- Department of Neurosurgery, King Faisal University, AlAhsa, Saudi Arabia
- Department of Surgery, University of Tabuk, Tabuk, Saudi Arabia
- Department of Surgery, Jazan University, Jazan, Saudi Arabia
- Department of Nursing, College of Applied Medical Sciences, AlAhsa, Saudi Arabia
Correspondence Address:
Abdulrahim Saleh Alrasheed, Department of Neurosurgery, King Faisal University, AlAhsa, Saudi Arabia.
DOI:10.25259/SNI_913_2024
Copyright: © 2025 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.How to cite this article: Abdulrahim Saleh Alrasheed1, Abdulsalam Mohammed Aleid1, Reema Ahmed Alharbi2, Maryam Ali Alamer3, Kawthar Abdullah Alomran4, Sarah Abdullah Bin Maan4, Sami Fadhel Almalki1. Stereotactic radiosurgery versus whole-brain radiotherapy for intracranial metastases: A systematic review and meta-analysis. 24-Jan-2025;16:18
How to cite this URL: Abdulrahim Saleh Alrasheed1, Abdulsalam Mohammed Aleid1, Reema Ahmed Alharbi2, Maryam Ali Alamer3, Kawthar Abdullah Alomran4, Sarah Abdullah Bin Maan4, Sami Fadhel Almalki1. Stereotactic radiosurgery versus whole-brain radiotherapy for intracranial metastases: A systematic review and meta-analysis. 24-Jan-2025;16:18. Available from: https://surgicalneurologyint.com/?post_type=surgicalint_articles&p=13349
Abstract
Background: Brain metastasis has a negative influence on the morbidity and mortality of cancer patients. Conventionally, whole-brain radiotherapy (WBRT) was favored as the standard treatment for brain metastases. However, it has been linked to a significant decline in neuro-cognitive function and poor quality of life. Stereotactic radiosurgery (SRS) has recently gained prominence as an alternative modality, considering that it provides targeted high-dose radiation while minimizing adverse effects. This study evaluates the efficacy and safety of SRS versus WBRT in patients with intracranial metastases.
Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, through July 2024, we searched PubMed, Scopus, and Web of Science for articles comparing WBRT and SRS in patients with intracranial metastases. Outcomes included local and distant recurrence, leptomeningeal disease (LMD), and survival. We also used a random-effect model to perform a meta-analysis.
Results: The findings revealed no significant differences in local (risk ratio [RR] = 0.70, 95% confidence interval [CI] [0.46, 1.06]) or distant recurrence rates (RR = 0.83, 95% CI [0.54, 1.28], P = 0.41) between WBRT and SRS. However, SRS was associated with a greater risk of post-radiation LMD (hazard ratio [HR] = 3.09, 95% CI [1.47, 6.49], P = 0.003). Survival rates at 1 year (RR = 1.03, 95% CI [0.83, 1.29], P = 0.76) and 5 years (RR = 0.89, 95% CI [0.39, 2.04], P = 0.78) demonstrated no significant differences.
Conclusion: SRS and WBRT exhibited similar recurrence rates and overall survival (OS) at 1 and 5 years, with WBRT being more effective in managing post-radiation LMD. SRS patients, on the other hand, had longer OS when measured in months.
Keywords: Brain, Metastases, Stereotactic radiosurgery, Whole-brain radiotherapy
INTRODUCTION
Brain metastases are a growing consequence of systemic malignancies and are a significant cause of illness and death in cancer patients.[
Hematogenous dissemination is the most frequent method of metastatic spread leading to brain metastases; this implies that the entire brain is likely affected by micrometastatic illness, even if just one intracranial lesion is seen.[
Until the early 2000s, WBRT was the sole radiation-based treatment available for brain metastases. However, SRS was then offered as an alternative option for brain metastases of a restricted number, typically defined as 1–3. Evidence from prospective trials has demonstrated that postoperative adjuvant WBRT decreases the likelihood of recurrence in the surgical site and lowers the occurrence of new metastases.[
METHODS
Database search
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement,[
Screening
Electronic database search results were uploaded to Rayyan Software for selection, screening, and duplicate removal. Potentially relevant papers found through the database searches were screened by title and abstract by four independent reviewers. The eligibility of articles that satisfy the inclusion criteria was assessed by four other independent reviewers based on the full text of the studies. A PRISMA flow diagram was used to record the search and screening process.
