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  1. CNS Malignanciesfor 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

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

  4. 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

  5. T1 Contrast

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

  7. 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

  8. 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 review Patchell 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.

  9. Primary brain tumors

  10. 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

  11. 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

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

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

  14. 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; 352:987-96.

  15. Molecular genetics • MGMTpromotormethylation (GMB) • Decreased DNA repair activity • Increased susceptibility to TMZ • 1p 19q deletion (anaplasticoligodendrogliomas and anaplasticoligoastrocytomas) • Increased sensitivity to PCV • Reason unknown

  16. Brain metastases

  17. 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

  18. Brain Metastases Prognosis • 1-6 month survival • Improved by (RTOG prognostic index): • Age <65 • KPS >70 • Controlled primary w/out extracranialmets • Other favorable factors: • Solitary met • Response to corticosteroids • Longer disease-free interval • Breast cancer diagnosis

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

  20. Brain Metastases • 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

  21. Leptomeningeal metastases

  22. 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 • Lipsomalcytarabine • Thiotepa

  23. PCNSL

  24. 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

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

  26. 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

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

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

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

  30. Memory failure, gait ataxia, incontinence

  31. references