Purpose/Objective

Brain metastases are common in patients with metastatic melanoma. Poor local control and cognitive consequences mean that the indications for Radiosurgery continue to increase. We analyze the effectiveness of treatment with radiosurgery. We try to evaluate the safety and initial response of brain metastases treated with immunotherapy or a combination of targeted therapy and radiosurgery with gamma knife.

Material/Methods

We present our experience with 25 treatment sessions in the Leksell gamma unit in 8 patients with metastatic melanoma, 7 of whom underwent treatment concurrently with immunotherapy or a combination of targeted therapies.

Results

The population was composed of 7 men and 1 woman. The average age of the patients was 64 years (age range, 42-75 years). The median time from diagnosis of primary melanoma to discovery of brain metastasis was 35 months (range, 1-132 months). At the time of diagnosis of the brain disease, 50% of the patients had neurological symptoms, only one patient debuted with seizures. 95% developed lymph node metastases. Eighty-six percent of the lesions were cortical, 13% were cerebellar, 1% were thalamic. 88% of the sessions (22 of 25 sessions) were treated in a single session. The mean treatment volume was 3 cc, with a mean prescription of 22 Gy up to the mean 60% isodose line. Median survival was 42 months from the time of diagnosis of primary melanoma and 7 months from Gamma knife radiosurgery. No complications occurred within 24 hours after the procedure; 3 of the patients presented with mild headache, nausea and transient vomiting. Our series has a short following. There was 1 death due to intracranial hemorrhage in the third month of treatment and in relation to disease progression. In the magnetic resonance images, 3 patients with at least 5 treated lesions progressed after the first 3-month control, the rest of them remain with stable disease. Tolerance to treatment was good.

Conclusion

Concurrent treatment with immunotherapy or a combination of targeted therapy and gamma knife radiosurgery does not seem to increase toxicity; in our series, those patients who have progressed the earliest are those with 5 or more lesions.

[Objectives] Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment. We compared the treatment results of brain metastases with those of the primary tumor.

[Methods] We retrospectively analyzed 1635 patients (a total of 2394 treatments) with brain metastases who underwent Gamma Knife Icon using mask fixation between September 25th, 2017 and December 31th, 2023 at Rakusai Shimizu Hospital. Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. For large tumors, we selected fractionated schedules as follows; 4.2-4.7Gy x 10Fr (5-20ml), 3.7-4.2Gy x 10Fr (20-30ml), 3.2-3.7Gy x 10Fr (30ml-). If the tumor number was large, we selected a multisession schedule.

[Results] The most common origin was lung (1103 patients, 1646 times), followed by breast (183, 287), gastro-intestinal (GI) tracts (176, 221), urogenital (104, 150), and others (69, 90). Tumor volume tended to be larger in GI tracts and urogenital. Single session tended to be more common in urogenital, and fractionated schedule tended to be more common in GI tract. The median survival time after icon therapy was 27.6 months for lung, 26.6 months for breast, 6.9 months for GI tract, and 14.4 months for urogenital. There were no differences in neurological death, local control, ADL maintenance, and serious complications among the groups.

[Conclusions] Although these results are limited to short periods, survival rates, local control rates and qualitative survival rated in patients unsuitable for stereotactic radiosurgery, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges among various primary sites.

Title: Stereotactic Radiosurgery using the Mask System of Leksell Gamma Knife Icon for Patients with Over Ten Brain Metastases.

Authors: Yuta Oi, Gaku Fujiwara, Takuya Kawabe, Manabu Sato
Maizuru Medical Center, Rakusai Shimizu Hospital

Purpose: Following the JLGK0901 report, guidelines for multiple brain metastases have been revised, easing limitations on stereotactic radiotherapy based on tumor numbers. We present initial results of treatment utilizing the Gamma Knife Icon's mask system for over 10 metastatic brain tumors.

Methods: We retrospectively reviewed 280 patients (comprising 329 treatments) with brain metastases who underwent Gamma Knife Icon treatment using mask fixation between September 25th, 2017, and December 31st, 2023, at Rakusai Shimizu Hospital. The cohort included 146 males and 134 females, with a median age of 69 years (range: 20-93). The most prevalent primary tumor sites were lung (207 patients, 245 treatments), followed by breast (40, 47), gastro-intestinal (17, 19), and others (16, 18). The median number of tumors was 16 (range: 11-64), with a median maximum tumor volume of 1.3 mL (IQR: 0.3-5.0) and a median cumulative tumor volume of 3.4 mL (IQR: 1.1-10.4).

Patients with large, recurrent, or eloquent lesions received fractionated irradiation. Irradiation time with mask fixation was divided into multiple sessions, approximately 30 minutes each, based on patient comfort. The median treatment time was 31.1 minutes (IQR: 25.8-38.9).

Results: Median survival post-Icon therapy was 9.9 months, with only 3/8/11% experiencing neurological death at 6/12/24 months post-treatment. Local control failure rates were 7/13/23% at 6/12/24 months after treatment. New lesions emerged in 16/56/67/72/76/80% of patients at 3/6/9/12/15/18 months post-treatment, requiring early intervention as deemed necessary. Preservation of neurological function measured at 6/12/24 months post-treatment was 92/86/83%. Serious complications were observed in 0/1/1% at 6/12/24 months post-treatment.

Conclusions: While the medium- to long-term efficacy requires further follow-up, our findings suggest that highly accurate fractionated irradiation and multiple irradiation sessions are feasible using the Gamma Knife Icon, potentially leading to reduced treatment complications.

Purpose: We have developed a novel GK-specific knowledge-based planning (KBP) pipeline utilizing 3-dimensional dose prediction in conjunction with inverse optimization (IO) for the generation of deliverable treatment plans.

Methods: Data was obtained for 349 patients treated for either brain metastases or intracranial schwannomas at Sunnybrook Health Sciences Centre. The data from 322 patients was modified using a GK-specific data modification method, then used to train a neural network model for GK dose prediction. The trained model was then applied to predict dose predictions for 27 out-of-sample patients.

Subsequently, we developed a generalized IO model, based on an established inverse planning model¹, to learn objective function weights from dose predictions. This model was solved using the obtained dose predictions for the out-of-sample patients. The resulting weights were then used in the inverse planning model to generate deliverable treatment plans.

The quality of the resulting KBP plans was compared to manual clinical plans and plans resulting from a dose mimicking (DM) model using standard GK quality metrics and overall treatment time. Finally, we evaluated the overall average usage time of the pipeline and plan delivery characteristics to help determine its potential applicability in a clinical setting.

Results: Across all quality metrics, plans generated using the KBP pipeline performed at least as well as or better than the respective clinical plans. The average conformity and gradient of IO plans were 0.737 ± 0.158 and 3.356 ± 1.030, respectively, compared to 0.713 ± 0.124 and 3.452 ± 1.123 for the clinical plans. IO plans also outperformed DM plans for five of the six quality metrics. Additionally, plans generated using the IO pipeline had an average treatment time comparable to clinical plans.

The average time required to generate deliverable plan using the pipeline was 5 minutes 43 seconds and varied depending on target complexity. Compared to clinical plans, KBP plans utilized block sectors significantly more frequently and 4 mm collimators significantly less frequently. Additionally, KBP plans favor using multiple shots per isocenter in contrast to manual clinical plans, which are based on one shot per isocenter.

Conclusion: Plans resulting from an IO KBP pipeline consistently match or surpass the quality of manual plans. The results demonstrate the potential for the usage of KBP to generate GK treatment plans with minimal human intervention. 

Background:    The safety of a radiosurgery plan may be estimated based upon metrics of radiation dose (e.g. V12Gy) which are only available after a plan has been created and may be a function of the planning system, platform, or planner.   Using a standardized automated treatment planning system for single isocenter multiple target radiosurgery (HyperArc^TM) which produces consistent plan quality generally independent of planning expertise, we hypothesize that geometric metrics of brain metastases will predict V12 and inform the treating team to select radiosurgery prescription prior to planning.

Methods:        HyperArc^TM clinical plans utilizing a single isocenter for all targets were queried to investigate the utility of various pre-planning geometric metrics to predict V12 (prescription doses 20 Gy and 24 Gy) and V18 (9Gy x 3).   A total of 1717 clinical radiosurgery plans included 3399 targets. These plans were generated without an explicit target margin and planned for treatment delivery using an Edge^TM linear accelerator with a high-definition multi-leaf collimator (central resolution 2.5mm).   The target hotspot was not penalized in the optimizer.   The volume of the target was included in the V12 calculations.   V12 was calculated per lesion unless this isodose volume bridged between targets, in which the targets were excluded from the analysis.   Potential predictive geometric measures included target volume, equivalent sphere diameter, largest axial diameter, mesh surface area, and pseudo surface area.

Results:           All the pretreatment geometric metrics had some utility to predict V12.  The best fit to predict V12 (and V18 for 3 fractions) was for target volume.   Linear and power models were generated for various radiation dose schedules.  An example linear equation to predict V12Gy for a 20 Gy prescription is shown below:

V12Gy(cc) = 2.22*targetvolume + 1.84

This linear equation predicts V12Gy of 10cc occurs with a target volume of ~3.7 cc for a 20 Gy prescription for a HyperArc^TM plan treated with the HD-MLC.

Conclusions:   Target volume and other geometric predictors can be utilized to predict dosimetric measures of radiosurgery toxicity for automated single isocenter VMAT (HyperArc^TM) radiosurgery.   This knowledge prior to planning allows the treating team to run a single plan iteration with the optimal prescription.

Background:

Brain metastases can significantly increase patient morbidity. Stereotactic radiosurgery (SRS) is an effective technique for treatment and can improve quality of life. Earlier detection of brain metastases when compared to standard T1 magnetic resonance imaging (MRI) may lead to improved outcomes.

Purpose:

We created a machine learning (ML) model using longitudinal diffusion weighted images (DWI) and radiomics to improve detection of brain metastases in SRS patients.

Methods:

We analyzed 117 patients who had received multiple imaging sessions prior to SRS. Apparent diffusion coefficient (ADC) maps, contrast enhanced Gd-T1 MRI, and clinical computed tomography images from all time points were registered for each patient. Radiomic maps were calculated for every ADC map. Data features were extracted by generating spherical binary masks with a radius of 1 cm and sampling both healthy and metastatic regions within the brain. Difference features were added to the dataset by calculating the radiomic change between imaging sessions. Radiomic stability was used to select features by sampling healthy brain tissue with no known abnormalities. Features that were unstable (mean intraclass correlation coefficient < 0.75) were excluded from further analysis. Clinical features (age, gender, and primary cancer) were included for ML training. Final output labels were based on whether a metastasis was clinically confirmed within a sampled region during imaging.

The dataset was split 80/20 training-validation with stratification. XGBoost was used for training, with hyperparameters tuned using five-fold group cross validation, prioritizing macro-averaged recall. Standard classification metrics were calculated on the unseen validation dataset to assess model performance in detecting metastatic growth from patient ADC maps. A cerebellum-only ML model was created and tested, with cerebrum data to be calculated and trained in the future.

Results:

XGBoost was able to correctly identify metastatic tissue within the cerebellum prior to manifestation on Gd-T1 (balanced accuracy: 74.8±0.4%, recall: 84.7±0.4%). The area under the receiver operating characteristic was 86.0±0.4%. Local ADC intensity variance was the most important radiomic feature. The patient’s age and whether they received a melanoma diagnosis were the most important clinical features for the model to classify potential metastases.

Conclusions:

A DWI-based radiomics model was developed and trained using longitudinal SRS imaging data. Our cerebellum model results suggest that ML can be effective in detecting brain metastases. This can aid clinicians in deciding whether increased monitoring via imaging is recommended. Future work includes training the cerebrum model and prospective testing on patients with high metastatic incidence rates.