Eligibility criteria
Following the PICO framework, our inclusion criteria were as follows: Population (P): adults aged 18 and above diagnosed with single or multiple brain metastases; Intervention (I): Postoperative SRS targeting intracranial metastases, Comparison (C): Postoperative WBRT targeting intracranial metastases, and Outcomes (O): safety and effectiveness in terms of tumor control (local recurrence, distant recurrence, and leptomeningeal disease [LMD]) and survival rates (1-year survival, 5-year survival, and overall survival [OS]). Reviews, case reports, editorial letters, conference abstracts, and study protocols were excluded from the study.
Quality and risk of bias (Rob) assessment
Quality and Rob assessments were conducted using the Newcastle–Ottawa Scale tool for cohort studies,[
Data extraction
Two independent reviewers extracted the baseline data from the eligible articles, including the study design, sample size, age, and gender of patients. We also extracted the outcome data, including local recurrence, distant recurrence, LMD, OS, and 1- and 5-year OS rates. Any disagreements were resolved by consulting a third reviewer.
Statistical analysis
All the statistical procedures were conducted using Review Manager software (version 5.2) by applying the random effect model for heterogeneous outcomes and the fixed effect model for homogenous outcomes and 95% confidence intervals (CI). For the categorical data, we calculated the pooled risk ratio (RR) or hazard ratio (HR), while for continuous variables, we calculated the pooled mean difference between the two groups. Heterogeneity was assessed using I2, and P = 0.05 was applied for all steps. Subgroup analysis according to study design (cohort and RCTs) was done. Sensitivity analysis by leave-one-out was done to resolve heterogeneity.
RESULTS
Database searching and screening
After searching the databases, a total of 388 articles were produced with 144 duplicates, so we conducted title and abstract screening for 244 studies. We excluded 229 studies and conducted full-text screening for the remaining 15 studies. A total of 11 studies were included in the final meta-analysis[
Baseline characteristics of the included studies
Multiple studies with different study designs carried out between 2010 and 2023 were included in the study. Among these, seven were cohort studies, three RCTs, and a non-randomized trial. Sample sizes ranged from 26 to 194 participants, with varying male representation across the studies. The proportion of males receiving WBRT ranged from 31% to 72.2%, while those receiving SRS showed an almost similar representation. The mean ages of participants varied, with WBRT mean ages ranging from 53 to 65 years, while SRS patients’ mean ages ranged from 53 to 66 years. These baseline characteristics indicate a diverse population across the studies. The baseline characteristics of the included studies are fully illustrated in
Quality and Rob assessment
Five of the cohort studies were of high quality, and two were of moderate quality [
Local recurrence
Local recurrence is a crucial indicator of the effectiveness of treatment, reflecting the need for further therapeutic interventions. Data were extracted from seven included studies, and the meta-analysis revealed no statistically significant no statistically significant difference between WBRT and SRS groups, whether in the cohort studies or RCTs with a total effect size (RR = 0.78, 95% CI [0.52, 1.17]) as indicated by P = 0.22. Data were homogenous among studies (P = 0.4, I2= 3%), as illustrated in
Distant recurrence
Extracted data from five included studies were used to perform a meta-analysis. Pooled effect estimate calculation revealed no statistically significant difference between WBRT and SRS groups in the cohort and RCTs with (RR = 0.83, 95% CI [0.54, 1.28], P = 0.41) with marked heterogeneity detected (P = 0.05; I2 = 59%). Sensitivity analysis was conducted, leaving out Bodensohn et al.,[
LMD
Results of the meta-analysis showed a statistically significant difference between WBRT and SRS, favoring WBRT as SRS is associated with higher hazards of post-radiation LMD (HR = 3.09, 95% CI [1.47, 6.49], P = 0.003) with no significant heterogeneity detected (P = 0.28; I2 = 15%), as shown in
One year survival
