Treatment of brain metastases in uncommon tumors

Melanoma spreads to the CNS with an incidence of 4 to 20%. Metastases from cancer of the colorectal and genitourinary tract, as well as sarcoma, are less frequent (1%). Surgery should be considered for single brain metastases in patients with controllable disease. Stereotactic needle biopsy may still be worthwhile to confirm diagnosis, and also in patients whose tumors are considered unresectable. Whole-brain radiotherapy is the treatment of choice for most brain metastases, since more than 70% of patients have multiple metastases at the time of diagnosis. Radiosurgery is particularly useful for patients unable to tolerate surgery and for patients with lesions inaccessible to surgery. Chemotherapy could be useful in patients with asymptomatic brain metastases and uncontrolled extracranial disease, depending on performance status and previous chemotherapy received.     

Treatment of brain metastases in uncommon tumors

Melanoma spreads to the CNS with an incidence of 4 to 20%. Metastases from cancer of the colorectal and genitourinary tract, as well as sarcoma, are less frequent (1%). Surgery should be considered for single brain metastases in patients with controllable disease. Stereotactic needle biopsy may still be worthwhile to confirm diagnosis, and also in patients whose tumors are considered unresectable. Whole-brain radiotherapy is the treatment of choice for most brain metastases, since more than 70% of patients have multiple metastases at the time of diagnosis. Radiosurgery is particularly useful for patients unable to tolerate surgery and for patients with lesions inaccessible to surgery. Chemotherapy could be useful in patients with asymptomatic brain metastases and uncontrolled extracranial disease, depending on performance status and previous chemotherapy received.     

乳腺癌脑转移的治疗

乳腺癌是仅次于肺癌易发生脑转移的恶性肿瘤,常规放射治疗可以提高生存率,孤立病灶可以外科手术切除,化学疗法有利于杀灭脑内亚临床病灶,放化疗结合能提高疗效,立体定向放射外科是安全、精确、有效的治疗方法。     

Treatment options for brain metastases from melanoma

Brain metastases are a common complication of metastatic malignant melanoma, conferring an exceedingly poor prognosis. Diagnosis of brain metastasis often has significant implications for duration and quality of life, and management can be difficult due to rapid progression of disease and resistance to conventional therapies. This review focuses primarily on the published evidence for treatment modalities for brain metastases from melanoma, emerging technologies and outlines future directions for research. In summary, external-beam radiation alone appears effective in palliating symptoms. Surgical management of solitary or acutely symptomatic lesions appears to alleviate symptoms and provide the possibility of local control of disease. Stereotactic radiosurgery is an increasingly utilized technique for patients with a limited number of metastases and presents a less-invasive alternative to craniotomy. Chemotherapy alone is relatively ineffective, although combined chemotherapy with external-beam radiation is being investigated. Future directions include combined modality therapy, the incorporation of novel agents and careful consideration of the structure of clinical trials for this disease.     

Treatment options for brain metastases from melanoma

Brain metastases are a common complication of metastatic malignant melanoma, conferring an exceedingly poor prognosis. Diagnosis of brain metastasis often has significant implications for duration and quality of life, and management can be difficult due to rapid progression of disease and resistance to conventional therapies. This review focuses primarily on the published evidence for treatment modalities for brain metastases from melanoma, emerging technologies and outlines future directions for research. In summary, external-beam radiation alone appears effective in palliating symptoms. Surgical management of solitary or acutely symptomatic lesions appears to alleviate symptoms and provide the possibility of local control of disease. Stereotactic radiosurgery is an increasingly utilized technique for patients with a limited number of metastases and presents a less-invasive alternative to craniotomy. Chemotherapy alone is relatively ineffective, although combined chemotherapy with external-beam radiation is being investigated. Future directions include combined modality therapy, the incorporation of novel agents and careful consideration of the structure of clinical trials for this disease.     

乳腺癌脑转移的治疗

乳腺癌是仅次于肺癌易发生脑转移的恶性肿瘤,常规放射治疗可以提高生存率,孤立病灶可以外科手术切除,化学疗法有利于杀灭脑内亚临床病灶,放化疗结合能提高疗效,立体定向放射外科是安全、精确、有效的治疗方法。     

Treatment strategies for breast cancer brain metastases

Brain metastases from breast cancer (BCBM) constitute the second most common cause of brain metastasis (BM), and the incidence of these frequently lethal lesions is currently increasing, following better systemic treatment. Patients with ER-negative and HER2-positive metastatic breast cancer (BC) are the most likely to develop BM, but if this diagnosis remains associated with a worse prognosis, long survival is now common for patients with HER2-positive BC. BCBM represents a therapeutic challenge that needs a coordinated treatment strategy along international guidelines. Surgery has always to be considered when feasible. It is now well established that stereotaxic radiosurgery allows for equivalent control and less-cognitive toxicities than whole-brain radiation therapy, which should be delayed as much as possible. Medical treatment for BCBM is currently a rapidly evolving field. It has been shown that the blood–brain barrier (BBB) is often impaired in macroscopic BM, and several chemotherapy regimens, antibody–drug conjugates and tyrosine-kinase inhibitors have been shown to be active on BCBM and can be part of the global treatment strategy. This paper provides an overview of the therapeutic option for BCBM that is currently available and outlines potential new approaches for tackling these deadly secondary tumours.Subject terms: Breast cancer, Metastasis     