Purpose: Advances in systemic therapy for driver mutation-positive lung cancer brain metastases have prolonged prognosis. We investigated treatment strategies using Gamma Knife Icon.

Objective: We retrospectively analyzed 229 patients (a total of 388 treatments) with brain metastases who underwent Gamma Knife Icon using mask fixation between September 25th, 2017 and August 31th, 2023 at Rakusai Shimizu Hospital. Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. If the tumor number was large, we selected a multisession schedule. The most common driver mutation was EGFR mutation (193 cases), followed by ALK fusion (23), and others (KRAS, BRAF, ROS-1, RET, MET, ERBB2) (13). There were 87 males and 142 females with a mean age of 69 (34-89) years. Seventy patients had both primary tumor and brain metastasis, and 159 patients had brain metastasis after prior treatment of the primary tumor. The median number of metastases was 4 (IQR: 1-8), and the median maximum lesion volume was 0.6 (IQR: 0.2-2.7) mL.

Results: Single session was performed 118 times, fractionation 156 times, and multisession 114 times. The median survival after Icon therapy was 51.8 (95%CI:47.6-NA) months, including 53.3 months for EGFR-positive patients and 51.8 months for ALK-positive. Neurological death was only 2/4/4/7% at 12/24/36/48 months after treatment. Local control failure was 18/31/38% at 12/24/36 months after treatment. New lesions appeared in 49/65/71% at 12/24/36 months after treatment. Preservation of neurological function was 93/88/86% at 12/24/36 months post-treatment. Serious complications were only 1/1/1% at 12/24/36 months after treatment.

Conclusions: Although these results are limited to short periods, survival rates, local control rates and qualitative survival rated in patients unsuitable for stereotactic radiosurgery, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges.

Objective:

We compare the clinical outcome of patients with <10 radiosurgically treated brain metastases (BM) to patients with ≥10 BM.

Methods:

A retrospective analysis of all patients with an age >18 years, at least one Gamma Knife radiosurgical treatment (GKRS) for at least one BM between 2012 and 2022 and at least one follow-up was performed. Based on the number of BM on the planning MRI, the patients were divided into two groups: 1) <10 BM and 2) ≥10 BM.

Results:

In our study population, 1253 patients with radiosurgically treated BM from different primary tumors (lung cancer = 795/1253, 63%; melanoma = 261/1253, 16% and breast cancer = 197/1253, 21%) could be identified. 

At the time of first GKRS treatment (GKRS1), 115/1253 (9%) patients had more than 10 BM. The estimated median survival after GKRS1 did not show any significant differences between patients with <10 BM and ≥10 BM, even after analyzing for each primary tumor. Furthermore, even in patients with worse clinical condition, defined as a Karnofsky Performance Status Scale of <80%, the estimated median survival after GKRS1 did not differ between patients with <10 and ≥10 BM.

Conclusion: 

GKRS represents an effective treatment option for patients with multiple BM, even with more than 10 BM. 

Objectives: The management of large posterior fossa metastases presents a unique challenge in neuro-oncology, demanding an approach that balances efficacy, safety, and preservation of neurological function. Traditionally, the treatment paradigm for large brain metastases, particularly those in the posterior fossa, has heavily relied on surgical resection. In recent years, hypofractionated Gamma Knife radiosurgery (hf-GKRS) has emerged as a promising modality, offering a targeted, minimally invasive approach with a favorable side-effect profile. This retrospective, single-center study evaluated patient outcomes of upfront frameless hf-GKRS for large posterior fossa metastases. 

Methods: Thirty-one patients with 37 large (>4 cm³) posterior fossa metastases were included for analysis. There were 20 male patients, and the median age of the patients was 64 years (range, 26-83 years). The most common primary diagnosis was non-small cell lung cancer (n=12). The median target volume was 8.1 cm³ (range, 4.10 cm³-34.80 cm³). hf-GKRS was administered in 3 daily fractions for 11 lesions (median volume=6.7 cm³) and 5 daily fractions for 26 lesions (median volume=8.25 cm³). The median total dose to the margin was 30 Gy (range, 24-30 Gy), with a dose per fraction of 6 Gy (range, 5-9 Gy). Key outcomes assessed included local control, distant progression-free survival, overall survival, and associated toxicities.

Results: The mean follow-up was 12.6 months (range, 2-44 months). LC was achieved in 89.2% of metastases. LC estimates at 6, 12, and 24 months were 100%, 92.9%, and 69.6%, respectively. Distant progression-free survival rates were 73.3% at six months, decreasing to 55.9% at one year. At the end of the follow-up, 83.9% of patients were alive. Radiation necrosis occurred in 2 patients (8.1%), while no cases of leptomeningeal disease were observed.

Conclusions: A high tumor control rate was achieved over sufficient follow-up, which demonstrates the efficacy and safety of upfront hypofractionation in unresected, large posterior fossa metastases in selected patients.

Prupose:

SRS offers a non-invasive alternative to surgery. Linac-based SRS typically uses DCA and VMAT. Currently no unified guidelines exist for selecting the best technique based on lesion geometry, crucial for high-conformity single lesion treatments. This study provides radiation therapists with a tool to evaluate DCA and VMAT for various tumor sizes and shapes, thereby optimizing technique selection to improve outcomes.

Material and method:

75 brain lesions from 19 patients were analyzed. For patients with multiple lesion, separate plans were created. The objective was to assess the percentage differences in the Conformity Index (DeltaCI) and the Spillage Index (DeltaDSI) as benchmarks for technical selection in the treatment of brain lesions, while also examining the influence of lesion size and asymmetry. This method enabled a detailed analysis of the percentage differences in CI and DSI for individual lesions and the identification of discrepancies between both techniques (Tab.1). Effects such as increased CI with smaller volumes or enhanced spillage with larger volumes were thus minimized. The lesions were categorized based on their volumes into 4 categories, category 1 up to 1 ml, category 2 1-2 ml, category 3 3-4 ml, and category 4 >4 ml, therefore identical field geometry was used for both VMAT and DCA-plans to ensure a fair comparison. Geometric parameters such as sphericity and an innovative asymmetry index Qasym (relates the maximum diameter of the lesion to the effective diameter derived from the lesion volume) were utilized for an in-depth examination, to understand and potentially improve how lesion size and shape influence technical selection.

Results:

Scatter plot (Fig. 1) illustrates the relationships between DeltaCI, DeltaDS90%, DeltaDS50%, and DeltaDS25% relative to Qasym across four defined volume categories. These visuals emphasize the correlation between Qasym and dosimetric differences. Our findings indicate that for smaller lesions (categories 1 and 2) with Qasym values ≥ 1.2, VMAT shows better dose conformity and less spillage than DCA. In larger lesions (>2 ml, categories 3 and 4), VMAT consistently outperforms DCA, highlighting its benefits for treating both larger lesions and smaller lesions with higher Qasym values.

Conclusion:

Our study provides guidance for choosing between DCA and VMAT in treating intracranial lesions. For lesions >2 ml or with a Qasym over 1.2, VMAT is preferred due to DCA's limitations. For smaller lesions up to a Qasym of 1.2, DCA is recommended. This approach helps assess the most suitable technique based on lesion size and asymmetry.

Objective: Multi-fraction, mask-based stereotactic radiosurgery (SRS) expands the patient cohort amenable to Gamma Knife (GK) SRS, specifically large lesions and lesions in close proximity to eloquent areas of the brain.  However, mask-based GK Icon (GKI) treatment could also potentially allow more patient inter- and intra-fraction motion which could result in compromising the original treatment objectives, including loss of target coverage, excess organ at risk doses, etc.  In this study, a patient-based motion model using pre-treatment cone beam CT (CBCT) was created.  The dosimetric effects of this uncertainty model are presented and any correlation to lesion characteristics investigated.

Methods: A retrospective cohort study of 227 lesions in 100 patients receiving five fraction GKI SRS between April 2018 to May 2022 was conducted.  Each of the five daily set up CBCT taken prior to treatment delivery was retrospectively defined as the stereotactic reference coordinate system and the treatment dose distribution was calculated on this shifted reference system.  These five shifted three-dimensional doses were subtracted from the original dose distribution and summed to create a mean and standard dose uncertainty for each treatment plan.  Dose volume histograms were extracted to determine the effect of the dosimetric uncertainty on target coverage and dose falloff.

Results: The percent dosimetric uncertainty for the dose covering 99% and 1% of the target was 0.04±0.83% and -0.54±0.69% (average and 95% confidence interval), respectively.  All dosimetric uncertainties were less than 0.75% for both single and multiple lesions treated in a session.  The percent dosimetric uncertainty was showed no dependence on target size, obliquity, volume or position.  Linear fits of the uncertainty versus these variables all yielded fitting parameters consistent with zero.  In this dosimetric uncertainty model, the dose to 95% of a one-millimeter shell inside of target was found to be 104% the target prescription dose and average dose to a one millimeter shell outside the target was 101% the prescribed dose. 

Conclusions: Within the patient-specific dosimetric uncertainty model, five fraction GKI SRS treatments caused minimal deviations from the intended dose distribution when both single and multiple targets are treated.  The dosimetric uncertainty was independent of any lesion characteristic, and also demonstrated that target coverage and dose falloff were not compromised.  This model approximates the maximum inter- and intra-fraction motion during mask-based treatment, and that five fraction can be delivered safely.  However, any uncertainty model needs to include patient outcomes to determine true clinical significance.

Purpose: The irradiated metastatic brain tumor (BM) has been investigated with cell-type based approach. Single-cell level discoveries revealed the cell-states have a critical role in tumor biology and, its cell-state-specific response was not reported in the irradiated BM. Preoperative stereotactic radiosurgery (SRS) is a new paradigm, and it enabled post-irradiation radiation biology study. Here, we aimed to find biological responses and cell-state specific dynamics after preoperative SRS: especially focusing on preoperative gamma knife surgery (or neoadjuvant gamma knife surgery, neoGKS).

Methods and Materials: From 2008 to 2022, a retrospective analysis was done on a total of 120 patietns treated at a single institution. Among them, we examined the transcriptomic data with deconvolution analysis. Irradiated neoGKS samples were validated with immunohistochemistry, western blot, RNA-sequencing (neoGKS n = 9 vs control n = 10).

Results: neoGKS group showed apoptosis and DNA damage responses. Transcriptomic analyses confirmed the post-irradiation change with the overexpression of CDKN1A, MDM2, and B2M in the neoGKS group than the control group (P < 0.01). Deconvolution revealed that neoGKS reduced the tumor-cell-state score (P < 0.01) and elevated immune-cell-state score after neoGKS (P = 0.012).

Conclusions: Transcriptome revealed neoGKS irradiation-associated gene expression and cellular-state-wise dynamics. The significantly reduced tumor-cell-state score after neoGKS may support post-

resection survival benefit after neoGKS. Transcriptome-based cell-state-specific changes would be applied to compare different preoperative SRS modalities and make optimized irradiation plans.

