Jason P. Sheehan

Background Cavernous sinus hemangiomas (CSHs) are rare, benign vascular tumors with high morbidity due to their critical location and vascularity. While microsurgical resection was the historical standard, its risks of intraoperative bleeding and cranial nerve deficits have led to the adoption of stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT). This systematic review and meta-analysis evaluate outcomes of these modalities, focusing on tumor control, symptom relief, and safety. Methods Following PRISMA guidelines, a systematic search of PubMed, Embase, Web of Science, and Scopus (up to March 2024) identified studies reporting outcomes of SRS or HSRT in CSHs. Eligible studies were assessed for quality using the Joanna Briggs Institute checklist. All statistical analysis was performed using STATA v.17. Results Twenty studies with 682 patients were included. Tumor volume reduction was substantial, with a pooled estimate of 71% (95% CI: 57–84%) and a standardized mean difference of -2.07 (95% CI: -2.47 to -1.67). Symptom recovery rates were highest with HSRT (64%, 95% CI: 9–119%) compared to SRS (44%, 95% CI: 21–67%). Adverse radiation effects were minimal, with an overall rate of 5% (95% CI: 2–7%). Cranial nerve improvement was observed but varied by nerve and treatment type. Conclusion SRS and HSRT are effective and safe for CSHs, with HSRT showing particular benefits for larger tumors due to fractionation. Future studies should optimize protocols and refine patient selection to maximize therapeutic outcomes. Radiation-based therapies now represent a cornerstone in CSH management.

OBJECTIVE: Ruptured, large pediatric arteriovenous malformations (AVMs) pose a significant management challenge due to high rerupture risk and the morbidity of conventional treatments. Volume-staged stereotactic radiosurgery (VS-SRS) has emerged as an alternative; however, evidence for its use in this specific population is limited. This study aimed to evaluate the long-term efficacy and safety of VS-SRS for ruptured, large AVMs in a dedicated pediatric cohort. METHODS: This international, multicenter, retrospective cohort study from 21 centers analyzed outcomes for 42 pediatric patients (age < 18 years) with previously ruptured, large AVMs treated with VS-SRS. The primary outcome was complete AVM obliteration, and secondary outcomes included post-SRS hemorrhage, radiation-induced changes (RICs), and favorable outcome. Favorable outcome in this study was defined as obliteration without post-SRS hemorrhage or permanent RIC. RESULTS: At the initial SRS, the median patient age was 14.5 years, and the median AVM volume was 15.0 cm ³ ; most AVMs were high grade (Spetzler-Martin grades IV and V). With a median follow-up of 41.5 months, complete AVM obliteration was achieved in 21 patients (50.0%). The cumulative obliteration rate was 37% at 5 years and 56% at 10 years. Patients with a nidus volume of ≤ 10 cm ³ had significantly higher cumulative obliteration rates than those with a nidus volume > 10 cm ³ (log-rank test, p = 0.021). Similarly, patients treated with a prescription dose > 17 Gy showed significantly higher cumulative obliteration rates compared to those treated with a dose ≤ 17 Gy (log-rank test, p = 0.012). The cumulative 5-year incidences of hemorrhage and RICs following VS-SRS were 19% and 7%, respectively. In multivariable analysis, only larger total AVM volume was an independent predictor of a lower likelihood of favorable outcome (hazard ratio 0.89, 95% CI 0.80–0.99; p = 0.036). CONCLUSIONS: In this multicenter pediatric cohort, VS-SRS for ruptured, large AVMs provides a reasonable chance of long-term obliteration, but generally acceptable risks of post-SRS hemorrhage and RICs exist. VS-SRS should be considered as an option for pediatric patients with large, ruptured AVMs.

Brain metastases (BM) pose a significant challenge due to limited treatment options and poor prognosis. Combining PD-1/PD-L1 inhibitors with stereotactic radiosurgery (SRS) may enhance tumor control through synergistic effects. This study assessed the efficacy and safety of this combined approach for BM. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Embase, Web of Science, and Scopus up to 27 June 2024. Studies involving PD-1/PD-L1 inhibitors and SRS for BM were included. Outcomes included local control (LC), progression-free survival (PFS), overall survival (OS), radiological response, and adverse events. Data were analyzed using STATA V.17 with a random-effects model. Sixteen studies with 1529 patients were included. Pooled 6- and 12-month LC rates were 85% (95% CI 75–95%) and 84% (95% CI 75–93%), respectively. One- and three-year PFS rates were both 51% (95% CI 39–64% and 41–62%), while one- and two-year OS rates were 67% (95% CI 57–78%) and 30% (95% CI 16–45%). Overall response rate was 61% (95% CI 44–78%), with a complete response rate of 39% (95% CI 25–53%). Adverse radiation effects occurred in 31% (95% CI 3–58%), with radiation necrosis in 12% (95% CI 2–23%). Subgroup analyses showed no significant impact of drug type, primary tumor site, prior treatment, or SRS fractionation on outcomes. Combining PD-1/PD-L1 inhibitors with SRS for BM yields robust local control and improved one-year survival compared to historical data, with manageable toxicities. However, variability in outcomes and lack of comparator groups highlight the need for standardized protocols and prospective trials to optimize treatment strategies and identify predictive biomarkers.

