Whole Brain Radiotherapy Versus Stereotactic Radiosurgery in Poor-Prognosis Patients with One to 10 Brain Metastases: A Randomised Feasibility Study

AimsA significant proportion of patients with brain metastases have a poor prognosis, with a life expectancy of 3–6 months. To determine the optimal radiotherapeutic strategy for brain metastases in this population, we conducted a randomised feasibility study of whole brain radiotherapy (WBRT) versus stereotactic radiosurgery (SRS).Materials and methodsPatients with a life expectancy of 3–6 months and between one and 10 brain metastases with a diameter ≤4 cm were enrolled at six Canadian cancer centres. Patients were randomly assigned (1:1) to receive either WBRT (20 Gy in five fractions) or SRS (15 Gy in one fraction). The primary end point was the rate of accrual per month. Secondary feasibility and clinical end points included the ratio of accrued subjects to screened subjects. This trial is registered with ClinicalTrials.gov (number NCT02220491).ResultsIn total, 210 patients were screened to enrol 22 patients into the trial; 20 patients were randomised between the two arms. Two patients did not receive treatment because one patient died and another patient withdrew consent after being enrolled. Patients were accrued between January 2015 and November 2017; the accrual rate was 0.63 patients/month. The most common reasons for exclusion were anticipated median survival outside the required range (n = 40), baseline Karnofsky Performance Score below 70 (n = 28) and more than 10 brain metastases (n = 28). The median follow-up was 7.0 months and the median survival was 7.0 months for all patients in the trial. The median intracranial progression-free survival was 1.8 months in the SRS arm and 9.2 months in the WBRT arm. There were five grade 3+ toxicities in the SRS arm and one grade 3+ toxicity in the WBRT arm; no grade 5 toxicities were observed. The cumulative rates of retreatment were 40% in the SRS arm and 40% in the WBRT arm.ConclusionsA randomised trial evaluating WBRT versus SRS in patients with one to 10 metastases and a poor prognosis is feasible. A slower than expected accrual rate and difficulties with accurate prognostication were identified as issues in this feasibility study. A larger phase III randomised trial is planned to determine the optimal treatment in this patient population.     

Survival Outcomes after Whole Brain Radiation Therapy and/or Stereotactic Radiosurgery for Cancer Patients with Metastatic Brain Tumors in Korea: A Systematic Review

Aim: To compare survival outcomes after whole brain radiation therapy (WBRT), stereotactic radiosurgery(SRS), and WBRT plus SRS combination therapy in Korea, by performing a quantitative systematic review.Materials and Methods: We searched 10 electronic databases for reports on Korean patients treated with WBRTor SRS for brain metastases published prior to July 2010. Independent reviewers screened all articles andextracted the data. When a Kaplan-Meier survival curve was available, median survival time and standard errorswere calculated. Summary estimates for the outcomes in each study were calculated using the inverse variancerandom-effects method. Results: Among a total of 2,761 studies, 20 studies with Korean patients (n=1,053) wereidentified. A combination of 12 studies (n=566) with WBRT outcomes showed a median survival time of 6.0months (95%CI: 5.9-6.2), an overall survival rate of 5.6% (95%CI: 1-24), and a 6-month survival rate of 46.5%(95%CI: 37.2-56.1). For nine studies (n=412) on SRS, the median survival was 7.9 months (95%CI: 5.1-10.8),and the 6-month survival rate was 63.1% (95%CI: 49.8-74.8). In six studies (n=75) using WBRT plus SRS, themedian survival was 10.7 months (95%CI: 4.7-16.6), and the overall and 6-month survival rates were 16.8%(95%CI: 6.2-38.2) and 85.7% (95%CI: 28.3-96.9), respectively. Conclusions: WBRT plus SRS showed better1-year survival outcome than of WBRT alone for Korean patients with metastatic brain tumors. However, theresults of this analysis have to be interpreted cautiously, because the risk factors of patients were not adjustedin the included studies.     

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.     

