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IntroductionThere is a cumulative risk of 20-40% of developing brain metastases (BM) in solid cancers. Stereotactic radiotherapy (SRT) enables the application of high focal doses of radiation to a volume and is often used for BM treatment. However, SRT can cause adverse radiation effects (ARE), such as radiation necrosis, which sometimes cause irreversible damage to the brain. It is therefore of clinical interest to identify patients at a high risk of developing ARE. We hypothesized that models trained with radiomics features, deep learning (DL) features, and patient characteristics or their combination can predict ARE risk in patients with BM before SRT.MethodsGadolinium-enhanced T1-weighted MRIs and characteristics from patients treated with SRT for BM were collected for a training and testing cohort (N = 1,404) and a validation cohort (N = 237) from a separate institute. From each lesion in the training set, radiomics features were extracted and used to train an extreme gradient boosting (XGBoost) model. A DL model was trained on the same cohort to make a separate prediction and to extract the last layer of features. Different models using XGBoost were built using only radiomics features, DL features, and patient characteristics or a combination of them. Evaluation was performed using the area under the curve (AUC) of the receiver operating characteristic curve on the external dataset. Predictions for individual lesions and per patient developing ARE were investigated.ResultsThe best-performing XGBoost model on a lesion level was trained on a combination of radiomics features and DL features (AUC of 0.71 and recall of 0.80). On a patient level, a combination of radiomics features, DL features, and patient characteristics obtained the best performance (AUC of 0.72 and recall of 0.84). The DL model achieved an AUC of 0.64 and recall of 0.85 per lesion and an AUC of 0.70 and recall of 0.60 per patient.ConclusionMachine learning models built on radiomics features and DL features extracted from BM combined with patient characteristics show potential to predict ARE at the patient and lesion levels. These models could be used in clinical decision making, informing patients on their risk of ARE and allowing physicians to opt for different therapies.

Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with brain metastases from gastroesophageal (GE) cancers remains unclear despite recent advances in systemic therapies. The authors present a large single-institution experience in the use of stereotactic radiosurgery (SRS). Methods: A retrospective review of 71 GE cancer patients (64 male, 90.14%) who underwent Gamma Knife SRS was conducted. Overall, 243 brain metastases were treated and the median number of metastases per patient was 2 (range:1–21). The median age at SRS was 66 years (range: 26–85) and the median treatment day KPS was 80 (range: 50–100). The median cumulative tumor volume was 6.7 cc (range: 0.27-104.76) and the median single-session margin dose was 18 Gy (range: 12–20). Results: The median overall survival after SRS was 7 months (range: 1–64). At last follow up, 54 (76.06%) patients were deceased, 8 of whom (14.81%) expired secondary to their intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2–13) after SRS. Ten patients (14%) experienced new remote tumor development at a median time of 4 months (range: 0–14) after SRS. Whole-brain radiation therapy (2 patients, 20%) and repeat SRS (8 patients, 80%) were used for newly developed tumors. The incidence of transient adverse radiation effects was 8.45%. Conclusions: In this study, the 12-month local tumor control rate was 90%. Incidences of adverse radiation effect rates were rare. The median overall survival of 7 months indicates the poor prognosis of patients with brain spread of their GE cancer. [ABSTRACT FROM AUTHOR]

