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At least 19 recordsLinked to original sources
PubMed2005

S100beta as a predictor of brain metastases: brain versus cerebrovascular damage.

BACKGROUND: The identification of brain metastases in patients with malignant disease has important implications for determining their treatment and prognosis. Asymptomatic metastatic brain tumors may be detected by surveillance imaging techniques, but longitudinal follow-up of patients who are at risk is sporadic primarily due to cost. Because the development of brain metastases is accompanied and detected by extravasation of contrast agents across the blood-brain barrier (BBB), the authors hypothesized that peripheral analysis of the BBB indicator S100beta may be useful as a screening tool for brain metastases in patients who have no neurologic symptoms. METHODS: Thirty-eight patients were enrolled for the current study. All patients had newly diagnosed lung carcinoma and had no neurologic symptoms or known history of brain metastasis. Patients underwent an initial magnetic resonance imaging (MRI) scans and S100beta blood tests. S100beta tests were repeated in a subset of patients at the time of routine follow-up MRI scans. RESULTS: Based on imaging studies and on serum S100beta analyses, the patients were divided in 3 categories: 1) patients with normal S100beta levels (0.08 +/- 0.02 microg/L; n = 22 patients) and normal MRI scans; 2) patients with elevated S100beta levels (0.5 +/- 0.28 microg/L; n = 8 patients) and pronounced microvascular changes on MRI scans but with no metastases; and 3) patients with elevated S100beta levels (0.28 +/- 0.19 microg/L; n = 7 patients) and metastatic brain tumor(s) on MRI scans. CONCLUSIONS: Because of the significant overlap in S100beta levels between patients with cerebral microvascular diseases and patients with brain metastases, the authors concluded that the serum S100beta level may be used as a surveillance tool to predict or detect brain metastases if appropriate prescreening radiologic tests are obtained and if patients who are candidates for false-positive results are identified and excluded.

Adult↗
PubMed2005

Current treatment paradigms for the management of patients with brain metastases.

Brain metastases continue to be a major and growing challenge in oncology, but recent advances in surgery, radiosurgery, and chemotherapy have broadened the number of treatment options. Current approaches to the management of brain metastases focus on individualizing patient care based on factors including the Karnofsky Performance Status, the tumor histology, the number of metastases, and the status of the systemic disease. A number of treatment approaches have been shown to be effective for brain metastases, including surgery; radiosurgery; whole-brain radiotherapy; and, more recently, chemotherapy. The use of adjuvant whole-brain radiotherapy with local therapies, such as surgery or radiosurgery, along with newer chemotherapy options, such as targeted biological agents, temozolomide, and implantable 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) Gliadel wafers, are at the forefront of recent advances in the treatment of patients with brain metastases that may provide longer survival and improved quality of life. Although there is no current standard treatment, some general guidelines are recommended for single metastases, oligometastases (two to three brain metastases), and multiple (four or more) brain metastases, and for new or recurrent disease. With advances in systemic therapy for cancer, the treatment of brain metastases is becoming an increasingly important determinant of the length of survival and quality of life for cancer patients.

Brain Neoplasms↗
PubMed1992

Management of brain metastases.

Brain metastases are common and often occur in patients whose systemic cancer is quiescent. When brain metastases occur, they considerably decrease the quality of life in patients who otherwise might be functional. An early diagnosis and vigorous treatment of the brain metastasis, while only rarely curative, may lead to a useful remission of the brain symptoms and may both enhance the quality of the patient's life and prolong survival. Patients with known cancer and neurological symptoms should all undergo appropriate diagnostic tests which include either CT scan or magnetic resonance imaging and, if a lesion is found and a definitive diagnosis can not be established, biopsy. Single or solitary brain metastases in patients with good systemic performance status should be strongly considered for surgical extirpation which will both make the diagnosis and deliver definitive treatment to the lesion. Patients with poor systemic performance status and/or multiple brain metastases are candidates for whole brain radiation therapy. Whole brain radiation therapy is also indicated in patients after successful surgical extirpation of a single metastasis. The role of focal radiation therapy and chemotherapy in the treatment of brain metastases is still being evaluated. Preliminary evidence suggests that focal radiation therapy is probably useful for the treatment of relapsed metastases and that chemotherapy may be useful in the primary treatment of small or asymptomatic brain metastases. Appropriate use of therapeutic modalities directed at brain tumors will ameliorate symptoms in most patients and usually increase survival and enhance the quality of the patient's life.

