Objective Meningiomas are typically benign extra-axial tumors treated with surgery or radiosurgery, but extracranial extension from skull base lesions is rare and poorly defined. This study reports outcomes of stereotactic radiosurgery for skull base meningiomas with extracranial extension, focusing on tumor control, clinical outcomes, and patterns of failure. Methods We conducted a retrospective single-institution review of patients treated with gamma knife radiosurgery (GKRS) for skull base meningiomas with extracranial extension. Clinical, radiographic, and treatment variables-including extension patterns, cranial nerve involvement, and dosimetry-were analyzed. Tumor control and symptom outcomes were assessed using univariate and multivariable analyses. Kaplan-Meier and Cox regression analyses compared primary versus salvage GKRS. A management algorithm was developed based on a literature review. Results Thirty-four patients were included: 13 treated with primary GKRS and 21 with salvage GKRS after prior treatment. The most common extracranial extension sites were the pterygopalatine fossa and orbit, and visual changes were the most frequent symptom. Symptomatic deterioration was associated with larger tumor volume, higher maximum dose, foraminal extension, female sex, and prior treatment. Hyperostosis, prior treatment, and higher histologic grade predicted retreatment. At the last follow-up, over 90% of patients achieved radiographic tumor control and symptom stability. Primary GKRS was associated with fewer complications and better tumor control than salvage treatment. Conclusion GKRS provides durable tumor control and favorable clinical outcomes for selected skull base meningiomas with extracranial extension. When feasible, primary radiosurgery may be preferable to salvage therapy. Predominant intracranial marginal progression supports targeted surveillance and a multidisciplinary, risk-adapted management strategy.

PURPOSE:To define tumor control, cranial nerve toxicity, and progression patterns after Gamma Knife radiosurgery (GKRS) for glomus jugulare tumors using a systematic review/meta-analysis and an institutional cohort. METHODS AND MATERIALS:A PRISMA-compliant systematic review identified studies reporting outcomes of GKRS for glomus jugulare tumors. Random-effects meta-analyses of proportions were performed for radiographic tumor control, tumor shrinkage, new or worsened cranial nerve deficits, and hearing worsening using endpoint-specific denominators. Heterogeneity was quantified with I2. Sensitivity analyses excluding the institutional cohort were performed. The institutional jugulare subset contributed to pooled estimates, whereas the full institutional jugulotympanic cohort was analyzed descriptively for progression-free survival, failure pattern, and salvage. RESULTS:Twenty-six cohorts were included. Across 590 tumors, pooled radiographic tumor control after GKRS was 0.91 (95% CI, 0.88-0.94; I2 = 0.0%). Across 518 tumors, pooled radiographic shrinkage was 0.51 (95% CI, 0.43-0.59; I2 = 58.4%). Across 463 patients, pooled new or worsened cranial nerve deficit was 0.11 (95% CI, 0.08-0.14; I2 = 0.0%). Hearing worsening was reported in a limited subset of 114 evaluable patients, with a pooled proportion of 0.16 (95% CI, 0.10-0.24; I2 = 0.0%). Sensitivity analyses excluding the institutional cohort did not materially change pooled estimates. In the institutional cohort (n = 27), radiographic control at last follow-up was 85.2%. Kaplan-Meier PFS was 100.0% at 24 months and 77.8% at 60 months. Among 4 progression events, failures were predominantly marginal or out-of-field, with no clearly in-field failures; salvage GKRS was feasible in most recurrent cases. CONCLUSIONS:GKRS provides durable tumor control with a favorable cranial nerve toxicity profile in glomus jugulare tumors. Treatment response is characterized more by stability than regression. In the institutional cohort, progression events were marginal or out-of-field rather than clearly in-field, supporting GKRS as an effective local-control strategy within the treated target while highlighting the importance of careful target delineation and long-term surveillance.