Gamma Knife Radiosurgery (GKRS) is now an established standard of treatment for the small‑sized arteriovenous malformations (AVMs), meningiomas, schwannomas, metastasis, and other benign diseases. With an exponential rise in the indications for GKRS, we have witnessed an increase in the adverse radiation effects (ARE) following GKRS. The common AREs and associated risk factors following GKRS have been described for pathologies including vestibular schwannomas, arteriovenous malformations, meningiomas, and metastases based on the authors’ experience, and a simplified management protocol has been provided for radiation‑induced changes based on clinical and radiologic parameters. The dose, volume, location, and repeat stereotactic radiosurgery (SRS) are implied as the risk factors for ARE. Clinically symptomatic AREs require oral steroids for weeks to alleviate symptoms. In refractory cases, bevacizumab and surgical resection can be offered as a treatment modality. Appropriate dose planning strategy and hypofractionation for larger lesions help in mitigating the AREs. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the role and outcomes of Gamma Knife radiosurgery (GKRS) in the management of pituitary metastases. Methods: The records of brain metastases patients who underwent GKRS at the University of Pittsburgh Medical Center during the 10-year interval of 2010–2020 were systematically reviewed. Outcome measures included patient survival, tumor control rate, pituitary hormonal outcomes, visual outcomes, adverse radiation effects (AREs), and need for adjuvant therapy. Results: Eighteen patients with pituitary metastases (eight male; median age of 65.5 years) had sufficient clinical follow-up for analysis. The most common primary cancers were non-small cell lung cancer (n = 6) and breast cancer (n = 4). Patients presented with headache (n = 9) and visual difficulties (n = 6). One patient underwent resection before GKRS. The median tumor volume was 0.78 cc (range 0.04–6.42 cc). The median overall survival after GKRS was 6.5 months (range 0.5–58 months). The overall survival after GKRS at 3-, 6-, and 12-months were 72.2%, 50.0% and 38.9%, respectively. The tumor control rate was 94.4%. One patient had further progression that required additional GKRS. None of the patients developed AREs after GKRS. Conclusion: GKRS is an effective treatment modality for the multidisciplinary management of patients with pituitary metastases. This minimally-invasive strategy is associated with optimal tumor control rate and low risk to adjacent optic nerves or neurovascular structures. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate local control (LC) of tumors, patient overall survival (OS), and the safety of stereotactic radiosurgery (SRS) for esophageal cancer brain metastases (EBMs)., Methods: This retrospective cohort study used data from 15 International Radiosurgery Research Foundation facilities encompassing 67 patients with 185 EBMs managed using SRS between January 2000 and May 2022. The median patient age was 63 years, with a male predominance (92.5%). Most patients (64.2%) had a single brain metastasis, while 7.5% had more than 5 metastases. The median tumor volume was 0.9 cm3, and the median margin dose delivered to the tumor was 20 Gy., Results: The median OS post-SRS was 15.2 months, with 1- and 2-year OS rates of 65.7% and 32.3%, respectively. A significant inverse correlation was found between the number of EBMs and OS in the univariable analysis. LC rates at 1 and 2 years were 89% and 76%, respectively. Adverse radiation effects (AREs) were observed in 17.9% of patients, with 13.4% being mild and transient and 4.5% severely symptomatic (Common Terminology Criteria for Adverse Events grade 3). New intracranial disease developed in 58.2% of patients, with 1- and 2-year rates of 58% and 73%, respectively., Conclusions: SRS for EBMs demonstrated high survival rates and effective tumor control, with a low incidence of severe AREs. These findings highlight the potential role of SRS in the multidisciplinary multimodality management paradigm of EBM.

