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).     

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.     

Carcinoid metastasis to the brain

BACKGROUND: Carcinoid tumors rarely metastasize to the brain. The objectives of the current study were to assess the frequency of brain metastasis from carcinoid tumors, determine correlates of survival, and describe treatment modalities and their outcomes. METHODS: Between January 1977 and December 2003, 1633 patients with a carcinoid tumor were registered at The University of Texas M. D. Anderson Cancer Center. Of those, 24 patients (1.5%) had a diagnosis of brain metastasis. The authors collected demographic and clinical data and performed a statistical analysis. RESULTS: The median age at the time patients were diagnosed with brain metastasis was 60 years. The metastases were treated with whole-brain radiotherapy (WBRT) alone in 7 patients (29%), and 12 patients (50%) underwent surgical resection, 7 of whom (29%) also received WBRT. The median survival time for the entire cohort after diagnosis of the primary tumor was 2.3 years (95% confidence interval [CI], 0.5-4.1 years), and the median survival time after the diagnosis of brain metastasis was 10.0 months (95% CI, 4.0-16.0 months). The longest median survival observed after the diagnosis of brain metastasis (3.2 years) occurred in patients who underwent resection and received WBRT. In the multivariate analysis, the adjusted rate ratio for comparison of all treatments versus combination of neurosurgical intervention and WBRT was 5.7 (95% CI, 1.3-26.1; P = 0.024). A positive effect of surgery followed by WBRT on the duration of survival was detected in patients with a single metastasis (P = 0.084) as well as in those with multiple metastases (P = 0.018). CONCLUSIONS: Prolonged survival was observed in patients < 65 years old as well as in those who underwent surgery and received WBRT in comparison with other treatments. Whenever feasible, neurosurgical resection followed by WBRT seems to be the indicated treatment in patients with brain metastases from carcinoid tumors.     

Effectiveness of stereotactic radiosurgery alone or in combination with whole brain radiotherapy compared to conventional surgery and/or whole brain radiotherapy for the treatment of one or more brain metastases: a systematic review and meta-analysis

PURPOSE: To assess the effectiveness of SRS alone or in combination with WBRT compared to surgery and/or WBRT in prolonging survival and improving the quality-of-life and functional status of patients with brain metastases. METHODS AND MATERIALS: A meta-analysis of randomized controlled trials and concurrent cohort studies examining SRS versus SRS + WBRT, SRS versus WBRT +/- surgical resection, SRS versus surgical resection only, or SRS + WBRT versus WBRT was conducted. Trial registers, bibliographic databases, and reference lists from selected studies and recent issues of relevant journals were searched. Neuro-oncology specialists were also contacted. All studies were analyzed independently by two reviewers, applying validated critical appraisal techniques. RESULTS: The review identified three RCTs and one cohort study. Among patients with multiple metastases, no difference in survival between those treated with WBRT + SRS and those treated with WBRT was found. However, in patients with one metastasis, a statistically significant difference, favoring those treated with WBRT + SRS, was observed. Regarding local tumor control at 24 months, rates were significantly higher in the WBRT + SRS treatment arm, regardless of the number of metastases. CONCLUSIONS: Adding SRS to WBRT improves survival in patients with one brain metastasis. Combining SRS and WBRT improves local tumour control and functional independence in all patients.     

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.     

Palliative surgery for brain metastases of malignant melanoma.

Forty patients with melanoma brain metastases were treated by surgery. Single brain metastases were found in 32 cases and multiple in eight. The most frequent tumor location was the frontal and frontoparietal lobes. Neurological improvement was observed in 25 patients and surgical mortality rate was less than 5%. The median survival time for all patients was 8 months. When patients with multiple cerebral metastases were excluded the median survival time was 13 months. The 3- and 5-year survival was 25% and 15%, respectively. Seventeen patients with extracerebral metastases received treatment and were without known extracerebral tumor at the time of brain metastases diagnosis. These patients had a median survival time that did not significantly differ from those without occurrence of extracerebral metastases. Quality of life as judged by Karnofsky index was improved after surgery and maintained on an acceptable level for the remaining time of survival.     

