Efficacy and indications of gamma knife radiosurgery for recurrent low-and high-grade glioma.

PURPOSE: To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma. METHODS: This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on. RESULTS: The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS. CONCLUSION: GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects.

Long-term outcomes of Gamma Knife radiosurgery in treating glossopharyngeal neuralgia.

Glossopharyngeal neuralgia (GPN) is an unusual disorder causing severe, brief pain episodes in the areas supplied by the glossopharyngeal nerve. Initial treatment involves medications like carbamazepine, but if these are ineffective or cause side effects, interventional pain management techniques or surgery may be considered. Gamma Knife radiosurgery is becoming popular in managing GPN due to its lower risk of complications than surgical interventions like microvascular decompression or rhizotomy. In this retrospective case series, we examined the outcomes of Gamma Knife radiosurgery in eight patients with GPN. The decision to utilize Gamma Knife radiosurgery was made following specific criteria, including failed surgical interventions, patient preference against surgery, or contraindications to surgical procedures. Patients were administered radiation doses within the range of 80 to 90 Gy, targeting either the cisternal glossopharyngeal nerve or glossopharyngeal meatus of the jugular foramen. Evaluations were conducted before the Gamma Knife radiosurgery; at 3, 6, and 12 months after Gamma Knife radiosurgery; and annually thereafter. Pain severity was assessed using the modified Barrow Neurological Institute scale grades, with patients achieving grade I-IIIa considered to have a good treatment outcome and grade IV-V to have a poor treatment outcome. Pain control and absence of radiosurgery-related complications were primary endpoints. The median age of the patients was 46.5 years, varying from 8 to 72 years. The median duration of pain was 32 months (range, 12-120 months). All patients, except one, were on polydrug therapy. All cases exhibited preoperative grade V pain. The median follow-up duration after Gamma Knife radiosurgery was 54.5 months, varying from 14 to 90 months. The overall clinical assessments revealed a gradual neurological improvement, particularly within the first 8.5 weeks (range, 1-12 weeks). The immediate outcomes at 3 months revealed that all patients (8/8, 100%) experienced pain relief, with 25% (2/8) achieving a medication-free status (Grade I). Three patients (37%) experienced a recurrence during the follow-up and were managed with repeat Gamma Knife radiosurgery (n = 2) and radiofrequency rhizotomy (n = 1). At the last follow-up, 88% (7/8) of patients had pain relief (Grades I-IIIa), with three (37%) achieving a medication-free status (Grade I). No adverse events or neurological complications occurred. The patient who underwent radiofrequency rhizotomy continued to experience inadequately controlled pain despite medication (Grade IV). Gamma Knife radiosurgery is a non-invasive, efficacious treatment option for idiopathic GPN, offering short- and long-term relief without permanent complications.

Investigation of the effects of Gamma Knife radiosurgery on optic pathways using diffusion tensor MRI within the first year after treatment.

PURPOSE: To investigate the radiation-induced effects of Gamma Knife radiosurgery (GKRS) for sellar-parasellar tumors on optic pathways using DTI parameters within the first year after treatment. METHODS: Twenty-five patients with sellar-parasellar tumors underwent MRI before and 3 months after GKRS, including T1WI, DTI, T2WI. Moreover, 21 patients underwent follow-up DTI 6-8 months after radiosurgery. ROIs were set on optic nerves, optic radiations, and control localizations; DTI parameters for each were calculated. Pre- and post-radiosurgery differences in DTI values were statistically compared and assessed with respect to tumor size changes. RESULTS: Following GKRS, DTI parameters, notably ADC, FA, and RD, showed statistically significant changes in optic nerves and anterior optic radiations. DTI changes were more significant in the group of cases with tumor shrinkage. In this group, DTI of the anterior optic radiations further deteriorated 3 months post-GKRS, whereas acute changes in DTI parameters of the optic nerves resolved within 6-8 months. DTI of central and posterior optic radiations did not differ significantly following radiosurgery; 6-8 months after radiosurgery, visual function was stable in 14 (56%) patients and improved in 11 (44%), showing no correlation with tumor size changes or DTI parameters. CONCLUSION: White Matter (WM) injury in the optic pathways can be induced by Gamma Knife radiosurgery targeted to sellar and parasellar tumors. Following GKRS, microstructural abnormalities occurred in the optic radiations as well as the optic nerves within the first post-treatment year. Our findings could support modifications to radiosurgical treatment strategies to minimize the risk of permanent WM injury.