Adrenal Cortex Hormones↗
PubMed2001

Considerations in the diagnosis and management of brain metastases.

Brain metastases are a common complication of systemic cancer and a significant cause of morbidity. For patients whose brain metastases remain untreated, the prognosis is poor. The advent of contrast-enhanced magnetic resonance imaging has made accurate diagnosis of brain metastases among symptomatic patients a much more manageable task. However, approximately one-third of patients with intracranial metastases are asymptomatic, and therefore, greater awareness of the risk factors for developing brain metastases may permit better targeting of "at risk" patients for further evaluation. Advances in technology and surgical techniques have created more options for the management of brain metastases via the use of various combinations of surgery, irradiation, and stereotactic radiosurgery. However, successful application of these therapies has redefined the potential for long-term morbidity associated with radiation therapy. Thus, considerable effort is now being directed toward finding a balance between the use of whole-brain radiotherapy, surgery, and radiosurgery, and tailoring those treatment modalities to the unique needs of the patient. Although more prospective, randomized studies are needed before an informed consensus regarding the optimal means for managing brain metastases can be established, this article provides an overview of some of the advantages and disadvantages of therapeutic approaches recently under study.

Age Factors↗
PubMed2003

[Guidelines for the diagnosis and management of brain metastases].

Brain metastases are one of the most common palliative oncologic problems. Approximately 20% to 40% of all cancer patients eventually develop metastases to the brain. In this review, we discuss the clinical presentation, diagnostic work-up, prognostic factors and appropriate therapeutic choices for these patients. Radiotherapy is the treatment of choice for most patients with brain metastases. Surgery and whole brain radiotherapy for the treatment of single brain metastasis in patients with stable extracranial disease is at the present time the best treatment option for this particular group. Radiosurgery, treatment that is a possible replacement for surgery, is not yet established as an effective treatment. Chemotherapy is not the primary therapy for these patients. The overall prognosis for patients with brain metastases remains poor.

Adult↗
PubMed2006

Chemotherapy and the treatment of brain metastases.

Brain metastases have traditionally been treated with a surgical or radiotherapeutic approach. Chemotherapy is used occasionally as salvage therapy. The blood-brain barrier excludes most chemotherapeutic agents, rendering many systemic options ineffective within the CNS. Intrathecal chemotherapies do not penetrate into brain tissue or bulky parenchymal tumors, so are ineffective in treatment of brain metastases. However, some patients with brain metastases benefit from chemotherapy, and temozolomide or targeted therapies like gefitinib have demonstrated activity. A better understanding of the biological behavior of brain metastases may lead to development of effective treatments for this common complication of systemic cancer. The review discusses the biology of brain metastases and provides an update on current chemotherapeutic strategies.

Antineoplastic Agents↗
PubMed2002

Management of brain metastases.

Brain metastases occur in 20-40% of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3-3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not improve. Late neurotoxicity in long surviving patients after WBRT is not negligible; to avoid this complication patients with favorable prognostic factors must be treated with conventional schedules of RT, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases. A small subgroup of these latter may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors). New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated.

Adrenal Cortex Hormones↗
PubMed1999

Management of brain metastases.

Brain metastases are the most common type of brain tumor in adults and are an increasingly important cause of morbidity and mortality in cancer patients. In recent years, important advances have been made in the diagnosis and management of brain metastases. These advances include the widespread use of magnetic resonance imaging (MRI), enabling small metastases to be detected; the introduction of stereotactic radiosurgery; and the performance of studies that have clarified the role of surgery and postoperative radiation therapy for single brain metastases. As a result, most patients receive effective palliation, and the majority do not die from their brain metastases. However, further studies are needed to define the optimal role of conventional treatments and to develop more effective novel therapies.