Background: Intraventricular meningiomas (IVMs) are rare tumors with considerable treatment-associated morbidity due to their challenging location. Treatment with stereotactic radiosurgery (SRS) is sparsely reported in the literature. We describe our experience over the last 35 years using Gamma knife radiosurgery (GKRS) for IVMs. Methods: We retrospectively reviewed the GKRS database identifying 2501 meningiomas treated at the University of Pittsburgh Medical Center over the last 35 years. Nineteen patients with (12 males, mean age = 53.2 years, range 14–84) 20 IVMs were identified. Headache was the most frequent presenting symptom (N = 12), and the trigone of the lateral ventricle was the most common location (N = 18). The median tumor volume was 4.8 cc (range, 0.8–17). The median margin dose was 14 Gy (range, 12–25) delivered at 50% isodose line. Results: At a median follow-up of 63.1 months (range, 6–322.4) symptom control was achieved in 18 (94.7%) patients. The overall progression-free survival (PFS) was 95% at 5 years, and 85% at 10-years. After Log-rank test, patients who underwent GKRS within 12 months after diagnosis (vs. ≥ 12 months, X2: 4.455, p = 0.035), patients treated with primary GKRS without prior biopsy (vs. prior biopsy, X2: 4.000, p = 0.046), and patients with WHO grade I meningioma (vs. WHO II, X2: 9.000, p = 0.003) had a longer PFS. Imaging showed peritumoral edema in seven cases at a median of 10.5 (range, 6.13–24.3) months after GKRS. Only three of these patients were symptomatic and were successfully managed with oral medications. Cox´s regression revealed that a V12Gy ≥ 10 cc [HR: 10.09 (95% CI: 2.11–48.21), p = 0.004], and tumor volume ≥ 8 cc [HR: 5.87 (95% CI: 1.28–26.97), p = 0.023] were associated with a higher risk of peritumoral edema. Conclusion: GKRS is an effective and safe management option for intraventricular meningiomas. Early GKRS should be considered as a primary management modality for small and medium sized IVM and adjuvant management for residual IVMs. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant radiotherapy could damage the heart in left-sided breast cancer patients. The deep-inspiration-breath-hold technique may limit the heart exposure to radiation. As non-beneficiaries exist, there is some need to do an upfront cost-effective selection. Some easy-to-use anatomical predictors may help insiders in the treatment decision. The awareness of such findings may improve the efficiency of practitioners' workflows. Radiotherapy represents an essential part of the therapeutic algorithm for breast cancer patients after conservative surgery. The treatment of left-sided tumors has been associated with a non-negligible risk of developing late-onset cardiovascular disease. The cardiac risk perception has especially increased over the last years due to the prolongation of patients' survival owing to the advent of new drugs and an ever earlier cancer detection through screening programs. Improvements in radiation delivery techniques could reduce the treatment-related heart toxicity. The deep-inspiration-breath-hold (DIBH) irradiation is one of the most advanced treatment approaches, which requires specific technical equipment and uses inspiration to displace the heart from the tangential radiation fields. However, not all patients benefit from its use. Moreover, DIBH irradiation needs patient compliance and accurate training. Therefore, such a technique may be unjustifiably cumbersome and time-consuming as well as unnecessarily expensive from a mere healthcare cost point of view. Hence the need to early select only the true beneficiaries while tailoring more effective heart-sparing techniques for the others and streamlining the workflow, especially in high-volume radiation oncology departments. In this literature overview, we collected some possible predictors of cardiac dose sparing in DIBH irradiation for left breast treatment in an effort to provide an easy-to-consult summary of simple instruments to insiders for identifying patients actually benefitting from this technique. We critically reviewed the reliability and weaknesses of each retrieved finding, aiming to inspire new insights and discussions on this much-debated topic. [ABSTRACT FROM AUTHOR]

Introduction: There is a cumulative risk of 20-40% of developing brain metastases (BM) in solid cancers. Stereotactic radiotherapy (SRT) enables the application of high focal doses of radiation to a volume and is often used for BM treatment. However, SRT can cause adverse radiation effects (ARE), such as radiation necrosis, which sometimes cause irreversible damage to the brain. It is therefore of clinical interest to identify patients at a high risk of developing ARE. We hypothesized that models trained with radiomics features, deep learning (DL) features, and patient characteristics or their combination can predict ARE risk in patients with BM before SRT. Methods: Gadolinium-enhanced T1-weighted MRIs and characteristics from patients treated with SRT for BM were collected for a training and testing cohort (N = 1,404) and a validation cohort (N = 237) from a separate institute. From each lesion in the training set, radiomics features were extracted and used to train an extreme gradient boosting (XGBoost) model. A DL model was trained on the same cohort to make a separate prediction and to extract the last layer of features. Different models using XGBoost were built using only radiomics features, DL features, and patient characteristics or a combination of them. Evaluation was performed using the area under the curve (AUC) of the receiver operating characteristic curve on the external dataset. Predictions for individual lesions and per patient developing ARE were investigated. Results: The best-performing XGBoost model on a lesion level was trained on a combination of radiomics features and DL features (AUC of 0.71 and recall of 0.80). On a patient level, a combination of radiomics features, DL features, and patient characteristics obtained the best performance (AUC of 0.72 and recall of 0.84). The DL model achieved an AUC of 0.64 and recall of 0.85 per lesion and an AUC of 0.70 and recall of 0.60 per patient. Conclusion: Machine learning models built on radiomics features and DL features extracted from BM combined with patient characteristics show potential to predict ARE at the patient and lesion levels. These models could be used in clinical decision making, informing patients on their risk of ARE and allowing physicians to opt for different therapies. [ABSTRACT FROM AUTHOR]

