Tumors of the Nervous System - Brain Flashcards
What is overall estimated incidences of canine and feline nervous system tumors?
Canine: 14,5/100 000 cases; 2-4.5% at necropsy
Feline: 3,5/100 000 at risk; 2% at necropsy
Classify the different subtypes of PBT in descending order based on their frequency
+/- 90% of PBT are represented by meningioma (45%), glioma (40%) and choroid plexus tumor (5%)
Less common: ependymoma, lymphoma, PNETs, GC, HS
What’s more frequent: Primary vs Secondary brain tumors?
Pretty much 50/50
What are the most common secondary brain tumors?
HSA (29-35%), pituitary tumors (11-25%), lymphoma (12-20%), metastatic carcinoma (11-20%) = total of 77-86% of all SBTs
Is there a sex predisposition in canine brain tumors?
No
Median age at diagnosis ?
Middle-aged to older dogs; majority > 5yo
Meningioma 10.5yo
Glioma 8 yo
CPT 5.5 yo
PBT in juvenile animals are of what origin?
Propensity to be neuroepithelial tumors of glial, neuronal, or embryonal origin
Is there a relationship between age and BW in PBT occurrence ?
large-breed dogs at increased risk for meningioma and CPTs
What breeds are overrepresented with canine meningioma?
Golden Retr, boxers, schnauzer, rat terrier
What breeds are overrepresented with canine CPTs?
One report said golden retrievers but other reports did not confirm
What breeds are overrepresented with canine gliomas?
Brachycephalic!
Boxer, Boston, bullmastiff, bulldogs
What tumor has been identified with a genetic defect association? What is that defect?
- Gliomas
- Locus on canine chromosome 26 –> single nucleotide variant in 3 genes (DENR, CAMKK2, P2RX7)
What is the ratio of PBT vs SBT in cats? What is the most common PBT?
70% of PBTs; more than 50% of those are meningiomas
Most common SBTs in cats?
- Lymphoma (50%)
- Pituitary tumors (30%)
Median age at diagnosis in cats?
11yo for meningiomas; 7-8 yo for neuroepithelial tumors and lymphoma
Sex predisposition in cat brain tumors?
No
% of seizures in dogs with forebrain tumor?
50%
Risk factors for tumor-associated structural epilepsy based on MRI?
presence of tumor involving frontal lobe, falcine or subtentorial brain herniation, marked contrast enhancement
Incidence of tumor-associated epilepsy in cats?
< dogs; 25%
Possibly more common with glioma (27%) and lymphoma (26%) than meningioma (15%)
What is the most common clinical sign in cats with brain tumors?
Behavioral changes (16-67%)
Based on the appearance, what is your likely diagnosis?
Butterfly glioblastoma
How frequent is it to detect multiple tumors in cats vs dogs?
Cats 20% vs dogs only occasionally
What is the unique presentation of metastasis in choroid plexus carcinoma ?
Drop metastases
What tumor may metastasize in the CNS in a unique way called ‘drop metastases’ ?
Choroid plexus carcinomas
What is the incidence of contemporanous and unrelated neoplasms in dogs with PBTs?
3-23%
Accuracy of MRI to predict PBT type?
70%
MRI features of meningiomas
Extra-axial, broad-based, distinct margins, marked and uniform contrast enhancement; some can display intratumoral fluid, cysts, mineralization, calvarial hyperostosis, dural tail sign
Accuracy of MRI to correctly identify meningioma in dogs vs cats?
between 60-100% in dogs; 96% in cats
Glioma’s features on MRI?
intra-axial, poorly marginated, may or may not show contrast enhancement (highly variable), ‘ring enhancing’ pattern often seen in gliomas but not specific
What tumors are most commonly found in intraventricular locations?
Choroid plexus tumors and ependymomas
MRI features of CPT and ependymomas?
Usually intra-ventricular; often uniformaly contrast enhancing
What MRI finding car discriminate between grade III choroid plexis carcinoma and grade I papilloma?
Identification of intraventricular or subarachnoid metastatic tumor implants
What brain tumors are known to be occult (normal MRI) on imaging studies of the brain?
Lymphamatosis and gliomatosis cerebri
What are the different subtypes of meningiomas?
angiomatous, meningothelial, transitional, fibroblastic, psammomatous, microcystic, papillary
What subtypes of meningiomas are more frequent?
Meningothelial, transitional and psammomatous (in both species)
Frequency of grade 1, 2 and 3 meningiomas? in both species
Majority of feline meningiomas = grade 1
Dogs: 40% are grade 2
Anaplastic, grade 3, meningiomas = 1% in dogs and cats
Frequency of CPT grades in the dog?
Grade 1: 40%
Atypical (grade II) not yet recognized in vet med
Grade 3: 60%
Nearly 50% occur in 4th ventricule
Is CSF helpful in the diagnosis of choroid plexus tumors?
Helpful to discriminate between CPC and CPPs –> CSF tot protein > 80 mg/dL exclusively associated with diagnosis of CPC
What tumors seem to exfoliate more in the CSF?
CPTs, lymphoma, HS and cats with caudal brainstem oligodendrogliomas are the most frequently reported
What is the prevalence of head and neck hyperesthesia in dogs with brain tumors?
12%
MST of PBTs with palliative care?
+/- 9 weeks, range 1-13wks but dogs with supratentorial tumors treated palliatively > outcome with 25 weeks compared to 4 weeks for infratentorial
MST for pituitary tumors treated palliatively?
MST 51 weeks in one study
Efficacy of chmotherapy for PBTs?
