Epidemiology, clinical manifestations, and diagnosis of brain metastases
- Jay S Loeffler, MD
Jay S Loeffler, MD
- Section Editor — Neurooncology
- Professor of Radiation Oncology
- Harvard Medical School
- Patrick Y Wen, MD
Patrick Y Wen, MD
- Section Editor — Neurooncology
- Professor of Neurology
- Harvard Medical School
Brain metastases are the most common intracranial tumors in adults, accounting for significantly more than one-half of brain tumors. In patients with systemic malignancies, brain metastases occur in 10 to 30 percent of adults and 6 to 10 percent of children [1-5].
The incidence of brain metastases may be increasing, due to both improved detection of small metastases by magnetic resonance imaging (MRI) and better control of extracerebral disease resulting from improved systemic therapy [4-10].
The etiology, clinical manifestations, and diagnosis of brain metastases will be reviewed here, along with an overview of the approach to treatment. Specific treatment approaches to good and poor risk patients, as well as the use of systemic therapy, are discussed separately. (See "Overview of the treatment of brain metastases" and "Systemic therapy for brain metastases".)
In adults, the most common primary tumors responsible for brain metastases are carcinomas, and include lung, breast, kidney, and colorectal cancers, and melanoma. In contrast, carcinomas of the prostate, esophagus, and oropharynx and non-melanoma skin cancers rarely metastasize to the brain. In children, the most common sources of brain metastases are sarcomas, neuroblastoma, and germ cell tumors [3,9,10].
For all types of cancer, brain metastases diagnosed during life are relatively uncommon. This was illustrated in two large series, one from the Metropolitan Detroit Cancer Surveillance System and the other from a Dutch series [11,12]. In both studies, the cumulative incidence of brain metastases detected was similar:
- Posner JB. Management of brain metastases. Rev Neurol (Paris) 1992; 148:477.
- Sawaya R, Bindal RK. Metastatic brain tumors. In: Brain Tumors, Kaye AH, Laws ER (Eds), Churchill Livingstone, Edinburgh 1995. p.923.
- Graus F, Walker RW, Allen JC. Brain metastases in children. J Pediatr 1983; 103:558.
- Wen PY, Loeffler JS. Management of brain metastases. Oncology (Williston Park) 1999; 13:941.
- Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am 1996; 7:337.
- Loeffler JS, Patchell RA, Sawaya R. Metastatic brain cancer. In: Cancer: Principles and Practice of Oncology, Davita VT, Hellman S, Rosenberg SA (Eds), JP Lippincott, Philadelphia 1997. p.2523.
- Posner JB. Neurologic Complications of Cancer, FA Davis, Philadelphia 1995.
- Paterson AH, Agarwal M, Lees A, et al. Brain metastases in breast cancer patients receiving adjuvant chemotherapy. Cancer 1982; 49:651.
- Sundermeyer ML, Meropol NJ, Rogatko A, et al. Changing patterns of bone and brain metastases in patients with colorectal cancer. Clin Colorectal Cancer 2005; 5:108.
- Bouffet E, Doumi N, Thiesse P, et al. Brain metastases in children with solid tumors. Cancer 1997; 79:403.
- Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004; 22:2865.
- Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 2002; 94:2698.
- Lassman AB, DeAngelis LM. Brain metastases. Neurol Clin 2003; 21:1.
- Slimane K, Andre F, Delaloge S, et al. Risk factors for brain relapse in patients with metastatic breast cancer. Ann Oncol 2004; 15:1640.
- Crivellari D, Pagani O, Veronesi A, et al. High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann Oncol 2001; 12:353.
- Miller KD, Weathers T, Haney LG, et al. Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol 2003; 14:1072.
- Tham YL, Sexton K, Kramer R, et al. Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 2006; 107:696.
- Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res 2007; 13:1648.
- Gori S, Rimondini S, De Angelis V, et al. Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist 2007; 12:766.
- Kruser TJ, Chao ST, Elson P, et al. Multidisciplinary management of colorectal brain metastases: a retrospective study. Cancer 2008; 113:158.
- Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol 2005; 75:5.
- Mongan JP, Fadul CE, Cole BF, et al. Brain metastases from colorectal cancer: risk factors, incidence, and the possible role of chemokines. Clin Colorectal Cancer 2009; 8:100.
- Nieder C, Pawinski A, Balteskard L. Colorectal cancer metastatic to the brain: time trends in presentation and outcome. Oncology 2009; 76:369.
- Aprile G, Zanon E, Tuniz F, et al. Neurosurgical management and postoperative whole-brain radiotherapy for colorectal cancer patients with symptomatic brain metastases. J Cancer Res Clin Oncol 2009; 135:451.
- Baek JY, Kang MH, Hong YS, et al. Characteristics and prognosis of patients with colorectal cancer-associated brain metastases in the era of modern systemic chemotherapy. J Neurooncol 2011; 104:745.
