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Background: So far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT)., Methods: Survival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported., Results: Multivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT., Conclusion: Good local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management., (© 2023. The Author(s).)

Objective: Since the publication of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the management of unruptured brain arteriovenous malformations (bAVMs) has been controversially discussed. Long-term follow-up data on the exclusively conservative management of unruptured bAVMs are scarce. The authors evaluated the long-term outcomes of patients with unruptured untreated bAVMs in a real-life cohort., Methods: A retrospective observational cohort of 107 patients (of 897 bAVM patients referred to the authors' institution) with a diagnosis of unruptured and conservatively managed bAVMs is presented. AVMs of all Spetzler-Martin grades were observed. The mean follow-up period was 84 months. In 44% of patients, a follow-up period of 5 years or longer was observed. A national death register comparison completed the outcome analysis., Results: The median age at diagnosis, sex distribution, neurological presentation, and modified Rankin Scale score were comparable to the patients in the medical management arm of the ARUBA study. Patients were mainly young, predominantly male, and in good clinical condition. Similar to the ARUBA cohort, 77% of this study's cohort presented in an excellent clinical status at the time of last follow-up. However, 17% of patients had at least one hemorrhage, resulting in an overall annual hemorrhage risk of 2.7% in the observation period. Moreover, the cumulative 1-, 5-, and 10-year overall hemorrhage rates were 3.0%, 11.3%, and 15.3%, respectively. Consequently, the long-term follow-up AVM-related mortality rate amounted to 8%. The estimated median overall survival after AVM diagnosis was 19.3 years (95% CI 14.0-24.6 years). A multivariate Cox regression model revealed temporal and deep-seated localization as an independent risk factor for AVM hemorrhage, while the presence of seizures reached borderline significance as a risk factor., Conclusions: The authors' results represent the long-term course of unruptured untreated bAVMs. Their data support the conclusion that even in the post-ARUBA era, tailored active treatment options may be offered to patients with unruptured bAVMs. For patient counseling, individual risk factors should be weighed against the center's treatment-specific risks.

Objective: The authors sought to evaluate clinical outcome in patients with large, high-risk brain metastases (BMs) treated with different dose strategies by use of two-fraction dose-staged Gamma Knife radiosurgery (GKRS)., Methods: A retrospective analysis was performed with data from 142 patients from two centers who had been treated with two-fraction dose-staged GKRS between June 2015 and January 2020. Depending on the changes in marginal dose between the first (GKRS1) and second (GKRS2) GKRS treatments, the study population was divided into three treatment groups: dose escalation, dose maintenance, and dose de-escalation., Results: The 142 study patients underwent two-fraction dose-staged GKRS treatments for 166 large, high-risk BMs. The median tumor volume of 7.4 cm3 decreased significantly from GKRS1 to GKRS2 (4.4 cm3; p < 0.001), and to the last follow-up (1.8 cm3; p < 0.001). These significant differences in BM volume reduction were achieved in all three treatment groups. However, differences according to the primary tumor histology were apparent: while dose maintenance seemed to be the most effective treatment strategy for BMs from lung cancer or melanoma, dose escalation was the most beneficial treatment option for BMs from breast, gastrointestinal, or genitourinary cancer. Of note, the vast majority of patients who underwent dose-staged BM treatment did not show any significant postradiosurgical complications., Conclusions: In patients with large, high-risk BMs, dose-staged GKRS treatment represents an effective local treatment method with acceptable complication risks. Different dose-strategy options are available that may be chosen according to the primary tumor histology and treatment volume but may also be tailored to the findings at GKRS2.

Purpose: To investigate the clinical value of the inflammation based prognostic scores for patients with radiosurgically treated brain metastases (BM) originating from non-pulmonary primary tumor (PT)., Methods: A retrospective analysis of 340 BM patients of different PT origin (melanoma, breast, gastrointestinal, or genitourinary cancer) was performed. Pre-radiosurgical laboratory prognostic scores, such as the Neutrophil-to-Lymphocyte Ratio (NLR), the Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), and the modified Glasgow Prognostic Score (mGPS), were investigated within 14 days before the first Gamma Knife radiosurgical treatment (GKRS1)., Results: In our study cohort, the estimated survival was significantly longer in patients with NLR < 5 (p < 0.001), LMR > 4 (p = 0.001) and in patients with a mGPS score of 0 (p < 0.001). Furthermore, univariate and multivariate Cox regression models revealed NLR ≥ 5, LMR < 4 and mGPS score ≥ 1 as independent prognostic factors for an increased risk of death even after adjusting for age, sex, KPS, extracranial metastases status, presence of neurological symptoms and treatment with immunotherapy (IT) or targeted therapy (TT)., Conclusions: Summarizing previously published and present data, pre-radiosurgical mGPS and NLR groups seem to be the most effective and simple independent prognostic factors to predict clinical outcome in radiosurgically treated BM patients., (© 2021. The Author(s).)