Retrospective study of 71 dogs –> CCNU 93d vs palliative 60d; not statistically significant
MST for cats with meningiomas treated surgically?
Often > 2 years, reported MST from 23-37 months
% of recurrence of feline meningiomas after surgery?
25%, time to recurrence very variable (3-69 months)
MST of canine meningiomas treated with sx?
7-16 months
MST of canine meningioma treated with sx + RTH ?
16-30 months
What are two types of SBTs that have a good prognosis following surgery?
Pituitary tumors and calvarial MLO
% of surgical complications ?
+/- 11%
MST for presumed meningiomas treated with RT?
MST 9-19 months
MST for intra-axial masses treated with RT?
MST 9-13 months
What biomarker holds prognostic value in meningiomas?
- VEGF; MST 25 mo with low VEGF vs 15 mo high VEGF (> 75%)
- Progesterone receptor expression has
also been shown to be inversely related to the tumor proliferative index (PFPCNA index), which was predictive of survival in dogs with meningiomas after surgery and postoperative RT. The 2-year
progression-free survival rate was 42% for tumors with a PFPCNA index 24% or greater and 91% for tumors with a PFPCNA index less than 24%
What is the standard treatment for pituitary tumors ? How does it compare to palliative care ?
Compared with palliative therapy, RT is effective at reducing tumor size, improving neurologic signs, and providing a survival benefit in dogs and cats with pituitary tumors.80,108,113–117
RT is the preferred therapeutic modality for pituitary macrotumors
Chances of endocrinologic remission with RT for PDH ?
In cases of PDH treated with RT, the reported rates of
endocrinologic remission are variable, with some studies reporting persistent hypercortisolinemia for up to a year after RT.80,113,116
Thus continued medical management and serial endocrinologic evaluations are necessary after RT of PDH.
What are negative prognostic factors for pituitary masses treated with RT ?
Negative prognostic indicators associated with RT for pituitary masses include severe neurologic dysfunction at presentation and large relative tumor
size
SRT for pituitary tumors ?
Preliminary data suggest that SRT results in tumor control that is comparable to standard fractionated RT protocols with potentially fewer short-term adverse effects and, in the case of pituitary tumors, provide results that are similar to those of hypophysectomy
NEED TO LOOK UP THE STUDIES
What is the % of RT mortality for brain cases ? What are frequent adverse events ?
Approximately 10% of brain tumor cases treated with RT will experience treatment-related mortality or adverse effects.78 Frequently reported adverse effects include aspiration pneumonia,
pulmonary thromboembolism, acute CNS toxicity which often manifests as a decreased level of consciousness, damage to organs
in the treatment field including deafness, cataract formation, and keratitis, and late-onset radiation necrosis
What are radiobiologic considerations when treating brain tumors ? What has been reported with hypofractionated RT in one study ?
Important radiobiologic considerations when treating brain tumors include the radiation dose per fraction, total radiation dose, and the volume of the brain irradiated. In one study of hypofractionated RT, delivery of a high dose per fraction resulted in the death of nearly of 15% of treated dogs because of suspected delayed radiation side effects.110
Although significant adverse events associated with SRT have been uncommonly reported in animals to date, the more frequent use of high-dose per fraction prescriptions may eventually influence the incidence of observed toxicity
Examples of safe brain tumor ablation techniques ?
The safety
and feasibility of brain tumor ablation techniques using lasers
and pulsed electrical fields have also been demonstrated in canine
gliomas.119 Technologies capable of focally disrupting the BBB to
allow for CNS drug delivery, such as transcranial focused ultrasound and irreversible electroporation, are also being used to treat
canine brain tumors
Examples of Approaches that bypass the BBB ?
Approaches that bypass the BBB and allow for direct intratumoral delivery of therapeutically relevant concentrations of macromolecular drugs, such as convection-enhanced delivery (CED) of chemotherapeutics and implantation of various biodegradable nanomaterial drug carriers, have also been investigated in dogs. CED of nonselective chemotherapy drugs, such as liposomal CPT-11, and novel agents targeting the overexpression of cell surface EGFR (EGFRvIII-antibody bioconjugated nanoparticles), EphA2, and IL-13RA2 (recombinant
bacterial cytotoxins) receptors that occur in canine and human gliomas, have been performed in dogs with glioma.7,9,67,119–121
These studies have illustrated the safety of the CED procedure and have provided preliminary evidence of efficacy of these investigational agents
Which proof of concept trial has been realised in dogs with brain tumors ?
In a proof-of-concept trial, bacterially derived
minicells were packaged with doxorubicin, targeted to EGFR using bispecific antibodies to EFGR, and administered intravenously to dogs with brain tumors. Durable and objective tumor
responses were seen in 24% of dogs and no significant toxicities were observed
Is there a role for immunotherapy in canine brain tumors ?
IT approaches that involve tumor vaccinations
with stimulated patient-derived dendritic cells and autologous tumor
lysates combined with toll-like receptor ligands have demonstrated
the safety, feasibility, and potential efficacy of IT for use in canine
glioma and meningioma
What drug has been studied in vitro for canine brain tumor that could potentially be repurposed as anti cancer drug ?
Recent studies have provided data that indicates that novel repurposing approaches using existing drugs are capable of achieving intratumoral drug concentrations that may result in favorable
therapeutic and adverse effects profiles compared with traditionally administered doses or other chemotherapy agents with the same
mechanism of action.84 An in vitro study of benzimidazole anthelmintics in canine glioma cell line demonstrated that drug treatment
increased depolymerization of tubulin and increased tumor cell apoptosis compared with the controls