Prostate-specific membrane antigen-targeted molecular imaging with positron emission tomography (PSMA/PET) is being increasingly incorporated into the clinical care of patients with suspected metastatic or biochemically recurrent prostate cancer, allowing for metastasis-directed therapies. Brain metastases from prostate cancer are rare and portend a poor prognosis. We present a case series of patients with intracranial prostatic brain metastasis detected on PSMA/PET and discuss its application for cranial radiosurgery. A prospectively collected database was queried for prostate cancer patients who presented with intracranial metastasis based on PSMA/PET from January 2020 to December 2024 in a single institution. The clinical course, imaging findings, and treatments were reviewed. Among the prostate cancer patients treated at the Gamma Knife radiosurgery (GKRS) department, ten had undergone PSMA/PET after biochemical recurrence, yielding a new diagnosis of single or multiple intracranial metastases, with brain, calvarial, or dural lesions (mean standardized uptake value of 12.5). Their median age was 64 years. Two patients presented with headaches and two suffered from neurologic changes. The prescribed dose ranged from 12 to 21 Gy in one to three fractions. Brain MRI was acquired for all patients and showed that lesions up to 0.061 cc presented a false negative result. Patients were monitored for a median of 6.5 months with brain MRIs, only two with PSMA/PET. Four patients underwent GKRS in addition to treatment with 177Lu-PSMA, with no evidence of acute radiation toxicity. Brain metastases from prostate cancer are rare and can be effectively treated with GKRS. PSMA/PET combined with MRI allows for improved detection of new or recurrent brain metastases and treatment response evaluation.

BACKGROUND:Meningiomas involving the motor cortex pose a therapeutic challenge due to the risk of treatment-related neurological morbidity. This study evaluates the clinical, imaging, and survival outcomes of patients with motor cortex meningiomas treated with Gamma Knife radiosurgery (GKRS). METHODS:Clinical, imaging, and survival data were retrospectively obtained from an institutional radiosurgery registry. Serial magnetic resonance imaging was reviewed to assess treatment volumes and longitudinal tumor response. Progression-free survival and tumor control were analyzed using standard survival methods. RESULTS:Between 2008 and 2024, 47 patients with 58 meningiomas involving the motor cortex underwent either upfront definitive GKRS or adjuvant GKRS following surgical resection. Prescribed margin doses ranged from 12 to 17 Gy, normalized to the 50-80% isodose line. Patients with WHO Grade 1 meningiomas demonstrated significantly longer progression-free survival compared with those harboring Grade 2-3 tumors (p = 0.0014). Lesions with treatment volumes <5 cc were associated with superior progression-free survival relative to larger tumors (p = 0.0008). On univariate analysis, meningioma grade (p = 0.0014) and treatment volume (p = 0.0015) were significantly associated with tumor control. While GKRS Dmax showed only a marginal association with tumor control across the full cohort (p = 0.0882), a significant positive correlation between Dmax and percentage tumor volume reduction was observed in Grade 1 meningiomas (r = 0.53, p = 0.0287). CONCLUSIONS:GKRS provides effective tumor control for meningiomas involving the motor cortex, particularly in patients with small-volume, WHO Grade 1 lesions. These findings support GKRS as a safe and efficacious treatment option in this eloquent location when careful patient selection and dose planning are applied.

INTRODUCTION:Salvage Gamma Knife radiosurgery (sGKRS) is increasingly used to treat trigeminal neuralgia (TN) after failed microvascular decompression (MVD) or percutaneous procedures, but predictors of durable pain control are not well defined. We evaluated the outcomes and predictors of pain relief following sGKRS in a single-institution cohort. METHODS:We screened all patients treated with GKRS for TN at our institution (1998-2025) and identified 72 patients who had received sGKRS for pain relapse after prior non-radiation interventions. Demographics, treatment plans, radiologic metrics, and pain scores were collated. Response was defined both dichotomously and continuously (change in Roswell Park pain scale/BNI). Multivariate logistic and linear regression were run to identify independent predictors of dichotomous and continuous outcomes. RESULTS:Mean age was 63.3 years; 70.8% were female. Most patients received 80 Gy to the 100% isodose (median ANEZ dose: 11 Gy). sGKRS achieved a 78.1% response rate overall, rising to 81.2% in patients with prior MVD. Strikingly, a lower biologically effective dose (BED) to the trigeminal nerve - specifically BED below 2,000 Gy - was the single independent predictor of response, on multivariate analysis, both overall (p = 0.015) and within the prior-MVD subgroup (p = 0.026). On univariate analysis, higher pretreatment pain severity, V1 involvement, and higher body weight each correlated with better outcomes, though no factor independently predicted the degree of pain improvement on multivariate analysis. CONCLUSIONS:sGKRS delivers meaningful pain relief in approximately 78% of patients who have failed other interventions - including those with prior MVD. Counterintuitively, a lower BED to the trigeminal nerve, rather than a higher dose, independently drives response in the salvage setting, suggesting that a neuromodulatory rather than ablative mechanism could be in play. Keeping the BED below 2,000 Gy is the single most impactful modifiable target for treatment planning, and should reframe how salvage radiosurgery prescriptions are designed.

