Natural History and Histopathology of Expanding Cysts and Hematomas After Stereotactic Radiosurgery for Arteriovenous Malformations of the Brain: A Case Series.

BACKGROUND: We reviewed the clinical course and histopathologic findings for cases involving the formation of expanding cysts and/or hematomas after gamma knife surgery (GKS) for arteriovenous malformations (AVMs). METHODS: We report a single-center retrospective review of 18 patients who presented with cyst and/or hematoma expansion after GKS for AVMs between 1993 and 2023. Expanding cysts and hematomas were defined as well-demarcated cavities filled with fluid or well-marginated heterogenous hematomas presenting with expansion proximal to or in the location of the original AVM, respectively. Patient demographics, AVM characteristics, history of interventions and surgeries, and imaging and histopathologic features of expanding cysts and hematomas were collected for analysis. RESULTS: Among 1072 AVM patients treated using GKS, 18 presented with expanding cysts or hematomas during a total follow-up period of 16,757 patient-years (0.11 case/100 persons/patient-year). The time to cyst or hematoma identification was 4-13 years after initial GKS, with a mean duration of 8.6 years. Among the patients examined, 7 (38.9%) presented mainly with hematoma, 10 (55.6%) presented mainly with cysts, and 1 presented with approximately equal components of both. Among the 18 patients, 13 (72.2%) underwent craniotomy to treat cyst or hematoma expansion. All the specimens had similar histopathologic characteristics, including organizing hematoma with fresh and old hemorrhage, fibrinoid necrosis of the vessels, gliosis of normal brain tissue, infiltration of hemosiderin-laden histiocytes, and extravascular protein leakage. CONCLUSIONS: Our findings suggest that the formation of these 2 complications can be attributed to a common mechanism involving radiation-induced vascular damage in brain tissue adjacent to the AVM and subsequent chronic inflammation and capillary dilatation.

Natural history of lung squamous cell brain metastases in patients treated with radiosurgery: a thirty-year experience at a tertiary medical center.

PURPOSE: In this study we report our 30-year experience in stereotactic radiosurgery (SRS) treatment of lung squamous cell carcinoma (LUSC) brain metastases (BMs). It will serve to provide detailed longitudinal outcomes and predictors of efficacy in treating LUSC-BMs with SRS. METHOD: We retrospectively reviewed 51 patients and 109 tumors treated with SRS at our center between 1993 and 2022. Patient demographics, PDL1 genotype, immunotherapy use and mortality cause were recorded. Radiological and clinical outcomes were followed at 1-3-month intervals post-SRS. Cox-regression analysis and Kaplan-Meier survival curves were performed in statistical analysis. RESULTS: We included 37 male and 14 female patients (median age 62.7 years at BM diagnosis). Median overall survival (OS) time was 6.9 months, 6-month OS rate was 62.1%, and Karnofsky performance scale (KPS) was the only independent predictor. Median time for local control maintenance was 7.6 months, 6-month local control rate was 69.1%, with TKI as the only independent predictor. Median time to distant failure was 5.13 months, 6-month distant failure rate was 51.1%, and factors with significant impact included gender (p = 0.002), presence of extracranial metastases (p < 0.001), use of immunotherapy(p < 0.001), PDL1 genotype (p = 0.034), and total intracranial metastases number (p = 0.008). However, no definitive benefits of immunotherapy were identified in patients with higher PDL1 mutational tumors. CONCLUSION: In this study we defined the natural history of disease progression and outcomes in SRS-treated LUSC-BM patients. We also identified predictors of OS and tumor control among these patients. The findings of this study will serve as a guide when counseling these patients for SRS.

Gamma Knife radiosurgery for cerebral cavernous malformation.

This is a retrospective study examining the efficacy and safety of Gamma Knife radiosurgery (GKS) in treating patients with cerebral cavernous malformations (CCMs). Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities.

Epidermal growth factor receptor mutations: association with favorable local tumor control following Gamma Knife radiosurgery in patients with non-small cell lung cancer and brain metastases.

OBJECTIVE: The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS). METHODS: This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival. RESULTS: The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001). CONCLUSIONS: The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.

Intervening Nidal Brain Parenchyma and Risk of Radiation-Induced Changes After Radiosurgery for Brain Arteriovenous Malformation: A Study Using an Unsupervised Machine Learning Algorithm.