- Mamon HJ, Yeap BY, Jänne PA, et al. High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation. J Clin Oncol 2005; 23:1530.
- Delattre JY, Krol G, Thaler HT, Posner JB. Distribution of brain metastases. Arch Neurol 1988; 45:741.
- Quattrocchi CC, Errante Y, Gaudino C, et al. Spatial brain distribution of intra-axial metastatic lesions in breast and lung cancer patients. J Neurooncol 2012; 110:79.
- Clouston PD, DeAngelis LM, Posner JB. The spectrum of neurological disease in patients with systemic cancer. Ann Neurol 1992; 31:268.
- Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology 1993; 43:1678.
- Coia LR, Aaronson N, Linggood R, et al. A report of the consensus workshop panel on the treatment of brain metastases. Int J Radiat Oncol Biol Phys 1992; 23:223.
- Cohen N, Strauss G, Lew R, et al. Should prophylactic anticonvulsants be administered to patients with newly-diagnosed cerebral metastases? A retrospective analysis. J Clin Oncol 1988; 6:1621.
- Glantz MJ, Cole BF, Friedberg MH, et al. A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors. Neurology 1996; 46:985.
- Forsyth PA, Weaver S, Fulton D, et al. Prophylactic anticonvulsants in patients with brain tumour. Can J Neurol Sci 2003; 30:106.
- Nutt SH, Patchell RA. Intracranial hemorrhage associated with primary and secondary tumors. Neurosurg Clin N Am 1992; 3:591.
- Sze G, Milano E, Johnson C, Heier L. Detection of brain metastases: comparison of contrast-enhanced MR with unenhanced MR and enhanced CT. AJNR Am J Neuroradiol 1990; 11:785.
- Davis PC, Hudgins PA, Peterman SB, Hoffman JC Jr. Diagnosis of cerebral metastases: double-dose delayed CT vs contrast-enhanced MR imaging. AJNR Am J Neuroradiol 1991; 12:293.
- Schaefer PW, Budzik RF Jr, Gonzalez RG. Imaging of cerebral metastases. Neurosurg Clin N Am 1996; 7:393.
- Muroff LR, Runge VM. The use of MR contrast in neoplastic disease of the brain. Top Magn Reson Imaging 1995; 7:137.
- Elster AD, Mathews VP, King JC, Hamilton CA. Improved detection of gadolinium enhancement using magnetization transfer imaging. Neuroimaging Clin N Am 1994; 4:185.
- Peretti-Viton P, Taieb D, Viton JM, et al. Contrast-enhanced magnetisation transfer MRI in metastatic lesions of the brain. Neuroradiology 1998; 40:783.
- Akeson P, Larsson EM, Kristoffersen DT, et al. Brain metastases--comparison of gadodiamide injection-enhanced MR imaging at standard and high dose, contrast-enhanced CT and non-contrast-enhanced MR imaging. Acta Radiol 1995; 36:300.
- Runge VM, Wells JW, Nelson KL, Linville PM. MR imaging detection of cerebral metastases with a single injection of high-dose gadoteridol. J Magn Reson Imaging 1994; 4:669.
- Yuh WT, Fisher DJ, Runge VM, et al. Phase III multicenter trial of high-dose gadoteridol in MR evaluation of brain metastases. AJNR Am J Neuroradiol 1994; 15:1037.
- Sze G, Johnson C, Kawamura Y, et al. Comparison of single- and triple-dose contrast material in the MR screening of brain metastases. AJNR Am J Neuroradiol 1998; 19:821.
- Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990; 322:494.
- Schoenberg BS, Christine BW, Whisnant JP. Nervous system neoplasms and primary malignancies of other sites. The unique association between meningiomas and breast cancer. Neurology 1975; 25:705.
- Drlicek M, Bodenteich A, Urbanits S, Grisold W. Immunohistochemical panel of antibodies in the diagnosis of brain metastases of the unknown primary. Pathol Res Pract 2004; 200:727.
- Latief KH, White CS, Protopapas Z, et al. Search for a primary lung neoplasm in patients with brain metastasis: is the chest radiograph sufficient? AJR Am J Roentgenol 1997; 168:1339.
- Merchut MP. Brain metastases from undiagnosed systemic neoplasms. Arch Intern Med 1989; 149:1076.
- van de Pol M, van Aalst VC, Wilmink JT, Twijnstra A. Brain metastases from an unknown primary tumour: which diagnostic procedures are indicated? J Neurol Neurosurg Psychiatry 1996; 61:321.
- Mavrakis AN, Halpern EF, Barker FG 2nd, et al. Diagnostic evaluation of patients with a brain mass as the presenting manifestation of cancer. Neurology 2005; 65:908.