BACKGROUND:For small- to medium-sized vestibular schwannomas, especially in patients with preserved hearing and no mass-effect symptoms, Gamma Knife radiosurgery (GKRS) is a preferred initial treatment. It provides effective tumor control and long-term hearing preservation. In the event of a tumor progression, reirradiation remains an option. A rare occurrence is the development of a second schwannoma along the same nerve. In such cases, repeat GKRS can be challenging, as it requires balancing local control with minimizing integral radiation dose and potential toxicity from reirradiation. The authors highlight the feasibility of repeat GKRS and the dosimetric considerations involved in radiating a second schwannoma along the same nerve. OBSERVATIONS:A 35-year-old woman with a history of headaches and a right-sided vestibular schwannoma underwent GKRS as treatment for the tumor. After being under surveillance from 2013 to 2025, the patient's vestibular schwannoma remained stable. After experiencing a worsening right-sided tinnitus, an updated MRI study revealed a new intracanalicular nodular formation along the nerve, which was treated with GKRS. LESSONS:This case demonstrates the safety and efficacy of GKRS as a retreatment option in the rare occurrence of a second vestibular schwannoma developing along the same cranial nerve. https://thejns.org/doi/10.3171/CASE25667.

Glioblastoma (GBM) is an aggressive, malignant central nervous system tumor with a poor prognosis, often recurring despite standard care using a multimodal approach. This study investigates the recurrence patterns and survival outcomes in patients with GBM who underwent Gamma Knife radiosurgery (GKRS) for tumor recurrence following initial treatment with external beam radiation therapy (EBRT). A single-institution retrospective study was conducted on 41 patients with newly-diagnosed, Isocitrate Dehydrogenase (IDH)-wildtype GBM between 2020 and 2024. All patients received standard EBRT (60 Gy in 30 fractions or 5940 cGy in 33 fractions) followed by salvage GKRS for recurrence. Recurrence patterns were defined as in-field (>80% of recurrence volume), marginal (20-80% of recurrence volume), or distant (<20% of recurrence volume) based on the recurrence volume found within the 95% isodose volume from initial EBRT. Clinical, imaging, and survival data were obtained from our patient registry. Serial imaging was analyzed to obtain tumor volume data. Of the 41 patients, recurrences were in-field in 35 patients (85.4%), marginal in 1 patient (2.4%), and distant in 5 patients (12.2%). Maximum ( P = 0.01) and mean ( P = 0.002) EBRT dosing was found to be significantly associated with in-field versus distant recurrence patterns. However, the recurrence pattern was not found to be significantly associated with overall survival (OS) ( P = 0.53) or recurrence-free survival ( P = 0.45). Univariate analysis identified a significant association between initial EBRT dose and OS ( P = 0.0087). GKRS is an effective salvage therapy for recurrent GBM, with survival outcomes independent of recurrence pattern. These findings support the use of limited radiation margins to potentially reduce radiation exposure and treatment toxicity while maintaining tumor control, reinforcing GKRS as a valuable treatment modality in recurrent GBM management.

Postoperative Gamma Knife Radiosurgery (GKRS) to resection cavities is standard for intracranial metastases, but the dynamics of these cavities after treatment and their relationship to local control remain incompletely defined. We retrospectively reviewed 98 patients with 98 resection cavities treated with single- or hypofractionated Gamma Knife radiosurgery (GKRS) between 2011 and 2025. Cavity volumes were segmented from serial contrast-enhanced MRI and compared with GKRS planning volumes. Longitudinal changes in log-transformed volumes were modeled using linear mixed-effects regression. Local recurrence–free survival (LRFS) and overall survival (OS) were estimated using Kaplan–Meier analysis, and associations with outcomes were tested using Cox proportional hazards models. Median imaging follow-up was 9.1 months (IQR 4.9–16.5), and cavities showed significant volume reduction over time (β = −0.031 ln[cc]/month, p < 0.001). Modeling indicated a nonlinear pattern, with greater reduction early and relative stabilization thereafter. At 12 and 24 months, actuarial local control was 74.5

Glioblastoma (GBM) has proved difficult to treat, and there is dire need for more effective therapies. In a single arm phase IIa trial (NCT02455557), treatment of newly diagnosed GBM patients with the peptide vaccine SurVaxM resulted in promising median progression-free and overall survival. To investigate molecular features that associate with GBM responsiveness to SurVaxM, retrospective whole exome and RNA sequencing was performed on patient tumors (n = 34) collected prior to standard of care treatment plus SurVaxM. Differential gene expression and mutational profiles were characterized between patients with short-term (OS < 18 months) or long-term (OS ≥ 18 months) overall survival. Greater expression of interferon, complement, and humoral immunity signatures were associated with long-term survival. Deconvolution of transcriptomes identified enrichment of intratumoral memory B cell populations in long-term survivors that were validated by CD20 staining in matched samples. A five-gene expression signature and a B cell specific signature predicted survival within the SurVaxM-treated cohort, however, these signatures were not associated with improved outcomes in a similarly treated population obtained from The Cancer Genome Atlas (TCGA) that did not receive immunotherapeutic intervention. Although prospective validation is ongoing, the findings in this discovery cohort specify molecular features of GBM associated with better overall survival and potential responsiveness to immunotherapy with SurVaxM.