Brain Neoplasms↗
PubMedDate not supplied

Altered expression and new mutations in DNA mismatch repair genes MLH1 and MSH2 in melanoma brain metastases.

Brain metastases, including those of malignant melanoma (known for its high genomic instability), are the most common intracranial tumors. The main objective of this study was to investigate expression and mutation in the DNA mismatch repair system in melanoma brain metastases. Expression of MLH1, MSH2, PMS1 and PMS2 was investigated immunohistochemically in 31 melanoma metastatic tumors. Mutational analysis of MLH1 and MSH2 was performed in 17 melanoma brain metastases. Loss of MLH1 and MSH2 expression was found in 10/31 and 12/31 tumors. PMS1 (27/31) and PMS2 (28/31) expression was preserved in the majority of lesions. Potential missense mutation was found in MSH2 (exon 13) in 2/17 melanomas. Mutation in the intron sequence between exon 14 and 15 of MLH1 (exon 15) was observed in 4/17 cases. Our results indicate that the two major DNA mismatch repair genes, MLH1 and MSH2, are more frequently affected by alterations in the DNA mismatch repair system than the helper genes PMS1 and PMS2. The presence of mutations of MSH2 and MLH1 in melanoma brain metastases, which has not been found in primary melanomas, indicates the high genomic instability of melanoma brain metastases.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Stereotactic radiosurgery with and without whole-brain radiotherapy for newly diagnosed brain metastases.

Brain metastases develop in 20-40% of cancer patients and can cause significant morbidity. In selected patients with one to three lesions, stereotactic radiosurgery may be used to improve local control. However, it is unclear whether whole-brain radiotherapy is necessary for all patients who are candidates for stereotactic radiosurgery. While whole-brain radiotherapy may improve the locoregional control of brain metastases, it may cause long-term side effects and may not improve overall survival in some patients. Its benefits should be evaluated in the context of risks of neurocognitive deterioration, either from whole-brain radiotherapy or from uncontrolled brain metastases, and the possible need for salvage treatments with the omission of initial whole-brain radiotherapy. For certain radioresistant brain metastases, the benefit of whole-brain radiotherapy to patients who have stereotactic radiosurgery is uncertain.

Brain Neoplasms↗
PubMed1994

Management of brain metastases.

Brain metastases usually develop in patients with disseminated systemic disease. Effective palliation is available for the vast majority of patients with brain metastases, but many will die within 6 months, usually from progressive systemic tumor. However, in a substantial proportion of patients, a vigorous therapeutic approach using surgery, radiotherapy, and possibly chemotherapy leads to years of productive life. Recurrent brain metastases can often be retreated using newer techniques of brachytherapy and stereotactic radiosurgery as well as conventional treatments. Brain metastases do not necessarily mean imminent death for every patient, and physicians can now offer patients a growing range of therapeutic options. Furthermore, attention to symptomatic therapies can improve the quality of life for all patients, even those whose survival will be relatively short.

Adrenal Cortex Hormones↗
PubMed2006

Resectable brain metastases.

Brain metastases are the most common brain tumors seen in clinical practice, comprising well over half of all brain tumors. For many years, surgical resection of brain metastases was considered a form of palliative therapy only, but more recently it has been shown to have a more important role in extending survival in appropriately selected patients. Newer surgical techniques have helped to reduce the morbidity associated with tumor resection. Although randomized studies have demonstrated the need for postoperative whole-brain radiotherapy, there remains interest in the use of other surgical adjuncts to delay or eliminate the need for fractionated radiotherapy. The use of various treatment modalities, particularly image-guided surgery and stereotactic radiosurgery, allows clinicians who are focused on the treatment of brain metastases to achieve superior levels of tumor control within the brain. As a result, overall survival is much more dependent on the status of the patient's systemic disease.

Brain Neoplasms↗
PubMed2006

Temozolomide with or without radiotherapy in melanoma with unresectable brain metastases.

Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m2 temozolomide on days 1 to 5 every 28 days as first or second-line therapy. This therapy regimen was combined with radiotherapy of the brain metastases in 22/35 patients. Grade III and IV toxicity was observed in 8/35 patients (leukopenia, granulocytopenia, thrombocytopenia, anemia, nausea and obstipation). Complete remission was observed in 1/34, partial remission in 2/34 and stable disease in 9/34 patients. In 5/34 a mixed response was assessed, 17/34 had disease progression and in one patient tumor response was not evaluable. The median progression free time was 5 (0-8) months for all patients, the median survival time for all patients from start of therapy was 8 (0-28) months, 9 (2-28) months in patients with concurrent stereotactic radiotherapy and 7 (3-17) months in patients with concurrent whole brain radiotherapy. Our results demonstrate that temozolomide can be combined with radiotherapy for the treatment of brain metastases in malignant melanoma, and that this combination may prolong survival in this patient group.

Antineoplastic Agents, Alkylating↗
PubMed2005

Pathobiology of brain metastases.

Brain metastasis is a major cause of systemic cancer morbidity and mortality. Many factors participate in the development and maintenance of brain metastases. The survival of the metastasis depends upon crucial interactions between tumour cells and the brain microenvironment during its development at the new site. This review focuses on the pathobiological mechanisms involved in the establishment and regulation of brain metastases. Developments in molecular biology have vastly expanded our knowledge about the mechanisms of invasion, proliferation, metastatic cell signalling, and angiogenesis in brain metastases. Advances in this understanding of the pathobiology of brain metastasis may lead to novel targeted treatment paradigms and a better prognosis for patients with brain metastatic disease.

Brain Neoplasms↗
PubMedDate not supplied

Treatment of brain metastases.

Brain metastases are a common complication of cancer, found in approximately 20% of patients at autopsy. The diagnosis is usually established by neuroimaging and carries a poor overall prognosis. 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. Definitive antitumor treatment may include whole-brain radiotherapy, surgery, stereotactic radiosurgery, and chemotherapy. 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.

Adrenal Cortex Hormones↗
PubMed2003

The management of brain metastases.

Brain metastases are neoplasms that originate in tissues outside the brain and then spread secondarily to the brain. Metastases to the brain are the most common intracranial tumours in adults. Substantial progress has been made in the treatment of these tumours, and radiotherapy, surgery, and stereotactic radiosurgery are now established treatments. With aggressive treatment, most patients experience meaningful symptom reduction and extension of life.

Brain Neoplasms↗
PubMed2000

Brain metastases.

Brain metastases are an increasingly common complication in patients with systemic cancer. The optimal treatment for each patient depends on careful evaluation of several factors: the location, size, and number of brain metastases; the patient's age, general condition, and neurologic status; and the extent of systemic cancer to name a few. For patients with a single brain metastasis and limited systemic disease, the standard treatment is surgical resection followed by whole brain radiation therapy. In patients with a small, single metastasis, stereotactic radiosurgery is probably comparable to surgery. Patients with several metastases (up to three) and controlled systemic disease can be treated with whole-brain radiation and stereotactic radiosurgery. Patients with multiple metastases (more than three) are generally treated with whole-brain radiation alone. Radiosurgery is effective in treating patients with a limited number of recurrent brain metastases and stable systemic diseases. Surgery may have a role in patients with a large symptomatic recurrent lesion producing mass effect. Reirradiation and chemotherapy may have a limited role in patients with multiple recurrent metastases.

Adrenal Cortex Hormones↗
PubMed1991

Brain metastases.

Brain metastases are frequent, accounting for 20% of all brain tumours. The most common primary tumours responsible for brain metastases are lung cancer in man and breast cancer in women. Most metastases are located at the grey matter-white matter junction, in junctional vascular territories and in the rolandic region. Although non-specific, MRI is the most sensitive neuroradiological method for the lesions, especially when accompanied by gadolinium injection. MRI must absolutely be performed before surgical treatment, as gadolinium might detect other metastatic lesions or show metastatic tumours so small that they were not visible at computerized tomography (CT).

Aged↗