IntroductionThere is a cumulative risk of 20–40% of developing brain metastases (BM) in solid cancers. Stereotactic radiotherapy (SRT) enables the application of high focal doses of radiation to a volume and is often used for BM treatment. However, SRT can cause adverse radiation effects (ARE), such as radiation necrosis, which sometimes cause irreversible damage to the brain. It is therefore of clinical interest to identify patients at a high risk of developing ARE. We hypothesized that models trained with radiomics features, deep learning (DL) features, and patient characteristics or their combination can predict ARE risk in patients with BM before SRT.MethodsGadolinium-enhanced T1-weighted MRIs and characteristics from patients treated with SRT for BM were collected for a training and testing cohort (N = 1,404) and a validation cohort (N = 237) from a separate institute. From each lesion in the training set, radiomics features were extracted and used to train an extreme gradient boosting (XGBoost) model. A DL model was trained on the same cohort to make a separate prediction and to extract the last layer of features. Different models using XGBoost were built using only radiomics features, DL features, and patient characteristics or a combination of them. Evaluation was performed using the area under the curve (AUC) of the receiver operating characteristic curve on the external dataset. Predictions for individual lesions and per patient developing ARE were investigated.ResultsThe best-performing XGBoost model on a lesion level was trained on a combination of radiomics features and DL features (AUC of 0.71 and recall of 0.80). On a patient level, a combination of radiomics features, DL features, and patient characteristics obtained the best performance (AUC of 0.72 and recall of 0.84). The DL model achieved an AUC of 0.64 and recall of 0.85 per lesion and an AUC of 0.70 and recall of 0.60 per patient.ConclusionMachine learning models built on radiomics features and DL features extracted from BM combined with patient characteristics show potential to predict ARE at the patient and lesion levels. These models could be used in clinical decision making, informing patients on their risk of ARE and allowing physicians to opt for different therapies.

• Hemorrhagic AREs display primordial cavernous-like changes and telangiectasias • Hemorrhagic AREs have been called cavernous-like malformations or pseudocavernomas • Gene sequencing shows variants in PIK3CA and PTEN but not in CCM genes • Mutations converge on pathways implicated in endothelial dysfunction Radiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations. We retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies. One lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes. Despite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study. [ABSTRACT FROM AUTHOR]

Purpose: The workshop on 'Individual Radiosensitivity and Radiosusceptibility' organized by MELODI and CONCERT on Malta in 2018, evaluated the current state of assays to identify sensitive and susceptible subgroups. The authors provide an overview on potential screening assays detecting individuals showing moderate to severe early and late radiation reactions or are at increased risk to develop cancer upon radiation exposure. Conclusion: It is necessary to separate clearly between tissue reactions and stochastic effects such as cancer when comparing the existing literature to validate various test systems. Requirements for the assays are set up. The literature is reviewed for assays that are reliable and robust. Sensitivity and specificity of the assays are regarded and scrutinized for modifying factors. Accuracy of an assay system is required to be more than 90% to balance risks of adverse reactions against risk to fail to cure the cancer. No assay/biomarker is in routine use. Assays that have shown predictive potential for radiosensitivity include SNPs, the RILA assay, and the pATM assay. A tree of risk guideline for radiologists is provided to assist medical treatment decisions. Recommendations for effective research include the setup of common retrospective and prospective cohorts/biobanks to validate current and future tests. [ABSTRACT FROM AUTHOR]