BACKGROUND:The adipofascial anterolateral thigh (AF-ALT) free flap represents a versatile technique in head and neck reconstructions, with its applications increasingly broadening. The objective was to detail the novel utilization of the AF-ALT flap in orbital and skull base reconstruction, along with salvage laryngectomy onlay in our case series. METHOD:We conducted a retrospective analysis at Roswell Park Comprehensive Cancer Center, spanning from July 2019 to June 2023, focusing on patient demographics and reconstructive parameters data. RESULTS:The AF-ALT flap was successfully employed in eight patients (average age 59, body mass index [BMI] 32.0) to repair various defects. Noteworthy outcomes were observed in skull base reconstructions, with no flap failures or major complications over an average 12-month follow-up. Donor sites typically healed well with minimal interventions. CONCLUSION:Our series is the first to report the AF-ALT flap's efficacy in anterior skull base and orbital reconstructions, demonstrating an additional innovation in complex head and neck surgeries.

Introduction: Adult medulloblastoma is a rare entity with a predilection for the development of radiation-induced malignant glioma (RIMG). Management of RIMG in the setting of prior craniospinal irradiation is a challenging scenario. Case: We report a case of a 51-year-old male with short-interval development of multicentric malignant glioma with MET mutation who previously underwent craniospinal radiation for adult medulloblastoma. Due to radiographic findings, linear accelerator (LINAC)-based fractionated stereotactic/IMRT was delivered to the right temporal lesion alongside systemic therapy. The patient had interval development of an IDH wildtype, high-grade left cerebellar glioma and underwent surgical resection and subsequent gamma knife stereotactic radiosurgery (GKRS) to the cavity. Discussion: GKRS targeting the surgical cavity was delivered with a fractionated regimen of 27 Gy in 3 fractions to the margin. One year after completion of GKRS, the patient had not developed any symptomatic radiation necrosis or neuroimaging changes reflective of treatment toxicity. In this patient, GKRS to minimise the integral dose exposure of normal tissues surrounding the target volume proved to be particularly advantageous in the setting of prior craniospinal irradiation. Recommendation: RIMG poses significant challenges for radiation oncologists, particularly in the reirradiation setting. Decision-making involving multidisciplinary input balanced the necessity of dose escalation achieved by GKRS, while minimising the cumulative dose in the setting of prior craniospinal irradiation.

BACKGROUND:Implementing the thermoplastic mask as a treatment option in Gamma Knife radiosurgery (GKRS) has madethe discussion of the relative benefits of frame- or mask-based fixation for treatment a frequent occurence. Based on a case review, the authors discuss factors that need to be understood and considered by the treating team. OBSERVATIONS:The authors describe the case of an 81-year-old patient with pleomorphic dermal sarcoma that extended to and infiltrated the dura mater, who underwent extensive resection requiring a skin flap. Adjuvant GKRS was recommended. The fixation type was limited by the extent of the flap that would cause a suboptimal frame fixation (less than 3 points) and its compression by the lateral aspect of the mask. Creating a tailored mask with its lateral table-fixation cut out was required. To guarantee appropriate immobilization, an understanding of the primary stability points of the mask was needed, which was achieved by monitoring the intrafraction motion. The patient tolerated the treatment delivery well, with minimal movement and proper positioning maintenance. LESSONS:The option of a rigid frame or a mask allows for personalized treatment for each patient based on their unique needs. Understanding the advantages and limitations of each modality allowed a safe and precise treatment for the described case. https://thejns.org/doi/10.3171/CASE24852.