Introduction: The predictive value of the pre-radiosurgery Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR) and the modified Glasgow Prognostic Score (mGPS) was assessed for the first time in a homogenous group of NSCLC brain metastaes (BM) patients., Methods: We retrospectively evaluated 185 NSCLC-BM patients, who were treated with Gamma Knife Radiosurgery (GKRS). Patients with immunotherapy or targeted therapy were excluded. Routine laboratory parameters were reviewed within 14 days before GKRS1., Results: Median survival after GKRS1 was significantly longer in patients with NLR < 5 (p < 0.001), PLR < 180 (p = 0.003) and LMR ≥ 4 (p = 0.023). The Cox regression model for the continuous metric values revealed that each increase in the NLR of 1 equaled an increase of 4.3% in risk of death (HR: 1.043; 95%CI = 1.020-1.067, p < 0.001); each increase in the PLR of 10 caused an increase of 1.3% in risk of death (HR: 1.013; 95%CI = 1.004-1.021; p = 0.003) and each increase in the LMR of 1 equaled a decrease of 20.5% in risk of death (HR: 0.795; 95%CI = 0.697-0.907; p = 0.001). Moreover, the mGPS group was a highly significant predictor for survival after GKRS1 (p < 0.001) with a HR of 2.501 (95%CI = 1.582-3.954; p < 0.001). NLR, PLR, LMR values and mGPS groups were validated as independent prognostic factors for risk of death after adjusting for sex, KPS, age and presence of extracranial metastases., Conclusion: NLR, PLR, LMR and mGPS represent effective and simple tools to predict survival in NSCLC patients prior to radiosurgery for brain metastases.

Background: Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT., Methods: We evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era., Results: The median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7-1.2 years). Patients treated with anti-PD-1 or a combination of anti-CTLA-4/PD-1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti-PD-1, anti-CTLA-4, or a combination of anti-CTLA-4/PD-1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT., Conclusion: In MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Gamma Knife radiosurgery (GKRS) in the treatment of arteriovenous malformations (AVMs) is still controversially discussed., Objective: To present long-term follow-up data on patients after Gamma Knife radiosurgery for cerebral AVMs., Methods: Overall, 516 patients received radiosurgery for cerebral AVMs between 1992 and 2018 at our department, of whom 265 received radiosurgery alone and 207 were treated with a combined endovascular-radiosurgical approach. Moreover, 45 patients were treated with a volume-staged approach. Two eras were analyzed, the pre-modern era between 1992 and 2002 and the modern era thereafter., Results: In GKRS-only treated patients, median time to nidus occlusion was 3.8 years. Spetzler-Ponce (SP) class was a significant predictor for time to obliteration in the whole sample. Median time to obliteration for the combined treatment group was 6.5 years. Patients in the pre-modern era had a significantly higher obliteration rate than those treated in the modern era. Overall, the calculated yearly hemorrhage risk in the observation period after first GKRS was 1.3%. Permanent post-radiosurgical complications occurred in 4.9% of cases but did not differ between the treatment groups or treatment eras. The obliteration rate was significantly lower and the hemorrhage rate was higher in volume-staged treated patients than in conventionally treated patients., Conclusion: GKRS is an effective treatment option for SP class A and B cerebral AVMs. After combined endovascular-radiosurgical treatment, the outcome of selected SP class C AVMs aligns with that of SP class B lesions. Both the combined therapy and radiosurgery alone constitute sound methods for treatment of cerebral AVMs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The study aim was to evaluate the utility of 2-fraction, dose-staged Gamma Knife radiosurgery (GKRS) in patients with large, high-risk brain metastases (BMs)., Methods: A total of 63 large BMs in eloquent areas in 61 patients were treated with GKRS in 2 reduced doses. Treatment planning was conducted on the 50% isodose line and included the whole tumor volume as seen on T1 contrast-enhanced and T2-weighted magnetic resonance imaging sections. The median margin and central dose were 12 Gy and 24 Gy, respectively, for both fractions. Patients were assessed using the Graded Prognostic Assessment, Recursive Partitioning Analysis, and Score Index for Radiosurgery., Results: Thirty-two patients (53%) had been diagnosed with multiple BMs, and extracranial metastases were present in a majority of patients before GKRS treatment. Significant decreases in tumor volume were observed between the first and second treatment stages. At 3-month follow-up, a majority of patients presented with stable or decreased lesion volumes. The remaining patients showed intralesional hemorrhaging or increasing edema that was managed conservatively. Three patients were diagnosed with tumor progression at the last follow-up and received microsurgical treatment. The median time to radiologic progression was 7 months. The median survival time after initial BM diagnosis was 6 months. Survival times were significantly longer than 3 of 4 calculated prognostic survival estimates., Conclusion: The new 2-fraction, dose-staged GKRS concept seems to be a well-tolerated and effective treatment option for large BMs. This method may be indicated in elderly patients or patients with surgical contraindications with large or high-risk brain metastases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: We evaluated Gamma Knife radiosurgery (GKRS) as a treatment option for patients with recurrent glioblastoma., Patients and Methods: 42 patients with histopathologically diagnosed recurrent grade IV tumor were treated with GKRS. All patients had undergone standard multimodal first-line treatment. The average time from diagnosis to GKRS was 17.0 months. The median target volume was 5.1 cm3. The median margin dose was 10 Gy and the median central dose 20 Gy. In a subset of patients, O6-methylguanine methyltransferase (MGMT) promoter methylation analysis by pyrosequencing was performed., Results: Most patients did not develop complications after GKRS. Time to radiological progression after initial GKRS was 4.4 months (95% CI: 3.1-5.7 months). Radiological progression mainly occurred beyond the GKRS-irradiated area. The median survival time after initial GKRS was 9.6 months (95% CI: 7.7-11.5 months). The median overall survival time from diagnosis was 25.6 months (95% CI: 21.8-29.3 months). Patients with MGMT promoter methylation survived significantly longer (33.4 months; 95% CI: 21.2-45.5 months) compared to patients without MGMT promoter methylation (16.0 months; 95% CI: 8.0-23.9 months)., Conclusion: GKRS seems to be a relatively safe salvage treatment option for recurrent glioblastoma for highly selected patients but must be seen as part of a multimodal treatment algorithm., (© 2016 S. Karger AG, Basel.)