Treatment of brain metastases from germ cell tumors

Brain metastases occur in approximately 10% of patients with advanced metastatic germ cell tumors. Patients with nonseminomatous histology, lung metastases, and high β-human chorionic gonadotropin levels are at higher risk for synchronous brain metastases at first diagnosis and for relapsing with brain metastases after successful cisplatin-based chemotherapy. Patients with brain metastases should undergo multimodal treatment strategies, including cisplatin-based combination chemotherapy plus radiotherapy or surgery. However, the optimal combination and sequence of these strategies remain unclear and may differ between subgroups. But in all cases, chemotherapy must be part of treatment, even in patients with isolated cerebral relapse without systemic disease.     

Treatment and prognosis of brain metastases from breast cancer

Background To analyze retrospectively the results of treatments for patients with brain metastases from breast cancer. Materials and Methods The records of 65 breast cancer patients with brain metastases who were treated between 1985 and 2005 were reviewed. For brain metastases, 11 patients (17%) were treated with surgical resection followed by radiotherapy, and the remaining 54 patients were treated with radiotherapy alone. Systemic chemotherapy was also administered to 11 patients after brain radiotherapy. Results The overall median survival for all patients was 6.1 months (range, 0.4–82.2 months). In univariate analysis, treatment modality, Karnofsky performance status (KPS), administration of systemic chemotherapy, extracranial disease status and total radiation dose each had significant impact on overall survival, and in multivariate analysis, treatment modality, KPS and administration of systemic chemotherapy were significant prognostic factors. Eight patients survived for more than 2 years after the diagnosis of brain metastases, and all these patients were treated with surgical resection and/or systemic chemotherapy in addition to radiotherapy. For the 45 patients treated with palliative radiotherapy (without systemic chemotherapy), the improvements in neurological symptoms were observed in 35 patients (78%), with the median duration of improvement of 3.1 months (range, 1.5–4.4 months). Conclusions The prognoses for patients with brain metastases from breast cancer were generally poor, although selected patients may survive longer with intensive brain tumor treatment, such as surgical resection and/or systemic chemotherapy in addition to brain radiotherapy. For patients with unfavorable prognoses, palliative radiotherapy was effective in improving the quality of the remaining lifetime.     

Treatment of brain metastases from lung cancer: chemotherapy

Brain metastases are a frequent complication in patients suffering from Lung cancer, and a significant cause of morbidity and mortality. Brain metastases are found in about 10% of patients at the time of diagnosis, and approximately 40% of all patients with lung cancer develop brain metastases during the course of their disease. The prognosis of these patients is rather poor. The standard treatment for brain metastases, so far, has been whole-brain radiation therapy and surgery focussing on symptom palliation. The use of chemotherapy for the treatment of brain metastases has been limited because of a presumed lack of effectiveness due to the blood-brain barrier. However, the importance of the blood-brain barrier is probably overrated in the case of macroscopic metastases or relapsed disease as the blood-brain barrier has already been disrupted at this stage resulting from the newly developed blood vessels not provided with the physiological properties of the common blood-brain barrier. Chemotherapeutic agents initially lipid-insoluble or liquor-impermeable can also penetrate into the brain and, therefore, trigger action against tumour cells. A number of clinical trials have demonstrated that brain metastases resulting from both small-cell lung cancer and non-small-cell lung cancer are susceptible to systemic chemotherapy. In small-cell lung cancer, cerebral response rates up to 50% were observed even in the second-line situation and were comparable to the response rates observed in the primary tumour. In non-small-cell lung cancer, similar results were achieved. Therefore, it seems justified to further evaluate the significance of chemotherapy compared to whole-brain radiation therapy. Whether chemotherapy alone is superior to whole-brain radiation therapy, or whether the combination of both therapeutic modalities should be preferred for the management of brain metastases, has not yet been proven, and further randomised phase-III studies are clearly needed. Based on the current available data, and the promising response rates in patients with lung cancer, chemotherapy should be considered for the management of brain metastases as part of a multimodality (or "interdisciplinary") treatment concept.     

