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.     

Whole Brain Radiotherapy Combined with Stereotactic Radiosurgery versus Stereotactic Radiosurgery Alone for Brain Metastases

Background: The aim of this study was to evaluate the effect of whole brain radiotherapy (WBRT) combined with streotactic radiosurgery versus stereotactic radiosurgery (SRS) alone for patients with brain metastases. Materials and Methods: This was a retrospective study that evaluated the results of 46 patients treated for brain metastases at Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiation Oncology Department, between January 2012 and January 2015. Twenty-four patients were treated with WBRT+SRS while 22 patients were treated with only SRS. Results: Time to local recurrence was 9.7 months in the WBRT+SRS arm and 8.3 months in SRS arm, the difference not being statistically significant (p= 0.7). Local recurrence rate was higher in the SRS alone arm but again without significance (p=0,06). Conclusions: In selected patient group with limited number (one to four) of brain metastases SRS alone can be considered as a treatment option and WBRT may be omitted in the initial treatment.     

Surgical Resection for Patients with Solid Brain Metastases: Current Status

Brain metastases occur in up to 40% of patients with cancer. Their management has been revolutionized in the last decade by three developments: improved imaging and detection of metastases, better treatment of systemic disease with the result that metastases occur more often; and improved surgical techniques including image-guided surgery to treat metastatic lesions. Class 1 data suggest that surgery is a better treatment for metastases than whole brain radiation. Other data suggest that metastases even in eloquent cortex can be removed safely. The complication rate is low and the recurrence rate is less than 10%. In general, indications for surgery include a mass with an unknown primary; a symptomatic mass including one in eloquent areas; a mass with considerable edema requiring high dose steroids; a mass greater than 3 cm; or patient preference when radiosurgery may also be an option. The question of radiosurgery or whole brain radiation as adjunct to surgical removal requires further evaluation.     

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 Radiosurgery for Multiple Brain Metastases From Renal-Cell Carcinoma

Background

Brain metastases (BM) pose a significant problem in patients with metastatic renal-cell carcinoma (mRCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.

Upfront and Repeated Stereotactic Radiosurgery in Patients With Brain Metastases From NSCLC

IntroductionApproximately 40% of non-small-cell lung cancer (NSCLC) patients develop brain metastases (BM). Stereotactic radiosurgery (SRS) instead of whole-brain radiotherapy (WBRT) is increasingly administered as an upfront treatment to patients with a limited number of BM. We present outcomes and validation of prognostic scores for these patients treated with upfront SRS.MethodsWe retrospectively analyzed 199 patients with a total of 268 SRS courses for 539 brain metastases. Median patient age was 63 years. For larger BM, dose reduction to 18 Gy or hypofractionated SRS in 6 fractions was applied. We analyzed the BMV-, the RPA-, the GPA- and the lung-mol GPA score. Cox proportional hazards models with univariate and multivariate analyses were fitted for overall survival (OS) and intracranial progression-free survival (icPFS).ResultsSixty-four patients died, 7 of them of neurological causes. Thirty eight patients (19,3%) required a salvage WBRT. Median OS was 38, 8 months (IQR: 6-NA). In univariate analysis as well as multivariate analysis, the Karnofsky performance scale index (KPI) ≥90% (P = 0, 012 and P = 0, 041) remained as independent prognostic factor for longer OS. All 4 prognostic scoring indices could be validated for OS assessment (BMV P = 0, 007; RPA P = 0, 026; GPA P = 0, 003; lung-mol GPA P = 0, 05).ConclusionIn this large cohort of NSCLC patients with BM treated with upfront and repeated SRS, OS was markedly favourable, in comparison to literature. Upfront SRS is an effective treatment approach in those patients and can decidedly reduce the impact of BM on overall prognosis. Furthermore, the analysed scores are useful prognostic tools for OS prediction.     

Utilization of Stereotactic Radiosurgery for Renal Cell Carcinoma Brain Metastases

Background

Because renal cell carcinoma (RCC) has been traditionally considered a “radioresistant” histology, it may be advantageous to treat brain metastases (BMs) with ablative dosing by means of stereotactic radiosurgery (SRS). This is the first known analysis evaluating utilization of SRS for RCC BMs in the United States.

