Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases.

PURPOSE: Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases. METHODS: Patients with two to four brain metastases (all < or =25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care. RESULTS: The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was 6 months after WBRT alone (95% confidence interval [CI], 3.5-8.5) in comparison to 36 months (95% CI, 15.6-57) after WBRT plus radiosurgery (p = 0.0005). The median time to any brain failure was improved in the radiosurgery group (p = 0.002). Tumor control did not depend on histology (p = 0.85), number of initial brain metastases (p = 0.25), or extent of extracranial disease (p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months (p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease (p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery. CONCLUSIONS: Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.     

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PurposeTo systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases.Methods and MaterialsKey clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management.ResultsThe choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation).Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3).Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3).Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3).It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful.ConclusionsRadiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).     

Strategy of surgery and radiation therapy for brain metastases

Cancer patients with brain metastases have poor prognoses and their median survival time is about 1 year. Surgery with whole-brain radiation therapy (WBRT) has been used in the treatment of single brain metastasis measuring 3 cm or more. Stereotactic radiosurgery (SRS) including the use of the Gamma knife and Cyberknife is widely used for the treatment of small and multiple brain metastases; however, recent clinical studies have revealed that SRS + WBRT is superior to WBRT or SRS alone in terms of survival time and local tumor control rates. Here, surgical indications and the strategy of surgery and radiation therapy are discussed, based on many clinical trials of treatments for brain metastases. To improve the survival rate and quality of life for these cancer patients with brain metastases, it is necessary to choose the most suitable mode of surgery and radiotherapy with the close cooperation of physicians, surgeons, radiologists, and neurosurgeons, based on accumulated evidence.     

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.     

Guidelines for the initial management of metastatic brain tumors: role of surgery, radiosurgery, and radiation therapy

Brain metastases are an increasingly important determinant of survival and quality of life in patients with cancer. Current approaches to the management of brain metastases are driven by prognostic factors, including the Karnofsky Performance Status, tumor histology, number of metastases, patient age, and status of systemic disease. Most brain metastases are treated with radiosurgery, computer-assisted surgery, or whole brain radiation therapy. Remarkable advances in computer-assisted neuronavigation have made neurosurgical removal of metastases safer, even in eloquent areas of the brain. Computerization also enhances the efficacy and safety of conformal radiosurgery planning using various modern stereotactic radiosurgery (SRS) technologies, including newer frameless-based systems. Controversial issues include whether to defer whole brain radiotherapy (WBRT) in patients undergoing SRS or image-guided surgery and when to use SRS "boost" in a patient undergoing WBRT. The determination of how best to apply these treatments for individual patients cannot be standardized to a single paradigm, but data from well-controlled studies help physicians make informed decisions about the benefits and risks of each approach.     

The efficacy of gamma knife radiosurgery for advanced gastric cancer with brain metastases

The aim of this study was to retrospectively investigate the efficacy of gamma knife radiosurgery for brain metastases from advanced gastric cancer (AGC) comparing whole brain radiotherapy (WBRT). Between January 1991 and May 2008, 56 patients with brain metastases from AGC, treated with GKR or WBRT, were reviewed to assess prognostic factors affecting survival. Most brain metastases were diagnosed based on MRI, both metachronous and synchronous brain metastases, adenocarcinoma and signet ring carcinoma were included, but excluded cases of gastric lymphoma. Fifteen patients with a median age of 54.0 years (range, 42–67 years) were treated with GKR: 11 were treated with GKR only, 2 with surgery plus GKR, 1 with repeated GKR, 1 with GKR plus WBRT, and the other 1 with WBRT plus GKR. Forty-one were treated with WBRT only. The median number of metastatic brain lesions was 3 (range, 1–15), and treatment involved 17.0 Gy (range 14–23.6 Gy), or 30 Gy with fractionated radiotherapy. The median survival after brain metastases for GKR treatment was 40.0 weeks [95% confidence interval (CI) 44.9–132.1 weeks] and WBRT was 9.0 weeks 95% CI, 8.8–21.9 weeks). The progression free survival of 15 GKR treated patients was 56.5 weeks (95% CI 33.4–79.5 weeks). The recursive partitioning analysis (RPA) (class 2 vs. class 3) and use of GKR were correlated with prolonged survival in univariate and multivariate analyses. Age, sex, pathology, leptomeningeal seeding, tumor size (≥3 cm), extracranial metastases, single metastasis, chemotherapy, and synchronous metastases were not correlated with a good prognosis in both univariate and multivariate analysis. Based on our study, the use of GKR and RPA class 2 resulted in more favorable clinical outcomes in patients with brain metastases from AGC.     

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

Opinion statement 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 three 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 patients 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.     