Purpose: Single isocenter dynamic conformal arc stereotactic radiosurgery using Elements software and Exactrac system (BrainLab^TM) allows to treat multiple brain metastases. Factors that may influence the effectiveness of this method should be evaluated. Our study aimed was to assess the effectiveness of a linac-based single-isocenter SRS (SI-MM-SRS) for multiple brain metastases in relation to various clinical factors

Methods: The analysis included a group of 123 patients with MBM lesions (median 4, range 2-12) treated at the Department of Neurooncology and Radiosurgery at Franciszek Lukaszczyk Oncology Center in Bydgoszcz between 02.08.2018 r. and 15.09.2020 r. A total of 560 brain metastases were treated. The minimum follow-up was 12 months and the median follow-up was 23 months. All patients were treated with the BrainLab Elements MultiMets software using single isocenter Dynamic Conformal Arcs. The ExacTrac system was used to monitor the position during SRS. Thirty-six patients with 195 metastatic lesions had follow-up MRI 6 months after treatment, 36% received immunotherapy within 4 months of SRS. Local control was analyzed with RANO criteria.

Results: Sixteen percent of patients was still alive in time of analysis (>3 years of fu). The 6- and 12-months rate was 60% and 33%. In the multivariate
analysis the sum of PTV volumes (p=0.0007) but not a number of lesions was related to survival. Patients whose sum of PTV volume was less than
10 cm3 had longer survival than patients with a volume above 10 cm3 (p=0,007, Fig.1). Surprisingly, patients treated with 5 or more metastases lived
statistically longer than patients with 4 or below brain metastases (p=0,041, Fig.2). Local control was achieved in 93% of the lesions. Lesions with
a margin of at least 0.5 mm had better local control 6 months after treatment (p=0,049; Fig 3.). A better response was also associated with a conformality
index (CI) below 1.42 (p=0,0006; Fig.4) and with the use of immunotherapy within 4 months of SRS (p=0,026). No correlation was found between
DTI (p=0,419) and GI (p=0,599) parameters and local control of metastatic lesions.

Conclusions: SI-MM-SRS is a highly effective method of treating multiple brain metastases. The survival of patients depends on the sum of the volume of metastatic lesions, not their number. Parameters such as margin and CI seem to influence the effectiveness of treatment.

Objectives:

The goal of this study is to evaluate an automatic lesion detection algorithm available as a beta test version software at our institution.

Methods:

The automatic lesion detection algorithm is integrated into BrainLAB Element treatment planning software packages. It is based on neural network and powered by GPU. It will automatically delineates multiple cranial tumors based on contrast-enhanced T1-weighted MRI scans. The results comprise the contrast-enhancing tumor core (active tumor with cystic or necrotic portions). The auto-detection process is automatically started once a new MRI is loaded using the “SmartBrush” Element.

In this study, we used 30 patients’ MRI containing a total of 190 clinical contoured brain metastases as the test sample (range 2 ~ 23). The number of automatic detected targets, matching targets, missing targets were recorded and reported. The number of new found targets is also reported and then further categorized into two groups: sizable target (>=0.05 cc), and tiny target (<0.05 cc). This is because for the tiny targets, clinical decision may have varied depending on specific patient situations. Therefore, there is lack of basis for the comparison.

Results:

A total of 204 objects were contoured by the auto-detection. 173 objects are matching with the clinical contoured targets, and 31 targets were new found (10 sizable targets and 21 tiny targets). The overall successful detection rate is 91%. 17 (9%) clinical contoured targets were not identified by the auto-detection. They are mostly concentrated on two specific MRI images where the image contrast is visibly lower than normal. Visible examples of such images and missing targets will be presented.

Conclusions:

An automatic lesion detection algorithm is evaluated with 30 brain metastases patients’ MRI scans. It apparently showed the detection accuracy is highly depending on the MRI quality and contrast enhancing. 2/3 of the new found targets are in the range of <0.05cc in volume. We will look further into those targets on patients’ follow-up MRIs to determine if it was not clinical identified due to their tiny size. It would be helpful if a confidence level measure for each auto-detected targets being available to help with the clinical teams' decision making when reviewing the auto detection results.

Objective:

Linac-based stereotactic radiosurgery (SRS) and HyperArc technique has gained increasing popularity for managing brain metastasis due to the greater accessibility, standardized process and high delivery efficiency from single-isocenter multiple-targets (SIMT) treatments. However, due to the small field condition and increasing modulation complexity, the plan dosimetry highly relies on the modeling of multi-leaf collimator (MLC). In  Eclipse v18, an enhanced leaf model (ELM) is introduced by constructing the actual rounded leaf end design and attenuation, to replace the current dosimetric leaf gap (DLG). We intended to investigate its impact to SIMT HyperArc plans and compare it against the conventional DLG-based V16 model.

Methods:

22 multi-mets patients received Linac-based SRS treatments were retrospectively selected. The number of metastases ranges from 2 to 19 (average 6, median 6), volumes of PTVs ranges from 0.03 to 17.12cc (average 1cc, median 0.33cc), and distance of PTV centers to isocenter ranges from 1.2 to 9.5cm (average 5cm, median 5cm). The original clinical plans were created in Eclipse v16 using HyperArc technique for an Edge Linac with HD-MLC, using 10FFF energy, Analytical Anisotropic Algorithm(AAA), and DLG optimized for SRS treatment (AAA-SRS-16). We recalculated clinical plans using the original AAA-16 models, whose DLG was for conventional treatments (AAA-16). The recalculation with ELM model was performed in a test Eclipse v18 environment. The original beam data was from Eclipse v16 and the ELM was configured from ion chamber and solid water measurement (AAA-18). We also repeat the comparison with 6FFF plans made retrospectively.

Results:

For 10FFF, AAA-18 SIMT plans are similar to AAA-SRS-16 plans, with an average 1%/1mm gamma rate of 100%.  The average dose difference between them is -3.9%, and between AAA-18 and AAA-16 is -7.1%. For 6FFF, we observed an average dose difference of 7.4% between AAA-18 and AAA-16. The main difference occurs at peak dose and valley dose region, while the dose falloff region is similar. The configuration of DLG in AAA-SRS-16 model involved several rounds of adjustment from AAA-16, recalculation and revalidation, while the ELM(AAA-18) configuration was one-time effort, which greatly improves the efficiency of commissioning and reduces the uncertainties and user variability.

Conclusion:

The new enhanced leaf model introduced in Eclipse v18 substantially improves the efficiency of dose algorithm modeling. It showed similar dosimetry compared with finely tuned DLG for SRS in the current MLC model for HyperArc SIMT plans, while changes the doses about 7% from the DLGs tuned for conventional treatments.

Objectives:

To ascertain the degree of variability in stereotactic radiosurgery (SRS) dosing for breast and renal cancer metastases in the central nervous system (CNS), in centers across Latin America and Spain, through a survey conducted among radio-oncologists and neurosurgeons

Materials and Methods:

Responses from a survey conducted through Google Drive among 106 SRS specialists in Latin America and Spain were reviewed. Specific questions about SRS dosing for CNS metastases of breast and renal cancer were selected, focusing on single-fraction SRS practice. Descriptive statistics were calculated to demonstrate variability among respondents in the reported doses for the same clinical case with identical histology, and the Student's t-test for independent samples was used to detect statistically significant differences between the prescriptions for both histology.

Results:

Among the surveyed participants, 93.4% were from LATAM and 6.6% from Spain, with an 85% participation from LATAM countries. Respondents included 87% radiation oncologists and 13% neurosurgeons. The technologies used were: LINAC (70%), Gamma Knife (15%), CyberKnife (7%), Halcyon (5%), and ZAP (3%).

The average dose for breast metastases was 20.48 Gy [15-25 Gy], with a standard deviation of 1.04 Gy. Most prescriptions were concentrated in the 20-21 Gy range, accounting for 54.43% of the total.

The average dose for renal metastases was 21.91 Gy [15-25 Gy], with a slightly higher variability (standard deviation of 1.06 Gy). A more balanced distribution was observed in the higher ranges, with 31.11% of doses in the 24-25 Gy range and 21.11% in 22-23 Gy.

The difference in average dose between the histological types was statistically significant (t = -4.35, p = 0.000024), indicating a trend to prescribe higher doses for renal cancer.

Conclusions:

The variability found in dose prescription for the same histological type suggests the need for a consensus in SRS practice for CNS metastases, at least in LATAM. The results highlight the importance of establishing international guidelines for standardization in SRS dosing for single-fraction CNS metastases. Uniformity in prescription would allow more homogeneous comparisons between studies and technologies, yielding more robust results.

Background and Objectives

Triple negative breast cancer (TNBC) remains an aggressive disease with a poor prognosis. Although ongoing studies are assessing the efficacy of new systemic therapies for patients with TNBC, the overwhelming majority have excluded patients with brain metastases (BM). Therefore, we aim to characterize systemic therapies and outcomes in a cohort of patients with TNBC and BM managed with stereotactic radiosurgery (SRS) and delineate predictors of increased survival.

Methods

We used our prospective patient registry to evaluate data from 2012-2023. We included patients who received SRS for BM. A competing risk analysis with the Fine and Gray method was conducted to assess local and distant control where death was the competing risk.

Result

Forty-three patients with 262 tumors were included. The median OS was 16 months (95% CI 13-19 months). Predictors of increased OS after initial SRS include modified Breast GPA score >1 (HR= 0.183, 95% CI 0.088-0.496, p<0.001) and use of immunotherapy such as pembrolizumab (HR= 0.360, 95% CI 0.175-0.830, p=0.011). The median time on immunotherapy was 8 months (IQR 4.4, 11.2). The cumulative rate for development of new CNS metastases after initial SRS at 6 months, 1 year, and 2 years was 23%, 40%, and 70%, respectively. The quotient of total tumor volume to the sum of tumors at initial SRS (adjusted tumor burden) was developed to predict new CNS metastasis. An adjusted tumor burden of ≥3 was a significant and reliable negative predictor of development of new CNS metastasis (SHR 0.813, 95% CI 0.696- 0.949,  p=0.009).

Conclusions

TNBC patients with BM can achieve longer survival than might have been previously anticipated with median survival now surpassing one year. The use of immunotherapy is associated with increased median overall survival of 23 months and the adjusted tumor burden may be considered as a useful predictive tool for determining distant CNS tumor progression.

Background/Objectives:

The diagnosis of brain metastases (BM) places a major burden on both patients and providers. Stereotactic radiosurgery (SRS) is a primary or adjuvant option for this disease, but underlying socioeconomic factors may delay access to SRS and subsequent follow-up care. Patients with higher household income, higher educational attainment, and who are enrolled in an insurance plan are more likely to receive SRS. This study explores the impact of social determinants of health on time to SRS delivery after diagnosis of brain metastases.  

Methods:

This is a retrospective study of patients with brain metastases who underwent Gamma Knife® (GK) SRS as the primary modality at a single institution from 2008-2023. Patients with prior surgical resection or whole brain radiotherapy (WBRT) were excluded. Time from first BM diagnosis to initial SRS was analyzed across patient demographics, median household income based on U.S. Census Bureau 5-year estimates, and insurance carrier (private, Medicare, Medicaid). 

Results:

1216 patients with 4576 brain metastases were included in the analysis. The median time from diagnosis of BM to SRS was 15 days (IQR:20). White patients had a significantly lower time to SRS (13 days, IQR:17) compared to Black (21 days, IQR:24, p < 0.001) and Asian patients (20 patients, IQR:23, p < 0.001). Medicare patients had a significantly lower time to SRS (12 days, IQR:15) compared to private insurance (15.5 days, IQR:21, p = 0.006) and Medicaid (20 days, IQR:24, p < 0.001). Patients with median household income > $75,000 had a shorter time to SRS (14 days, IQR:18) compared to those below this income bracket (17.5 days, IQR:22, p = 0.004).

Conclusion:

There are differences in time from diagnosis of brain metastases to first-line SRS across patients of different ethnicities and socioeconomic strata. Efforts to reduce healthcare disparities are critical in ensuring timely SRS delivery to brain metastasis patients.