The increasing prevalence of brain metastases in cancer patients due to longer life expectancy and improvements in neuroimaging highlights the need for effective local treatments. Despite advancements in systemic targeted therapies, their low blood–brain barrier (BBB) penetrance limits their intracranial efficacy. Stereotactic radiosurgery (SRS) has largely supplanted whole-brain radiation therapy (WBRT) for patients with up to 10 brain lesions due to superior neurocognitive outcomes and high local control. While single-fraction SRS provides low radiation toxicity with smaller lesions, high-volume metastases necessitate doses above tolerance limits to achieve comparable local control. As tumor volume increases, the number of tumor cells also increases, requiring higher doses of radiation than the maximum tolerated doses reported in the RTOG 9005 study to achieve tumor control. Hypo-fractionated SRS (HySRS) permits the delivery of high radiation doses over 2–5 fractions, thus mitigating the risk of radiation toxicity while maintaining high local control. This review presents the available evidence and ongoing clinical trials on HySRS for the management of brain metastases.

Resection is often the primary treatment for large brain tumors but is less practical for multiple brain metastases (BM). Current guidelines recommend stereotactic radiosurgery (SRS) for untreated BMs or following the surgical removal of a solitary BM to reduce the risk of local tumor recurrence. Preoperative SRS (pre-SRS) shows promise with fewer complications and more precise targeting, but it lacks tissue diagnosis and may hinder wound healing. This study aims to compare the safety and efficacy of pre-SRS and postoperative SRS (post-SRS) for BM treatment. A comprehensive literature search was conducted in PubMed, Embase, Scopus, and Cochrane Library. Studies were selected based on PICO criteria, including patients with metastatic intracranial lesions undergoing preoperative or postoperative radiosurgery. Data related to outcomes and complications were extracted. Meta-analysis was performed, employing the fixed effect model due to study design similarities and limited patient numbers. Four studies encompassing 616 BM patients (221 preoperative, 405 postoperative) were included. Patient characteristics, including age, gender, cancer source, and lesion location, were similar between groups. Radiosurgery modalities included LINAC and Gamma Knife, with hypofractionated treatments more common postoperatively. Outcomes showed comparable overall survival (p = 0.07), local failure (p = 0.26), and distant failure rates (p = 0.84) between groups. The preoperative group had lower risks of radiation necrosis (p = 0.02) and leptomeningeal disease (p = 0.03) in 1-year follow-up, with significantly better composite outcomes (p = 0.04). No significant difference in wound issues was observed (p = 0.98). This review reveals pre- and post-SRS for BM have similar outcomes for LF, DF, and OS. Pre-SRS potentially lowers RN and LMD risks, with better tumor targeting and less radiation to healthy tissue, while post-SRS targets residual disease but with higher complication risks. Future research should optimize SRS protocols.