Radiosurgery to the Postoperative Surgical Cavity: Who Needs Evidence?

There is a growing interest in adjuvant radiosurgery after resection of hematogenous brain metastases. This is exemplified by the approximately 1000 cases reported in mainly retrospective series. These cases fall into four paradigms: adjuvant radiosurgery as an alternative to whole-brain radiotherapy (WBRT), radiosurgery neoadjuvant to the surgical resection, radiosurgery as an intensification of adjuvant WBRT, and adjuvant radiosurgery for patients having failed prior WBRT. These procedures seem well tolerated, with an approximate 5% risk of radiation necrosis. Although crude local control rates for each strategy seem improved over surgery alone, multiple biases make comparisons with standard WBRT difficult without prospective data. Because evidence lags behind clinical practice, an upcoming intergroup trial will aim to clarify the value of the most common tumor bed radiosurgery strategy by randomizing oligometastatic patients between adjuvant WBRT and adjuvant radiosurgery.     

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.     

Prognostic Factors in Patients with Non-small Cell Lung Carcinoma and Brain Metastases: a Malaysian Perspective

Background: Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma(NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used butincreasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotacticradiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomesin NSCLC patients receiving local therapy for brain metastases. Materials and Methods: The case records of 125patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres fromJanuary 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patientsreceiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariatetesting. Results: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients withmultiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure(yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgeryor SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use ofpost-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All fourfactors remained statistically significant on multivariate analysis. Conclusions: ECOG ≤2, presence of seizures,oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapysystemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.     

非小细胞肺癌脑转移瘤的治疗进展

脑转移瘤是非小细胞肺癌最常见的并发症之一。全脑放疗(whole brain radiotherapy,WBRT)、立体定向放射外科(stereotactic radiosurgery,SRS)、外科手术和化疗是非小细胞肺癌脑转移瘤的重要治疗方式,但其疗效仍不令人满意,而综合治疗能有效地延长患者生存期、改善生活质量。近年来随着治疗技术的进步,分子靶向治疗和患者的生存期及生活质量越来越受到重视。本文就非小细胞肺癌脑转移瘤的治疗现状和综合治疗的进展做一综述。     

Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases

PURPOSE: To better evaluate tumor control and toxicity from radiosurgery for brain metastases, we analyzed these outcomes in patients who had survived at least 1 year after radiosurgery. METHODS AND MATERIALS: We evaluated the results of gamma knife stereotactic radiosurgery (SRS) for 208 brain metastases in 137 patients who were followed for a median of 18 months (range 12-122) after radiosurgery. The median patient age was 53 years (range 3-83). Ninety-nine patients had solitary metastases. Thirty-eight had multiple tumors. Sixty-nine patients underwent initial SRS with whole brain radiotherapy (WBRT), 39 had initial SRS alone, and 27 patients had failed prior WBRT. The median treatment volume was 1.9 cm(3) (range 0.05-21.2). The median marginal tumor dose was 16 Gy (range 12-25). The most common histologic types included non-small-cell lung cancer, breast cancer, melanoma, and renal cell carcinoma, which comprised 37.0%, 22.6%, 13.0%, and 9.13% of the lesions, respectively. Forty-five tumors were associated with extensive edema. RESULTS: At 1 and 5 years, the local tumor control rate was 89.6% +/- 2.1% and 62.8% +/- 6.9%, distal intracranial relapse occurred in 23% +/- 3.6% and 67.1% +/- 8.7%, and postradiosurgical sequelae developed in 2.8% +/- 1.2% and 11.4% +/- 3.5% of patients, respectively. Multivariate analysis found that local control decreased with tumor volume (p = 0.0002), SRS without WBRT (p = 0.008), and extensive edema (p = 0.024); distal intracranial recurrence correlated with younger patient age (p = 0.0018); and postradiosurgical sequelae increased with increasing tumor volume (p = 0.0085). CONCLUSION: Long-term control of brain metastases and complication rates in this selective series of patients surviving >or=1 year after radiosurgery were similar to previously reported actuarial estimates. Large metastases and metastases associated with extensive edema can be difficult to control by radiosurgery, particularly without WBRT.     

The Role of Whole Brain Radiation Therapy for the Management of Brain Metastases in the Era of Stereotactic Radiosurgery

The goals of treatment for brain metastases (BMs) include preservation of function and improvement of survival. Although whole brain radiotherapy (WBRT) has been a mainstay in the treatment of BMs, stereotactic radiosurgery (SRS) monotherapy has been increasingly used because of concern about the deterioration of neurocognitive function as a late adverse effect of WBRT. The results of four randomized controlled trials comparing focal treatment alone versus focal treatment combined with WBRT have shown, however, that SRS monotherapy significantly increases the risk of brain tumor recurrence (BTR) and that this increased risk of BTR may cause deterioration of neurocognitive function. We suggest identifying patients according to their risk of BTR when selecting treatment. Patients who have solitary BM with the absence of extracranial metastases may be indicated for SRS monotherapy given the lower risk of BTR compared with those having multiple BMs or extracranial metastases.     