Introduction/Objectives

In the era of targeted therapies, antibody drug conjugates (ADCs) are being used more frequently in patients with breast cancer brain metastases (BCBM) treated with SRS. A recent report raised the possibility of increased risk of symptomatic necrosis when ADCs are used concurrent with SRS. Therefore, we investigated if similar risk is observed in our institutional experience.

Methods

We queried our prospective patient registry from 2012-2023 to identify BCBM patients with a minimum of three-months of follow-up who received at least one dose of trastuzumab-emtansine, trastuzumab-deruxtecan, ladiratuzumab-vedotin, or sacituzumab-govitecan and underwent concurrent SRS. Adverse radiation effects (AREs) were determined via radiographic follow-up with peritumoral patchy enhancement with a mismatch on the long relaxation time images was coded as an inflammatory change consistent with ARE. Concurrent use of ADC was noted if SRS was done 7 days before or 30 days after ADC delivery. A competing risk analysis with the Fine and Gray method was conducted.

Results

In total, 46 BCBM patients that received ADC with 290 tumors were included. The median age was 56.5 (IQR, 48-63) and the median follow-up time was 23 months (IQR, 15-42). At the time of analysis, 19 patients (41%) were alive while 22 patients (48%) were deceased due to non-neurologic causes and 5 patients (11%) were deceased due to neurologic causes. Sixteen patients (35%) received whole-brain radiotherapy (WBRT) prior to SRS and ADC treatments. Twenty-seven patients (59%) received ADC concurrently with SRS while 19 patients (41%) received ADC sequentially. The median marginal dose was 16 Gy (IQR, 15-18) and the median total tumor volume was 1.8 cm³ (IQR, 0.48-6). Amongst the entire cohort, the median number of SRS treatments was 2 (IQR, 2-3). Overall, 6 tumors (2%) exhibited ARE and the 12 and 24-month cumulative incidence of ARE for the entire cohort were 1% and 2%, respectively. Five of the tumors were symptomatic requiring a short course of corticosteroids and no further sequalae. The cumulative Concurrent ADC was not associated with increased risk of ARE (SHR, 0.024 [95% CI, 0-248]; P=0.428). Local tumor control was 96% throughout the follow-up period. 

Conclusions

Analysis of our institutional experience did not identify an increased risk of symptomatic ARE with concurrent SRS and ADC. Notably, our median marginal dose was lower than previous reports. A larger multi-institutional study may shed additional light on the incidence of AREs with the use of concurrent ADCs.

As the only neuroradioloigst at the Gamma Knife Center of the Pacific since 1998 in Honolulu, Hawaii, and with a 'captured' Island population, I have the resposibility of reviewing all of the pre and post GK MRI scans and have discovered an interesting post treatment phenomenon of complete enhancment resolution of certain metastsis, consistent with successful GK tumor obliteration, but then with delayed recurrent enhancment at the treatement site between 6 and 35 months later, mimicking recurrent tumor but actually being benign post GK dealyed blood brain barrier breakdown and not active tumor. This pattern needs to be understood by all treating GK physiicians and interpreting radiologists to avoid potentially dangerous retreatment or changing ongoing and otherwise successful chemo or immunotherapy.  This is now more important due to the success of GK and the mobility of patients, often seen at a other medical facilities distant to the original treatment location.

Objectibe: 

Pilocytic astrocytomas (PA) are the most common gliomas (WHO I) in children. in current protocols, The irradiation usuallyt is not used due to the potential risks of long-term complications and  postponed until recurrence. Burdenko Neurosurgical Institute has the greatest experience in modern stereotactic radiotherapy for this pathology.

Materials and  Methods:

152 patients with Optic Pathway PA were irradiated at Burdenko Neurosurgical Institute between April 2005 and January 2018. The study group consisted of 38 adults and 114 children.  The median age was 13,7 years. 80 (52,6%) patients had a prior histological tumor verification (tumor resection or biopsy). In 72 (47,4%) patients the diagnosis was based on clinical evidence and radiological data. Neurofibromatosis type 1 was detected in 28 patients (18.4%). In 111 (73%) patients, radiotherapy was the primary treatment (58 patients) or was performed immediately after non-radical surgery (53 patients) . In 41 (27%) patients, treatment was due to continued tumour growth after non-radical surgery (20 patients) or after polychemotherapy (vincristine+carboplatin) (21 patients). Endocrine disorders were detected in 23 (55%) patients (out of 42) examined. Most of the patients (129 pts – 84,8%) underwent SRT in standard fractionation (1,8 Gy/fr, mean dose 54 Gy), 23 patients (15,2%) underwent hypofractionated SRT (5-6 Gy per fraction, mean dose 25-30 Gy).

Results:

149 patients (98%) were available for the follow-up. The median follow-up period was 75 months (11-197) after the patients were diagnosed PA. At the end of the follow-up (9.2023) 144  patients (97,5%) were alive. The median follow-up period after irradiation was 57 months (range, 6-196 months). Fifteen (10.4%) patients developed pseudoprogression followed by spontaneous regression or partial removal/emptying of cysts. Recurrences (3 local and 3 distant) occurred in 6 (4.2%) patients. Finally tumor control or regression was achieved in 138 patients (95.8%). Five-year recurrence-free survival was 97.7%. Endocrine function decline occurred in 33% of the examined patients. No malignant transformation, radiation necrosis, secondary tumors, hearing impairment or moya-moya disease were observed in patients. 

Conclusion: 

Stereotactic irradiation (SRT, SRT hypo) is an effective method of treatment for optic pathway PA in patients with residual tumors and patients with progressive disease. The method provides the highest rates of tumor growth control compared to other treatment methods. With the available follow-up period, we did not identify any complications that may justify postponing the radiation treatment. Further study of the results of stereotactic irradiation and revision of the indications for this treatment are required.

Purpose: Radiation necrosis (RN) is a major late toxicity after radiation therapy for brain metastases, with oral corticosteroids being the primary but suboptimal long-term management due to side effects and drug interactions. Boswellia serrata (BS), known for its anti-inflammatory properties, has shown promise in reducing cerebral edema post-brain radiation therapy. This study evaluates the effectiveness of BS in patients with brain metastases treated with stereotactic radiosurgery (SRS) who subsequently developed RN.

Methods: We analyzed patients who developed RN post-SRS for brain metastases between 2020-2022 at our institution and were treated with BS (4.2-4.5g daily). Follow-up MRI was conducted every 2-3 months, with responses assessed using Response Assessment in Neuro-Oncology (RANO) criteria. The primary endpoint was a ≥25% decrease in edema volume on T2-FLAIR MRI from baseline. Patients were censored for tumor progression, repeat RT, or death.

Results: Among 50 patients treated with BS for Grade 1-3 RN, median age was 62.8 years, and median RT dose was 24 Gy in 3 fractions. Median time to RN onset post-SRS was 10 months, with a follow-up period of 6 months. Out of 40 patients with follow-up MRIs, 15% achieved complete response (CR), 40% partial response (PR), 35% had stable disease, and 10% progressive disease. Median time to response was 9 months for CR and 6 months for PR. Symptomatic improvement was seen in 35.7% of patients using BS alone, while 64% required steroids. Salvage treatments included steroids, surgery, Bevacizumab, or hyperbaric oxygen therapy. Side effects were minimal, with 6% experiencing mild gastrointestinal issues. Two patients discontinued BS due to enrollment in an immunotherapy trial.

Conclusion: BS demonstrated over 50% response rates in treating Grade 1-3 RN post-SRS, with a significant portion avoiding long-term steroid use. BS emerges as a safe, accessible, and promising alternative for RN management, warranting further prospective studies.

Gamma knife radiosurgery （GKRS） is recommended as the first-line treatment for brain metastases of lung adenocarcinoma （LUAD） in many guidelines, but its specific mechanism is unclear. We aimed to study the changes in the proteome of brain metastases of LUAD in response to the hyperacute phase of GKRS and further explore the mechanism of differentially expressed proteins (DEPs). Cancer tissues were collected from a clinical trial for neoadjuvant stereotactic radiosurgery before surgical resection of large brain metastases (ChiCTR2000038995). Five brain metastasis tissues of LUAD were collected within 24 hours after GKRS. Five brain metastasis tissues without radiotherapy were collected as control samples. Proteomics analysis showed that 163 proteins were upregulated and 25 proteins were downregulated. GO and KEGG enrichment analyses showed that the DEPs were closely related to ribosomes. Fifty-three of 70 ribosomal proteins were significantly overexpressed, while none of them were underexpressed. The risk score constructed from 7 upregulated ribosomal proteins (RPL4, RPS19, RPS16, RPLP0, RPS2, RPS26 and RPS25) was an independent risk factor for the survival time of LUAD patients. Overexpression of ribosomal proteins may represent a desperate response to lethal radiotherapy. We propose that targeted inhibition of these ribosomal proteins may enhance the efficacy of GKRS.

Aim

Recent advanced technologies allowed different treatment modalities and different dose calculation alghorithms with different output dose characteristics. The aim of this study was to compare and to evaluate dosimetric aspects of stereotactic radiotherapy through the use of two techniques: LINAC-based versus helical tomotherapy (HT).

Material and methods

Eight patients with solitary brain metastasis received stereotactic radiotherapy and were included in the analysis. Patients were subjected to 1-mm slice thickness computed tomography simulation with Gross Tumor Volume (GTV) defined by contouring the visible lesions on MRI images and Planning Treatment Volume (PTV) obtained by 2 mm isotropic extension of the GTV. Each contouring dataset of the patients was planned with both tomotherapy (Raystation v11B TPS) and LINAC-based treatment planning system (BrainLab Elements v3.0 TPS). The LINAC-based modality was realized with 6 MV FFF beams and no-coplanar arcs. The delivered dose was 27 Gy in three fractions for each treatment plan. The Paddick Conformity Index (PCI), the inverse Paddick Conformity Index (iPCI), the Gradient Index (GI), the PTV-coverage, the beam-on time and the volume receiving 18Gy (V18) were calculated and compared for both treatment modalities. Results were analyzed with Wilcoxon signed-rank test.

Results

The median volume of lesions was 3 cc. PTV coverage, PCI and iPCI were similar for both treatment modalities: mean values were respectively 95.7%, 0.84, 1.2 for LINAC-based and 95.7%, 0.81, 1.2 for tomotherapy.

GI and beam-on time were statistically significantly lower with LINAC, with a mean value of GI of 4.0 versus 6.6 for HT and with a beam-on time of 199 seconds for LINAC versus 517 seconds for tomotherapy.

Also V18 improved with LINAC, with a median value of 6.7 cc compared to 8 cc with HT.

Conclusion

In our analysis, the LINAC-based system offered the best dose gradient with similar values of PTV coverage, PCI and iPCI compared to tomotherapy. Also the beam-on time obtained with LINAC system was lower respect to the tomotherapy one. The LINAC-based approach also provided significantly better V18 values compared with HT improving toxicity profile with the same efficacy. The outcome of our preliminary analysis has encouraged us to preferably treat patients with LINAC-based modality in order to obtain better dose distribution improving toxicity profile and shortening treatment time.

Objective: To describe the experience and results from coordinated and closely scheduled Gamma Knife radiosurgery (GKRS) and cochlear implantation (CI) in a vestibular schwannoma (VS) cohort.  Unfortunately, studies of this patient population have demonstrated the negative influence of non-functional hearing as well as minimal hearing changes on quality-of-life measures. Further, subjective testing shows that VS patients with hearing loss experience notable functional deficits in comparison to binaural hearing controls.  Thus, current hearing function and potential for rehabilitation are critical considerations when discussing tumor management via GKRS given the detrimental effects of non-functional hearing.

