brain metastases
Jump to navigation
Jump to search
Etiology
- lung cancer (most common)
- ~37% metastasize to brain
- accounts for ~50% of metastatic brain tumors
- breast cancer
- ~23% metastasize to brain
- account for ~15-20% of metastatic brain tumors
- melanoma
- ~40% metastasize to brain
- accounts for ~10% of metastatic brain tumors
- adenocarcinoma of the colon/rectum
- ~11% metastasize to brain
- accounts for ~5% of metastatic brain tumors
- renal cell carcinoma: ~19% metastasize to brain
- lymphoma & leukemia tend to involve leptomeninges more than brain parenchyma (see carcinomatous meningitis)
- adenocarcinoma of the esophagus
- cervical carcinoma: ~9% metastasize to brain
- prostate carcinoma: ~2% metastasize to brain
- unknown primary 10%
Single metastasis more common:
Multiple metastases more common:
Epidemiology
- most common form of brain tumor, accounting for > 50% of brain tumors in adults
- occurs in ~10-30% of adults with cancer; ~6-10% of children with cancer
- ~98,000 -170,000 new cases per year
- generally occurs is adults > 60 years of age[2]
Pathology
- distribution:
- ~80% cerebral hemispheres
- ~15% cerebellum
- ~5% brainstem
- GI & pelvic tumors have predilection to metastasize to posterior fossa
- metastases tend to be located at the gray-white junction where blood vessels decrease in diameter
- central necrosis of metastatic lesions with surrounding edema[2]
- mass effect
- leptomeningeal metastases common with lymphoma/leukemia but may occur with any cancer metastasizing to the brain
Genetics
- defects in EPHB2 may be associated with prostate cancer metastasis to the brain
Clinical manifestations
- headache is the most common symptom of increased intracranial pressure
- vomiting
- mental status changes
- focal neurologic deficit
- loss of consciousness
- seizures
- leptomeningeal metastasis
Diagnostic procedures
- funduscopy may reveal papilledema & increased intracranial pressure
- lumbar puncture with CSF analysis
- indications:
- suspected leptomeningeal metastasis, but negative MRI
- contraindications: increased intracranial pressure
- CSF findings
- elevated CSF protein
- diminished CSF glucose
- positive CSF cytology
- indications:
- brain biopsy not indicated with biopsy-proven cancer & multiple enhancing brain lesions[2]
Radiology
- magnetic resonance imaging (MRI)
- all patients with cancer & new neurologic findings[2]
- multifocal ring-enhancing lesions at the gray-white junction[2]
- computed tomography (CT) if MRI is unavailable
- communicating hydrocephalus may be apparent with leptomeningeal metastases
Complications
- intracranial hemorrhage 20-50%
- not increased with enoxaparin for DVT[5]
- risk of intracranial hemorrhage was 4-fold higher with melanoma or renal cell carcinoma than lung cancer[5]
Differential diagnosis
- primary brain tumor
- intracranial abscess
- progressive multifocal leukoencephalopathy
- demyelination
- cerebral infarct/bleed
- radiation necrosis
Management
- control intracranial pressure & edema
- urgent dexamethasone IV for increased intracranial pressure[2]
- oral glucocorticoid ok for minimal symptoms
- osmotic diuresis (mannitol, hypertonic saline)
- urgent dexamethasone IV for increased intracranial pressure[2]
- if source unknown, evaluate for most common sources of brain metastases
- stereotactic radiosurgery (gamma knife) vs surgery for single brain metastasis
- stereotactic radiosurgery (gamma knife)
- single brain metastasis (< 3.5 cm)
- case decribing excision of lesion 3 x 2 x 2 cm[2]
- good performance status
- single brain metastasis (< 3.5 cm)
- surgery
- larger lesions (> 3.5 cm) or multiple lesions
- good performance status
- minimal to limited or no evidence of extracranial disease
- accessible lesion that can be completely excised
- metastatic melanoma in particular may benefit from surgical excision[2][4]
- postoperative whole brain radiotherapy
- stereotactic radiosurgery (gamma knife)
- radiotherapy for multiple brain metastases
- whole brain radiation[6]
- 3,000 cGy in 10 fractions or 2,000 cGy in 5 fractions
- optimal use of radiosurgery undefined
- whole brain radiation[6]
- chemotherapy followed by radiation therapy
- indication: leptomeningeal metastasis
- not indicated for parenchymal brain metastases from most solid cancers[2]
- ib drugs may cross blood brain barrier[8]
- pembrolizumab may be of benefit in patients with metastases due to melanoma[10]
- glucocorticoids as initial adjunctive therapy for parenchymal & leptomeningeal metastasis
- supportive care
Prognosis:
- neither whole brain radiation nor stereotactic radiosurgery seems to significantly prolong life[11]
- median survival is 10-16 months[2]
- limited or stable extracranial disease improves prognosis[12]
More general terms
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1068-70
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 Medical Knowledge Self Assessment Program (MKSAP) 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Khasraw M, Posner JB. Neurological complications of systemic cancer. Lancet Neurol. 2010 Dec;9(12):1214-27 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21087743
- ↑ 4.0 4.1 Eigentler TK, Figl A, Krex D, Mohr P et al Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma. Cancer. 2011 Apr 15;117(8):1697-703 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21472716
- ↑ 5.0 5.1 5.2 Donato J Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study. Blood. May 18, 2015 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25987658 www.bloodjournal.org/content/early/2015/05/18/blood-2015-02-626788
- ↑ 6.0 6.1 Patil CG, Pricola K, Garg SK, Bryant A, Black KL. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD006121 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20556764
- ↑ Patel TR, Knisely JP, Chiang VL. Management of brain metastases: surgery, radiation, or both? Hematol Oncol Clin North Am. 2012 Aug;26(4):933-47 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22794291
- ↑ 8.0 8.1 Bulbul A, Forde PM, Murtuza A et al Systemic Treatment Options for Brain Metastases from Non-Small-Cell Lung Cancer. Oncology (Williston Park). 2018 Apr 15;32(4):156-63. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29684234 Free Article
- ↑ Lin X, DeAngelis LM. Treatment of Brain Metastases. J Clin Oncol. 2015 Oct 20;33(30):3475-84. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26282648 Free PMC Article
- ↑ 10.0 10.1 Furst ML with expert commentary by Klil-Drori AJ Melanoma Brain Metastases Respond to Pembrolizumab. Patients who are healthy enough should receive dual checkpoint inhibitors, researchers say. MedPage Today. ASCO Reading Room 12.06.2018
Kluger HM, Chiang V, Mahajan A et al Long-Term Survival of Patients with Melanoma With Active Brain Metastases Treated with Pembrolizumab on a Phase II Trial. J Clin Oncol 2018; Nov 8, PMID: https://www.ncbi.nlm.nih.gov/pubmed/30407895 - ↑ 11.0 11.1 Agency for Healthcare Research & Quality (QHRQ) Effective Health Care Program Radiation Therapy for Brain Metastases AHRQ Systematic Review. June 9, 2021 https://effectivehealthcare.ahrq.gov/products/radiation-therapy-brain-metastases/research
- ↑ 12.0 12.1 Li AY, Gaebe K, Zulfiqar A et al Association of Brain Metastases With Survival in Patients With Limited or Stable Extracranial DiseaseA Systematic Review and Meta-analysis. JAMA Netw Open. 2023;6(2):e230475 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36821113 PMCID: PMC9951042 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2801743