Fifty percent patients avoid whole brain radiotherapy: stereotactic radiotherapy for multiple brain metastases. A retrospective analysis of a single center

Purpose

To summarize the outcomes of stereotactic radiotherapy (SRT), with or without whole-brain radiotherapy (WBRT), in the treatment of multiple brain metastasis and to explore the status of WBRT and SRT in the management of multiple brain metastasis.

Methods

From May 1995 to April 2010, 98 patients with newly diagnosed, multiple brain metastasis were treated in our center. Forty-four patients were treated with SRT alone for the initial treatment, and 54 were treated with SRT?+?WBRT. Kaplan?CMeier and Cox proportional hazards regression analyses were used for the survival analysis.

Results

The median survival time (MST) was 13.5?months. No difference was observed in MST between the SRT and the SRT?+?WBRT groups (p?=?0.578). The Karnofsky Performance Score at the time of treatment (p?=?0.025), the interval time between diagnosis of primary tumor and brain metastasis (P?=?0.012) and the situation of extracranial disease (p?=?0.018) were significant predictors of survival. The crude distant intracranial recurrence (DIR) rates were 47.7?% in the SRT group and 24.1?% in the SRT?+?WBRT group (p?=?0.018). In addition, 52.3?% patients in the SRT group were free from DIR and did not require WBRT in their whole lives.

Conclusions

Our data suggest that use of SRT as the initial treatment while reserving WBRT as the salvage therapy in case of distant intracranial recurrence made about 50?% of the patients avoid WBRT throughout the course of their lives and may be another optional treatment modality for multiple brain metastases.     

Mangement of brain metastases based on EBM

Some three hundred thousand of patients die of cancers yearly and at least 20-40%, i. e., 60,000-120,000 of them suffered from brain metastases. Those with such metastases have a generally poor outcome with a median survival of 1-2 months with steroids only, and approximately 6 months with whole-brain radiation therapy (WBRT). The results of important and historical clinical trials including surgery, WBRT, stereotactic radiosurgery (SRS), and chemotherapy are reviewed. Surgery with WBRT has been used in the treatment of a single brain metatasis with a diameter of more than 3 cm, while survival time of those patients is approximately 12 months. SRS including gamma knife is widely used for treatment of small and multiple brain metastases. However, many clinical studies have revealed that SRS+WBRT is superior to WBRT or SRS alone in survival time and local control rates. The accurate incident rates of radiation-induced dementia or neurological deficit are still unclear, so the problem and possible avoidance of an additional WBRT after surgery or SRS are discussed. To improve neurologic function and survival, the treatment for patients with brain metastases should be selected with accurate knowledge of EBM.     

COAPC方案联合脑部放射治疗非小细胞肺癌脑转移

背景与目的：放射治疗具有治疗脑转移癌的主要手段。而到目前为止化疗与放疗联合治疗脑转移癌的研究较少,本研究旨在观察COAPC方案化疗与脑部放射同时治疗非小细胞肺癌（non-small cell lung cancer,NSCLC)脑转移患者疗效,不良反应及生存率。方法：45例NSCLC脑转移患者接受COAPC方案化疗,环磷酰胺0．3g/m^2第1天静推,长春新碱1．4mg/m^2第1天静推,阿霉素50mg/m^2第1天静推,顺铂20mg/m^2第1－5天静滴,司莫司汀80mg/m2第1天口服,每3－4周为1疗程,脑部放射治疗于化疗第1疗程的第6天开始,每次2Gy,每天1次,每周5天,脑转移灶1－3个者,全脑放疗40Gy后,缩野放疗至总量60Gy,脑转移灶＞3个者,全脑放疗至总量40Gy.结果：治疗后80％患者神经系统症状改善,对脑转移灶的客观有效率为64．4％,对肺原发灶的有效率为40％,治疗的主要不良反应为骨髓抑制(Ⅲ-Ⅳ度占35％）,中位生存期10个月,1年生存率44．1％,5年生存率6．7％,单纯脑转移患者的中位生存期14个月,高于多发远处转移患者的9个月（P＝0．012）。结论：化疗联合脑部放射治疗NSCLC脑转移患者有效率与生存率较高,且患者耐受性较好。     

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.     

