Intrinsic Tumour Flashcards

Question

IDH

Answer 1

Isocitrate dehydrogenase Deactivatin occurs in 75% of Grade 2 and 3 diffuse gliomas and 80% of secondary GBM

Answer 2

Incomplete resection patients have 4.9x risk of death

Answer 3

No benefit to high vs low More likely to result in impaired cognition and executive functioning. Imrpoved OS when upfront RTx and PCV given vs RTx alone.

Answer 4

\>40y/o Partial resection/residual \>10mL Astrocytoma histology Triple negative or TERT mutation status Rapid growth Difficult to control seizures

Answer 5

PCV Temozolamide

Answer 6

Temozolomide (TMZ) is an oral alkylating chemotherapeutic agent that prolongs the survival of patients with glioblastoma (GBM). Despite that high TMZ potential, progression of disease and recurrence are still observed.

Answer 7

Procarbazine Lomustine Vincristine

Answer 8

Alkylating agent

Answer 9

Microtubule inhibitor

Answer 10

Alkylating agent

Answer 11

Results in reduced expression of this DNA repair gene thus conferring increased sensitivity to alkylating CTx

Answer 12

Hedgehog or Wnt/Beta-catenin pathway

Answer 13

Grade III or IV glioma

Answer 14

Based on the predominant cell type Grade based on appearances under light microscopy

Answer 15

Anaplastic astrocytoma Anaplastic oligodendrolgioma

Answer 16

Glioblastoma Gliosarcoma Glioblastoma with oligodendrocyte component

Answer 17

Diffusely infiltrating gliomas with focal or dispersed anaplasia Marked proliferative potential with increased cellularity, distinct nuclear atypia and high mitotic activity

Answer 18

Cellular polymorphism Nuclear atypia Brisk mitotic acitivity Vascular thrombosis Microvascular proliferation and necrosis

Answer 19

High-grade glioma (account for 85% of all newly diagnosed primary malignant brain tumours)

Answer 20

Glioblastoma (60-70%) Amnaplastic astrocytomas (10-15%) Anaplastic oligodendrogliomas (10%) Anaplastic ependymoma and anaplastic ganglioglioma make up the rest

Answer 21

Ionising radiation Genetics (5% of patients with HGG have a FHx of glioma)

Answer 22

Li–Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder[1] that predisposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni, Jr., who first recognized the syndrome after reviewing the medical records and death certificates of 648 childhood rhabdomyosarcoma patients.[2] This syndrome is also known as the sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome. The syndrome is linked to germline mutations of the p53 tumor suppressor gene,[3] which encodes a transcription factor (p53) that normally regulates the cell cycle and prevents genomic mutations. The mutations can be inherited, or can arise from mutations early in embryogenesis, or in one of the parent's germ cells. The classical LFS malignancies - sarcoma, cancers of the breast, brain, and adrenal glands - comprise about 80% of all cancers that occur in this syndrome.

Answer 23

Mismatch repair cancer syndrome (MMRCS) is a cancer syndrome associated with biallelic DNA mismatch repair mutations. It is also known as Turcot syndrome (after Jacques Turcot, who described the condition in 1959) and by several other names. In MMRCS, neoplasia typically occurs in both the gut and the central nervous system (CNS). In the large intestine, multiple colonic polyps develop; in the CNS, brain tumors.

Answer 24

CMV thought to have an oncomodulatory role. Treatment with valganciclovir in an RCT showed no benefit

Answer 25

IDH WT IDH mutated IDH NOS Within this classification, 1pq19 codeletion for oligodendroglioma has also been included

Answer 26

P13K TP53 Rb Activating mutations of EGFR, PDGFR and MET LOF in PTEN, NF-1, RB1 and TP53

Answer 27

Develop either as primary tumours or arise from pre-existing low-grade gliomas These are separate and distinct disease entities. GBM are usually de novo manifestations in older patients with short clinical history, in contrast to secondary where they represent a malignant progression from LGG to HGG with a variable interval.

Answer 28

Local WM invasion is a key pathological hallmark of gliomas and a major cause of treatment failure. Mostly progress by the invasion of WM tracts, They can also grow along the pial surface (subpially) Subependymally along the ventricular surface. This can result in drop metastasis to the spine. Metastases of HGG is very rare and is mostly related to spreading down VP shunts to the peritoneal cavity. There are cases of HGG metastases developing in patients receiving transplants from HGG patients.