Efficacy and Challenges: Minimally Invasive Procedures for Trigeminal Neuralgia Treatment in Multiple Sclerosis - A Systematic Review and Meta-Analysis.

INTRODUCTION: Trigeminal neuralgia (TGN) poses a therapeutic challenge, particularly within the context of multiple sclerosis (MS). This study aimed to conduct a comprehensive meta-analysis and systematic review of four less-invasive treatment modalities for TGN in MS patients, namely, gamma knife radiosurgery (GKRS), glycerol rhizotomy (GR), balloon compression (BC), and radiofrequency ablation (RFA). METHODS: Single-armed meta-analyses were employed to assess the overall efficacy of each treatment, while double-armed analyses compared the efficacy between different treatment options in double-armed studies. Outcome evaluations included acute pain relief (within 1 month post-procedure), recurrence rates throughout 18 months of follow-up, and reported complication rates. RESULTS: The meta-analysis revealed diverse outcomes for each intervention. GKRS demonstrated favorable outcomes, achieving a 77% success rate in alleviating pain among a pooled cohort of 863 patients, reinforcing its status as a viable therapeutic option. Additionally, GR, BC, and RFA exhibited efficacy, with success rates of 77%, 71%, and 80%, respectively, based on outcomes observed in 611, 385, and 203 patients. Double-armed analyses highlighted distinctions between the treatments, providing nuanced insights for clinical decision-making. CONCLUSION: This meta-analysis provides a comprehensive overview of less-invasive treatments for TGN in MS patients. GKRS emerges as a leading option with comparable efficacy and fewer complications. However, the study underscores the nuanced efficacy and considerations associated with GR, BC, and RFA. The findings offer valuable insights for clinicians navigating treatment choices in this challenging patient population, considering acute pain relief, recurrence rates, and complication profiles.

Factors Influencing Long-Term Outcomes of Single-Session Gamma Knife Radiosurgery in Large-Volume Meningiomas >10 cc.

INTRODUCTION: Meningiomas are the most common primary intracranial tumour. Gamma knife radiosurgery (GKRS) is a frequently employed non-invasive method of treatment, with good remission rates and low morbidity in literature. However, the role of GKRS in the management of "large" meningiomas is unclear, with reported outcomes that vary by centre. We aimed to assess the factors that influence long-term outcomes following GKRS in meningiomas >10 cc in volume. METHODS: A retrospectively analysed all patients with meningiomas exceeding 10 cc in volume who underwent GKRS between January 2006 and December 2021 at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. Demographic, clinical, radiological, and follow-up data were acquired, and factors associated with progression following GKRS were assessed. RESULTS: The cohort comprised 76 patients 29 males (38.2%) and 47 females (61.8%) with a mean age of 46.3 ± 11.02 years. Thirty-nine patients had been previously operated (51.3%). Meningiomas were most frequently located in the parasagittal region (26 tumours, 34.2%) and sphenopetroclival region (23 tumours, 30.3%), with mean lesion volume of 12.55 ± 5.22 cc, ranging 10.3 cc-25 cc. The mean dose administered to the tumour margin was 12.5 Gy ± 1.2 Gy (range 6-15 Gy). The median duration of clinical follow-up was 48 months, over which period radiological progression occurred in 14 cases (20%), with unchanged tumour volume in 20 cases (28.6%) and reduction in size of the tumour in 36 cases (51.4%). Progression-free survival after GKRS was 72% at 5 years, was significantly poorer among meningiomas with tumour volume >14 cc (log-rank test p = 0.045), tumours presenting with limb motor deficits (log-rank test p = 0.012), and tumours that underwent prior Simpson grade 3 or 4 excision (log-rank test p = 0.032). CONCLUSIONS: Meningiomas >10 cc in volume appear to display a high rate of progression and subsequent need for surgery following GKRS. Primary surgical resection, when not contraindicated, may be considered with GKRS serving an adjuvant role, especially in tumours exceeding 14 cc in volume, and presenting with limb motor deficits. Long-term clinical and radiological follow-up is essential following GKRS as the response of large meningiomas may be unpredictable.

