cns malignancies for internists. cns malignancy primary brain tumors – 2% of all cancers –...
TRANSCRIPT
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CNS Malignancies
for internists
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CNS Malignancy
• Primary brain tumors– 2% of all cancers– Mortality 4.6/100,000 person years– Incidence increasing
• Brain mets can occur in up to 40% of all solid tumors
• PCNSL incidence increasing
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Clinical presentation
• Headache• Seizure• Focal neurologic deficit• Confusion• Memory loss• Personality change• Nausea/vomiting
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Differential Diagnosis• Primary brain tumor
– Malignant • Glioma• Lymphoma
– Benign meningioma, adenoma, schwannoma• Metastatic brain tumor• Vascular
– Cerebellar hemorrhage: vascular anomaly, hypertensive, intratumoral– Cerebellar infarct: embolic, thrombotic
• Infection: – Abcess, virus, progressive multifocal leukoencephalopathy
• Inflammatory:– Multiple sclerosis– Post-infectious encephalomyelitis
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T1 Contrast
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Imaging
• Diagnosis– CT– MRI– SPECT
• Treatment planning– Functional MRI
• Monitoring response– Diffussion-weighted, diffusion tensor, dynamic-
contrast-enhanced, perfusion
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Additional work-up
• History and physical for evidence of an extracranial primary or other disease
• Appropriate imaging to look for that primary
• Avoid corticosteroids if lymphoma or infection is suspected
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Neurosurgery
• Who should get a biopsy?– Diagnosis in question– Results will influence management– Do not need immediate relief of symptoms– Non resectable; critical location– Suspect low-grade glioma or PCNSL
• Alternate diagnosis? – 11% of 56 enrolled on surgery trial had alternate diagnosis
on central pathology reviewPatchell RA, et al., A randomized trial of surgery in the treatment of single metastases to
the brain. N Engl J Med 322:494-500, 1990.
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Primary brain tumors
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Primary Brain Tumors
• Malignant gliomas– 70% of primary brain malignancy– 14,000 cases/year in US– Incidence increasing, esp. in elderly– 40% more common in men– Twice as common in whites– Median age 64 (GBM) or 45 (AA)
• Others
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Primary Brain Tumors
• Etiology– Ionizing radiation risk factor– No association with head injury, food, occupation,
electromagnetic fields, cell phones– Reduced risk with atopy, high IgE levels
• Family history– 5% are familial, most without known cause– NF type 1 or 2, Li-Fraumeni syndrome, Turcot
syndrome
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Initial medical management
• Corticosteroids: oral dex 4-16 mg/day
• Anti-epileptics: leviteracitam
• VTE treatment/prophy
• Stimulants: modafenil, methylphenidate, donepezil, memantine
• Anti depressants
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CORTICOSTEROIDS
ANTI EPILEPTICS
VTE TREATMENT/PROPHY
ANTI NEOPLASTIC THERAPY
STIMULANTS
ANTI DEPRESSANTS
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Anti-neoplastic therapy
• Surgery: maximal resection
• Radiotherapy: WBRT
• Chemotherapy: TMZStupp R, et al., Radiotherapy plus concomitant and adjuvant
temozolomide for glioblastoma. N Engl J Med 2005; 352:987-96.
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Molecular genetics
• MGMT promotor methylation (GMB)– Decreased DNA repair activity– Increased susceptibility to TMZ
• 1p 19q deletion (anaplastic oligodendrogliomas and anaplastic oligoastrocytomas)– Increased sensitivity to PCV– Reason unknown
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Brain metastases
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Brain metastases
• Rates– Represent >50% of all intracranial tumors– 40% of cancers will develop brain mets
• Common tumors– Lung– Breast– melanoma
• Sites– 90-95% solid parenchymal, 5-10% meningeal– 37-50% solitary, 50-63% multiple
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Brain Metastases
Prognosis– 1-6 month survival– Improved by (RTOG prognostic index):
• Age <65• KPS >70• Controlled primary w/out extracranial mets
– Other favorable factors:• Solitary met• Response to corticosteroids• Longer disease-free interval• Breast cancer diagnosis
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Brain metastases
Differential diagnosis–Primary brain tumor–Infection–Inflammation–Demyelinating disorders–Infarction–Radiation necrosis
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Brain Metastases
• Surgery + WBRT >>> SurgeryReduced brain recurrance and neuro death
• Surgery + WBRT === SRS +/- WBRT
• But you must know:– radiosensitivity of the tumor– # of tumors– Accessibility for resection
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Leptomeningeal metastases
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Leptomeningeal Metastases
• Diagnosis: – MRI 76% sen, 77% spec
(false pos with intracranial hypotension, infection, connective tissue disease, deymelinating disease)
– CSF 90% sen, 100% spec
• Prognosis: <3 months
• Treatment:– Radiotherapy for bulky disease or CSF flow obstruction– IT chemotherapy through Ommaya:
• MTX• Lipsomal cytarabine• Thiotepa
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PCNSL
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PCNSL
• Rare: 2.7% of all primary brain tumors
• Incidence increased 3-fold from 1978-84
• Immunocompetent: – male>female– age >60
• Immunodeficiency is only risk factor– HIV 3,600-fold increased risk– CD4+ cell count <50 cells/uL highest risk
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PCNSL
• Site– 65% solitary– 38% in hemispheres– 20% occular involvement
• Histology– DLBCL (90%)– Low-grade lymphoma– Burkitt’s lymphoma– T-cell lymphoma
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PCNSL
• Imaging: MRI preferred
• CSF: cytology, flow, IgH PCR
• Eye exam• Rule out systemic disease• Rule out testicular and bone marrow
involvement
• Biopsy is essential
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T2
T1
Non con
Con
CSF-- high WBC >7 cells/uL-- high protein-- low glucose
Initial positive in only 15%
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PCNSL
• International Extranodal Lymphoma Study Group– Age >60– ECOG PS >1– Elevated LDH– High CSF protein– Deep location
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PCNSL
• Chemotherapy: High dose MTX + IT MTX
• Radiotherapy: WBRT for those <60
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Memory failure, gait ataxia, incontinence
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references