Radiological Kinetics of Brain Metastases and Clinical Implications for Patients Treated With Stereotactic Radiosurgery

Aims

Select patients with brain metastases receive stereotactic radiosurgery (SRS) with the objective of improving survival and intracranial disease control. Brain metastases number and volume are prognostic factors used to inform patient selection. The aim of this study was to assess the rate of change of brain metastases size and number (growth kinetics) between the diagnostic and day of SRS magnetic resonance imaging (MRI) scans.

Treating Brain Metastases from Breast Cancer: Outcomes after Stereotactic Radiosurgery

AimsStereotactic radiosurgery (SRS) is an alternative to surgery or whole brain radiotherapy for the control of single or multiple brain metastases in patients with breast cancer. To date, there is no clear consensus on factors that might predict overall survival following SRS. The aim of this study was to assess the overall survival of breast cancer patients with brain metastases treated with SRS at a single centre and to examine the factors that might influence survival.Materials and methodsA retrospective analysis of consecutive patients with breast cancer and brain metastases, considered suitable for SRS by the regional neuro-oncology multidisciplinary team. All patients were treated at a single National Health Service centre.ResultsIn total, 91 patients received SRS between 2013 and 2017, of whom 15 (16.5%) were alive at the time of analysis. The median overall survival post-SRS was 15.7 months (interquartile range 7.7–23.8 months) with no significant effect of age on survival (67 patients ≤ 65 years, 16.3 months; 26 patients > 65 years, 11.4 months, P = 0.129). The primary tumour receptor status was an important determinant of outcome: 31 oestrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2–) patients had a median overall survival of 13.8 months, 14 ER+/HER2+ patients had a median overall survival of 21.4 months, 30 ER–/HER2+ patients had a median overall survival of 20.4 months and 16 patients with triple negative breast cancer (TNBC) had a median overall survival of 8.5 months. A larger total volume of tumour treated (>10 cm³), but not the number of individual metastases treated, was associated with worse survival (P = 0.0002) in this series. Patients with stable extracranial disease at the time of SRS had improved overall survival compared with those with progressive extracranial disease (30 patients stable extracranial disease overall survival = 20.1 months versus 33 patients progressive extracranial disease overall survival = 11.4 months; P = 0.0011). Seventeen patients had no extracranial disease at the time of SRS, with a median overall survival of 13.1 months.ConclusionsThis single-centre series of consecutive patients with brain metastases from breast cancer, treated with SRS, had a similar overall survival compared with previous studies of SRS. TNBC and ER+/HER2– histology, metastatic volumes >10 cm³ and progressive extracranial disease at the time of SRS were associated with worse survival.     

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。      

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.     

Cost-Effectiveness of Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy in Treating Brain Metastases

Single-fraction stereotactic radiosurgery (SRS) is a highly used tool in managing brain metastases, alongside its multifraction counterpart – stereotactic body radiation therapy (SBRT). These radiation therapy techniques have been associated with excellent clinical outcomes, such as decreased local recurrence, increased survival, and improved palliative effects. However, present literature concerning the cost-effectiveness of these techniques remain scarce. Based on the current procedure terminology codes involving services provided during radiation consultation, treatment, and follow-up in our institution, 3-fraction SBRT with a 3-dimensional plan and intensity modulated radiation therapy cost 27% and 17% more than SRS, respectively. A 32% and 34% price increase can, respectively, be seen in 5-fraction SBRT with 3-dimensional plan and intensity modulated radiation therapy delivery sessions relative to 3-fraction SBRT administration. Cost savings between these procedures were associated with the radiation therapy delivery sessions instead of the treatment planning process. These analyses indicate that SRS appears to be a less expensive and time-intensive option than SBRT in our institution. However, additional comparative analyses regarding SRS and SBRT are needed to explore the clinical and financial benefits of these radiation therapy techniques.     

脑转移立体定向放射外科中共面与非共面模式下剂量学分析

目的:比较脑转移立体定向放射外科中共面与非共面模式下剂量学差异,对单组非共面模式在脑转移立体定向放射外科中的应用进行可行性分析。方法:回顾性分析14例脑转移患者,采用容积旋转调强放疗与无均整块技术技术,处方剂量25 Gy,在计划设计中用共面弧、单组非共面弧、多组非共面弧3种模式,比较3种模式下靶区剂量、适形指数(conformity Index,CI)、梯度指数(gradient index,GI)和脑组织受量以及出束时间、执行效率等差别。结果:共面计划无论相对于单组非共面计划还是多组非共面计划而言,出束时间以及CI差异均无统计学意义(P>0.05)。3种模式都能达到临床要求,但剂量分布上差异有统计学意义。共面计划中GI(GI₅₀=4.84±0.52,GI₂₅=16.13±2.73),要远远高于单组非共面计划GI(GI₅₀=3.66±0.44,GI₂₅=9.94±1.41)(P <0.001,P <0.001)和多组非共面计划GI(GI₅₀=3.73±0.42...     