Gamma Knife radiosurgery for central neurocytoma: a quantitative systematic review and metanalysis.

Central neurocytomas (CN) are rare tumors within the central nervous system. Originating from the septum pellucidum and subependymal cells, they are typically found in the third and lateral ventricles. For this reason, they may lead to hydrocephalus and increased intracranial pressure. CNs are generally benign lesions that exhibit locally aggressive behavior and a high recurrence rate. Complete surgical resection is the preferred treatment; however, due to their anatomical location, this is often not feasible. Based on these findings, Gamma Knife radiosurgery (GKRS) has been introduced for managing both residual and recurrent tumors and as an initial therapy in selected cases. This study aimed to systematically review the available knowledge regarding GKRS for CN. A systematic investigation of the scientific literature was undertaken through an exhaustive search across prominent databases, including PubMed, Web of Science, and Google Scholar, by employing precise MeSH terms such as "Central neurocytoma," "Radiosurgery," "Gamma Knife," and "Stereotactic Radiosurgery." A comprehensive quantitative systematic review and meta-analysis were meticulously conducted, focusing on cases of CN treated with GKRS for a thorough evaluation of outcomes and efficacy. Seventeen articles, including 289 patients, met the inclusion criteria. Random effects meta-analysis estimates for disease control and local tumor control were 90% (95% CI 87-93%; I2 = 0%, p < 0.74) and 94% (95% CI 92-97%; I2 = 0%, p < 0.98), respectively. When considering only studies with at least 5 years of follow-up, progression-free survival was 89% (95% CI 85-94%; I2 = 0.03%, p < 0.74). The mean clinical control rate was 96%. This systematic review and meta-analysis confirmed the safety and efficacy of GKRS in managing CN.

Surgical management of large lower cranial nerves schwannomas: long term results of a less aggressive resection strategy.

In an effort to reduce the high morbidity and life-threatening complications after radical resection in large schwannoma surgery, alternative strategies of nontotal resections have emerged. To evaluate the long term clinical and oncological outcome after lower cranial nerves (LCN) schwannoma surgery operated on with a cranial nerve-sparing technique. Single center retrospective cohort study of 8 consecutive patients harboring LCN schwannomas operated on between March 2005 and October 2021. The mean LCN schwannoma diameter was 33 mm (range 26-51). Seven patients (87,5%) underwent a modified retrosigmoid approach. Three patients underwent gross total resection (37,5%), 3 had received neartotal resection (mean tumor residue 0,25 cc) and subtotal resection in 2 patients who presented with an extracranial extension of the tumor (mean tumor residue 2,44 cc). Both patients had received upfront additional GKRS. The three patients who presented with preoperative CN IX & X injuries recovered within 6 months after surgery. All of the five patients freed from any preoperative CNs IX & X symptoms experienced transient (80%) or definitive (one patient) disturbances after surgery. They all improved within 6 months but one who required long term gastrostomy feeding tube. This patient harbored a schwannoma originating from the glossopharyngeal nerve, which could not be anatomically preserved during surgery. Tumor control was achieved in 100% of cases with a mean follow-up of 91 months. LCN schwannomas could be surgically removed through a less aggressive non-radical resection strategy with acceptable functional results and excellent tumor control.

Stereotactic radiosurgery in the management of skull base chordomas: a comprehensive systematic review and meta-analysis.