 Methods:  Data were retrospectively collected from patients undergoing cochlear implantation immediately (within 24 hours) after GKRS from December 2003 to August 2022 at a single, large tertiary center. 

Main Outcome Measures: Tumor control defined by tumor growth on post-treatment surveillance and audiometric outcomes including Consonant-Nucleus-Consonant (CNC) words and AzBio sentences in quiet.

Results: In total, 6 patients were identified that met inclusion criteria, with an age range of 38- to 69-years-old and tumor sizes ranging from 2.0 to 16.3 mm.  Margin dose was 13 Gy and maximum dose was 26 Gy.   One patient was local and the remaining five lived 105 to 1447 miles from our center.  Four patients had NF2-associated schwannomatosis.  All patients successfully underwent GKRS and CI on the same or next day. Postoperatively, all patients obtained open-set speech recognition. CNC word scores ranged from 40 to 88% correct, and AzBio scores ranged from 44 to 94% correct.  During post-treatment MRI surveillance, which ranged from 12 to 68 months, all tumors were noted to be adequately visualized, and no tumor progression was noted.  This mirrors our previous experience with CI following GKRS in 17 patients (18 ears implanted).

Conclusions: Coordinated GKRS and CI can be safely performed in patients with VS on the same day or immediately subsequent day , serving to decrease burden on patients and increase access to this vital rehabilitative strategy.  

In severe and refractory cases of Obsessive-Compulsive Disorder (OCD), neurosurgical procedures may be proposed as a therapeutic option. Ventral Anterior Capsulotomy using Gamma Rays (GVC) is one of the psychosurgery options for OCD. The aim of this study was to evaluate tractographic differences between refractory OCD patients who underwent GVC and healthy controls. This involved a non-probabilistic convenience sample of refractory OCD patients who underwent GVC, as well as randomly selected healthy controls matched for gender, age, and imaging apparatus/protocol. Pre-processing steps were conducted using MRtrix3 software, and tractography was processed using constrained spherical deconvolution (CSD) to enable segmentation of the Anterior Limb of the Internal Capsule (ALIC) based on connectivity with the frontal cortex. After pre-processing, tractographies were automatically segmented using a convolutional neural network called Tractseg into 72 fiber bundles. Tractometric profiles for the control and OCD groups were constructed for each bundle, considering three metrics (fractional anisotropy, mean diffusivity, and peak length). In this study, 27 participants were included in a 1:2 ratio, comprising 9 OCD patients (5 with 3T MRI) and 18 controls (10 with 3T MRI). The mean age of the OCD patients was 36.9 years (95% CI 32.4 – 46.5), with 7 (77.8%) being male. Brodmann areas 11 and 47 have predominantly ventral distribution, whereas BA06 and BA08 are located dorsally in the ALIC. BA09, BA10, and BA46 have an intermediate craniocaudal distribution, with BA46 predominantly lateral. There were no differences between the OCD and control groups regarding the topographical distribution of fibers in the ALIC. All participants had their diffusion images processed using the CSD algorithm, with subsequent automated segmentation of the 72 fiber bundles as predicted by Tractseg. Differences between the OCD and control groups were identified in at least one segment of the tractometric profile for all considered metrics, in tracts diffusely distributed in both hemispheres and not restricted to the cortico-striato-thalamo-cortical pathway. Despite the apparent topographical distribution similarity, refractory OCD patients who underwent GVC, when compared to the control group, exhibited discrepancies in their tractometric profiles.

Background: In single-session stereotactic radiosurgery (SRS) for treating cerebral metastases, the tumor size primarily constrains the dosage, and guidelines recommend a fractionated treatment approach for metastases that exceed 3 cm in diameter or have a volume surpassing 10 cm³. Standard fractionated regimens include 27 Gy delivered in three fractions over three days or 30 Gy administered in five fractions from Monday to Friday within the same week. However, these daily regimens may not always align with the scheduling constraints of the radiosurgical unit, other planned treatments, or reimbursement policies. Our objective was to investigate the outcomes of hypo-fractionated SRS with a two to three-week interval between fractions instead of the daily regimens.

Methods: We analyzed patients with at least 1-year follow-up who received either double- or triple-session SRS for the same cerebral metastasis within four weeks. In addition to background data, we reviewed the time between fractions, tumor volumes, 1-year tumor control rate, latest tumor control rate, perilesional edema, radionecrosis, and any relevant clinical worsening.

Results: We are currently collecting data. The typical fractionated treatment regimen was 12-14 Gy x 2 administered with a three-week split between the fractions. The goal of the first fraction was to decrease the tumor size, allowing for a second fraction to achieve improved long-term tumor control.

Conclusion: We have good experience with a two- or three-staged SRS over several weeks instead of the recommended daily treatment regimen. Two- or three-staged SRS is an effective treatment technique for large brain metastasis that significantly reduces tumor volume at the later SRS stages, and the long-term tumor control is likely comparable to high-dose, single-session SRS. The final results from our analyses will be presented. 

Background: Brain metastases has been the ideal target for stereotactic radiosurgery (SRS) for several decades, whereas new techniques have been implemented such as “hyper arc” (HA) by using the EDGE VARIAN SRS system. With this presentation we are reporting our experience with the first implementation of HA technique in Greece, in Radiation Oncology center of Mediterraneo General Hospital.

Patients and Methods: We retrospectively analyzed 42 patients with metastatic brain lesions. The SRS with HA was delivered via the EDGE VARIAN system and the HA technique. The primary was as following: breast (25 patients), lung (14 patients) and rectum (3 patients).

Results: The range of lesions was between one and ten The delivery of treatment was realized in single fraction for lesions with diameter less than 3cm. Three to five fractions were used with multiple lesions, whereas the criterion of v12 for normal brain tissue was not met. There were no acute or late toxicities from the skin or cognitive affairs related to the CNS.   Local control (LC) was achieved in 100% of patient at the time of the first follow-up and the projected 6-month local progression-free survival (LPFS) was 95%.

Conclusion: High LC and LPFS can be achieved with SRS for brain metastatic lesions with HA technique. The study continues to recruit patients to obtain mature results in the following years.

Background: Symptomatic patients' outcomes following motor cortex brain metastases (BMs) treated with Stereotactic Radiosurgery (SRS) are not well-described in the literature. Most cohorts include mixed cohorts of symptomatic as well as asymptomatic patients, various sized lesions, treated with either SRS or surgery. The available evidence is, therefore, inconclusive.  

Methods: Here, we studied the data of 70 patients, treated with SRS, combined either with or without surgery in Sheba Medical Center between the years 2010 to 2022. Patients were diagnosed with BMs located within the motor cortex or adjacent to it and presented accordingly with hemiparesis or hemiplegia. Patients' demographics, and clinical and oncological outcomes, were retrieved using a novel institutional AI algorithm software. SRS and surgical treatment paradigms as well as their associated outcomes were collected. BMs were, in turn, classified according to their location with respect to the motor cortex, and their volumetric data was measured and documented.

Results: Patients' demographics showed that their median age-at-diagnosis was 65 years (range, 38-89), male-to-female ratio was 2.3:1, and median follow-up duration was 7 months (range, 0-154). BMs' originated as follows: lung, n=33, melanoma, n=17, breast n=5, gastrointestinal, n=10, others, n=5, and the median duration of time from primary cancer diagnosis to BMs diagnosis was 11 months (range, 0-199). Patients were treated with SRS alone (n=37), or SRS combined with tumor resection or Ommaya reservoir insertion (n=33). The mean radiation dosage was 19 Gy (range, 12-32), delivered in 1-5 fractions according to the acceptable treatment protocols. The entire cohort's median overall survival (OS) was 9.8 months (95% CI 7.3-13.5). The median OS of patients treated with SRS and surgery was 14.9 months (n=32, 95% CI 9.9-23.3) while patients treated with SRS alone demonstrated OS of 6.8 months (n=38, 95% CI 3.4-9.1), p=0.0012. 41% of the patients demonstrated motor deficit improvement, demonstrated to be related to favorable OS (p=0.05). Due to low numbers, preliminary analysis showed that it was not possible to perform further analysis regarding clinical improvement and specific treatment types. The average tumor volume treated was 5.7 cc (range, 0.5-42), and was not correlated with patient's outcomes. 

Conclusion: This study aims to comprehensively explore the clinical and oncological outcomes of a homogenous cohort of symptomatic motor cortex BMs patients treated with SRS alone or SRS combined with surgery. Favorable OS was demonstrated in patients treated with SRS and surgery and in patients who exhibited post-treatment clinical improvement.  

Background and Objectives: Involvement of the cranial nerves is a rare feature of cancer and is a marker of poor survival. Cranial nerve metastases (CNM) can be primary via leptomeningeal metastasis or secondary by spread due to head and neck cancers or due to distant tumor metastasis to the skull base. In addition, cranial nerve metastases may cause cranial nerve-related symptoms that can impact patient quality of life.

Methods: We performed a single-center retrospective cohort study of all patients with CNM treated with SRS at our institution between April 2003 and February 2021. Demographic and clinical information were retrieved from the electronic medical record. Median follow-up was 12.9 months.

Results: Our study cohort consisted of 9 patients with primary CNM and 8 with secondary CNM – for a total of 17 patients, with a total of 33 lesions (23 primary, 10 secondary). Eleven patients (64.7%) had symptoms caused by cranial nerve metastases. Symptoms were resolved in 5 of 11 patients (45.5%) after SRS. Patients with secondary CNM were more likely to have cranial nerve symptoms and more likely to have resolution of symptoms following SRS. The median time between SRS and symptom improvement was 3 months. Local tumor control was achieved in 30 of 33 lesions (90.9%). Local tumor control at 6 months and at 1 year were 100%. Overall survival at 6 months was 76.5% for the entire cohort, with 55.6% and 100% for the primary and secondary subgroups, respectively. Only one patient had an adverse event (5.9%).

Conclusion: Our study suggests that SRS may be a safe and effective treatment for cranial nerve metastasis providing 90.9% local tumor control at final follow-up, and symptomatic stability or improvement in 90.9% of symptomatic cases. Patients with secondary CNM may stand to benefit more from a symptom management standpoint.

Background: Pineocytomas are a rare type of tumor that arise from the parenchyma of the pineal gland. Gross total resection can potentially cure these benign lesions but is associated with significant risks of morbidity. Stereotactic radiosurgery (SRS) is thought to provide adequate tumor control, but the current literature is mostly limited to small single institution case series. This study was designed to provide multi-institutional data to strengthen the evidence related to the use of SRS for pineocytomas.

Methods: Centers participating in the International Radiosurgery Research Foundation were asked to review their database and provide data for patients who had SRS for a histology confirmed grade 1 pineocytoma, for whom clinical and imaging follow-up of at least 6 months was available. 

Results: We identified 38 patients (23 male and 15 female) who underwent SRS as part of the management of a pineocytoma. Median age at SRS was 39 years (range 8-76). SRS was performed as primary treatment in 68%, adjuvant after partial resection 19%, and at recurrence in13% of patients. The median margin dose used was 15 Gy (range 11-25 Gy). The median treatment volume was 3.35 cc (range 0.1-17.9 cc).Local tumor control was achieved in 92% of pineocytomas after SRS treatment, with mean actuarial progression-free survival of 21.6 years. At last follow-up, 82% were still controlled, 8% had local recurrence and 10% had cerebrospinal fluid dissemination. The only significant factor associated with tumor control was the indication for treatment. Mean actuarial local control was 26.1 years for primary treatments, 4.8 years for residual tumors after partial resection, and 4.6 years for recurrent tumors (p=0.016). Five patients (13%) died during follow-up, all due to tumor progression. The actuarial mean survival duration was 24.3 years, with a 5-year survival rate of 91%, and an estimated rate of 76% at 29 years. Transient symptomatic adverse radiation effects (ARE) were observed in 4 patients (11%). No parameter was identified as a risk factor for death or ARE.