脑转移瘤的立体定向放射治疗

单纯立体定向放射外科能取得全脑放疗联合立体定向外科治疗相同的生存率,对于局部控制来说,结果有冲突。全脑放疗较局部治疗（立体定向放射外科和手术）减少颅内新发病灶。单纯立体定向放射外科组颅内治疗病灶外以及颅内总体复发率均增加,而且联合全脑放疗不增加认知功能损伤。对于1-3个脑转移瘤患者,单纯立体定向放射外科生存好于单纯全脑放疗。全脑放疗联合立体定向外科治疗较全脑放疗能改善局部控制,并在不增加并发症的基础上改善KPS评分。对于单发脑转移灶,联合治疗有生存获益。但2个及2个以上的脑转移灶是否有生存优势,尚有争论。对于多发脑转移瘤、KPS〈70分的患者联合治疗能改善生存。全脑放疗联合立体定向外科治疗和手术联合全脑放射治疗两组无生存差异。     

Salvage Surgical Resection after Linac-Based Stereotactic Radiosurgery for Newly Diagnosed Brain Metastasis

Background: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for newly diagnosed brain metastasis. Methods: Between November 2009 and May 2020, 318 consecutive patients with 1114 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During this study period, 21 of 318 patients (6.6%) and 21 of 1114 brain metastases (1.9%) went on to receive SSR after SRS/fSRT. Three patients underwent multiple surgical resections. Twenty-one consecutive patients underwent twenty-four SSRs. Results: The median time from initial SRS/fSRT to SSR was 14 months (range: 2–96 months). The median follow-up after SSR was 17 months (range: 2–78 months). The range of tumor volume at initial SRS/fSRT was 0.12–21.46 cm³ (median: 1.02 cm³). Histopathological diagnosis after SSR was recurrence in 15 cases, and radiation necrosis (RN) or cyst formation in 6 cases. The time from SRS/fSRT to SSR was shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.067). The median survival time from SSR and from initial SRS/fSRT was 17 and 74 months, respectively. The cases with recurrence had a shorter survival time from initial SRS/fSRT than those without recurrence (p = 0.061). Conclusions: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.     

立体定向放疗联合全脑放疗和福莫司汀治疗脑转移瘤的临床观察

  目的  观察立体定向放疗联合全脑放疗和福莫司汀治疗脑转移瘤的近期疗效、颅内无进展生存时间以及不良反应。  方法  72例脑转移瘤患者, 随机分为36例立体定向放疗联合全脑放疗组(SRS联合组)和36例单纯全脑放疗组(WBRT组)。两组均在放疗的第1、8、15天静脉给予福莫司汀(2 mg/kg)。  结果  SRS联合组和WBRT组的有效率分别是91.7%和72.2%, 差异有统计学意义(χ2=4.600, P < 0.05), 两组中位颅内无进展生存时间分别为9.0个月和7.0个月, 差异有统计学意义(χ2=4.159, P < 0.05)。SRS联合组的中枢神经系统反应较WBRT组轻, 两组差异有统计学意义。两组的主要不良反应为骨髓抑制, 但大部分患者能耐受。  结论  立体定向放疗联合全脑放疗可提高脑转移瘤的缓解率及颅内无进展生存时间。立体定向放疗联合全脑放疗和福莫司汀治疗脑转移瘤疗效高, 不良反应可以耐受, 是治疗脑转移瘤的较好选择。      

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.     

Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases

Aims

Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments.

Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases

PURPOSE: To report on the outcome of patients with melanoma brain metastases treated with stereotactic radiosurgery (SRS). PATIENTS AND METHODS: One hundred three patients with 153 intracranial melanoma metastases consecutively underwent Linac-based SRS between November 1991 and October 2001. The Kaplan-Meier method, univariate comparisons with log-rank test, and multivariate analyses with classification and regression tree models were performed. Calculations were based on last imaging date rather than the date of the last visit. RESULTS: Median age was 51 years (range, 18-93 years). Median Karnofsky performance status was 90. Sixty-one patients (59%) had single brain metastasis at presentation. Treatment sequence was SRS alone (61 patients), SRS + whole-brain radiotherapy (WBRT) (12 patients), and salvage SRS after WBRT (30 patients). The median tumor volume was 1.9 cm(3) (range, 0.06-22.3 cm(3)). The median SRS minimum peripheral dose and isodose was 18 Gy (range, 10-24 Gy) and 85% (range, 60%-100%), respectively. The median follow-up was 6 months for all patients and 13 months (range, 2-46 months) for patients alive at the time of analysis. The 1-year local control (LC) for all patients treated with SRS was 49%. Among the patients treated with initial SRS alone, the 1-year LC was better for patients with tumors < or =2 cm(3) than with tumors >2 cm(3): 75.2% vs. 42.3% (p < 0.05). The 1-year distant brain metastasis-free survival incidence was 14.7% for the 73 patients receiving either initial SRS alone or SRS +WBRT. The initial number of brain lesions (single vs. multiple) was the only factor with a significant effect on distant brain metastasis-free survival at 1 year: 23.5% for single metastases and 0% for multiple lesions (p < 0.05). The 1-year overall survival was 25.2%. Stratification by Score Index for Radiosurgery (SIR) revealed a significant effect on survival, which was 29% at 1 year for SIR >6 and 10% for SIR <==6 (relative hazard ratio, 2.1; p < 0.05) in classification and regression-tree multivariate analysis involving age, Karnofsky performance status, primary tumor control, tumor volume, SRS dose, SIR (>6 vs. < or =6), and systemic disease status. CONCLUSIONS: Initial SRS alone was an effective treatment modality for smaller cerebral melanoma metastases, achieving a 75% incidence of 1-year LC for < or =2 cm(3) single brain metastases and should be considered in patients with SIR >6. The role of WBRT in melanoma brain metastases cannot be addressed, owing to retrospective bias toward administering this treatment to patients with more aggressive disease. A prospective study is needed to assess the role of WBRT in patients with melanoma brain metastasis.     

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.     

伽玛刀治疗肺癌脑转移瘤生存与预后分析

目的:分析伽玛刀治疗肺癌脑转移瘤患者的生存及预后影响因素。方法:回顾性分析行伽玛刀治疗的56例肺癌脑转移瘤患者,单纯SRS组22例,单纯SRT组16例,联合全脑放疗(WBRT)组9例,行伽玛刀挽救组7例,行联合WBRT挽救组2例。Log rank法单因素分析影响预后的因素。结果:全组经治疗后6月、1年生存率分别为50%、10%,中位生存期为6个月。单纯SRS、单纯SRT、SRS联合WBRT、SRS/SRT挽救组、SRS+WBRT挽救组6月生存率分别为59%、55%、40%、33%、0%,中位生存期分别为8、9、6、5、3个月（P=0.005）。其中,SRS对SRT（P=0.157）、SRS对SRS+WBRT（P=0.551）、SRT对SRS+WBRT（P=0.266）、SRS/SRT挽救组对SRS+WBRT挽救组（P=0.177）无统计学意义。单因素分析显示影响总生存率的因素有原发灶的控制情况、病理、中枢外转移情况、KPS评分、RPA分级、病灶所处位置、前期化疗、前期颅内治疗、病灶数目(P=0.000、0.013、0.002、0.000、0.000、0.000、0.043、0.011、0.037)。多因素分析显示KPS评分、原发灶控制、病理、前期颅内处理影响生存（P=0.000、0.005、0.006、0.002）。结论:用伽玛刀行单次SRS或分次SRT或与WBRT联合治疗在对生存获益上相似;KPS评分、原发灶控制情况、病理类型、前期颅内处理是影响生存的主要因素。     

Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone

PURPOSE: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental State Examination (MMSE). Of the 132 enrolled patients, MMSE scores were available for 110. RESULTS: In the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and Karnofsky performance status. Of the 92 patients who underwent the follow-up MMSE, 39 had a baseline MMSE score of < or =27 (17 in the WBRT+SRS group and 22 in the SRS-alone group). Improvements of > or =3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (p = 0.85) were observed. Of the 82 patients with a baseline MMSE score of > or =27 or whose baseline MMSE score was < or =26 but had improved to > or =27 after the initial brain treatment, the 12-, 24-, and 36-month actuarial free rate of the 3-point drop in the MMSE was 76.1%, 68.5%, and 14.7% in the WBRT+SRS group and 59.3%, 51.9%, and 51.9% in the SRS-alone group, respectively. The average duration until deterioration was 16.5 months in the WBRT+SRS group and 7.6 months in the SRS-alone group (p = 0.05). CONCLUSION: The results of the present study have revealed that, for most brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effects of WBRT on neurocognitive function might not be negligible.     

Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases

PURPOSE: To evaluate the usefulness of whole brain radiotherapy (WBRT) and of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) for brain metastases among patients receiving stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A retrospective analysis was performed on 135 patients who underwent linear accelerator (Linac) (n = 73) or Gamma Knife (n = 62) SRS for newly diagnosed brain metastases at the Cleveland Clinic Foundation between 8/89 and 12/98. Univariate and multivariate analyses were performed to evaluate the effects of age, primary site, control of the primary, interval to development of brain metastases (disease-free interval [DFI]), number of brain metastases, presence of extracranial metastases, Karnofsky performance status (KPS), treatment of brain metastases, and RPA class on overall survival. RESULTS: Application of the RPA classification revealed 29 patients fit the criteria for class I, 96 for class II, and 10 for class III. All of the patients underwent SRS. Fifty-seven patients also received WBRT at the time of initial presentation (SRS and immediate WBRT), and 78 patients received WBRT only if CNS relapse occurred (SRS alone). The median survival for all patients was 7.9 months (range: 1.1-90.1), and was 11.2 months for RPA class I compared to 6. 9 months for RPA classes II-III (p = 0.016). Median survival was 10. 5 months following SRS alone compared to 6.4 months following SRS and WBRT (p = 0.07). On univariate analysis, KPS >/= 80% (p = 0.002) and absence of systemic disease (p = 0.013) were also associated with longer survival, whereas control of the primary, DFI, and number of brain metastases did not have an impact. Multivariate analysis revealed only RPA class (p = 0.023) to be an independent predictor for overall survival, whereas treatment group (p = 0.079) was only marginally significant. At 2 years, immediate WBRT improved control at the original site of metastases (80% vs. 52%, p = 0.03) and prevention of new metastatic sites within the brain, 74% vs. 48% (p = 0.06). The 2-year intracranial disease-free survival was 60% following SRS and WBRT compared to only 34% following SRS alone (p = 0.03). CONCLUSIONS: Despite the inherent biases to select more favorable patients for SRS, the RPA class retains its prognostic value. Omission of WBRT from the initial management was not detrimental in terms of overall survival; however, progressive disease occurred in over 50% of patients treated in this manner. Further studies are required to determine which, if any, patients should be considered for SRS with WBRT held in reserve.     

Prospective study of stereotactic radiosurgery without whole brain radiotherapy in patients with four or less brain metastases: incidence of intracranial progression and salvage radiotherapy

This prospective study was conducted to evaluate the treatment outcome after stereotactic radiosurgery (SRS) alone with special attention to its influence on intracranial freedom from progression (FFP), local control, time to whole brain radiotherapy (WBRT), and survival. Forty-one patients with brain metastases who met the inclusion criteria were enrolled in this prospective cohort and treated by SRS alone between January 1998 and September 2001. The overall local control rate was 76%. The one year actuarial intracranial FFP was 33%. Ten patients (24%) had relapse at treated site. Twenty-three patients (56%) had intracranial progression with a median time of 4.25 months (1–24.6). Salvage radiotherapy was given in 21 patients (51%). Only 12 (29%) patients required WBRT with the median time to WBRT after SRS of 4.85 months. Nine patients (22%) underwent additional SRS at the median time of 5 months after the first procedure. The median survival was 10 months. At the time of follow up, 16 patients (39%) were still alive with a range of 6–31 months. This prospective study suggests that the omission of WBRT in the initial treatment of patients with SRS for four or less brain metastases may allow up to 70% of patients to avoid WBRT.     

Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy

BACKGROUND.

The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole‐brain radiation therapy (WBRT).

METHODS.

The records of 1789 BM patients from August 1989 to November 2004 were reviewed. Of these, 111 underwent WBRT as part of their initial management and SRS as salvage. Patients were stratified by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, primary disease, dimension of the largest metastases and number of BM at initial diagnosis, and time to first brain recurrence after WBRT. Overall survival, survival after SRS, and time to local and distant failure were analyzed.

RESULTS.

The median OS from the initial diagnosis of BM was 17.7 months. Median survival after salvage SRS for the entire cohort was 9.9 months. Median survival after salvage SRS was 12.3 months in patients who had their first recurrence >6 months after WBRT versus 6.8 months for those who developed disease recurrence ≤6 months after (P = .0061). Primary tumor site did not appear to affect survival after SRS. Twenty‐eight patients (25%) developed local recurrence after their first SRS with a median time of 5.2 months. A dose <22 grays and lesion size >2 cm were found to be predictive of local failure.