Introduction: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has been shown to reliably improve several symptoms of Parkinson's disease (PD) in appropriately selected patients. Various factors may preclude patients from undergoing DBS and for them, non-invasive lesion-based therapies such as focused ultrasound and Gamma Knife (GK) radiosurgery may present a safer alternative. Materials and Methods: Based on preliminary positive reports of STN GK for PD, we conducted a prospective, open-label, single-center, pilot study in PD patients deemed potential candidates for unilateral DBS based on their disease characteristics, but contraindicated due to age >74, an irreversible bleeding diathesis, or significant comorbid medical disease. Stereotactic MRI-guided GK radiosurgery was performed using a single 110- or 120-Gy dose targeting the STN contralateral to the more symptomatic extremity. Clinical follow-up and imaging assessed the safety and efficacy of the procedure over a 12-month period. Results: Four PD patients with medication-refractory tremors and disabling dyskinesias underwent unilateral STN GK radiosurgery. Contraindications to DBS included high-risk comorbid cardiovas-cular disease in 3 patients and an irreversible bleeding diathesis in 1. There were no immediate post-procedural adverse events. One patient who underwent left STN GK radiosurgery developed right hemiparesis and dysarthria 7 months post-procedure followed by hospitalization at 9 months for bacterial endocarditis and liver failure from which he died. The remaining 3 patients were free of adverse events up to 12 months post-procedure and experienced a reduction in contralateral rigidity, bradykinesia, and tremor. Upon extended follow-up, 2 patients developed subacute worsening of gait. One died at 16 months due to complications of a fall whereas the other saw no change in gait up to 42 months post-procedure. All 3 patients with adverse events demonstrated a hyper-response in the targeted area on follow-up neuroimaging. Discussion/Conclusion: Despite the potential for clinical improvement, our results suggest that unilateral STN GK radiosurgery should be approached cautiously in medically frail PD patients who may be at higher risk of GK hyper-response and neurologic complications. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the efficacy and safety of stereotactic radiosurgery (SRS) in treating transverse-sigmoid sinus dural arteriovenous fistulas (TSS DAVFs), and to investigate post-SRS sinus patency, focusing on the risk factors associated with treated sinus occlusion., Methods: Data from 34 patients treated with SRS between January 2006 and April 2023 were analyzed. Detailed angioarchitecture was confirmed using digital subtraction angiography before SRS. Angiography of the ipsilateral internal carotid artery and vertebral artery was performed to evaluate whether the involved side of the TSS was used for normal venous drainage. TSS stenosis was defined as sinus diameter < 50% of the normal proximal diameter. DAVF shunt obliteration, TSS occlusion, neurological status, and adverse events were also evaluated., Results: Of the 34 patients, 21 had Borden type I and 14 had Borden type II DAVFs. The median age at SRS was 64 years (interquartile range 54-71 years), and the follow-up period was 31 months (interquartile range 15-94 months). Complete shunt obliteration was achieved in 24 (70.6%) patients. The cumulative 2-, 3-, and 5-year shunt obliteration rates were 49.6%, 71.2%, and 86.0%, respectively. Borden type I had higher obliteration rates (60.5%, 83.1%, and 94.4%, respectively) than Borden type II (41.7%, 51.4%, and 75.7%, respectively; p = 0.034). TSS occlusion occurred in 5 patients (14.7%). The cumulative 1-, 5-, and 10-year TSS occlusion rates were 2.9%, 8.3%, and 23.6%, respectively, across the entire cohort. All occlusions occurred exclusively in the sinuses that were not used for normal venous drainage. Cox proportional analyses revealed that TSS stenosis and the sinus not being used for normal venous drainage were significantly associated with a greater risk of TSS occlusion after SRS (HR 9.44, 95% CI 1.01-77.13; p = 0.049)., Conclusions: SRS is effective and safe for TSS DAVF and results in favorable shunt obliteration, symptom improvement, and low complication rates. TSS occlusion after SRS is asymptomatic and is limited to sinuses that are not used for normal venous drainage.