Introduction: Gamma Knife radiosurgery (GKRS) is an established treatment for trigeminal neuralgia; however, predictors of pain relief following treatment remain unclear. We aimed to identify the factors associated with pain relief after the index GKRS session for trigeminal neuralgia. Methods: We retrospectively analyzed a series of 204 patients with trigeminal neuralgia treated with GKRS between 1998 and 2023 (mean age 65.2 years, 68.5% female). Patient variables (pretreatment Roswell Park and Barrow Neurological Institute [BNI] pain scores, symptom duration, prior therapies, multiple sclerosis (MS) status), MRI metrics (neurovascular contact and trigeminal nerve dimensions), and radiosurgery parameters (isocenter location and radiation dose, including biologically effective dose [BED]) were assessed. Responders were defined as BNI

BACKGROUND:Hypofractionated stereotactic radiosurgery is an effective technique to treat larger brain metastases and post-surgical cavities. Adaptive Gamma Knife radiosurgery (aGKRS), involving repeat magnetic resonance imaging (MRI) and replanning based on modified lesion contours, has emerged as a solution to account for inter-fraction tumor dynamics. OBJECTIVE:To evaluate the impact of adaptive planning on treatment metrics, radiation dose to structures at risk (SARs), and clinical and radiologic outcomes in patients with brain metastases. METHODS:Over an 8-year period (2016-2023), 31 patients were treated with aGKRS to 48 brain metastases. Lesions were re-contoured and adaptive plans created using updated MRIs acquired prior to the second radiation fraction. Treatment metrics, including target coverage, Paddick Conformity Index (PCI), Gradient Index (GI), and doses to SARs, were analyzed. Clinical outcomes and radiologic response were assessed. RESULTS:Lesion volumes changed significantly between radiation fractions (mean change- 28.25%). aGKRS resulted in significant improvements in target coverage, from 91.9% on non-adaptive plans to 97.02% following adaptive replanning. The PCI improved by 35.3% across plans in this series. Adaptive plans also reduced the dose to SARs by an average of 4.7%. Radiologic response was excellent- median volume reduction of treated lesions was 98.9%. Clinically, 72% of patients either remained stable or improved in neurologic status; 32% improved in performance status by at least one grade. CONCLUSION:Lesion dynamics during hypofractionated treatments pose a significant challenge to the delivery of conformal and safe SRS treatments. aGKRS significantly improves dosimetric parameters, reduces radiation to SARs, and enhances clinical and radiologic outcomes for brain metastases.

BACKGROUND AND OBJECTIVES: To study the impact of early initiation of radiation therapy (RT) in elderly patients with newly diagnosed glioblastoma. METHODS: A total of 56 elderly patients (aged 65 and older) diagnosed with isocitrate dehydrogenase (IDH)-wildtype glioblastoma were analyzed from a prospective registry from 2020 to 2024. Survival analysis was conducted to evaluate the impact of timing of RT initiation after surgical resection on survival outcomes. A specific cutoff point for RT initiation was evaluated using the log-rank test, with P-values adjustment for multiple comparisons using the false discovery rate approach. Kaplan-Meier curves were used to illustrate survival distributions. Associations of various risk factors with survival were initially examined through univariate Cox regression models, followed by multivariate analysis to assess the combined effects of these factors. The results were reported as hazard ratios with 95% CIs. RESULTS: Elderly patients with glioblastoma who underwent initiation of RT < 20 days from date of surgery demonstrated improved overall survival (OS) (P = .0460) and progression-free survival (PFS) (P = .0075) in our cohort. Multivariate analysis demonstrated that adjuvant temozolomide significantly affected both OS (P = .0038) and PFS (P = .0133). Conventionally fractionated RT consisting of 60 Gy in 30 fractions demonstrated significantly improved PFS (P = .0164) in patients who underwent early initiation of RT (<20 days). By contrast, hypofractionated RT delivering 40 Gy in 15 fractions did not show significantly improved PFS (P = .0509) in patients who underwent early initiation of RT (<20 days). CONCLUSION: Early initiation of RT in elderly patients with newly diagnosed glioblastoma improves both OS and progression-free survival. Timing of RT is particularly of significance in this patient population who may not be optimal candidates for systemic chemotherapy.

Purpose: The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression (TRP) is a major decision-making point in the follow-up of patients with brain tumors. The advent of immunotherapy, targeted therapy and radiosurgery has made this distinction difficult to achieve in several clinical situations. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas.Methods This is a series of 7 patients, treated between 2018 and 2023, for various brain pathologies including brain metastasis, atypical meningioma, and high-grade glioma. MRI with contrast clearance analysis was used to inform clinical decisions and patients underwent surgical resection as indicated. The histopathology findings were compared with the CCA findings in all cases.Results All seven patients had been treated with gamma knife radiosurgery and were followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from radiation necrosis arose, and subsequently underwent surgery as indicated. Concordance of CCA findings with histological findings was found in all cases (100%).Conclusions Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology across a wide spectrum of brain tumor pathologies. CCA can provide a quick diagnosis and have a direct impact on patients’ treatment and outcomes.

a pdf file for supplemental methods and data