CONCLUSIONS.

In this study, patients who recurred after WBRT and were treated with salvage SRS were found to have good local control and survival after SRS. WBRT provided good initial control, as 45% of these patients failed >6 months after WBRT. Those with a longer time to failure after WBRT had significantly longer survival after SRS. Cancer 2008. © 2008 American Cancer Society.     

Stereotactic Radiosurgery for Patients with Solid Brain Metastases: Current Status

The goal of this article is to provide a contemporary update on the use of stereotactic radiosurgery (SRS) for the treatment of intracranial metastatic disease. We discuss the rationale for employing SRS in brain metastases and describe the critical factors that predict outcome. We highlight the main clinical indications for SRS including treatment of recurrent brain metastases after previous whole brain radiation therapy (WBRT), as a boost after WBRT, and as sole therapy for newly diagnosed tumors. For each clinical scenario, we offer a treatment algorithm based on our clinical experience. The article also addresses the most common complications associated with SRS and their treatment.     

Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method

PURPOSE: To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS: An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone. RESULTS: Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION: In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.     

Stereotactic Radiosurgery for Patients with Solid Brain Metastases: Current Status

The goal of this article is to provide a contemporary update on the use of stereotactic radiosurgery (SRS) for the treatment of intracranial metastatic disease. We discuss the rationale for employing SRS in brain metastases and describe the critical factors that predict outcome. We highlight the main clinical indications for SRS including treatment of recurrent brain metastases after previous whole brain radiation therapy (WBRT), as a boost after WBRT, and as sole therapy for newly diagnosed tumors. For each clinical scenario, we offer a treatment algorithm based on our clinical experience. The article also addresses the most common complications associated with SRS and their treatment.     

Radiosurgery for brain metastases at the Royal Adelaide Hospital: Are we treating the right patients?

Although non‐randomized data strongly suggest improved outcome from radiosurgery (RS) for brain metastases relative to whole brain radiotherapy (WBRT) alone, selection factors account for much of the observed differences. This retrospective review of the 16 brain metastases patients treated so far with RS at the Royal Adelaide Hospital confirms a median survival of 10.1 months, consistent with recent multi‐institutional pooled results and significantly longer than the median survival of 3?6 months typically reported for WBRT alone. The emerging randomized trials comparing surgery, RS and WBRT for brain metastases are reviewed in the context of the Radiation Therapy Oncology Group Recursive Partitioning Analysis prognostic Class concept in order to assess whether we are using this resource intensive technique to treat the ‘right’ patients. We conclude that it is reasonable to continue our current policy of considering RS primarily for patients of good performance status with solitary brain metastases. We have a flexible approach to adjuvant WBRT which appears to decrease brain relapse, but not improve survival.     

Whole Brain Radiotherapy Combined with Stereotactic Radiotherapy Versus Stereotactic Radiotherapy Alone for Brain Metastases: a Meta-analysis

Aim: This study was to evaluate the effect of whole brain radiation (WBRT) combined with stereotacticradiotherapy (SRS) versus stereotactic radiotherapy alone for patients with brain metastases using a metaanalysis.Materials and Methods: We searched PubMed, EMBASE, Cochrane Library from their inceptionup to October 2013. Randomized controlled trials involving whole brain radiation combined with stereotacticradiotherapy versus stereotactic radiotherapy alone for brain metastases were included. Statistical analyseswere performed using RevMan5.2 software. Results: Four randomized controlled trials including 903 patientswere included. The meta-analysis showed statistically significant lowering of the local recurrence rate (OR=0.29,95%CI: 0.17~0.49), new brain metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologicradiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No statistically significant differenceexisted in the 1-year survival rate (OR=0.78, 95%CI: 0.60~1.03). Conclusions: The results indicate that wholebrain radiotherapy combined with stereotactic radiotherapy has advantages in local recurrence and new brainmetastasis rates, but stereotactic radiotherapy alone is associated with better neurological function. However, asthe samples included were not large, more high-quality, large-sample size studies are necessary for confirmation.