Brain Metastases in Patients with Ovarian Carcinoma: Prognostic Factors and Outcome

Between January 1975 and April 2001, 8,225 patients with ovarian cancer were seen at The University of Texas M. D. Anderson Cancer Center. Brain metastases developed in 72 of these patients (0.9%). The medical records of these patients were reviewed to assess the incidence of these metastases and their correlates of survival, as well as to describe the various treatment modalities used against them and their respective outcomes. The mean age of patients at the time of brain metastasis diagnosis was 53.7 years. The median interval between the diagnosis of the primary cancer and brain metastasis was 1.84 years. Neurological deficit, headache, and seizure were the most common symptoms. The brain was the only site of metastasis in 43% of patients. Multiple metastases were seen in 65% of them, although this may be a slight underestimate, as brain metastases in 17% of patients were evaluated prior to the magnetic resonance imaging era. The median survival time after the diagnosis of brain metastases was 6.27 months (95% CI, 4.48–8.06 months). The combination of surgical resection and whole-brain radiation therapy (WBRT) resulted in a longer survival time (median, 23.07 months) than did WBRT alone (median, 5.33 months) or surgery alone (median, 6.90 months) (p < 0.01 in both instances, multivariate Cox proportional hazards model analysis). The prognosis for patients with brain metastases from ovarian cancer appears to be poor. The existence of systemic dissemination at the time of brain metastasis was associated with a worse survival trend. The only significant predictor of survival in our series was the treatment modality. In particular, the resection of brain metastasis from ovarian cancer followed by WBRT appeared to be superior to resection alone or WBRT alone.     

The treatment of brain metastases in melanoma patients

The incidence of central nervous system (CNS) metastases in patients with melanoma ranges from 10% to 40% in clinical studies and is even higher in autopsy series with as many as two-thirds of patients with metastatic melanoma having CNS involvement. Treatment options for patients with cerebral metastases are limited and depend largely on the number and the size of the lesions and on the extracranial extension of metastatic disease. This report gives the results of different treatment modalities in patients with melanoma metastases to the brain. As data from prospective randomized studies are lacking, the general recommendations based on clinical series reports are: (i) 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. (ii) Radio surgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that the lesion's diameter does not exceed 3 cm. With the use of WBRT after surgery or radio surgery the local control seems better (with the combined approach), but the overall survival does not improve. (iii) WBRT alone or in combination with chemotherapy is the treatment of choice in patients with single brain metastasis not amenable to surgery or radio surgery, with an active systemic disease, and in patients with multiple brain metastases. Chemotherapy may be also offered to patients with a good performance status, or after recurrence to local therapy.     

Metastasis of esophageal carcinoma to the brain

BACKGROUND: Esophageal carcinoma rarely metastasizes to the brain. The objectives of the current study were to assess the frequency of brain metastasis from an esophageal primary tumor, to determine correlates of survival, and to describe treatment modalities and their outcomes. METHODS: Between June, 1993 and July, 2001, 1588 patients with a primary esophageal carcinoma registered at The University of Texas M. D. Anderson Cancer Center; of those, 27 patients (1.7%) had a diagnosis of brain metastasis. The authors collected demographic and clinical data and performed a statistical analysis. RESULTS: The median age at the time patients were diagnosed with brain metastasis was 62 years. Tumor histologies were adenocarcinoma in 22 patients (82%), unclassified carcinoma in 3 patients (11%), and squamous cell carcinoma in 2 patients (7%). Twenty patients (74%) experienced symptoms related to the brain metastasis. The metastases were treated with whole-brain radiation therapy (WBRT) alone in 15 patients (56%), and 10 patients (37%) underwent surgical resection, 4 of whom (15%) also received WBRT. Two patients (7%) underwent stereotactic radiosurgery. The median survival for the entire cohort after diagnosis of the primary tumor was 12.6 months (95% confidence interval [CI], 2.17-22.5 months), and the median survival after the diagnosis of brain metastasis was 3.8 months (95% CI, 1.1-6.5 months). The longest median survival observed after the diagnosis of brain metastasis (9.6 months) occurred in patients with a single brain lesion who underwent resection and received WBRT. There was a trend toward worse survival in patients with liver metastases and patients in recursive partitioning analysis (RPA) Class II-III versus RPA Class I (P = 0.10 for both; multivariate Cox proportional hazards model analysis). CONCLUSIONS: Approximately 2% of patients with esophageal carcinoma had a diagnosis of brain metastasis. Improved outcome was associated with single brain lesions in patients who underwent surgery and received WBRT. Known liver metastasis and higher RPA scores were associated with a poorer survival trend.     