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Highlights • Severe adverse radiation effects may occur following radiosurgery to brain AVM. • Severe adverse radiation effects may be refractory to medical therapy. • Surgical cytoreduction of treated nidus can result in rapid clinical improvement. • Early surgery may avoid the adverse consequences of prolonged steroid treatment. Abstract Treatment of brain arteriovenous malformations (AVM) with stereotactic radiosurgery is rarely complicated by severe adverse radiation effects (ARE). The treatment of these sequelae is varied and often ineffectual. We present three cases of brain AVMs treated with SRS, all complicated by severe AREs. All three cases failed to respond to what is currently considered the standard treatment – corticosteroids – and indeed one patient died as a result of the side effects of their extended use. Two cases were successfully treated with surgical excision of the necrotic lesion resulting in immediate clinical improvement. Having considered the experience described in this paper and reviewed the published literature to date we suggest that surgical treatment of AREs should be considered early in the management of this condition should steroid therapy not result in early improvement. [ABSTRACT FROM AUTHOR]

Background: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy. Methods: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm3. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy. Results: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery. Conclusions: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event. [ABSTRACT FROM AUTHOR]

Background: Adverse radiation effects (AREs) can occur after stereotactic radiosurgery (SRS), and symptomatic cases are often treated with corticosteroids, pentoxifylline, and vitamin E. The supplement 5-Loxin (Boswellia serrata) is an extract of Indian frankincense that inhibits vascular endothelial growth factor expression and has been shown to reduce perilesional edema in brain tumor patients undergoing fractionated radiation., Observations: Three patients underwent SRS for meningioma or metastasis and developed symptomatic AREs at 4 to 8 months. They were initially treated with corticosteroids, pentoxifylline, and vitamin E with transient improvement followed by recurrent neurological symptoms and imaging findings as steroids were tapered off. All patients were rescued by the administration of 5-Loxin with resolution of neurological symptoms and imaging changes, discontinuation of steroids, and no medication side effects., Lessons: The author's early experience with 5-Loxin has been encouraging, and this supplement has become the author's first-line treatment for acute radiation effects after SRS. The author reserves bevacizumab for significant mass effect or failure of oral therapy. 5-Loxin has many advantages including low cost, ease of use, and patient tolerability. More experience is needed to confirm the role of 5-Loxin in the upfront treatment of AREs.

Introduction: Post-radiation injury of patients with brain arteriovenous malformations (AVM) include blood-brain barrier breakdown (BBBB), edema, and necrosis. Prevalence, clinical relevance, and response to treatment are poorly known. We present a series of consecutive brain AVM treated with stereotactic radiosurgery describing the appearance of radiation injury and clinical complications. Methods: Consecutive patients with annual clinical and radiological follow-up (median length 63 months). Edema and BBBB were classified in four groups (minimal, perilesional, moderate, or severe), and noted together with necrosis. Clinical symptoms of interest were intracranial hypertension, new neurological deficits, new seizures, and brain hemorrhages. Results: One hundred two cases, median age 34 years, 52 % male. Median irradiated volume 3.8 cc, dose to the margin of the nidus 18.5 Gy. Nineteen patients underwent a second radiosurgery. Only 42.2 % patients remained free from radiation injury. Edema was found in 43.1 %, blood-brain barrier breakdown in 20.6 %, necrosis in 6.9 %. Major injury (moderate or severe edema, moderate or severe BBBB, or necrosis) was found in 20 of 102 patients (19.6 %). AVM diameter >3 cm and second radiosurgery were independent predictors. Time to the worst imaging was 60 months. Patients with major radiation injury had a hazard ratio for appearance of focal deficits of 7.042 ( p = 0.04), of intracranial hypertension 2.857 ( p = 0.025), hemorrhage into occluded nidus 9.009 ( p = 0.079), appearance of new seizures not significant. Conclusions: Major radiation injury is frequent and increases the risk of neurological complications. Its late appearance implies that current follow-up protocols need to be extended in time. [ABSTRACT FROM AUTHOR]

Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy. [ABSTRACT FROM AUTHOR]

