الفهرس Only 14 pages are availabe for public view
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Abstract
Brain metastases are a dreaded yet common complication of cancer. Approximately 97, 800–170, 000 new cases are diagnosed in the USA each year. The most common primary cancers responsible for brain metastases generally correlate with the distribution of neoplasms in the population. Lung and breast carcinomas together account for about 60% of all brain metastases. Other cancers with a predilection for seeding the central nervous system (CNS) include melanoma, colon, and renal carcinoma. The most common presenting clinical features are cognitive impairment, headache, hemiparesis, seizures, ataxia, and visual changes. The diagnosis is best established by magnetic resonance imaging (MRI) or, alternatively, computed tomography in patients unable to have an MRI scan (eg, patients with an implanted pacemaker). The identification on neuroimaging of an enhancing lesion, commonly at the gray-white matter junction with surrounding edema, in a patient with known cancer usually suffices to establish the diagnosis of brain metastasis. Tissue confirmation is necessary in patients without a prior cancer, in those whose history of cancer is remote, and in those for whom clinical or neuroimaging features may suggest an alternative diagnosis, such as a primary brain tumor.
15- A comprehensive approach to managing a patient with brain metastases includes therapies that (1) reduce mass effect and increased intracranial pressure; (2) provide treatment for medical complications, such as seizures, venous thromboses, and side effects from medication; (3) offer definitive treatments that prolong survival and quality of life; and (4)All of the above are considered in tandem with the patient’s underlying systemic disease and end-of-life directives.
16- Therapies are divided into two main categories: supportive and definitive. Supportive therapies, such as corticosteroids, anticonvulsants, and anticoagulants, are necessary for most patients to address the common medical complications that often accompany brain metastases. These treatments often ameliorate symptoms and signs and improve neurologic function, but they require careful management to minimize their common toxicities.
17- The initial drug of choice for treating cerebral edema associated with a brain metastasis is a corticosteroid (dexamethasone or methylprednisolone). The benefit of corticosteroids is often dramatic and may be evident within hours, but ultimately they are insufficient unless definitive tumor management is pursued. Control of vasogenic cerebral edema and removal of the offending mass can result in improved control of the seizure disorder. There has been a trend away from phenytoin toward levetiracetam, because of decreased rash, no need for lab monitoring and no induction of CYP3A4. Carbamazepine, phenobarbital, valproic acid and levetiracetam are often added for breakthrough seizures or to replace phenytoin if toxicity or allergic reactions occur.
18- Multimodality venous thrombosis prophylaxis should begin at the time of the original surgery with external leg compression and UFH or LMWH. Patients with symptomatic venous thrombosis or pulmonary embolism can be anticoagulated safely with warfarin or with LMWH.
19- Definitive antitumor treatment of Metastatic brain tumors require multimodal management including drugs, surgery, radiosurgery, radiation therapy, chemotherapy, gene therapy and other innovative approaches. A multimodal approach can yield prolonged survival of a year or more in some patients, particularly those with limited intracranial disease, high performance status, limited systemic cancer burden, young age, and certain tumor pathologies. However, even patients with poor prognostic factors can have some relief of neurologic symptoms and signs with the institution of therapy. Patients with recurrent brain metastases can also benefit from additional treatment, including all the modalities available at diagnosis.
20- Surgery is usually the optimal approach for an accessible single lesion as it may significantly improve function and survival. Resection of the lesion may relieve tumor-associated mass effect, allowing for reduction or discontinuation of glucocorticoids. Surgery is also the optimal approach when the nature of the lesion is not entirely clear to secure diagnosis. Finally, surgery may be considered in the setting of multiple metastases if there is a lesion that is clearly causing symptoms that may be relieved with resection.
21- Whole brain radiation therapy (WBRT) is considered for patients who have multiple metastatic lesions or as a “consolidating” therapy after surgical resection. WBRT has been shown to increase the time to recurrence after surgical resection and reduce the incidence of death due to neurologic disease, but there is no difference in overall survival between patients who receive post-operative WBRT and those who do not. The choice to use WBRT must be weighed against the risk of neurologic sequelea.
22- Stereotactic radiosurgery (SRS) is an increasingly popular therapy that can be used for both single and multiple metastases as long as the lesions are <4 cm. Although there are good responses with this therapy, it is not clear that SRS, with or without WBRT, improves survival. In general, some combination of surgery, SRS, and WBRT is commonly applied, especially to radiosensitive cancers such as small cell lung cancer and breast cancer.
23- Chemotherapy has traditionally been ineffective due to an inability of most agents to cross the blood brain barrier (BBB) and reach tumors. However, medications such as temozolomide, topican, and lapatinib have increasingly been tried in various forms of brain metastases with encouraging response rates and are currently undergoing formal investigation in clinical trials both as single agents and in combination therapy.
24- There is increasing evidence that the newer biologic agents targeting cellular protein receptors or other components of the tumor microenvironment may work synergistically with conventional radiation and cytotoxic agents.