全脑联合三维适形放射治疗30例单病灶脑转移癌的疗效分析

背景与目的:全脑放疗是治疗脑转移癌的主要治疗手段。本文总结全脑联合三维适形放射治疗单病灶脑转移癌的疗效。方法:30例恶性肿瘤单病灶脑转移癌,全脑放疗DT39～45Gy后,以三维适形放疗追加转移病灶DT10～16Gy,常规分割1次/d,5次/w,总剂量DT55Gy。结果:6例CR,21例PR,3例NC,6个月、1年和2年生存率分别为73.3%(22/30)、40%(12/30)、13.3%(4/30),平均生存时间11.9个月。结论:全脑联合三维适形放射治疗单病灶脑转移癌,可以缓解颅脑神经症状,改善生活质量,延长生存期。     

Ovarian cancer metastatic to the brain: What is the optimal management?

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.     

Intracranial relapse rates and patterns,and survival trends following post-resection cavity radiosurgery for patients with single intracranial metastases

The objective of this study is to evaluate the patterns of relapse and survival trends in patients with single brain metastases treated with post-operative adjuvant Gamma knife stereotactic radiosurgery (GKS) without whole brain radiotherapy (WBRT). Retrospective analysis of all consecutive patients who underwent GKS to the tumor cavity following resection of solitary brain metastasis was performed at a single institution. Between March 2001 and June 2010, 56 patients underwent GKS to the resection cavity following resection of intracranial metastases; no patient received pre- or post-operative WBRT as an adjuvant (salvage WBRT was permissible). The mean marginal dose was 17.1 Gy (range 14–20 Gy). The mean follow-up period was 24 months (range 3–99 months). Five patients (8.9%) had local recurrence in the immediate vicinity of the resection cavity, qualifying as “local failures”, and 21 (37.5%) recurred at distant intracranial sites. Median intracranial recurrence free survival was 13 months. Median overall survival was 20.5 months. Salvage interventions were required in 26 patients, and included repeat radiosurgery in 17 patients, further surgery in two patients, and salvage WBRT in eight (14.3%; two of whom had also been locally salvaged with repeat radiosurgery) patients. As expected, avoidance of WBRT results in a high rate of intracranial failure (26/56 patients, 46%), even in well-selected patients with only single brain metastases. As anticipated, the majority of failures (21, 37.5%) are “distant intracranial”, and in this well-selected cohort the local failure rate is low (5/56 patients, <9%). All patients failing intracranially (46%) are potential candidates for salvage therapies, but WBRT as salvage was utilized in only 14.3% of patients. The median intracranial relapse-free was 13 months and overall survival was 20.5 months.     

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases

Introduction Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. Materials and method We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n=11) and 30 Gy/10 fractions (n=10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. Results Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2–6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0–7 months) without statistically significant differences (Log rank p=0.74). There was one complete response and two partial responses. Conclusions The results suggest that MST was not significantly affected by the total dose/fractionation schedule.     