Central nervous system Tumors, including metastasis, are a considerable source of morbidity and mortality. Currently, treatment options such as surgery, radiotherapy, and chemotherapy have been introduced to prevent the progression of the disease, but still, these patients do not have a good prognosis. Stereotactic radiosurgery (SRS) reduces the damage to the surroundings by focusing the radiation on the tumor tissue. In this paper, we aim to investigate the outcomes of SRS on patients with gastrointestinal-originated brain metastases. A systematic review and meta-analysis used the PRISMA guideline from inception until 27th March 2024, utilizing the relevant key terms. Records were screened and included based on pre-defined inclusion and exclusion criteria. Demanding data was extracted and analyzed using STATA v. 17. This meta-analysis of 29 studies examining SRS for brain metastases from gastrointestinal cancers revealed several significant findings. The pooled distant intracranial disease rate was 33% (95% CI: 0.21–0.45). Local tumor control rates were high, with an overall pooled rate of 88% (95% CI: 0.83–0.92). Survival outcomes showed a 6-month overall survival (OS) rate of 47% (95% CI: 0.42–0.52), decreasing to 32% at one year and 11% at two years. The 5-year OS rate was 2% (95% CI: 0.01–0.03). Subgroup analyses revealed variations in outcomes based on primary tumor site, with gastric cancer patients showing better short-term survival (73% at six months) compared to hepatic primaries (31% at six months). The 6-month progression-free survival (PFS) rate was 67% (95% CI: 0.12–1.22). Tumor control outcomes showed complete regression in 11% of cases, partial regression in 44%, stable disease in 30%, and progression in 20%. The overall mortality rate was 84% (95% CI: 0.75–0.93). This meta-analysis supports the efficacy of SRS in managing brain metastases from gastrointestinal cancers. SRS offers effective local control and may improve quality of life despite poor long-term outcomes. The high rates of distant intracranial progression underscore the need for comprehensive management strategies addressing both local and systemic disease. Future research should optimize patient selection, combine SRS with novel systemic therapies, and identify predictive biomarkers to improve outcomes in this challenging patient population.

Introduction: The radio-surgical literature increasingly uses biological effective dose (BED) as a replacement for absorbed dose to analyze outcome of stereotactic radiosurgery (SRS). There are as yet no studies which specifically investigate the association of BED to local tumor control in para-sellar meningioma. Methods: we did a retrospective analysis of patients underwent stereotactic radiosurgery (SRS) for para-sellar meningioma during the period of 1995–2022. Demographic, clinical, SRS parameters, and outcome data were collected. The target margin BED with and without a model for sub-lethal repair was calculated, as well as a ratio of BED at the target margin to the absorbed dose at the target margin. Factors related to local control were further analyzed. Results: The study was comprised of 91 patients, 20 (22.0%) and 71 (78.0%) of whom were male and female, respectively. The median age was 55.0 (interquartile range Q1, Q3:47.5,65.5years). 34 (37%) patients had a resection of their meningioma prior to SRS. The median interval from SRS to last clinical follow up or progression was 89 months. 13 (14.3%) patients were found to have progression. 3-, 5- and 10-years local tumor control were 98%, 92% and 77%, respectively. In cox univariate analysis, the following factors were significant: Number of prior surgical resections (Hazard Ratio [HR] = 1.82, 95% CI = 1.08–3.05, p = 0.024), BED (HR = 0.96, 95% CI = 0.92-1.00, p = 0.03), and BED/margin (HR = 0.44, 95% CI = 0.21–0.92, p = 0.028). A BED threshold above 68 Gy was associated significantly with tumor control (P = 0.04). Conclusion: BED and BED /margin absorbed dose ratio can be predictors of local control after SRS in parasellar meningioma. Optimizing the BED above 68Gy_2.47 may afford better long-term tumor control.

Stereotactic Radiosurgery (SRS) delivers a high dose of radiation to a specific brain area while limiting radiation to nearby healthy tissue. While most SRS has traditionally been performed with a stereotactic frame-based approach, this study aims to investigate the safety and efficacy of frameless radiosurgery in patients with brain metastases. Our study followed the recommended guidelines summarized in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. The electronic databases of PubMed/Medline, Scopus, Embase, and Web of Science (WOS) were searched from inception to 10 October 2023. The pooled rate of outcomes was calculated using random effect model and Restricted maximum–likelihood (REML) method. All statistical analysis was performed by STATA V.17. A total of 499 studies were recruited from the electronic databases. After removing duplicates (n = 117), 382 studies were used for title/abstract, and 329 were removed from the study selection process. A total of 53 articles were used for full-text assessment, and 35 studies were included for data extraction. Our analysis revealed a significant increase across all pooled survival rates and local control rates by initiating the radiosurgery for patients, estimating the pooled 6-month OSR of 75% (95% CI: 68-81%), 1-year overall survival rate (OSR) of 60% (95% CI: 51-69%), 18-month OSR of 48% (95% CI: 10-85%), 2-year OSR of 39% (95% CI: 19-58%), 1-year progression-free survival rate (PFSR) of 68% (95% CI: 39-98%), 2-year PFSR of 75% (95% CI: 58-91%), 6-month local control rate (LCR) of 93% (95% CI: 90-96%), and 12-month LCR of 86% (95% CI: 82-90%). Our meta-analysis findings confirm the efficacy of frameless radiosurgery in treating brain metastases. Using data from several trials, we were able to demonstrate stereotactic radiosurgery’s effectiveness as a therapy option for brain metastasis patients, demonstrating local control and reasonable overall survival.