1. CNS Malignancies for internists

2. 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

4. Clinical presentation
Headache
Seizure
Focal neurologic deficit
Confusion
Memory loss
Personality change
Nausea/vomiting

5. 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

6. T1
Contrast

7. Imaging Diagnosis Treatment planning Monitoring response CT MRI SPECT
Functional MRI
Monitoring response
Diffussion-weighted, diffusion tensor, dynamic-contrast-enhanced, perfusion

8. 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

9. Neurosurgery Who should get a biopsy? Alternate diagnosis?
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 review
Patchell RA, et al., A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322: , 1990.

10. Primary brain tumors

12. Primary Brain Tumors Malignant gliomas Others
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

13. Primary Brain Tumors Etiology Family history
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

16. Initial medical management
Corticosteroids: oral dex 4-16 mg/day
Anti-epileptics: leviteracitam
VTE treatment/prophy
Stimulants: modafenil, methylphenidate, donepezil, memantine
Anti depressants

18. ANTI NEOPLASTIC THERAPY
CORTICOSTEROIDS
ANTI EPILEPTICS
VTE TREATMENT/PROPHY
ANTI NEOPLASTIC THERAPY
STIMULANTS
ANTI DEPRESSANTS

19. Anti-neoplastic therapy
Surgery: maximal resection
Radiotherapy: WBRT
Chemotherapy: TMZ
Stupp R, et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352:

24. MGMT promotor methylation (GMB)
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

25. Brain metastases

26. Brain metastases Common tumors Sites 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

27. 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

28. Differential diagnosis
Brain metastases
Differential diagnosis
Primary brain tumor
Infection
Inflammation
Demyelinating disorders
Infarction
Radiation necrosis

29. Brain Metastases Surgery + WBRT === SRS +/- WBRT But you must know:
Surgery + WBRT >>> Surgery
Reduced brain recurrance and neuro death
Surgery + WBRT === SRS +/- WBRT
But you must know:
radiosensitivity of the tumor
# of tumors
Accessibility for resection

31. Leptomeningeal metastases

32. 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

33. PCNSL

34. PCNSL Rare: 2.7% of all primary brain tumors
Incidence increased 3-fold from
Immunocompetent:
male>female
age >60
Immunodeficiency is only risk factor
HIV 3,600-fold increased risk
CD4+ cell count <50 cells/uL highest risk

35. PCNSL Site Histology 65% solitary 38% in hemispheres
20% occular involvement
Histology
DLBCL (90%)
Low-grade lymphoma
Burkitt’s lymphoma
T-cell lymphoma

36. 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

37. -- high WBC >7 cells/uL -- high protein -- low glucose
Non con T2
CSF
-- high WBC >7 cells/uL
-- high protein
-- low glucose
Initial positive in only 15%
Con T1

38. PCNSL International Extranodal Lymphoma Study Group Age >60
ECOG PS >1
Elevated LDH
High CSF protein
Deep location

39. PCNSL Chemotherapy: High dose MTX + IT MTX
Radiotherapy: WBRT for those <60

41. Memory failure, gait ataxia, incontinence

42. references