Steroid (dexamethasone)
- Effect is more dramatic in metastatic than primary Ca
- Treatment of vasogenic oedema
- Decreasing the permeability of neoplastic capillaries and/or enhancing the clearance of extracellular water.
- Pharmacokinetics
- Most patients begin to improve symptomatically within hours of dexamethasone administration, achieving maximum benefit within 24–72 hours
- Steroid naïve:
- Adult: 10mg IV loading → 6mg PO/IVP QDS.
- Severe vasogenic edema 10mg 6x/day
- Paeds: 0.5–1mg/kg IV loading → 0.25–0.5 mg/kg/d PO/IVP divided QDS.
- Avoid prolonged treatment because of growth suppressant effect in children
- Non steroid naïve:
- For acute deterioration double the dose
- Give “stress doses”
- Dosing
- After surgery, a maximum dose of 16 mg daily, administered in 4 equal doses, is recommended for symptomatic patients. This protocol should ideally be started by the neurosurgeon.
- A rapid dexamethasone tapering schedule should be considered where appropriate.
- Patients who have high-grade tumours, are symptomatic, or have poor life expectancy, can be maintained on a 0.5–1.0 mg dose of dexamethasone daily.
Anticonvulsants
- Should not be routinely use
- Prophylactic AEDs do not provide substantial benefit (reduction of risk >25% for seizure-free survival), and there are significant risks involved.
- Not indicated for post fossa tumour
- Risk of seizure
- 20–40% will have had a seizure at tumour diagnosis. → these arent prophylactic
- Anticonvulsants are indicated in these patients.
- 20–45% more will ultimately develop a seizure
- There is no data to suggest that the prophylactic use of anticonvulsants reduces the risk of new onset seizures in patients with intrinsic brain tumours (Chang et al., 2005; Chang et al., 2008; de Oliveira Lima, 2015)
- Patients with brain tumours undergoing craniotomy, prophylactic AEDs may be used, and if there has been no seizure, it is appropriate to taper off AEDs starting 1 week post-op
- Seizure risk inc with
- Location:
- Highly epileptogenic areas such as the motor cortex
- Lesion
- Low- grade gliomas
- Multiple metastatic tumours
- Large amounts of vasogenic oedema, or leptomeningeal disease
- Choice
- Phenytoin
- Historical first line
- Keppra
- Low toxicity, minimal side- effect profile, and lack of need to monitor serum levels
Chemotherapy
Nitrosoureas: | BCNU (carmustine), CCNU (AKA lomustine), ACNU (nimustine) | DNA crosslinks, carbamoylation of amino groups |
Alkylating (methylation) agents: | Procarbazine, temozolomide (Temodar®) | DNA alkylation, interferes with protein synthesis |
Carboplatin, cisplatin | Chelation via intrastrand crosslinks | |
Nitrogen mustards: | Cyclophosphamide, isofamide, cytoxan | DNA alkylation, carbonium ion formation |
Vinca alkaloids: | Vincristine, vinblastine, paclitaxel | Microtubule function inhibitors |
Epidophyllotoxins | (ETOP-oside, VP16, teniposide, VM26) | Topoisomerase II inhibitors |
Topotecan, irinotecan (CPT-11) | Topoisomerase I inhibitors | |
Monoclonal antibodies | Bevacizumab (Avastin®) | Anti-VEGF antibody may be useful in vestibular neuromas |
Tamoxifen | Protein kinase C inhibitor at high doses |
- Temozolomide
- Methylating DNA guanine bases → cross linking of DNA → inhibited DNA and cellular replication
- Which is different from methylation of histones which reduces gene expression
- Work better with MGMT methylation → reduce MGMT functioning
- BBB and chemotherapy agents
- BBB excludes many chemotherapeutic agents from the CNS
- This concept has been challenged.
- With a notable exception being a favorable response of oligodendrogliomas and gliomas with deficient MGMT
- Considerations regarding chemotherapeutic agents in relation to the BBB include:
- Some CNS tumors may partially disrupt the BBB, especially malignant gliomas
- Lipophilic agents (e.g. nitrosoureas) may cross the BBB more readily
- Selective intra-arterial (e.g. intracarotid or intervertebral) injection: produces higher local concentration of agents which increases penetration of the BBB, with lower associated systemic toxicities than would otherwise occur
- BBB may be iatrogenically disrupted (e.g. with mannitol) prior to administration of the agent
- BBB may be bypassed by intrathecal administration of agents via LP or ventricular access device, e.g. methotrexate for CNS lymphoma
- Biodegradable polymer wafers containing the agent may be directly implanted
Surgical treatment
- Gliomas
- 5 ALA (gliolan)
Immediate post op MRI post contrast
- Reference: Hygino et al 2011
- Increased enhancement can be induced by a variety of nontumoral processes, such as treatment-related inflammation, postsurgical changes, ischemia, subacute radiation effects, and radiation necrosis.
- Micro-ischemic lesions immediately after surgery and RT can cause BBB disruption.
- Therefore, contrast-enhanced MR imaging should be used within the first 48 hours after surgery to identify residual tumour in the postsurgical bed, and no later than 72 hours after surgery to avoid confusion with nontumoral inflammation
- Regions with restricted diffusion on an immediately postoperative MR imaging will commonly enhance subacutely for up to 2–3 months after surgery; these are typically thought of as postoperative ischemic changes.
Post fossa tumour
- For children eg pilocystic astrocytoma, medulloblastoma
- CSF diversion for PFTs in children
- Avoid emergent diversion unless symptoms refractory to steroids or drop in GCS
- Risk factors for permanent shunt
- Age (<2)
- Pre-op CSF diversion
- Malignant histology
- CNS dissemination
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