OBJECTIVE: Chordoma is a primary bone tumor with limited literature on its management because of its rarity. Resection, while considered the first-line treatment, does not always provide adequate tumor control. In this systematic review, the authors aimed to provide comprehensive insights by managing these tumors with stereotactic radiosurgery (SRS). METHODS: A systematic review was conducted according to PRISMA guidelines using the PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases. Search terms included chordoma and radiosurgery and their equivalent terms. Data on baseline characteristics, SRS details, and outcomes were extracted. The Joanna Briggs Institute checklist was used to assess risk of bias. A meta-analysis was performed on relevant variables. RESULTS: A total of 33 eligible studies encompassing 714 patients with skull base chordomas were included. Most studies had a low risk of bias. Patients, predominantly male (57.37%) with a mean age of 46.54 years, exhibited a conventional chordoma subtype (74.77%) and primary lesions (77.91%), mainly in the clivus (98.04%). The mean lesion volume was 13.49 cm3, and 96.68% of patients had undergone prior surgical attempts. Gamma Knife radiosurgery (88.76%) was the predominant SRS method. Radiologically, 27.19% of patients experienced tumor regression, while 55.02% showed no signs of disease progression at the latest follow-up. Progression occurred after a mean of 48.02 months. Symptom improvement was noted in 27.98% of patients. Radiosurgery was associated with a relatively low overall adverse event rate (11.94%), mainly cranial nerve deficits (8.72%). Meta-regression revealed that age and primary lesion type influenced symptom improvement, while factors like extent of resection, radiotherapy, and SRS type affected adverse event rates. CONCLUSIONS: This systematic review provides evidence on the safety and effectiveness of radiosurgery in the management of skull base chordomas. Local tumor control was achieved in the majority of patients treated with SRS. Various baseline characteristics and SRS features have been analyzed to identify modifying factors for each outcome to provide a framework for informed decision-making when managing these patients.

Is two-staged gamma knife surgery a reasonable management option for very large cerebellar metastases? A case series of three patients.

OBJECTIVE: Two-staged gamma knife surgery (GKS) is a method that may extend the upper tumor volume limit for using GKS in the management of brain metastases. However, the safety of treating very large posterior fossa lesions with this technique has not been well demonstrated. Therefore, we analyzed our experience in treating cerebellar metastases larger than 12 cm3 with two-staged GKS. METHODS: Four consecutive patients harboring 12 to 30 cm3 cerebellar metastases scheduled two-staged GKS were included in the study, and all but one patient completed the treatment. The treatment doses were 10-13 Gy. All patients were followed with regular MR imaging and clinical assessments, and the tumor volumes were measured on all treatment and follow-up images. RESULTS: Tumor progression was not demonstrated in any of the patients. Tumor volumes decreased by, on average, more than half between the two stages. The median survival was 22 months, and no patient died due to intracranial tumor progression. Peritumoral edema at the first GKS resolved in all patients, replaced by asymptomatic mild T2 changes in two of them not requiring any treatment. No radiation-induced complication has developed thus far. CONCLUSION: Staged GKS seems to be a feasible management option for very large cerebellar metastases.

Palliative Gamma Knife Radiosurgery for a Small Part of a Large Vestibular Schwannoma in an Elderly Patient.

We report a case of a large vestibular schwannoma in an 80-year-old female patient that shrank after palliative Gamma Knife radiosurgery (GKS). Neurological symptoms included hearing deterioration and facial palsy. The tumor volume was 21.9 mL. Craniotomy was considered high-risk, and conventional GKS was risky, owing to the risk of transient enlargement. Therefore, GKS was performed on only a portion of the tumor. The marginal dose (12 Gy) volume was 3.8 mL (17.4%). The tumor began to shrink after transient enlargement. Sixty months later, the tumor volume was only 3.1 mL, and the patient was able to maintain independent activities of daily living without salvage treatment.

Leukoencephalopathy in patients with brain metastases who received radiosurgery with or without whole brain radiotherapy.

