CNS Malignancies

for internists

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

Clinical presentation

• Headache• Seizure• Focal neurologic deficit• Confusion• Memory loss• Personality change• Nausea/vomiting

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

T1 Contrast

Imaging

• Diagnosis– CT– MRI– SPECT

• Treatment planning– Functional MRI

• Monitoring response– Diffussion-weighted, diffusion tensor, dynamic-

contrast-enhanced, perfusion

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

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.

Primary brain tumors

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

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

Initial medical management

• Corticosteroids: oral dex 4-16 mg/day

• Anti-epileptics: leviteracitam

• VTE treatment/prophy

• Stimulants: modafenil, methylphenidate, donepezil, memantine

• Anti depressants

CORTICOSTEROIDS

ANTI EPILEPTICS

VTE TREATMENT/PROPHY

ANTI NEOPLASTIC THERAPY

STIMULANTS

ANTI DEPRESSANTS

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.

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

Brain metastases

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

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

Brain metastases

Differential diagnosis–Primary brain tumor–Infection–Inflammation–Demyelinating disorders–Infarction–Radiation necrosis

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

Leptomeningeal metastases

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

PCNSL

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

PCNSL

• Site– 65% solitary– 38% in hemispheres– 20% occular involvement

• Histology– DLBCL (90%)– Low-grade lymphoma– Burkitt’s lymphoma– T-cell lymphoma

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

T2

T1

Non con

Con

CSF-- high WBC >7 cells/uL-- high protein-- low glucose

Initial positive in only 15%

PCNSL

• International Extranodal Lymphoma Study Group– Age >60– ECOG PS >1– Elevated LDH– High CSF protein– Deep location

PCNSL

• Chemotherapy: High dose MTX + IT MTX

• Radiotherapy: WBRT for those <60

Memory failure, gait ataxia, incontinence

references