Initial treatment of melanoma brain metastases using gamma knife radiosurgery: an evaluation of efficacy and toxicity

BACKGROUND: Melanoma is the primary malignancy that is most likely to metastasize to the brain. Because such an event carries an almost uniformly poor prognosis, the current study reviewed outcomes and identified associated prognostic indicators for 51 consecutive patients receiving gamma knife (GK) radiosurgery in the initial treatment of 188 intracranial melanoma metastases. METHODS: Data were collected retrospectively from a single-center GK radiosurgery database and from primary patient medical records and radiographs. RESULTS: At presentation, 71% of patients had multiple intracranial metastases, and extracranial metastases were present in 66% of patients. Thirty-two patients (63%) were initially treated with GK radiosurgery alone, whereas the remainder received GK radiosurgery in combination with surgery and/or whole-brain radiotherapy (WBRT). Overall median survival from time of GK radiosurgery was 26 weeks. Subgroup analysis revealed a median survival of 77 weeks for patients presenting with a single lesion, compared with 20 weeks for patients presenting with multiple lesions (P = 0.003). Patients in recursive partitioning analysis (RPA) Class I survived a median of 57 weeks, compared with a median survival of 20 weeks for patients in RPA Class II or III (P = 0.002). Although long-term imaging follow-up revealed that a majority of patients experienced distant brain metastases, multivariate analysis showed that distant metastases occurred significantly sooner in patients with extracranial metastases (P = 0.0004). Addition of initial WBRT had no significant effect on the time to development of new brain metastases (P = 0.13). Local control (crude) was observed in 81% of lesions initially treated with GK. Patients experienced improved or stable symptoms for a median of 37 weeks post-GK radiosurgery. CONCLUSIONS: Survival analyses supported the use of GK radiosurgery in the initial treatment of patients with melanoma brain metastases, with best results occurring in patients presenting with a single lesion.     

非小细胞肺癌脑转移全脑及病灶局部大分割放射治疗

高达40%的非小细胞肺癌患者在疾病进程中出现脑转移,且非小细胞肺癌脑转移常为多发转移。脑转移患者的预后较差,中位生存期不到1年。脑转移的放射治疗已经从全脑放疗逐渐发展到多种放射治疗策略广泛应用的时代。目前已证实单纯全脑放疗、手术+全脑放疗、立体定向放射治疗+全脑放射治疗、同步调强全脑放射治疗等对比未治疗患者能提高总生存期。近年来,全脑放疗对认知功能的损害受到广泛关注,针对预期生存时间较长的患者,采取何种放疗模式尚存在争议。本文将分别论述非小细胞肺癌脑转移不同的全脑放射治疗策略及治疗副作用。     

Radiotherapeutic management of brain metastases: a systematic review and meta-analysis

BACKGROUND: The management of brain metastases is a significant health care problem. An estimated 20-40% of cancer patients will develop metastatic cancer to the brain during the course of their illness. METHODS: A systematic review of randomized trials on adult cancer patients with single or multiple brain metastases from cancer of any histology was conducted. Eligible studies investigated external beam radiotherapy or radiosurgery in one of the study arms. Outcomes of interest included survival, intracranial progression-free duration, response of brain metastases to therapy, quality of life, symptom control, neurological function, and toxicity. RESULTS: Twenty-seven trials were included in this systematic review of the evidence. Pooled results from three randomized trials of surgical excision combined with whole brain radiotherapy (WBRT) showed no improvement in overall survival as compared to WBRT alone in patients with single brain metastasis. One randomized study of postoperative WBRT following excision of a single brain metastasis versus surgery alone detected a significant reduction in intracranial tumour recurrence rates but no corresponding difference in overall survival. Nine trials of altered dose-fractionation schedules compared to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT showed no difference in probability of survival at 6 months. The addition of radiosensitizers, as assessed in five trials, did not confer additional benefit to WBRT in terms of overall survival or the frequency of brain metastases response. Three trials examined the use of WBRT and radiosurgery boost versus WBRT alone in selected patients with brain metastases. Overall survival did not improve for patients with multiple brain metastases. However, one trial reported an improvement in survival for patients with single brain metastasis treated with WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT versus supportive care alone (using oral prednisone). Results were not conclusive. CONCLUSION: For patients with a single brain metastasis, good performance status, and minimal or no evidence of extracranial disease, surgical excision and postoperative WBRT improves survival (as compared to WBRT alone). There may be a small survival advantage associated with the use of radiosurgery boost and WBRT as compared to WBRT alone in selected patients with a single brain metastasis. There is no difference in overall survival or in neurologic function improvement with the use of altered whole brain dose-fractionation schedules as compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000 cGy in 5 fractions). There is no survival benefit associated with the use of radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain metastases. Currently, neither chemotherapy nor radiosensitizers show a clear benefit in the objective parameters of survival and progression-free survival. For patients with poor performance status and active extracranial disease, steroids and supportive care are an option.     