BACKGROUND: Whole brain radiation therapy (WBRT) for brain metastases (BMs) is a common cause of radiation-induced leukoencephalopathy; however the safety of alternative stereotactic radiosurgery (SRS) remains unclear. This study examined the incidence of leukoencephalopathy in patients treated with SRS alone versus WBRT plus SRS for BMs with a focus on the relationship between prognostic factors and leukoencephalopathy. METHODS: Analysis was performed between 2002 and 2021. The total enrollment was 993 patients with the distribution: WBRT plus SRS (n = 291) and SRS only (n = 702). Leukoencephalopathy was graded from 0 to 3 for changes in white matter indicated by the MRI after WBRT or SRS. Patient characteristics and SRS dosimetric parameters were reviewed to identify factors that contributed to the incidence of leukoencephalopathy or overall survival. RESULTS: The incidence of leukoencephalopathy was consistently higher in WBRT plus SRS group than in SRS alone group (p < 0.001). Leukoencephalopathy was also associated with a larger total tumor volume (≧28cm3; p = 0.028) and age (> 77 years; p = 0.025). Nonetheless, the SRS integral dose to skull in the subgroup of WBRT plus SRS treatment was not demonstrated significance in development of leukoencephalopathy (p = 0.986 for integral dose 1-2 J, p = 0.776 for integral dose > 2 J). CONCLUSIONS: This study revealed that SRS is safe for oligo-BMs in terms of leukoencephalopathy development. Patient age and total tumor volume were identified as important factors in assessing the development of leukoencephalopathy. The additional of SRS (even at an integral dose > 2 J) did not increase the incidence of leukoencephalopathy.

Using the deformity index of vital structures to predict outcome of patients with large vestibular schwannomas after Gamma Knife radiosurgery.

PURPOSE: Microsurgery is the mainstay of treatment for large vestibular schwannomas (VS), but the benefits of radiosurgery remain incompletely defined. Here, we aim to use automated volumetric analysis software to quantify the degree of brain stem deformity to predict long-term outcomes of patients with large VS following GKRS. METHODS: Between 2003 and 2020, 39 patients with large VS (volume > 8 cc) undergoing GKRS with a margin dose of 10-12 Gy were analyzed. The reconstruction 3D MRI was used to evaluate the extent of deformity for predicting the long-term outcome of patients. RESULTS: Their mean tumor volume was 13.7 ± 6.3 cc, and their mean follow-up after GKRS was 86.7 ± 65.3 months. Favorable clinical outcome was observed in 26 (66.7%) patients, while 13 (33.3%) patients had treatment failure. Patients with small tumor volumes, low vital structure deformity indice [(TV/(BSV + CerV) and (TV + EV)/(BSV + CerV)], and long distance of tumor to the central line were more likely to have favorable clinical outcome after GKRS. Significant prognostic value was with tumor shrinkage ratio (< 50%) were CV, CV/TV, TV/CerV, (TV + EV)/(BSV + CerV), and the distance of tumor to the central line. In cox regression, favorable clinical outcome was correlated with the Charlson comorbidity index and cochlear dosage (both p < 0.05). In multivariant analysis, tumor regression was highly correlated with the CV/TV ratio (p < 0.001). CONCLUSIONS: The brainstem deformity ratio is likely a useful index to assess the clinical and tumor regression outcomes. Clinical outcomes are multifactorial and the tumor regression was highly correlated with the ratio of cystic components.

Gamma Knife radiosurgery for meningiomas of the confluence of the falx and tentorium.

PURPOSE: Meningiomas arising from the confluence of the falx and tentorium (CFT) are a rare and challenging subset of meningiomas. Gamma Knife radiosurgery (GKRS) is well-established as a safe and effective management strategy for intracranial meningiomas, but its role in treating CFT meningiomas is not well-described. This paper reports the largest series focused exclusively on the outcomes of GKRS for CFT meningiomas. METHODS: We retrospectively identified 20 CFT meningiomas out of 2031 meningioma patients who underwent GKRS at our institution between 1987 and 2021. Tumor control, overall survival (OS), and complications were recorded and analyzed. The median tumor margin dose was 13 Gy at the 50% isodose line. The median tumor volume treated was 4.4 cc (IQR 3.5-7.7). The median patient age was 58 years (range 33-83), the median MRI surveillance duration was 59 months (IQR 34-92), and the median overall follow-up duration was 92 months (IQR 42-201). RESULTS: The local tumor control rate (PFS) at 5 and 10-years were 100% (N=10) and 83% (N=4), respectively. Eight patients had stable tumor volumes and 11 patients had regression. One patient with a twice-operated tumor had delayed progression at 7.5 years and was retreated with GKRS. No patient had adverse radiation effects during the period of MRI surveillance. The 5 and 10-year OS were 100% (N=13) and 100% (N=7), respectively. CONCLUSIONS: GKRS is a valuable therapeutic strategy for patients with newly diagnosed CFT meningiomas or progressive residual tumors after surgical resection.

