Flashcards in Neuro-oncology Deck (22):
How is best outcome obtained?
Maximal safe resection is performed,
Surgical morbidity minimized
Adequate representative tumor tissue
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
What sort of tumor is Temozolomide recommended for?
MGMT-promotor methylated tumor
MGMT = Methylguanine methyl-transferase
What surgical options are there?
Subtotal resection (STR)
Complete resection = Gross total resection (GTR)
How common is seizure
81% of low-grade gliomas
more frequently a/w oligodendrogliomas
What is the most common non-infiltrative astrocytoma?
circumscribed, often resectable, rarely transform
What are the low-risk features for low grade gliomas?
40yo or less
Gross total resection performed
What are the features of Anapaestic oligodendrogiomas
They are relatively rare. Usually in frontal lobes
- High cellularity
- Nuclear pleomorphism
- Frequent mitosis
- Endothelial proliferation
Can be mixed up with GBM
Characteristic allelic loss of chr 1p and 19q
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
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)
What are the side-effects of Bevacizumab
Impaired wound healing
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
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.
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
Frequency of 1p 19q co-deletion in which tumors
Pathognomonic of oligodendroglioma
50-80% in anaplastic oligodendroglioma
30-60% in oligodendroglioma
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
What are the advanced imaging modalities that you know of?
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:
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
What are the advantages for surgery?
1) More accurate histology and grading
2) Remove mass effects and relives neurological deficits
4) Tissues for research
What is the current standard of RT?
1) Tumor bed + 2 cm margin
2) 60 Gy in 30#
What are the side effects of Temozolamide?
Temozolamide is an oral alkylating agent
Relatively mild hematotoxicity
Less toxic than PVC regimen