tell me about the Alternating Electric Field Therapy

Portable medical device, generates low-intensity electric fields termed Tumor Treating Fields) for tx of recurrent glioblastoma
Approval based on trial with n=240
2 arms, TTF vs chemotherapy
Similar survival, and TTF a/w lower toxicity and improved QoL

13

Tell me about the Stupp Trial re: concurrent and adjuvant Temozolomide.

Stupp t al, NEJM 2005

Purpose of this trial was to evaluate if concurrent and adjuvant Temozolomide to RT was better in terms of efficacy and safety.

N=570, newly Dx, histologically confirmed GMB.
2 arms:
1) RT+ Concurrent Tem --> Adjuvant Tem
2) RT alone

Concurrent Temo: 75 mg/m2 x 7 days per week, from D1 to last day of RT
Adjuvant RT: 150-200 mg/m2 for 5/7 Q28Days

80% had undergone debulking surgery.
Median survival at 28months, median survival 14.5m vs 12m.
2-yr survival rate 27% with RT+ Temo vs 10% for RT alone

5-yr update in Lancet Oncol 2009:
OS 10% vs 2%; HR 0.6
Methylation of MGMT promoter was the strongest predictor for outcome and benefit from Temo chemo

14

Frequency of 1p 19q co-deletion in which tumors

Pathognomonic of oligodendroglioma

50-80% in anaplastic oligodendroglioma
30-60% in oligodendroglioma

15

Frequency of IDH1/2 mutation

70-80% in Diffuse astrocytoma, oligodendroglioma/oligoastorcytoma

50-70% of anaplastic astrocytoma
50-80% in anaplastic oligodendroglioma
5-10% in GBM

Assessed by IHC
If negative, then do gene sequencing

16

What are the advanced imaging modalities that you know of?

MR Spectroscopy
MR Perfusion
Functional MRI
PET imaging

17

How do you assess tumor?

By the RANO response criteria, based on:
1) T1 Gadollinium-enhancing disease
2) T2/FLAIR sequence
3) New lesions
4) Corticosteroid usage
6) Clinical status

Response graded as:
CR
PR
SD
PD

18

What are the factors that limit extent of resection?

1) Location of tumor
- Surgically inaccessible
- located within eloquent areas of the brain
2) Patent's co-morbidities

19

What are the advantages for surgery?

1) More accurate histology and grading
2) Remove mass effects and relives neurological deficits
3) Cytoreduction
4) Tissues for research

20

What is the current standard of RT?

1) Tumor bed + 2 cm margin
2) 60 Gy in 30#

21

What are the side effects of Temozolamide?

Temozolamide is an oral alkylating agent

Fatigue
Constipation
N+V
Relatively mild hematotoxicity
Less toxic than PVC regimen

22

What is the EORTC prognostic score

It is for low-grade lipoma to decide if patients would benefit from upfront post-op RT

This is ESP so as the EORTC study done showed no OS benefit to post-op observation vs radiation.