Laboratory Studies
- Laboratory investigations include blood work, such as CBC, electrolyte panel, coagulation screen, and liver function panel.
- Specific markers, such as anti-Hu antibody in limbic encephalopathy, anti-Yo antibody in cerebellar degeneration, and anti-Ri antibody in opsoclonus and ataxia are of some value, especially in patients with small-cell lung cancer, ovarian cancer, and breast or lung cancers.
- Chronic anemia is common in systemic disease.
- Electrolyte imbalance, such as in hyponatremia (hypothyroidism or syndrome of inappropriate secretion of antidiuretic hormone [SIADH]), can be found in patients with metastasis to the pituitary gland and meninges.
- Abnormal coagulopathy can be observed in patients with breast cancer or leukemia.
- Abnormal liver function is common in patients with advanced systemic diseases or in those receiving chemotherapy.
- Specific markers, such as anti-Hu antibody in limbic encephalopathy, anti-Yo antibody in cerebellar degeneration, and anti-Ri antibody in opsoclonus and ataxia, are of some diagnostic value, especially in patients with small-cell lung cancer, ovarian cancer, breast cancer, or lung cancers.
- Recent advancement in proteomics and the use of serum markers may be useful in the future for target treatment and diagnosis.
Imaging Studies
- Imaging study for metastatic disease to the brain can be divided into systemic imaging and imaging of the neuraxis. Images provide information on tumor burden in the brain and associated structures, in addition to the rest of the body, and are integral part in formulating the optimal treatment plan.
- Systemic imaging studies
- Chest radiography should be included in the workup of any mass lesion in the brain, specifically in patients without a history of systemic cancer.
- Chest radiographs may reveal the primary cancer and suggest an alternative site for obtaining tissue for histologic diagnosis.
- Additional imaging modalities such as CT, positron emission tomography (PET), and bone scanning are used to stage the systemic disease.
- Imaging of the neuraxis (brain and spinal cord)
- Head CT imaging of the brain is not as reliable as MRI in determining the extent of brain metastases.
- Head CT can cause underestimation of the number of brain lesions. In 20% of cases and even when contrast medium is used, head CT shows a solitary lesion but subsequent MRI shows multiple lesions.
- High-resolution MRI can be used to detect additional brain metastases in patients undergoing Gamma Knife surgery.[5]
- Contrast medium enhances visualization of mass lesions in the brain and should be used in both CT and MRI.
- Newer imaging modalities, such as magnetization transfer imaging and perfusion imaging, are not particularly useful.
- Diffusion-perfusion MRI
- Diffusion-perfusion MRI has been used to differentiate poorly enhancing lesions.
- Tien et al reported that peritumoral edema and nonenhancing tumor have distinguishable features.[6]
- The utility of this imaging technique in metastatic diseases is not established, though peritumoral edema is prominent in most cases.
- Magnetic resonance (MR) spectrometry and PET scan (positron emission tomography).
- MR spectroscopy uses the chemical signature of rapid membrane turnover of proliferative cells to reveal the presence of cancer cells.
- Multiple voxel analysis is more commonly used because it has an advantage over signal voxel study to yield more information about the region of interest and to differentiate edema and possible necrosis.
- CT-PET and bone scans are used to stage the extent of the systemic disease. This helps to formulate the extensiveness of future treatments (see Treatment) and their justification. Patients with multiple systemic metastasis do not do well in intensive therapy.
- Other experimental imaging studies such as receptor-targeted and ligands-based molecular imaging are on the horizon. These imaging modalities are cancer specific.
- Both MRI spectrometry and PET studies are useful to differentiate radiation necrosis from tumor.
- Thallium-201 chloride PET seems to have high specificity (91%) in this regard.
- Neither of these methods is useful for differentiating metastasis from primary brain tumors, but they are helpful whenever the possibility of an abscess is being considered.
Procedures
- Tissue diagnosis: 11% of patients with cancer with a solitary mass in the brain have lesions other than metastatic disease. Hence, tissue diagnosis is sometime necessary to resolve this diagnostic uncertainty, especially when the imaging study results in ambiguity.