Survival rates after 1 year of treatment were calculated in 11 studies. A meta-analysis was conducted and showed no statistically significant difference between WBRT and SRS in 1-year survival rates (RR = 1.03, 95% CI [0.83, 1.29], P = 0.76), with moderate heterogeneity detected (P = 0.0006; I2 = 68%). This heterogeneity was observed in the RCTs subgroup and after the sensitivity analysis by leave-one-out with removal of Brown study, the heterogeneity was resolved. This heterogeneity was attributed to surgical bed control after SRS, which was reported to be worse than that reported in previous studies, as indicated by Brown et al.,[
Five-year survival
The 5-year survival rate is a long-term indicator of the therapeutic effect of interventional groups; the meta-analysis showed no statistically significant difference between WBRT and SRS in the RCTs and cohort subgroups (RR = 0.87, 95% CI [0.55, 1.38], P = 0.55) with no heterogeneity detected in cohort subgroup and RCTs subgroup was only one study [
OS (in months)
OS period data were extracted from five studies. Meta-analysis was conducted and showed a higher OS period in the SRS group compared to WBRT in the cohort subgroup Mean difference (MD) = 4.05 months, 95% CI [2.18, 5.91], P < 0.0001) with no heterogeneity detected (P = 0.54; I2 = 0%); however, no significant difference was obtained between the two groups in the RCTs subgroup [
DISCUSSION
In the present study, we observed that both treatment modalities were comparable regarding local and distant tumor recurrence. Moreover, both treatment strategies were similar in the OS for 1 and 5 years. However, the OS measured in months was higher in the SRS group than in WBRT. On the other hand, WBRT was superior regarding post-radiation LMD.
Consistent with the latest research conducted by Lamba et al.[
In 1998, Patchell et al. conducted a significant randomized experiment in which patients diagnosed with solitary brain metastasis were randomly allocated to receive either WBRT after surgery or to be observed without any additional treatment. Patients in the first group had a significantly decreased chance for local recurrence (10% vs. 46%, P < 0.001), distant brain recurrence (14% vs. 37%, P < 0.01), and neurologic mortality (14% vs. 44%, P = 0.003). However, the authors found no significant increase in median survival (48 weeks vs. 43 weeks, P = 0.39). They attributed this lack of improvement to inadequate treatment of the patient’s systemic disease rather than a lack of effectiveness in WBRT.[
SRS has emerged as the predominant treatment choice for patients with brain metastases. The effectiveness of SRS for brain metastases was initially documented in several retrospective investigations. In a study conducted by Sanghavi et al.,[
RTOG 9508 was a phase III trial that randomly assigned 333 patients with one to three brain metastases with a Karnofsky performance score (KPS) of 70 or above to receive either WBRT and SRS or WBRT alone.[
Patients who underwent both SRS and WBRT experienced extra benefits compared to those who only received WBRT in terms of maintaining or improving their KPS and reducing corticosteroid use. Subsequent studies assessed the efficacy of SRS alone without the addition of WBRT. Aoyama et al.[
While SRS is commonly provided to individuals with four or fewer brain metastases, it is now being more frequently used for patients with five or more tumors. A retrospective analysis revealed that the median OS in individuals with five or more brain metastases was 7.5 months following treatment with SRS.[
The present study is limited by the inclusion of observational studies with RCTs in the analysis, which may cause a Rob. However, this should have been done due to the limited number of published RCTs and to gather comprehensive evidence. We recommend future large-scale RCTs to validate our present findings.
CONCLUSION
The rates of tumor recurrence, whether local or distant, were similar between SRS and WBRT. Furthermore, both treatment methods had comparable OS rates at 1 and 5 years. Nevertheless, WBRT demonstrated superior efficacy in treating post-radiation LMD. Conversely, the duration of the OS evaluated in months was greater in the SRS group when compared to WBRT.
Ethical approval:
The Institutional Review Board has waived the ethical approval for this study.
Declaration of patient consent:
Patient’s consent was not required as there are no patients in this study.
Financial support and sponsorship:
Nil.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Disclaimer
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
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