Brain tumor Flashcards
List mutations in pilocystic astrocytoma
BRAFv600e aberrations, such as BRAFv600e mutation and
the BRAF KIAA-1549 fusion, are common in pilocytic astrocytomas, the most common low-
grade glioma in children.
Type of tumor in tuberous sclerosis
subependymal giant cell astrocytomas
Tovorafenib
type 2 RAF inhibitor and recent phase 2 data in relapsed and refractory LGG with BRAF fusion or rearrangement or BRAFV600 mutation revealed a high response rate and low toxicity profile. These data led to the FDA approval for this indication.
Everolimus
is FDA approved for use in Subependymal Giant Cell Astrocytoma, a tumor manifestation in Tuberous Sclerosis.
How to treat medulloblastoma ?
Medulloblastoma has the most evidence and success with this high dose chemo + auto SCT.
Most practitioners would use this approach for a child younger than 3 years with a diagnosis of medulloblastoma.
How to treat LGG with BRAFV600E?
comparing carboplatin/VCR, one of the standard of care chemotherapy for LGG to a combination of Dabrafenib (a BRAF inhibitor) and Trametinib (a MEK inhibitor) for children with previously untreated LGG with a BRAFV600E mutation.
The combination of Dabrafenib and Trametinib showed superior response rate, PFS, and less toxicity.
These data led to the FDA approval of this combination for those LGG patients whose tumor specifically harbors a BRAFV600E mutation.
NF2 patients what do they have ?
Bilateral vestibular schwannomas are most consistent with a diagnosis of neurofibromatosis type 2 (NF2). These patients also have an increased risk of ependymoma and meningioma.
Patients who receive CS XRT radiation have a risk of developing a secondary malignancy, typically 7 to 10 years after radiation exposure. What type ?
high-grade gliomas and meningiomas.
Low-grade glioma and ** pathway
Low-grade glioma and MAPK , mTor pathway
Diffuse midline glioma and *** pathway
H3K27M
Medulloblastoma and *** mutation ( best prognosis)
WNT
Bilateral vestibular schwannomas and ** mutation
NF2
survival for high grade glioma at 5 years
5% to 20% overall survival at 5 years.
Diencephalic Syndrome.
This syndrome most commonly is seen in infants and young children.
It is characterized by failure to thrive and severe emaciation despite normal or only slightly decreased intake. It also sometimes presents with hyperactivity and euphoria. It can go undiagnosed for many months because typically it does not initially present with the classic findings of obstructive hydrocephalus such as headaches and emesis.
it is most commonly caused by a low-grade glioma such as a pilocytic astrocytoma in the hypothalamic region.
Typically these patients are treated with low-grade glioma chemotherapy such as carboplatin/vincristine. Most commonly the failure to thrive improves with treatment.
It should be noted that this is a very rare cause of failure to thrive, but if all other etiologies have been eliminated, one should at least consider brain imaging.
LGG therapies
carboplatin/vincristine, vinblastine alone, or a combination of thioguanine, procarbazine, CCNU (Lomustine), and vincristine (TPCV). TPCV often is avoided for patients with NF-1 because the risks of secondary malignancy with alkylator use.
TP53 abnormalities are most commonly seen in *** brain tumors
high-grade gliomas and medulloblastomas.
The most common specific abnormality is the ** fusion, which is estimated to be present in 60-80% of all pilocytic astrocytomas.
BRAFKIAA1549 fusion (most common)
BRAFV600E