Treatment of melanoma brain metastases: a new paradigm

Brain metastases occur commonly in patients with metastatic melanoma, are associated with a poor prognosis, and cause significant morbidity. Both surgery and stereotactic radiosurgery are used to control brain metastases and, in selected patients, improve survival. In those with extensive brain involvement, whole-brain radiotherapy can alleviate symptoms. Historically, systemic therapy has had little role to play in the management of melanoma brain metastases; however, early clinical trials of BRAF inhibitors have shown promising activity. This review examines the evidence for local and systemic treatments in the management of patients with melanoma brain metastases. We present a new treatment algorithm for melanoma patients with brain metastases, which integrates the evolving evidence for the use of BRAF inhibitors.     

EGFR突变的非小细胞肺癌脑转移的治疗策略

约10%的非小细胞肺癌(NSCLC)患者初诊时出现脑转移,而脑转移为肺癌死亡的主要原因之一.目前全脑放疗(WBRT)仍为脑转移的标准治疗方案,但其疗效已达平台期.酪氨酸激酶抑制剂(TKI)在NSCLC脑转移治疗中取得了可观的疗效.TKI联合WBRT可能成为表皮生长因子受体(EGFR)突变的肺癌脑转移的主要治疗手段.     

Melanoma-induced brain metastases

Brain metastases are a common site of metastasis from malignant melanoma, and are associated with a poor prognosis. Diagnosis of brain metastasis may also have significant implications for quality of life, and management can be difficult due to rapid progression of disease and resistance to conventional therapies. In this article, we will review the published evidence for treatment modalities for melanoma-induced brain metastases and outline future directions for research. In brief, surgical management of solitary or acutely symptomatic lesions appears to alleviate symptoms and provide the possibility of local control of disease. Stereotactic radiosurgery is an increasingly utilized technique for patients with a limited number of metastases, and presents a less invasive alternative to craniotomy. External-beam radiation alone appears effective in palliating symptoms. Chemotherapy alone is relatively ineffective, though combined chemotherapy with external-beam radiation is being investigated. Future directions include combined-modality therapy, the incorporation of novel agents, and careful consideration of the structure of clinical trials for this disease.     

Melanoma-induced brain metastases

Brain metastases are a common site of metastasis from malignant melanoma, and are associated with a poor prognosis. Diagnosis of brain metastasis may also have significant implications for quality of life, and management can be difficult due to rapid progression of disease and resistance to conventional therapies. In this article, we will review the published evidence for treatment modalities for melanoma-induced brain metastases and outline future directions for research. In brief, surgical management of solitary or acutely symptomatic lesions appears to alleviate symptoms and provide the possibility of local control of disease. Stereotactic radiosurgery is an increasingly utilized technique for patients with a limited number of metastases, and presents a less invasive alternative to craniotomy. External-beam radiation alone appears effective in palliating symptoms. Chemotherapy alone is relatively ineffective, though combined chemotherapy with external-beam radiation is being investigated. Future directions include combined-modality therapy, the incorporation of novel agents, and careful consideration of the structure of clinical trials for this disease.     

Management of brain metastases

Patients with brain metastases have a generally poor outcome with a median survival after diagnosis of approximately 4 months. Management of brain metastases involves symptomatic treatment and definitive therapy, with the goal of stabilizing and improving neurologic function and survival. Traditional and novel therapies, including whole-brain radiation therapy (WBRT), surgery, radiosurgery, radiosensitizers, and chemotherapy are reviewed. The results of important clinical trials are discussed. In addition, current controversies in the management of brain metastases, such as the choice of surgery or radiosurgery for resectable lesions and the possible avoidance of (WBRT), are highlighted.     

Treatment of brain metastases: review of phase III randomized controlled trials

The optimal management of brain metastases remains controversial. Both whole brain radiotherapy (WBRT) and local treatment [surgery (S) or radiosurgery (RS)] are the cornerstones of treatment. The role of systemic therapy is also being explored. Randomized controlled trials (RCT) have tried to assess the individual and combined effects of different therapeutic strategies. (1) RCT in oligometastatic patients: WBRT alone vs. local treatment+WBRT. Combined treatment may improve both overall survival and local control in patients with a single metastasis, but it also leads to a local control benefit in patients with two to four lesions. Exclusive local treatment vs. WBRT plus local treatment. The addition of WBRT to local treatment may result in improved local control, improved freedom from new brain metastases and improved overall brain control. S+WBRT vs. RS+WBRT. There is no evidence of superiority of a combined treatment over the other one. (2) RCT addressing the point of improving WBRT outcome: differences in WBRT fractionation do not significantly alter outcome of treatments. Only a few systemic drugs may cause some significant advantages. (3) RCT that assessed neurocognitive impairment and quality of life: the baseline cognitive performance of most patients is significantly impaired. Intracranial tumor control is an essential factor in stabilizing neurocognitive function. The data on neurocognitive toxicity related to WBRT are still contradictory. Impairment of both neurocognitive function and quality of life of patients with brain metastases needs to be further addressed in RCT.     

Treatment options for brain metastases in patients with non-small-cell lung cancer

Brain metastases are a common complication for patients with non-small-cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole-brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small-cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than 3 metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and those with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.