OBJECTIVE: To assess the sensitivity and specificity of arteriovenous malformation (AVM) nidal component identification and quantification using an unsupervised machine learning algorithm and to evaluate the association between intervening nidal brain parenchyma and radiation-induced changes (RICs) after stereotactic radiosurgery. METHODS: Fully automated segmentation via unsupervised classification with fuzzy c-means clustering was used to analyze the AVM nidus on T2-weighted magnetic resonance imaging studies. The proportions of vasculature, brain parenchyma, and cerebrospinal fluid were quantified. These were compared with the results from manual segmentation. The association between the brain parenchyma component and RIC development was assessed. RESULTS: The proposed algorithm was applied to 39 unruptured AVMs in 39 patients (17 female and 22 male patients), with a median age of 27 years. The median proportion of the constituents was as follows: vasculature, 31.3%; brain parenchyma, 48.4%; and cerebrospinal fluid, 16.8%. RICs were identified in 17 of the 39 patients (43.6%). Compared with manual segmentation, the automated algorithm was able to achieve a Dice similarity index of 79.5% (sensitivity, 73.5%; specificity, 85.5%). RICs were associated with a greater proportion of intervening nidal brain parenchyma (52.0% vs. 45.3%; P = 0.015). Obliteration was not associated with greater proportions of nidal vasculature (36.0% vs. 31.2%; P = 0.152). CONCLUSIONS: The automated segmentation algorithm was able to achieve classification of the AVM nidus components with relative accuracy. Greater proportions of intervening nidal brain parenchyma were associated with RICs.

Early Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia.

OBJECTIVE: To evaluate effectiveness of early Gamma Knife radiosurgery (GKRS) in treatment of medically refractory trigeminal neuralgia (TN). METHODS: This retrospective review comprised 108 consecutive patients with medically refractory idiopathic TN between 2006 and 2014. All patients underwent GKRS targeting the root entry zone with a median maximum dose of 90 Gy and isodose line of 20%. Outcomes pertaining to pain and facial numbness were scored using Barrow Neurological Institute scales. RESULTS: Following a median latency period of 4 weeks, we observed complete or adequate pain relief (Barrow Neurological Institute scores of I-IIIB) in 86 of 108 patients (90%). At a median time of 17 months, 22 patients (26%) experienced pain recurrence. New-onset facial numbness was reported by 59 patients (55%). Treatment failure rates were highest among patients with a longer history of pain. Compared with patients with pain history of ≤5 years, patients with pain history of >5 years experienced longer latency before pain relief (P = 0.027). Univariate and multivariate analyses demonstrated that pain history of ≤5 years was a significant predictor of pain relief (P = 0.049 and P = 0.045, respectively). CONCLUSIONS: GKRS achieves a high rate of pain relief among patients with medically refractory idiopathic TN. Pain history of ≤5 years is a reliable predictor of pain relief and appears to be associated with shorter latency to pain relief after GKRS. Therefore, early GKRS for patients with medically refractory idiopathic TN is recommended.

Gamma Knife surgery for clival epidural-osseous dural arteriovenous fistulas.

OBJECTIVE Clival epidural-osseous dural arteriovenous fistula (DAVF) is often associated with a large nidus, multiple arterial feeders, and complex venous drainage. In this study the authors report the outcomes of clival epidural-osseous DAVFs treated using Gamma Knife surgery (GKS). METHODS Thirteen patients with 13 clival epidural-osseous DAVFs were treated with GKS at the authors' institution between 1993 and 2015. Patient age at the time of GKS ranged from 38 to 76 years (median 55 years). Eight DAVFs were classified as Cognard Type I, 4 as Type IIa, and 1 as Type IIa+b. The median treatment volume was 17.6 cm3 (range 6.2-40.3 cm3). The median prescribed margin dose was 16.5 Gy (range 15-18 Gy). Clinical and radiological follow-ups were performed at 6-month intervals. Patient outcomes after GKS were categorized as 1) complete improvement, 2) partial improvement, 3) stationary, and 4) progression. RESULTS All 13 patients demonstrated symptomatic improvement, and on catheter angiography 12 of the 13 patients had complete obliteration and 1 patient had partial obliteration. The median follow-up period was 26 months (range 14-186 months). The median latency period from GKS to obliteration was 21 months (range 8-186 months). There was no intracranial hemorrhage during the follow-up period, and no deaths occurred. Two adverse events were observed following treatment, and 2 patients required repeat GKS treatment with eventual complete obliteration. CONCLUSIONS Gamma Knife surgery offers a safe and effective primary or adjuvant treatment modality for complex clival epidural-osseous DAVFs. All patients in this case series demonstrated symptomatic improvement, and almost all patients attained complete obliteration.