Stereotactic radiosurgery alone versus resection plus whole-brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients

BACKGROUND: The objective of this study was to compare stereotactic radiosurgery (SRS) alone with resection plus whole-brain radiotherapy (WBRT) for the treatment of patients in recursive partitioning analysis (RPA) class 1 and 2 who had 1 or 2 brain metastases. METHODS: Two hundred six patients in RPA class 1 and 2 who had 1 or 2 brain metastases were analyzed retrospectively. Patients in Group A (n = 94) received from 18 grays (Gy) to 25 Gy SRS, and patients in Group B (n = 112) underwent resection of their metastases and received 10 x 3 Gy/20 x 2 Gy WBRT. Eight other potential prognostic factors were evaluated regarding overall survival (OS), brain control (BC), and local control (LC) of treated metastases: age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to treatment of brain metastases. RESULTS: A comparison of the 2 treatment groups did not reveal significantly different OS (P = .19), BC (P = .52), or LC (P = .25). In RPA subgroup analyses, outcome also did not differ significantly for either RPA class of patients (P values from .21 to .83). On multivariate analysis, improved OS was associated with age < or =60 years (relative risk [RR], 1.75; P = .002), better performance status (RR, 1.67; P = .015), no extracranial metastases (RR, 2.84; P < .001), interval from tumor diagnosis to treatment >12 months (RR, 1.70; P = .003), and RPA class 1 (RR, 1.51; P = .016). Improved BC was associated with a single metastasis (RR, 1.54; P = .034) and an interval from tumor diagnosis to treatment >12 months (RR, 1.58; P = .019), and improved LC was associated with an interval from tumor diagnosis to treatment >12 months (RR, 1.59; P = .047). CONCLUSIONS: SRS alone appeared to be as effective as resection plus WBRT in the treatment of 1 or 2 brain metastases for patients in RPA class 1 and 2. Patient outcomes were associated with age, Karnofsky performance status, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to treatment.     

Stereotactic radiosurgery in the treatment of brain metastases: The current evidence

Chemotherapy has made substantial progress in the therapy of systemic cancer, but the phar-macological efficacy is insufficient in the treatment of brain metastases. Fractionated whole brain radiotherapy (WBRT) has been a standard treatment of brain metastases, but provides limited local tumor control and often unsatisfactory clinical results. Stereotactic radiosurgery using Gamma Knife, Linac or Cyberknife has overcome several of these limitations, which has influenced recent treatment recommendations. This present review summarizes the current literature of single session radiosurgery concerning survival and quality of life, specific responses, tumor volumes and numbers, about potential treatment combinations and radioresistant metastases.     

The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints.     

A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases

BACKGROUND:

To perform a meta‐analysis on newly diagnosed brain metastases patients treated with whole‐brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone versus WBRT and SRS boost.

METHODS:

The meta‐analysis primary outcomes were overall survival (OS), local control (LC), and distant brain control (DBC). Secondary outcomes were neurocognition, quality of life (QOL), and toxicity. Using published Kaplan‐Meier curves, results were pooled using hazard ratios (HR).

RESULTS:

Two RCTs reported on WBRT and SRS boost versus WBRT alone. For multiple brain metastases (2‐4 tumors) we conclude no difference in OS, and LC significantly favored WBRT plus SRS boost. Three RCTs reported on SRS alone versus WBRT plus SRS boost (1‐4 tumors). There was no difference in OS despite both LC and DBC significantly favoring WBRT plus SRS boost. Although secondary endpoints could not be pooled for meta‐analysis, those RCTs evaluating SRS alone conclude better neurocognition using the validated Hopkins Verbal Learning Test, no adverse risk in deteriorating Mini‐Mental Status Exam scores or in maintaining performance status, and fewer late toxicities. We conclude insufficient data for QOL outcomes.

CONCLUSIONS:

For selected patients, we conclude no OS benefit for WBRT plus SRS boost compared with SRS alone. Although additional WBRT improves DBC and LC, SRS alone should be considered a routine treatment option due to favorable neurocognitive outcomes, less risk of late side effects, and does not adversely affect the patients performance status. Cancer 2012. © 2011 American Cancer Society.