The anterior visual pathway (AVP) can be at risk during gamma knife surgery (GKS). There is no standardised published methodology for protecting the AVP. This paper suggests such an approach in relation to the treatment of meningiomas. There were 67 patients with a mean age of 48.8 years and a minimum follow-up of 25 months. A recent perimetry was available on the day of treatment. The visual pathway was outlined and the maximum radiation dose was recorded. In some cases a dose volume histogram (DVH) of the AVP was constructed to assess the volume receiving more than the desired maximum dose. The aim was a maximum dose between 8 and 10 Gy. A principle of sub-optimal dose planning was used to protect vision. Follow-up included new visual field examinations. Various anatomical locations place different parts of the AVP at risk. No patient suffered a deterioration of vision. In 21 (38.7%) patients there was an improvement in the visual field and in 7 (44%) associated diplopia improved. Vision could improve without corresponding tumour shrinkage. A standard measure of radiation toleration of the AVP could be the maximum dose within its volume, probably at least 10 Gy. Computerised perimetry should be available on the day of treatment and at follow-up. There is no need to have a distance between the tumour margin and the visual pathway. Sub-optimal dose-planning has been advantageous. Improvement in vision is not necessarily a consequence of tumour shrinkage. [ABSTRACT FROM AUTHOR]

Abstract: Background: Adverse radiation effects are a known complication after the use of SRS for AVMs, although it is difficult to predict which patients will manifest with these side effects. Treatment of swelling due to ARE is usually medical, but refractory cases may require surgical decompression. Case Description: This report presents a case of a patient who experienced AREs after SRS (edema, headaches, and nausea) that failed to respond to steroid treatment but was successfully treated with HBO. The treatment characteristics of this and of 5 other cases of radiation injury after SRS for AVM managed with HBO therapy are reviewed, and the pathophysiology is discussed. Conclusion: Hyperbaric oxygen therapy provides a therapeutic option to treat AREs following SRS of cerebral AVMs. [Copyright &y& Elsevier]

The relationship between target volume and adverse radiation effects (AREs) at low prescription doses requires elucidation. The development of AREs in three series of patients treated in the Gamma Knife is analysed in relation to prescription dose and target volume. There were three groups. In group 1, there were of 275 patients with meningiomas; in group 2, 132 patients with vestibular schwannomas; and in group 3, 107 patients with arteriovenous malformations (AVMs). The minimum follow-up for each group was more than 24 months. All patients were followed up at six monthly intervals. The patients with tumours received a prescription dose of 12 Gy, which was varied to protect normal structures but not in relation to tumour volume per se. The desired AVM prescription dose was 25 Gy, but this was also reduced to protect normal structures and to keep the total dose within certain pre-defined limits. All AREs refer to intra-parenchymal increased perilesional T2 signal on MR irrespective of clinical correlation. There was no relationship between tumour volume and the development of ARE in the tumour groups. There was a highly significant relationship between target volume and the development of ARE for the AVMs with their much higher dose. Radiation-induced clinical trigeminal and facial nerve deficits with both vestibular schwannomas and meningiomas were always associated with an increased T2 signal in the neighbouring brainstem parenchyma. The relationship between target volume and the risk of adverse radiation effects may not apply with lower prescription doses. Individual radiosensitivity may explain why a minority suffer AREs unrelated to target volume. It is possible that radiation-induced brainstem parenchymal damage with concomitant cranial nerve deficits may be commoner after radiosurgery than is usually thought. If tumour control with lower doses is adequate, radiosurgery could be safely considered for larger targets associated with a high risk from microsurgery [ABSTRACT FROM AUTHOR]

The treatment of arteriovenous malformations (AVMs) has evolved over the last 10 years. It is now possible to see that obliteration continues for up to 10 years and that the final obliteration rate may be between 85% and 90%. Improved imaging has made the treatment more efficient and has reduced the complications. It is possible to treat larger AVMs in a single session than was previously thought possible without increases in the complication rates. In addition, treatments of larger lesions can be staged. The use of 3D rotating angiography produces remarkable images which can be imported into GammaPlan. On the other hand efforts are ongoing to avoid the need for digital subtraction angiography, which would make the treatment a lot more comfortable., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy., Methods: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm3. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy., Results: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery., Conclusions: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event., (© 2017 S. Karger AG, Basel.)