Conclusion: Stereotactic radiosurgery is a safe and effective treatment for pineocytomas. It can be offered to patients as a primary management option after histological confirmation of the diagnosis as an alternative to surgical resection.

Introduction. Oligodendrogliomas are primary brain tumors classified as IDH-mutant and 1p19q co-deleted in the 2021 WHO Classification. Surgery, fractionated radiotherapy and chemotherapy are well established treatments for these tumors, but there are few studies evaluating the efficacy of stereotactic radiosurgery (SRS). As these tumors are less infiltrative than astrocytomas and typically recur locally, they could be appropriate for local therapy such as SRS.

Methods. This was a retrospective multicenter study performed through the International Radiosurgery Research Foundation (IRRF). Adult patients were included if they underwent single-fraction SRS for a grade 2 or 3 histologically confirmed oligodendroglioma. Mixed tumors (formerly oligoastrocytomas) were excluded. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included clinical evolution and occurrence of adverse radiation events or other complications. 

Results. Eight institutions submitted data for a total of 55 patients with a median clinical follow-up of 24 months. The median age at treatment was 46 years (range, 18-75) and median pre-treatment KPS was 90% (range, 60-100%). Prior surgical management included gross-total resection in 54.5%, partial resection in 25.5% and biopsy in 20%. Prior radiotherapy had been used in 58% of patients and chemotherapy in 71%. The median treatment volume was 4 cc (range, 0.1-27) and median marginal dose delivered was 15 Gy (range, 9-24). After SRS, the median PFS was 17 months, with actuarial rates of 60.1% at 1 year, 31% at 2 years and 24.4% at 5 years after SRS. The median OS post-SRS was 58 months, with actuarial rates of 91.5% at 1 year, 83.4% at 2 years and 49.3% at 5 years. The KPS remained stable post-SRS in 51% and worsened in 46.7% of patients, most often due to tumor progression (73.1%). Adverse radiation-induced imaging changes occurred in 29.6% of patients but were symptomatic in only 7.5%. Factors significantly associated with worse PFS were WHO grade 3, prior radiotherapy and chemotherapy and higher treatment marginal dose. Factors significantly associated with worse survival were WHO grade 3 and prior radiotherapy and chemotherapy. 

Conclusion. SRS appears to be a valuable management option for oligodendrogliomas.

Introduction: Radiomics promises to revolutionize clinical decision making in the management of melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS). Radiomic features extracted from baseline (day-of-treatment) magnetic resonance imaging (MRI) can be integrated into clinicoradiological parameters to predict long term outcomes in order to tailor multimodal treatment strategies, permit individualized surveillance imaging frequency and facilitate early changes to therapy following SRS. We analyze the predictive accuracy of a baseline-only MRI radiomics machine-learning model in MBM patients to predict local failure following SRS.

Methods

Patients receiving single-fraction Cobalt-60 based SRS for MBM at a single Australian institution were analyzed. Progression of disease (PD) outcomes were defined either histologically or according to RANO-BM criteria. 3214 radiomic features were extracted from the pre-SRS day-of-treatment T1-weighted contrast-enhanced MPRAGE MRI sequences using in-house software developed in MATLAB. High and low pass wavelet filtering was applied and highly dependent radiomic features were selected using lease-absolute-shrinkage-and-selection-operator (LASSO) regression. Binary classifiers were trained and validated using a leave-one-out-cross-validation (LOOCV) technique to generate predictive models. Synthetic minority oversampling (SMOTE) was used to counter the effects of class imbalance. A multivariate model was additionally developed integrating radiomic features with baseline lesion volume, immunotherapy use and SRS dose. The final model was applied to a de-novo dataset to assess predictive accuracy.

Results: 101 MBM patients were treated with SRS. The median duration of follow-up was 29.2 months (IQR 19.7-39.8). Median dosage was 20Gy (IQR 18-20) in a single fraction. The median volume and diameter of the lesion at baseline were 0.24cc (IQR 0.06-1.02) and 7.7mm (IQR 4.8-12.2), respectively. 77.0% of patients received immunotherapy concurrently (4 weeks pre to 4 weeks post-SRS). Overall local control in the cohort was 87.1%. Adjusting for concurrent immunotherapy status, dose and lesion volume, radiomics analysis demonstrated that utilizing baseline imaging alone, long term PD following SRS was accurately predicted with an 88.9% accuracy in the training dataset. Radiological texture heterogeneity radiomics markers were most strongly associated with local failure. When applied to a de-novo (untrained) dataset in the clinical setting, the model demonstrated a 73% predictive accuracy (95% CI 60.6-85.6%).

Conclusion:

A pre-treatment baseline-MRI radiomics model has a high degree of accuracy in predicting long-term local failure in melanoma brain metastases treated with SRS. Additional integration of radiomics models utilizing multiparametric imaging combined with patient and treatment characteristics will optimize the use of radiomic tools into the clinic.

Introduction:

SRS for the treatment of limited-brain-metastases (BM) is widely accepted, but there are still limitations in the management of numerous-BM. Frameless-single-isocenter-multitarget SRS is a novel technique that allows a rapid treatment delivery to multiple-BM. We report preliminary clinical and dosimetric outcomes of our experience with this technique.

Methods and Materials

We have reviewed clinical and dosimetric-outcomes of patients with intact BM treated with SRS using single-iso-single-target (if 1met) and single-iso-multi-target-technique(if≥2mets). Immobilization was based on an SRS-stereotactic-mask. Brainlab® SRS Elements software was used for registration, image fusion, target contouring and treatment planning. Exactrac System and a 6degree of freedom couch were used for monitoring, correcting position and assessing and applying residual-errors also when couch rotations.  Patient positioning was monitored in real-time using surface-tracking.

Results

From 19/05/2022 to 11/12/2023, we treated 60 patients with a total of 255 BM. Patients and treatment characteristics are described in Figure-1. The 67% of patients had at least 2BM treated and the average of treated-BM per-patient per-course was 3.6 (range1-13). The average total treated BM per-patient (sum of all courses) was 4.4. Lung cancer was the most frequent (63%) primary tumor.The 77% of cases were patients with a brain relapse and the remaining 23% had BM at diagnosis.

The 92.5% of BM were treated with single fraction. The most used fractionations were 20 (27.8%) and 21Gy (43.5%) respectively and the median PTV target volume (if single fraction) was 0,2cc(range 0,016-4,32cc).The median Cumulative Target Volume per isocenter and the sum of all SRS courses were 1.37 and 1.46cc respectively. The 100% of patients completed the SRS-treatment with no incidences.

With an average follow-up of 5.3 months (0.1-19months), we have not identified any local-relapse although 27% developed an intracranial-relapse that was treated again with SRS in 44% of cases. We didn´t find any relation between overall-survival and the presence of any driver-mutation (p=0.97), BM at diagnosis vs. recurrences (p=0.113), number of SRS courses (p=0.688), number of isocenters (p=0.679) or number of treated-BM (1 vs. 2-3 vs. ≥4; p=0.7). Healthy-normal tissue constraints were adequately accomplished with a median V12 (if single-dose) and V20 (if 5-fractions) of 0.2 and 5cc respectively. No acute-toxicity >Grade2 was reported.

Conclusion:

Based on our preliminary experience and limited by the short follow-up, we find single isocenter and single and multi-target-SRS technique is feasible, well tolerated and allows excellent local control. Overall survival didn´t show differences regarding the number of treated BM.

BACKGROUND: The uncertainty surrounding the selection of an appropriate treatment for patients with a limited number (<=3) of large volume brain metastases (LBM) persists. Recent researches have indicated that staged or fractionated stereotactic radiosurgery yields a notable response rate and tolerable toxicity levels in such patients. This study aimed to assess the effectiveness and safety of hyperfractionated CyberKnife radiosurgery as a novel treatment approach for limited number of large volume brain metastases patients.

METHODS: Patients with LBM treated with hyperfractionated CyberKnife radiosurgery were included in this study. Hyperfractionated stereotactic radiosurgery (FSRS) dose was 21-34 Gy (3-5 fractions) with 64%-70% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included progression-free survival (PFS), clinical response (Karnofsky performance scale), imaging response (Magnetic Resonance Imaging, MRI) and treatment-related adverse events.

RESULTS: Between January 2020 and December 2022, a total of 40 patients were included in the study. The one-year overall survival rate following FSRS was 75%. Positive imaging responses were observed in 36 patients, accounting for 90% of the cohort, with a T1 weighted contrast MRI volume range from 10.4 to 47.2 cm3. The study also demonstrated a significant clinical improvement, as evidenced by the best Karnofsky performance scale score (P < 0.05, paired t-test). Among the participants, 12 patients (30%) experienced Grade 1 or 2 fatigue, while 4 patients reported Grade 3 headache. Additionally, the median CNS PFS of patients with LBM from non-small-cell lung cancer (NSCLC) was significantly longer compared to other cancer types (24.5 months vs. 12.5 months, P = 0.03).

CONCLUSIONS: FSRS showed favorable clinical and radiologic control as a new treatment regimen for limited number large volume brain metastases. NSCLC patients appear to benefit more from the treatment. To further evaluate this conclusion, an ongoing multicenter prospective observational study is being conducted to assess the efficacy of FSRS for LBM from NSCLC.

Background and purpose: Glioblastomas all eventually relapse after initial treatment, and an option to treat these recurrences is fractionated stereotactic body reirradiation (fSRT). The location of recurrences after reirradiation have been studied, but not precisely after fSRT delivered by a dedicated stereotactic device. We aimed to analyze the patterns of these recurrences after fSRT, as there is limited data to sharpen the choice of safety margins and dose and fractionation regimen.

 Materials and Methods: We retrospectively analyzed the data of patients with glioblastoma recurrence reirradiated by fSRT between October 2010 and December 2020, in 25 Gy in 5 fractions delivered by a CyberKnife® at Institut de Cancérologie de Lorraine. We matched the images of the relapse post-fSRT with the stereotactic radiation treatment planning scan to determine the relapse location.

 Results: Among 62 patients, we found that the localization of recurrences after fSRT was “out-field” in 54.8%, “marginal” in 40.3% and “in-field” in 4.8%. The median PFS from fSRT was 3.4 months (95% CI 2.9 – 4.8 months). KPS score ≥ 70% at recurrence (HR = 0.27 [95% CI 0.08 – 0.93], p = 0.038), PTV volume ≥ 35cc (HR = 3.61 [95% CI 1.23 – 10.6], p = 0.02) and existence of one or more previous recurrences (HR = 2.32 [95% CI 1.07 – 5.05], p = 0.033) were significantly associated with PFS. The median OS from diagnosis was 25.7 months (95% CI 22.2 – 32 months), and from fSRT was 10.8 months (95% CI 8.97 – 14.8 months).

Conclusion: Reirradiation of glioblastoma by fSRT with 25 Gy in 5 fractions provides good local control, with recurrences occurring mostly outside of the reirradiated area.

Objectives

To report clinical outcomes and identify predictive factors associated with improved treatment results in Linac-based Stereotactic Radiosurgery (SRS) and fractionated Stereotactic Radiosurgery (fSRS) for single and multiple brain metastases (BM).