Improved survival and intracranial tumor control of EGFR-mutated NSCLC patients with newly developed brain metastases following stereotactic radiosurgery and EGFR-TKI: a large retrospective cohort study and meta-analyses.

PURPOSE: To examine the differential effects of SRS and TKI on EGFR-mutated NSCLC patients with brain metastases (BMs) and outcomes following continuation of the same TKI agent in case of new BMs. METHODS: This study included 608 NSCLC patients (2,274 BMs) while meta-analyses included 1,651 NSCLC patients (> 3,944 BMs). Overall survival (OS) and intracranial progression free survival (iPFS) were estimated using Kaplan-Meier methods. Hazard ratios (95% CI) of prognostic factors were estimated using Cox regression models. RESULTS: The median OS/iPFS (95% CI) (months) for patients with wildtype EGFR/ALK, EGFR mutations, and ALK rearrangements were 17.7 (12.9-23.6)/12.1 (9.8-15.6), 28.9 (23.8-33.3)/17.7 (14.8-21.2), and 118.0 (not reached)/71.7 (15.1-not reached), respectively. In EGFR-mutated patients, meta-analyses combining our data showed significantly improved OS and iPFS of patients who received SRS and TKI (OS:35.1 months, iPFS:20.0 months) when compared to those who have SRS alone (OS:20.8 months, iPFS:11.8 months) or TKI alone (OS:24.3 months, iPFS:13.8 months). Having SRS for newly diagnosed BMs while keeping the existing TKI agent yielded OS (30.0 vs. 32.1 months, p = 0.200) non-inferior to patients who started combined SRS and TKI therapy for their newly diagnosed NSCLC with BMs. Multivariable analyses showed that good performance score and TKI therapy were associated with improved outcomes. CONCLUSIONS: Combined SRS and TKI resulted in favorable outcomes in EGFR-mutated NSCLC patients with newly diagnosed BMs. Continuation of the same TKI agent plus SRS in case of new brain metastases yielded good clinical outcomes and may be considered a standard-of-care treatment.

Predicting peritumoral edema development after gamma knife radiosurgery of meningiomas using machine learning methods: a multicenter study.

OBJECTIVES: Edema is a complication of gamma knife radiosurgery (GKS) in meningioma patients that leads to a variety of consequences. The aim of this study is to construct radiomics-based machine learning models to predict post-GKS edema development. METHODS: In total, 445 meningioma patients who underwent GKS in our institution were enrolled and partitioned into training and internal validation datasets (8:2). A total of 150 cases from multicenter data were included as the external validation dataset. In each case, 1132 radiomics features were extracted from each pre-treatment MRI sequence (contrast-enhanced T1WI, T2WI, and ADC maps). Nine clinical features and eight semantic features were also generated. Nineteen random survival forest (RSF) and nineteen neural network (DeepSurv) models with different combinations of radiomics, clinical, and semantic features were developed with the training dataset, and evaluated with internal and external validation. A nomogram was derived from the model achieving the highest C-index in external validation. RESULTS: All the models were successfully validated on both validation datasets. The RSF model incorporating clinical, semantic, and ADC radiomics features achieved the best performance with a C-index of 0.861 (95% CI: 0.748-0.975) in internal validation, and 0.780 (95% CI: 0.673-0.887) in external validation. It stratifies high-risk and low-risk cases effectively. The nomogram based on the predicted risks provided personalized prediction with a C-index of 0.962 (95%CI: 0.951-0.973) and satisfactory calibration. CONCLUSION: This RSF model with a nomogram could represent a non-invasive and cost-effective tool to predict post-GKS edema risk, thus facilitating personalized decision-making in meningioma treatment. CLINICAL RELEVANCE STATEMENT: The RSF model with a nomogram built in this study represents a handy, non-invasive, and cost-effective tool for meningioma patients to assist in better counselling on the risks, appropriate individual treatment decisions, and customized follow-up plans. KEY POINTS: • Machine learning models were built to predict post-GKS edema in meningioma. The random survival forest model with clinical, semantic, and ADC radiomics features achieved excellent performance. • The nomogram based on the predicted risks provides personalized prediction with a C-index of 0.962 (95%CI: 0.951-0.973) and satisfactory calibration and shows the potential to assist in better counselling, appropriate treatment decisions, and customized follow-up plans. • Given the excellent performance and convenient acquisition of the conventional sequence, we envision that this non-invasive and cost-effective tool will facilitate personalized medicine in meningioma treatment.

Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

VEGFR-TKI treatment for radiation-induced brain injury after gamma knife radiosurgery for brain metastases from renal cell carcinomas.

OBJECTIVE: Antiangiogenic vascular endothelial growth factor receptor tyrosine kinase inhibitors play an essential role in systemic therapy for renal cell carcinoma. Given the anti-edematous effect of bevacizumab, an antiangiogenic antibody targeting vascular endothelial growth factor, vascular endothelial growth factor receptor tyrosine kinase inhibitors should exert therapeutic effects on radiation-induced brain injury after stereotactic radiosurgery. This preliminary study aimed to investigate the therapeutic effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor against radiation-induced brain injury. METHODS: Magnetic resonance images for six patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors who were diagnosed with radiation-induced brain injury following gamma knife radiosurgery were retrospectively reviewed. RESULTS: The median brain edema volume and tumour mass volume in the pre-tyrosine kinase inhibitor period were 57.6 mL (range: 39.4-188.2) and 3.2 mL (range: 1.0-4.6), respectively. Axitinib, pazopanib (followed by cabozantinib) and sunitinib were administered in four, one and one cases, respectively. The median brain edema volume and tumour mass volume in the post-tyrosine kinase inhibitor period were 4.8 mL (range: 1.5-27.8) and 1.6 mL (range: 0.4-3.6), respectively. The median rates of reduction in brain edema volume and tumour mass volume were 90.8% (range: 51.9-97.6%) and 57.2% (range: 20.0-68.6%), respectively. The post-tyrosine kinase inhibitor values for brain edema volume (P = 0.027) and tumour mass volume (P = 0.008) were significantly lower than the pre-tyrosine kinase inhibitor values. Changes in volume were correlated with tyrosine kinase inhibitor use. CONCLUSION: This study is the first to demonstrate the therapeutic effects of vascular endothelial growth factor receptor tyrosine kinase inhibitors on radiation-induced brain injury in patients with brain metastases from renal cell carcinoma treated via gamma knife radiosurgery.

Health-related quality of life after stereotactic radiosurgery in patients with brain metastases.

PURPOSE: This study aimed to assess health-related quality of life (HRQoL) in patients with brain metastases treated with stereotactic radiosurgery (SRS) and to identify factors associated with this. METHODS: HRQoL was measured pre-SRS, at 3- and 6-month follow-up. Physical functioning, cognitive functioning, role functioning, and fatigue were analyzed with the EORTC QLQ-C30 questionnaire. Motor dysfunction, future uncertainty, visual disorder, communication deficit, and headaches were analyzed with the EORTC QLQ-BN20. Clinically important symptom or functional impairment was assessed following set thresholds. Factors associated with impairment were identified through multivariable logistic regression analyses. RESULTS: At baseline, 178 patients were included; 54% (n=96) completed questionnaires at 3 months and 39% (n=70) at 6 months. Before SRS, 29% of linear accelerator (LINAC) patients reported physical and cognitive impairment, while 25% reported impairment for fatigue. At 6 months, 39%, 43%, and 57% of LINAC patients reported impairment respectively. Forty-five percent of Gamma Knife (GK) patients reported impairment pre-SRS for physical, cognitive functioning, and fatigue. At 6 months, 48%, 43%, and 33% of GK patients reported impairment respectively. Except for role functioning, pre-SRS symptom and functioning scores were associated with impairment at 3 months, whereas scores at 3 months were associated with impairment at 6 months. Age, gender, systemic therapy, and intracranial progression were not associated with clinically important impairment. CONCLUSION: As 33-57% of patients with brain metastases reported symptom burden and functional impairments that were of clinical importance, it is recommended to pay attention to the HRQoL outcomes of these patients during clinical encounters.