Background and Purpose: We evaluated risk factors associated with the development of adverse radiation effects (ARE) after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs)., Methods: We evaluated 755 patients with AVM who underwent a single Gamma Knife SRS procedure with at least a 2-year minimum follow-up. Eighty-seven patients (12%) underwent previous resection and 128 (17%) had previous embolization. The median target volume was 3.6 mL (range, 0.1-26.3 mL). The median margin dose was 20 Gy (range, 13-27 Gy)., Results: Fifty-five patients (7%) developed symptomatic ARE at a median follow-up of 75 months. The cumulative rates of symptomatic ARE were 3.2%, 5.8%, 6.7%, and 7.5% at 1, 2, 3, and 5 years, respectively. Factors associated with a higher rate of developing symptomatic ARE included larger AVM volume, higher margin dose, larger 12-Gy volume, higher Spetzler-Martin grade, and higher radiosurgery-based score. The rates of developing symptomatic ARE were higher in the brain stem (22%) or thalamus (16%), compared with AVMs located in other brain locations (4%-8%). Nineteen patients (3%) sustained irreversible new neurological deficits related to ARE, and 1 patient died. The rates of irreversible symptomatic ARE were 0.8%, 1.9%, 2.1%, and 2.8% at 1, 2, 3, and 5 years, respectively. The 5-year cumulative rates of irreversible symptomatic ARE were 9.1% in thalamus, 12.1% in brain stem, and 1.4% in other locations., Conclusions: The knowledge of ARE risk rates after AVM radiosurgery can assist informed consent for patients with AVM, their families, and healthcare providers., (© 2016 American Heart Association, Inc.)

OBJECTIVE Vestibular schwannomas (VSs) represent a common indication of Gamma Knife surgery (GKS). While most studies focus on the long-term morbidity and adverse radiation effects (AREs), none describe the acute clinical AREs that might appear on a short-term basis. These types of events are investigated, and their incidence, type, and outcomes are reported in the present paper. METHODS The included patients were treated between July 2010 and March 2016, underwent at least 6 months of follow-up, and presented with a disabling symptom during the first 6 months after GKS that affected their quality of life. The timing of appearance, as well as the type of main symptom and outcome, were noted. The prescribed dose was 12 Gy at the margin. RESULTS Thirty-five (22%) of 159 patients who fulfilled the inclusion criteria had acute clinical AREs. The mean followup period was 30 months (range 6-49.2 months). The mean time of appearance was 37.9 days (median 31 days; range 3-110 days). In patients with de novo symptoms, the more frequent symptoms were vertigo (n = 4; 11.4%) and gait disturbance (n = 3; 8.6%). The exacerbation of a preexisting symptom was more frequently related to hearing loss (n = 10; 28.6%), followed by gait disturbance (n = 7; 20%) and vertigo (n = 3, 8.6%). In the univariate logistic regression analysis, the following factors were statistically significant: age (p = 0.002; odds ratio [OR] 0.96), hearing at baseline by Gardner-Robertson (GR) class (p = 0.006; OR 0.21), pure tone average at baseline (p = 0.006; OR 0.97), and Koos grade at baseline (with Koos Grade I used as a reference) (for Koos Grade II, OR 0.17 and p = 0.002; for Koos Grade III, OR 0.42 and p = 0.05). The following were not statistically significant but showed a tendency toward significance: the number of isocenters (p = 0.06; OR 0.94) and the maximal dose received by the cochlea (p = 0.07; OR 0.74). Fractional polynomial regression analysis showed a nonlinear relationship between the outcome and the radiation dose rate (minimum reached at a cutoff of 2.5 Gy/minute) and the maximal vestibular dose (maximum reached at a cutoff of 8 Gy), but the small sample size precludes a detailed analysis of the former. The clinical acute AREs disappeared in 32 (91.4%) patients during the first 6 months after appearance. Permanent and somewhat disabling morbidity was found in 3 cases (1.9% from the whole series): 1 each with complete hearing loss (GR Class I before and V after), hemifacial spasm (persistent but alleviated), and dysgeusia. CONCLUSIONS Acute effects after radiosurgery for VS are not rare. They concern predominantly de novo vertigo and gait disturbance and the exacerbation of preexistent hearing loss. In de novo vestibular symptoms, a vestibular dose of more than 8 Gy is thought to play a role. In most cases, none of these effects are permanent, and they will ultimately improve or disappear with steroid therapy. Permanent AREs remain very rare.