立体定向放射治疗肺癌脑转移疗效分析

目的探讨不同放射治疗方法对肺癌脑转移的疗效.方法176例由病理学证实的肺癌脑转移患者分为4组:单纯全脑放疗(WBRT)组、全脑放疗加立体定向放射外科(WBRT SRS)组、单纯立体定向放射治疗(SRT)组、全脑放疗加立体定向放射治疗(WBRT SRT)组.SRS治疗单次靶区平均周边剂量8～20Gy,总剂量20～32Gy;SRT治疗单次靶区平均周边剂量2～5Gy,总剂量25～60Gy;WBRT1.8～2Gy/次,总剂量30～40Gy.结果四组的局部控制率分别为47.0%、87.7%、86.5%和78.0%;中位生存期分别为5.0,11.0,11.5和10.0个月;局部无进展生存期分别为3.33,8.33,9.33和7.67个月;颅脑无新病灶生存期分别为4.11,8.57,9.03和6.12个月.在死因分析中,WBRT组死于脑转移的比率为57.6%,较其他三组高.而WBRT SRS组的晚期放射反应的发生率为12.2%,较其他组高.结论肺癌单发脑转移瘤患者的最佳治疗方式是单纯立体定向放射治疗,治疗失败后再行挽救性全脑照射或立体定向放疗.对于多发脑转移,全脑放疗加立体定向放射治疗(WBRT SRT)在提高生存率以及减少并发症方面优于其他治疗方法.     

Whole-brain radiotherapy and tumor bed radiosurgery following resection of solitary brain metastases

A standard approach to solitary brain metastases is resection followed by whole-brain radiation therapy (WBRT). Despite WBRT, the tumor bed remains a common site of failure. We reviewed outcomes following adjuvant WBRT with tumor bed radiosurgery (SRS). We retrospectively identified patients having undergone neurosurgical resection of a single brain metastasis followed by adjuvant WBRT and tumor bed SRS. SRS dose selection was independent of target volume (10 Gy peripheral dose). Outcomes were calculated actuarially. Patients were censured for local control at the time of last imaging. From 2005 to 2008, 27 patients were treated with WBRT and tumor bed SRS. Median age was 58.7 years, median KPS 80%. The primary malignancy was non-small cell lung cancer in 70%. Median follow-up was 9.7 months. Following the combination of surgery, WBRT and SRS the median overall survival was 17.6 months. Actuarial 2-year local control was 94%. The SRS boost was well tolerated with one patient (4%) requiring reoperation for symptomatic radiation necrosis 16 months post treatment. Radiosurgery can be safely added to WBRT as an adjuvant treatment following resection of a single brain metastasis. In our retrospective series, this combination treatment produced a high rate of local control.     

Single brain metastasis: radiosurgery alone compared with radiosurgery plus up-front whole-brain radiotherapy

BACKGROUND:

Neurosurgical resection is considered the standard treatment for most patients with a single brain metastasis. However, radiosurgery (RS) is a reasonable alternative. It was demonstrated that whole‐brain radiotherapy (WBRT) in addition to RS improves local control of 1‐3 brain metastases. Little information is available regarding WBRT in addition to RS for a single lesion.

METHODS:

Data of 63 patients who received RS alone for a single brain metastasis were retrospectively compared with 39 patients treated with WBRT+RS for local control of the treated metastasis, distant intracerebral control, and survival. Seven additional potential prognostic factors were investigated including age, sex, Karnofsky performance score, tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation.

RESULTS:

The 1‐year local control rates were 49% after RS and 77% after WBRT+RS (P = .040). The 1‐year distant control rates were 70% and 90%, respectively (P = .08). The 1‐year survival rates were 57% and 61%, respectively (P = .47). On multivariate analysis, improved local control was associated with WBRT+RS (risk ratio [RR], 1.95; P = .033) and interval from tumor diagnosis to irradiation >15 months (RR, 1.88; P = .042). Improved distant control was almost associated with WBRT+RS (RR, 2.24; P = .05) and age (RR, 2.20; P = .05). Improved survival was associated with KPS 90‐100 (RR, 1.73; P = .040), no extracerebral metastases (RR, 1.88; P = .013), RPA class 1 (RR, 2.06; P = .005), and interval from tumor diagnosis to irradiation >15 months (RR, 1.98; P = .009).

CONCLUSION:

The addition of WBRT to RS was associated with improved local control and distant intracerebral control but not survival. Cancer 2011;. © 2011 American Cancer Society.