Methods

Between March 2020 and June 2022, 70 patients for a total of 129 BM with at least one-month follow-up were retrospectively included. Patients received either 15-21 Gy in a single fraction (n=59) or 27 Gy in three fractions (n=11) using single-isocenter coplanar FFF-VMAT technique. Post-treatment MRI scans were used to assess local control (LC) according to the RECIST (Response Evaluation Criteria in Solid Tumors) scale. Kaplan-Meier analysis was performed to evaluate in-field progression-free survival (ifPFS), brain progression-free survival (bPFS), and overall survival (OS) rates. Log-rank test and logistic regression analyses were carried out to identify predictive factors associated with better outcomes.

Results

The population consisted of 33 females and 37 males, with a median age of 66 years [30-85]. Lung (44%) and visceral (47%) were the most frequent tumor histology and extracranial metastases site, respectively. The median follow-up period was 9 months [1-41]. The 1-year and 2-year LC rates for all lesions were 94% and 90%, respectively, with 13 (19%) patients experiencing local recurrence in at least one treated BM. The median ifPFS was 7.8 months, while the corresponding 1-year and 2-year rates were 80% and 72%, respectively. The median bPFS was 3.9 months, with 1-year and 2-year bFPS rates of 40% and 20%, respectively. The same features for OS were 13 months, 52%, and 29%, respectively. Lung primary tumor histology and non-visceral extracranial metastases were significantly associated with increased OS and bPFS. No statistically significant differences in clinical outcomes (P>0.05) were found for number of treated lesions, total target volume, BM minimum dose and systemic therapy. Patient age and gender showed borderline significant correlations with bPFS (P=0.055) and ifPFS (P=0.060), respectively. Extended bPFS was observed in younger than 66 years patients (mean, 9.9 vs 6.4 months), while female patients had superior ifPFS (mean, 11.6 vs 9.1 months). At multivariate analysis, lung primary tumor histology was independently related to brain progression (OR, 0.35; 95% CI, 0.12–0.98; P=0.043). 

Conclusions

Linac-based SRS/fSRS treatments with single-isocenter coplanar FFF-VMAT technique were feasible and resulted in encouraging LC outcomes. Patient prognosis remains unfavorable, mostly dependent on histology and extracranial disease status, rather than on the radiation treatment. Further analyses on a larger patient population are currently underway to confirm these findings.

Background: Lung cancer (LC) is an important health problem for its incidence and mortality, with 9 of each 10 death related with metastatic dissemination, and 20-50% of NSCLC present brain metastases during the follow up, with < 12 months survival).

Recent advances in LC treatment have incorporated immunotherapy and molecular therapies, and radical local treatment for oligometastases. Radiosurgery (SRS) represents a non-invasive treatment suitable for patients with intracranial relapse.

Nevertheless, not all patients get a good response to SRS, and the identification of the probability of success has been recognized as necessary, allowing a stratification useful to avoid an eventual overtreatment and the over costs associated.

Mean objective: To determinate the clinical utility of the circulating tumoral cell (CTC) and ctDNA to predict the efficacy of local ablative treatment of brain oligometastases in clinical outcomes, and stratify the recurrence risk of failure. 1) To associate CTC presence and phenotypic characteristics with progression free survival; 2) To associate genetics perfils and ctDNA with progression free survival, and 3) To determinate the role of radiosurgery treatment over fragments of ctDNA detected.

Material and Methods.

In this exploratory research, a successive group of 30 brain mets from NSCLC patients, treated with SRS (18-22 Gy Gamma Knife single session), will be collected for CTC and ctDNA determination. A 30ml of peripheral blood will be processed, 10ml will be allocated for CTCs analysis by semi-automatic technologies based on Isoflux isolation and CTC characterization through the Ammnis platform.

The remaining 20ml will be dedicated to molecular analyses (epigenomic analysis by the TruSight™ Oncology 500 ctDNA kit by Illumina).  The sequencing will be executed on a NovaSeq 6000 (Illumina) at the our hospital.

For fragmentomic analyses, we will adopt a whole-genome sequencing (WGS) approach based on LIFE-CAN, applying it to both NSCLC and healthy donors.

The Bioinformatic unit of Fundación Progreso y Salud will responsible of the bioinformatic analyses

Results. Patients will be subjected to a usual follow-up protocol including clinical assessment and brain MRI evaluation at 6 week and 3 months after SRS. Relationship among CTC amounts and genetic signature, will be related with response, disease free survival, place of relapse and overall survival.

For this preliminary study, a basic statistic will be carried out, and a significance difference would allow us for a posterior protocol, including other brain metastases from other primary location like melanoma, breast and colon cancer.  

Background: Brain metastases from gynecologic malignancies are rare. Stereotactic radiosurgery (SRS) is frequently employed in the treatment of these lesions; however, understanding of optimal treatment paradigms and SRS impact on overall clinical outcomes remains incomplete.

Objective: To assess the effectiveness of SRS on brain metastases from ovarian, cervical, and endometrial malignancies

Methods: Single-institution cohort study of all patients with pathologically confirmed primary ovarian, cervical, or endometrial malignancies who underwent SRS for brain metastases during the study period, 2000-2022.

Results: Sixty-six patients met study criteria and were included; primary histopathology was ovarian in 38, endometrial in 20, and cervical in 8. Median overall survivals after SRS for ovarian, endometrial, or cervical cancer were 16, 4, and 10 months, respectively. Among 66 patients, 131 lesions were treated (77 ovarian, 35 endometrial, and 19 cervical). Local tumor control at 3 months post-SRS was 89%, 73%, and 100% for ovarian, endometrial, and cervical cancer, respectively. Median prescription isodose (Gy), maximal treatment dose (Gy), and treated tumor volumes (mm³)  were 18/36/1090 for ovarian, 20/36/1859 for endometrial, and 18/30/1000 for cervical cohorts. SRS-related adverse events were low, with 3 patients (4.5%) developing symptomatic radiation necrosis and one patient with documented intratumoral hemorrhage after SRS.

Conclusion: SRS for management of brain metastases from ovarian, uterine/endometrial, and cervical primary cancer is effective and safe. As systemic disease therapies advance and overall survival increases in gynecologic malignancy, it is likely that an increasing number of patients will require management of brain metastases.

Background

For stereotactic radiosurgery (SRS) planning, linac-based dynamic conformal arc (DCA) or volumetric modulated arc therapy (VMAT) plan quality is highly dependent on the planner’s experience. Due to its superior normal tissue sparing, Gamma Knife is the gold standard for patients with 1-4 brain metastases, but treatment time could become prohibitively long for patients with many targets.

Aim

To develop a machine learning-based plan quality evaluation tool for linac-based multiple brain metastases SRS plans using the idealized Gamma Knife plans as the benchmark to assist treatment planning.

Methods

41 patients with multiple brain metastases (range: 5-22) treated with SRS were included in this retrospective study. Idealized Gamma Knife plans, without limiting treatment delivery time, were created for all patients to be used as the benchmark for model development. The dataset was split into 25/7/9 for training/validation/testing. A 3D U-Net was used to predict the benchmark dose around each target. The input is the target contour mask in a 6.4 cm wide region-of-interest (ROI) centered at a target, and the output is the 3D dose distribution in the ROI. To account for dose falloff outside the target and adjacent target outside the ROI, a 1-cm wide exponential falloff was added for each target. To focus on the dose falloff region, a modified mean absolute error was used as the loss function, which added a discount factor of 0.2 for voxels with benchmark dose below 2 Gy or above 16 Gy. The ROI dose for each target was predicted by the network and filled back in the patient volume to obtain a partially filled 3D dose distribution for evaluation.

Results

To avoid overfitting, the final model was trained for 21 epochs when minimal validation loss was reached. It was tested on 9 patients with 66 targets in total. The average PTV volume is 0.98±1.99 cc (range: [0.02,12.88]). The mean brain V12Gy, V8Gy, V4Gy errors were -1.07±0.65 cc, -0.51±0.52 cc, 2.53±8.22 cc for all patients and -0.22±0.28 cc, -0.19±0.39 cc, 0.77±1.36 cc for all targets. The dice coefficients for the benchmark and predicted 12 Gy, 8 Gy, 4 Gy isodose lines for all targets were 0.86±0.08, 0.86±0.11, and 0.81±0.10.

Conclusion

A deep learning model was trained to predict the dose distribution of an idealized Gamma Knife plan for multiple brain metastases SRS patients, which can be used as benchmark to guide treatment planning using other delivery techniques such as linac and CyberKnife.

Background and Purpose

Patients with EGFR-mutated NSCLC represent a unique subset of lung cancer patients with distinct clinical and molecular characteristics. Previous studies have shown a higher incidence of brain metastases (BM) in this subgroup of patients, and neurologic death has been reported to be as high as 40% and correlates with leptomeningeal disease (LMD).

Methods

Between 2012 and 2021, a retrospective review of our prospective registry identified 606 patients with BM from NSCLC, with 170 patients having an EGFR mutation. Demographic, clinical, radiographic, and treatment characteristics were correlated to the incidence of LMD and survival.

Results

LMD was identified in 22.3% of patients (n = 38) at a median follow-up of 19 (2–98) months from initial SRS. Multivariate regression analysis showed targeted therapy and a cumulative number of metastases as significant predictors of LMD (p = 0.034, HR = 0.44), (p = .04, HR = 1.02).

The median survival time after SRS of the 170 patients was 24 months (CI 95% 19.1–28.1). In a multivariate Cox regression analysis, RPA, exon 19 deletion, and osimertinib treatment were significant predictors of overall survival. The cumulative incidence of neurological death at 2 and 4 years post initial stereotactic radiosurgery (SRS) was 8% and 11%, respectively, and correlated with LMD.

Conclusion

The study shows that current-generation targeted therapy for EGFR-mutated NSCLC patients may prevent the development and progression of LMD, leading to improved survival outcomes. Nevertheless, LMD is associated with poor outcomes and neurologic death, making innovative strategies to treat LMD essential.

Purpose

Over the last decade Stereotactic Radiosurgery (SRS) and Fractionated Stereotactic Radiotherapy (FSRT) became standard of care for limited brain metastases.  We now evaluated our cohort with robotic SRS/FSRT of the past 10 years.

Material and Methods

323 patients (157 male, 166 female, age 27-86) of different histologies (lung cancer 132, melanoma 81, breast cancer 56, other 54) with a total of 1164 brain metastases (BM) were treated in 500 series. Simultaneous systemic targeted therapies and/or immunotherapy (TT) were given in 81 (25.1%) cases. Number of BM was 1, 2-10 and >10 in 110, 195 and 18 cases, respectively and 81 patients had received Whole-Brain-Radiotherapy (WBRT) before SRS/FSRT. The median PTV was 0.45ccm (0.01-78.8ccm) with a GTV-PTV-margin of 0-1mm. Median D_98%, D_50% and D_2% of all PTV calculated as biological effective dose with an alpha/beta-value of 10 Gy (BED₁₀) averaged 51.2Gy₁₀ (20.1-63.5Gy₁₀), 75.2 Gy₁₀ (24.8-120.7Gy₁₀) and 106.4 Gy₁₀ (27.8-143.6Gy₁₀), respectively.