Care Patterns for Stereotactic Radiosurgery in Small Cell Lung Cancer Brain Metastases

IntroductionThe historical standard of care for brain metastases (BMs) from small cell lung cancer (SCLC) has been whole-brain radiotherapy (WBRT). However, there is growing interest in upfront stereotactic radiosurgery (SRS) for select SCLC patients.Materials and MethodsWe invited United State-based Radiation Oncologists (ROs) via email to answer an anonymous survey using a branching logic system addressing their use of SRS and WBRT for SCLC BMs. Wilcoxon rank-sum test and Fisher's exact test were used to compare differences in continuous and categorical variables, respectively. Multivariable logistic regression analyses were fitted for outcome variables including covariates with P < .10 obtained on univariable analysis.ResultsIn total, 309 ROs completed the survey and 290 (95.7%) reported that they would consider SRS for SCLC BMs under certain clinical circumstances. Across patient characteristics, the number of BMs was the most heavily weighted factor (mean 4.3/5 in importance), followed by performance status, cognitive function, and response to prior therapy. Fewer BMs were correlated with increased SRS use (55.8% offered SRS “very frequently” [>75% of cases] or “often” [51%-75% of cases] for 1 BM vs. 1.1% for >10 BM, P < .001). In situations where WBRT was preferred, concern for rapid intracranial progression (45.3%) and lack of high-level data (36.9%) were the most important factors. The majority (60.6%) were aware of a large recent international retrospective analysis (the FIRE-SCLC study) reporting similar OS between upfront SRS and WBRT; awareness of this study was the only respondent variable predictive of SRS use for limited BMs (19.2% of those aware of the study preferring SRS for limited [≤4] BMs before vs. 61% preferring SRS after the publication, P < .001). The majority of respondents (88.2%) expressed a willingness to enroll patients on a recently opened recently opened randomized trial, NRG-CC009, comparing SRS versus hippocampal-avoidance WBRT.ConclusionsIn the first survey of SRS for SCLC BMs, we observed a high level of physician openness to upfront SRS in SCLC, particularly for patients with limited numbers of BMs, as well as significant interest in generating prospective randomized data to clarify the role of SRS in this population.     

Fractionated Radiosurgery for Brain Metastases in 43 Patients with Breast Carcinoma

About 15% of metastatic breast carcinoma patients are diagnosed with brain metastases. Historically, the majority are treated with palliative external whole-brain radiation with a median survival of 4 months. We examined stereotactic radiosurgery's effect on treatment outcome in such patients. Four hundred and fifty four consecutive patients with brain metastases were treated with stereotactic radiosurgery at Staten Island University Hospital, NY, between 1991 and 1999. The medical records of 60 women with histologically confirmed breast cancer were retrospectively reviewed. Forty-three patients (71%) received fractionated radiosurgery (4×600cGy) and form the core of this report. Sixty five percentage had been previously unsuccessfully treated by whole-brain radiation or had recurrence after craniotomy. Survival was calculated by the Kaplan–Meier method. The median age at diagnosis of brain metastases was 52 years, with median interval of 49 months following the diagnosis of tumor primary. Median survival from brain diagnosis reached 13.6 months. Overall median survival from radiosurgery treatment was 7.5 months. Fifteen patients with one or two brain lesions survived a median of 11.5 months. For the fractionated cohort of patients 1- and 2-year actuarial survival was 28.2% and 12.8%, respectively. Three patients are alive at 32, 34 and 64 months, respectively. We conclude that fractionated radiosurgery improves survival of patients with brain metastases from breast cancer, especially those with small lesions, good functional status and no other metastatic disease. These patients should be encouraged to consider radiosurgery, possibly before WBRT. Considering our 7.5 months overall survival including patients with multiple metastases, and patients with progressive brain metastases despite extensive standard therapy and often systemic disease, these results suggest that radiosurgery could benefit breast cancer patients with brain metastases and extend life.