- Tissue diagnosis should be performed in cases of uncertain etiology.
- Of note, most surgeons advocate excision biopsy for a solitary lesion in an accessible area of the brain.
- For stereotactic brain biopsy, the morbidity rate is 3% with a 1% rate of hemorrhage and a 1% rate of deficit without hemorrhage. The mortality rate is 3%.
- In the past, the morbidity rate associated with tumor resection was 20%, and mortality rate was 2%.
- With recent advances in intraoperative navigation, the morbidity and mortality rates of excisional biopsy have been reduced to 10% and 0.5-2%, respectively, which are still higher than the rates with biopsy alone.
- Brain biopsy
- The morbidity rate for stereotactic brain biopsy is 3% overall; 1% is due to hemorrhage and 1% to deficits without bleed. The mortality rate is 3%.
- The morbidity rate for tumor resection is 20%, and the mortality rate is 2%.
- With recent advances in intraoperative navigation, the morbidity and mortality rates of excision biopsy have been reduced to 10% and 0.5-2%, respectively, which are slightly higher than the rates of stereotactic brain biopsy alone.
Nussbaum ES, Djalilian HR, Cho KH, Hall WA. Brain metastases. Histology, multiplicity, surgery, and survival. Cancer. Oct 15 1996;78(8):1781-8. [Medline].
Santarelli JG, Sarkissian V, Hou LC, Veeravagu A, Tse V. Molecular events of brain metastasis. Neurosurg Focus. Mar 15 2007;22(3):E1. [Medline].
Rusciano D, Burger MM. Mechanisms of Metastases. In: levine AJ, Schmidek HH (eds). In Molecular Genetics of Nervous System Tumors. New York: John Wiley & Son; 1993.
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. Dec 8 2005;438(7069):820-7. [Medline].
Hanssens P, Karlsson B, Yeo TT, Chou N, Beute G. Detection of brain micrometastases by high-resolution stereotactic magnetic resonance imaging and its impact on the timing of and risk for distant recurrences. J Neurosurg. Sep 2011;115(3):499-504. [Medline].
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Galicich JH, French LA. Use of dexamethasone in the treatment of cerebral edema resulting from brain tumors and brain surgery. Am Pract Dig Treat. Mar 1961;12:169-74. [Medline].
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DeAngelis LM, Mandell LR, Thaler HT, et al. The role of postoperative radiotherapy after resection of single brain metastases. Neurosurgery. Jun 1989;24(6):798-805. [Medline].
Jensen CA, Chan MD, McCoy TP, et al. Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis. J Neurosurg. Jun 2011;114(6):1585-91. [Medline].
Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. Jan 10 2011;29(2):134-41. [Medline].
Bindal RK, Sawaya R, Leavens ME, Lee JJ. Surgical treatment of multiple brain metastases. J Neurosurg. Aug 1993;79(2):210-6. [Medline].
Bindal AK, Bindal RK, Hess KR, et al. Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg. May 1996;84(5):748-54. [Medline].
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Auchter RM, Lamond JP, Alexander E, et al. A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis. Int J Radiat Oncol Biol Phys. Apr 1 1996;35(1):27-35. [Medline].
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| Primary Tumor Site | Percentage (%) |
| Lung | 21 |
| Breast | 9 |
| Melanoma | 40 |
| Lymphoma, mainly non-Hodgkin | 1 |
| GI tract | 3 |
| Genitourinary tract | 11 |
| Osteosarcoma | 10 |
| Head and neck | 6 |
| Group | Karnofsky Performance Status | Systemic Disease | Median Survival (mo) |
| Age ≤ 65 y | ≥ 70 | Controlled primary disease, no extracranial metastases | 7.1; 13.5 for single metastasis, 6.0 for multiple metastases |
| Age ≥ 65 y | ≥ 70 | Controlled systemic disease, with extracranial metastasis | 4.2; 8.1 for single metastasis, 4.1 for multiple metastases |
| Any age | Any | Any | 2.3 |
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