Objective: To evaluate treatment options for brainstem cavernous malformations (BSCMs) using the results from a center with long-standing experience in microsurgical resection and Gamma Knife radiosurgery (GKRS) treatment of BSCMs., Methods: Study participants were 67 symptomatic patients with BSCMs who were treated either microsurgically (n = 29) or radiosurgically (n = 38). Patients were followed for a minimum of 2 years (median, 7.7 years). A recent follow-up was performed., Results: Patients receiving surgical treatment had mainly large, superficially seated lesions and experienced preoperative hemorrhages more often and presented with higher preoperative modified Rankin Scale scores. Patients receiving GKRS harbored smaller, deep-seated lesions, reflecting a selection bias. In both treatment groups, patients presented with significantly better modified Rankin Scale scores at follow-up than before intervention. Overall annual preoperative hemorrhage rates were 3.2% in microsurgery patients and 2.3% in radiosurgery patients. In the preoperative observation period, the rehemorrhage rate was 25.1% for microsurgery patients and 7.2% for radiosurgery patients. Hemorrhage rate after GKRS decreased significantly to 0.6% after 2 years. The postoperative hemorrhage rate was 8.8% but only for microsurgery patients with residual lesions. Advancements in microsurgical techniques improved surgical outcomes, resulting in a high total excision rate in the modern era., Conclusions: In the treatment of BSCM, patient selection and timing of surgery are crucial. If applied in a multidisciplinary neurosurgical center, microsurgery and radiosurgery are complementary treatment options that both result in reduced bleeding rates and improvement of clinical outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Treatment algorithms for brainstem cavernous malformations (BSCM) are still discussed controversially. The aim of our study is to provide the results of a centre with a long-standing experience in the micro-surgical resection and the radiosurgical treatment of BSCM and to elucidate how to best use the two different treatment options for the benefit of the patient. Patients an. Methods: 29 patients (female: male = 13: 16) were treated microsurgically. In 38 patients (female: male = 19:19) Gamma Knife radiosurgery (GKRS) was applied. Surgical approaches have been chosen according to the most direct approach with the lowest risk of neurological deficits. GKRS patients were treated with a Leksell Gamma Knife. Gamma Knife parameters were applied as following: median margin dose 12 Gy (6 -16 Gy), median maximum dose 24 Gy (8 - 32 Gy), median isodose line 50% (45 - 80%). Clinical data were obtained by retrospective chart review. A minimum follow up of 2 years was established and a recent follow up was evaluated for all patients resulting in a median follow up of 7.7 years (2.0 - 22.1 years). Patients were rated according to the modified Rankin scale (mRS). Results: Statistical significant differences revealed that radiosurgically treated patients harboured significantly smaller and deep seated lesions (p<0.001). Surgically treated patients more often showed intralesional or extralesional haemorrhage (p=0.002), were superficially seated but larger and presented with a significantly higher preoperative mRS score (p=0.019). In both treatment groups, patients presented with a significant better mRS score (p=0.002, p<0.001) at time of follow up compared to the mRS score prior to surgery or GKRS. Overall annual pre-operative haemorrhage rates were calculated as 3.2% among surgery patients and 2.3% among GKRS patients. The annual pre-operative re-hemorrhage rate amounted to 25.1% for surgery and 7.2% for GKRS patients in the observation period. The overall annual post-operative haemorrhage rate for GKRS patients was 1.3% at time of follow up. In the first two years after GKRS the haemorrhage rate was 2.6% but dropped to 0.6% after the first two years. The annual postoperative haemorrhage rate was 8.8% for surgically treated patients with residual lesions. Conclusion: GKRS and microsurgery are complimentary treatment options that both result in a favourable patient outcome if applied on accurately selected patients in a multidisciplinary setting. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]