Answer 29

In rapidly dividing areas of high-grade glioma, due to competition for metabolites, there will be the development of hypoxia. This causes three major behavioural changes: Stem cell division Angiogenesis due to VEGF expression Upregulation of invasive factors. As malignancy increases, this hypoxia will lead to necrosis and microvascular proliferation, histological hallmark features of GBM

Answer 30

Characteristic rthat is objectively measured and evaluated as an indicator of normal biological or pathogenic process or pharmaceutical response to a therapeutic intervention

Answer 31

Found in up to 12% of patients and seems to confer prognositc benefit for PFS Absence of IDH mutation confers very poor prognosis in LGG

Answer 32

Loss of heterogeneity of 1p19q in IDH mutated tumours is characteristic of oligodendroglioma or anaplastic oligodendroglioma in the WHO classification. This mutation has improved survival with CTx and RTx

Answer 33

Encodes O-6-methylguanine-DNA-methyltransferase enzyme. MGMT methylation status can be used to prognosticate response to alkylating chemotherapeutic agents. It is non-functional in its methylated state and is associated with significantly longer survival after TMZ + RTx vs RTx alone.

Answer 34

IDH mutations 1p19q codeletion TERT mutaiton

Answer 35

Gene that encodes for telomerase found in GBM and low grade gliomas. Suggests telomere maintenance may be important for tumorgenesis

Answer 36

Identified in paediatric brain stem and midline GBM

Answer 37

Layer 1: integrated diagnosis Layer 2: Histological Layer 3: WHO grade Layer 4: Molecular information

Answer 38

50% in comparison to 80% of LGG

Answer 39

Irregular, ill-defined intrinsic lesion with vasogenic oedema. Oedema typicaaly around the rim with a central area of non-enhancing tissue. Most commonly supratentorial (frontal lobe \> temporal \> parietal\> occipital\> cerebellum\> brainstem)

Answer 40

Tumour extends beyond imaging margins

Answer 41

Post-op MRI

Answer 42

Examines the diffusion of protons within an image. Areas where there are trapped protons, such as areas of ischaemic cytotoxic oedema, epidermoid cysts or abscesses appear bright on DWI. Not quantitative

Answer 43

MRI shows restricted diffusion

Answer 44

Used as a quantiative measure that relates to how far protons can diffuse. In areas of free diffusion, the ADC is large. Where there is retricted diffusion, the ADC is low.

Answer 45

In HGG, due to increased water from oedema, the ADC is larger than normal brain but as the cellularity increases, the ADC reduces.

Answer 46

DWI- dark, no restriction of diffusion ADC- light, due to free diffusion.

Answer 47

Extension of DWI imaging that is sensitive to the directional diffusion of water molecules. Can be used to assess the disruption of WM tracts and the location of tracts close to the tumour

Answer 48

Used to assess blood flow. Higher grade tumours have higher blood flow and there is some evidence that perfusion may be able to identify anaplastic foci within LGG

Answer 49

Can identify tumour metabolites in a volume of interest. HGG have a particulary spectral pattern

Answer 50

Reduced n-acetylaspartate (marker of WM integrity) Increased total choline (marker of membrane turnover) Lipid and lactate (necrosis)

Answer 51

HGG tend to be hypermetabolic though FDG PET may not be best for cortical imaging. MET PET or FET PET is more specfiic for tumour

Answer 52

Suggests radical surgical resection may cause a worsening neurological deficits

Answer 53

Obtain representative tissue sample Safely remove the tumour to improve pressure symptoms Improve the efficacy of adjuvant therapy Delay deterioration and improve survival Potential for delivery of surgically delivered treatments

Answer 54

Suffer resection bias in that selects for patients with better prognostic features Most surgeons would now consider it unethical to randomise patients to partial resection

Answer 55

Image guidance Intraoperative US ``` Intraoperateive MRI (most effective) 5-ALA ```

Answer 56

5-aminolevulinic acid is taken up and is converted in the normal haem biosynthesis pathway. In tumours there is a deficiency of the ferrochelatase enzyme that leads to the accumulation of the fluorophore protoporphyrin IX that fluoresces under blue light.

Intrinsic Tumour Flashcards

(83 cards)