Successful MRI-Guided Focused Ultrasound Thalamotomy after Ipsilateral Gamma Knife Radiosurgery for Essential Tremor: A Case Report with Video.

We report the case of a 67-year-old left-handed female patient with disabling medically refractory essential tremor who underwent successful right-sided magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus after ipsilateral gamma knife radiosurgery (GKRS) thalamotomy performed 3 years earlier. The GKRS had a partial effect on her postural tremor without side effects, but there was no reduction of her kinetic tremor or improvement in her quality of life (QoL). The patient subsequently underwent a MRgFUS thalamotomy, which induced an immediate and marked reduction in both the postural and kinetic tremor components, with minor complications (left upper lip hypesthesia, dysmetria in her left hand, and slight gait ataxia). The MRgFUS-induced lesion was centered more medially than the GKRS-induced lesion and extended more posteriorly and inferiorly. The MRgFUS-induced lesion interrupted remaining fibers of the dentatorubrothalamic tract (DRTT). The functional improvement 1-year post-MRgFUS was significant due to a marked reduction of the patient's kinetic tremor. The QoL score (Quality of Life in Essential Tremor) improved by 88% and her Clinical Rating Scale for Tremor left hand score by 62%. The side effects persisted but were minor, with no impact on her QoL. The explanation for the superior efficacy of MRgFUS compared to GKRS in our patient could be due to either a poor response to the GKRS or to a better localization of the MRgFUS lesion with a more extensive interruption of DRTT fibers. In conclusion, MRgFUS can be a valuable therapeutic option after unsatisfactory GKRS, especially because MRgFUS has immediate clinical effectiveness, allowing intra-procedural test lesions and possible readjustment of the target if necessary.

Effectiveness of gamma knife radiosurgery in the management of trigeminal neuralgia associated with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Trigeminal neuralgia (TN) is a chronic condition characterized by intense facial pain akin to electric shocks, often associated with the trigeminal nerve. It can be either idiopathic or secondary, with multiple sclerosis (Ms) being a significant contributing factor. Non-responsive patients may opt for minimally invasive procedures, such as gamma knife radiosurgery (GKRS), which offers precise, non-invasive treatment and is frequently chosen as a primary approach. This meta-analysis evaluates the long-term efficacy of GKRS in TN management in Ms patients. METHODS: We conducted a focused search across various databases. Inclusion criteria encompassed studies with ≥ 30 patients using GKRS for TN in Ms, reporting pertinent clinical outcomes. Primary outcomes assessed GKRS efficacy through Barrow Neurological Institute Pain scores. Secondary outcomes encompassed bothersome numbness, facial numbness, and recurrence. Data analysis employed OpenMeta, random effect models, and odds ratios with 95% confidence intervals. Heterogeneity was assessed using I2 statistics. RESULTS: Fourteen studies with 752 cases of GKRS for TN were included. Regarding the outcomes, 83% of patients experienced a positive initial pain response, while the overall treatment success rate was 51%. Additionally, 19.6% of patients reported facial numbness, 4.1% experienced bothersome numbness, and 40% faced recurrence. The odds ratio for positive initial pain response was 0.83 (95% CI, 0.76-0.89), while for treatment success, it was 0.51 (95% CI, 0.379-0.639). Facial numbness had an odds ratio of 0.196 (95% CI, 0.130-0.262), bothersome numbness had an odds ratio of 0.041 (95% CI, 0.013-0.069), and recurrence had an odds ratio of 0.403 (95% CI, 0.254-0.551). CONCLUSIONS: In conclusion, treating trigeminal neuralgia in multiple sclerosis patients remains challenging. GKRS shows promise, but customized treatment approaches tailored to individual patient characteristics are urgently needed to address the unique challenges of this condition.