Results

Mean follow-up period was 14.8 (0-109) months and the median overall survival (OS) was 8.7 months with 12- and 24-months OS of 45% and 21.6%, respectively. Significant differences in the 12-months OS were seen for melanoma patients with 12-month OS of 50% vs. 45% (whole cohort, p=0.05). Prior WBRT was associated with a non-significant reduction of 12-months OS after SRS/FSRT (10.0 vs. 12.8 months with and without WBRT, p=0.054). The most significant prognostic factor for longer OS was Karnofsky Performance Status (KPS) of ≥90% (p=0.001). Overall PTV (OPTV) <2.6ccm was also associated with a longer OS of 15 months vs. 10 months with OPTV ≥2.6ccm (p<0.01). Simultaneous TT-application led to prolonged OS of 14.5 vs. 10.6 months (w and w/o TT, p=0.227). Local control (LC) after 12 months was 92.4%. A higher PTV D_98% lead to better LC (96.0% vs. 81.5% for BED ≥51.2Gy₁₀, p=0.024), whereas a higher PTV D_2% had no significant effect (92.5% vs. 92.1% for BED ≥106.4 Gy₁₀, p=0.701). Localization of relapses was at the edge of the PTV in 16 and inside the PTV in 29 cases. Bigger metastases (GTV ≥0.45ccm, corresponding diameter of 0.95cm) recurred more often than smaller ones (p=0.047). Rate of side-effects was low (grade ≥3 2%). In 1 case repeated SRS with simultaneous BRAF inhibition led to an fatal intracerebral bleeding (grade 5).

Conclusion

Robotic SRS/FSRT is safe and effective. In the context of central dose-optimization higher PTV D_98% improved LC. Caution is advised for simultaneous re-treatment with BRAF inhibition.

OBJECTIVE

Treatment with immune checkpoint inhibitors (ICIs) has demonstrated clinical benefit for a wide range of cancer types. The neutrophil-to-lymphocyte ratio (NLR) reportedly correlates with survival time or progression-free survival in patients treated with ICIs. However, NLR has not yet been assessed in patients with brain metastases (BMs) in the setting of stereotactic radiosurgery (SRS) combined with concurrent ICIs. The present study sought to investigate the predictive impact of NLR on the survival data of patients with BMs who received SRS with concurrent ICIs.

METHODS

The clinical records of patients who received SRS with concurrent ICIs for BMs between January 2015 and August 2023 were retrospectively analyzed. Neutrophil-to-lymphocyte ratio (NLR) was calculated by using the data obtained from the latest examination prior to SRS. The optimal NLR cutoff value was identified by receiver operating characteristic (ROC) curve analysis for time-to -event data (overall survival (OS) ≤ 18 months). OS and intracranial disease progression-free survival (IC-PFS) rates were compared between two NLR groups.

RESULTS

Of the 185 eligible patients included, 132 patients were male. The median age of the patients was 69 years (IQR 61–75 years). The primary cancers were lung, genitourinary, skin, breast, gastrointestinal, and other cancers in 132, 23, 22, 2, 2 and 4 patients, respectively. The post-SRS median OS and IC-PFS time for the entire cohort was 18.9 months (IQR 14.0–23.1 months) and  9.8 months (IQR 7.5–11.6 months), respectively. ROC curve analysis identified NLR cutoff value as 5.0 (area under the curve: 0.63, Youden index: 0.30). Kaplan-Meier analysis revealed that patients with high NLR (> 5) had a significantly shorter OS (median survival time 10.1 months for 48 patients vs. 22.2 months for 137 counterparts, HR 1.9, 95% CI 1.3–2.9, p = 0.002). Similarly, a significant difference in the median IC-PFS was found: 5.6 months with NLR > 5 vs. 11.3 months with NLR ≤ 5 (HR 1.7, 95% CI 1.2–2.6, p = 0.009).

CONCLUSIONS

The present study found that an elevated pre-SRS NLR (> 5) was associated with shorter survival and worse intracranial disease control after SRS with concurrent ICIs for BMs. NLR is a simple, cost-effective and widely accessible biomarker, and can be used in SRS treatment for patients with BMs being treated with concurrent ICIs. Further investigation in other large datasets is however required to validate these findings.

Our institution upgraded the Gamma Knife radiosurgery (GKRS) system from Model 4C to ICON in 2019. Because about 30% of the patients were treated using the mask immobilization technique and single or multiple fraction scheme with this new unit, we wanted to confirm that the treatment outcome was as good as that obtained by the 4C unit with the Leksell G-frame and single fraction. This paper presents the outcome analysis of 71 patients with GKRS on the ICON unit from 2019 to 2022.

The patient population consisted of 30 (42%) males and 41 (58%) females, with a mean age of 60.8 years old (range: 16 - 92). 23 patients were treated for benign tumors, including 12 meningiomas and 4 vestibular schwannomas. 45 patients with malignant tumors were treated for their metastatic lesions, with a mean number of lesions of 1.85 per person. The most common primary histology of metastatic cancer patients was lung cancer (19), melanoma (8), and breast cancer (5). Ten patients had previous radiotherapy to the brain. All patients were treated with a head immobilization mask, daily cone-beam CT, and real-time motion management. After radiation oncologists and neurosurgeons drew target contours on the MRI, a 1-mm margin was uniformly added to generate the treatment volume. The prescription dose was 24 Gy on average (6 – 30). The mean tumor volume was 4.61+/- 6.53 ml (0.0040-31.4). Our institutional policy is to use fractioned GKRS with a maximum dimension of tumor size greater than 2 cm (or 4 ml). There were 58 patients treated with 3 or 5 fractions. The patients had follow-up MRI scans every three months. The mean follow-up length was 412 days (28-1176). The Kaplan-Meier (KM) analysis was done using R.

The survival rates of patients were 87%, 73%, and 66% for 6 months, 1 year, and 2 years respectively. There was no statistically significant difference between males and females (p=0.83). The patients with two or fewer malignant tumors lived longer than those with more than two tumors (p = 0.0001), but the total tumor volume did not affect survival. It is notable that only two lesions out of 131 locally failed.

The preliminary data of mask-based GKRS by a single institution showed promising outcome results. In the future, the brain toxicity of the new GKRS protocol needs to be analyzed to further confirm its clinical efficacy compared with the single fraction GKRS with the G-frame.

Objectives

The aim of this study is to present the results of GKRS for patients with brain metastases who survived more than 5 years. 

Methods

52 patients with brain metastases, who underwent radiosurgery with Leksell Gamma Knife 4C or Perfexion (Elekta AB, Sweden) and survived at least 5 years after the treatment, were included in the study. There were 21 men and 31 women. The most common primary tumors were breast cancer, lung cancer, melanoma and renal cell carcinoma for 14, 13, 9 and 7 patients, respectively. 15 patients were diagnosed with primary cancer simultaneously with the diagnosis of brain metastases. For 32 patients the brain was the only site of tumor spread. GKRS was performed for 1 to 30 brain metastases. The prescribed radiation dose varied from 16 to 24 Gy at 40-85% isodose. After treatment, the patients underwent regular follow-up examinations (MRI and/ or PET with amino acids). Differential diagnosis of tumor recurrence and radiation necrosis was performed with the help of amino acid PET. Overall survival, local control and radiation necrosis were evaluated with the help of the Kaplan-Meier function. Significance between groups was calculated with the Log-Rank test. 

Results

The median follow-up time after GKRS was 85 months (mean – 93, range 60 – 160). 32 patients were alive at the time of analysis (December 2023) and 11 patients survived more than 10 years after GKRS. The median OS was 121 months. The actuarial survival rates at 6 years were 78.5 %, 8 years – 62.3% and 10 years – 55.4%. Statistically significant factors for OS were the patient’s gender and primary tumor type (p=0.024 and p=0.002). Other factors (age, KPS, presence of extracranial metastases, number of brain metastases) were not significant. Tumor recurrence was detected in 15 metastases (14 patients) within a median of 35 months after GKRS (mean 39, range 10 – 81). Primary tumor type, brain metastasis volume and radiation dose were significant factors affecting local control (p < 0.01). Signs of radiation necrosis were observed on MRI in 27 metastases (20 patients) within a median time of 13 months after GKRS (mean 18, range 4 – 60). Tumor volume and radiation dose were significant factors associated with radiation necrosis (p < 0.01).

Conclusions

Gamma Knife radiosurgery is a reliable treatment for patients with brain metastases, with a high level of efficacy and safety estimated over a long-term observation period. 

Introduction Brain metastases during pregnancy poses complex conundrum in management. Gamma Knife (GK) stereotactic radiosurgery (SRS) offers a valuable option to clinicians in this scenario. We describe the safety and effectiveness of GK SRS in treating a solitary cerebellar metastasis in a woman with recurrent breast cancer in the third trimester of pregnancy. Dosimetry readings during a trial run and actual treatment were recorded and follow-up MRI was performed after one month. A Literature review on similar cases were carried out.

Methods A 42-year-old woman presented with dizziness and unsteady gait during her third pregnancy at 28 weeks of gestation. She was a known case of triple negative breast carcinoma with local recurrence in 2021 and had completed second line chemotherapy 10-months prior to referral. Upon presentation, she was fully conscious with neurological examination showing right cerebellar signs. MRI brain showed solitary right cerebellar enhancing mass, 2x2.7x2.1cm with perilesional edema and hemosiderin rim likely represent hemorrhagic metastasis. Chest radiograph depicted multiple cannon ball lesions. Obstetrical assessment revealed singleton fetus with gestation appropriate growth parameters and an estimated fetal weight of 1kg. Following multidisciplinary discussion, she agreed for urgent single session SRS to the brain metastasis with 2 cycles of 3-weekly paclitaxel chemotherapy. During frame-based GK SRS, a trial run with dosimeters placed on a phantom showed radiation exposure way below the 100mSv dose limit. Actual treatment was performed with 16Gy at 50% isodose in 24 shots over 39.7 minutes beam on time. The treatment plan showed 98% coverage, 89% selectivity and gradient index 2.98.

Results Dosimeters placed near uterine fundus and suprapubic region (consistent with concomitant ultrasound localization of the fetal head) recorded 2.83mSv and 0.27mSv respectively. The patient successfully completed SRS treatment without complications. She safely delivered a healthy baby boy at 36 weeks of pregnancy. Follow-up MRI at three months interval showed total resolution of the lesion. Our literature review revealed one other similar case report which was a patient with melanoma brain metastasis in the second trimester of pregnancy who successfully completed the planned GK treatment.

Conclusions GK SRS is known for the lowest extracranial dose of all SRS modalities. It is safe and effective in treating pregnant patients with brain metastases. It allows concurrent chemotherapy, eliminates anesthetic risk while giving time to achieve adequate gestational age and fetal weight before birth. It improves quality of life and fetal outcome with lower perinatal risk and maternal morbidity.

Objectives

To describe the state-of-the-art of Stereotactic Radiosurgery (SRS) for brain metastases in centers across Latin America and Spain, through a survey conducted among radio-oncologists and neurosurgeons. This study details technological platforms, SRS protocols, and examines regional variabilities.

Materials and Methods

We conducted a specific SRS survey (26 questions) via Google Drive, targeting professionals from Latin America and Spain, utilizing the database of the Ibero-Latin American Radiosurgery Society.

Responses from 106 specialists were analyzed. The survey was designed to provide a comprehensive overview of SRS practice in the region.

Results

1. Participation: 93.4% of respondents were from LATAM, and 6.6% from outside LATAM. A participation of 85% of LATAM countries was obtained. 87% of respondents were Radio-Oncologists, and 13% were Neurosurgeons.

2. Experience and Certification: 62% of specialists had more than10 years of experience in SRS practice, and 80% worked in centers with some SRS certification.

3. Technologies Used for SRS: LINAC 70%, Gamma Knife 15%, CyberKnife 7%, Halcyon 5%, and ZAP 3%.

4. Prescription Dose and Adjustment by Histology: The average dose for an example case of breast histology was 22 Gy [18-26 Gy], while for renal histology it was 24 Gy [20-28 Gy]. 45% of participants adjusted the prescription dose according to histology.

5. Dose Adjustments & OARs: 60% of respondents adhere to RTOG 90-05 guidelines (dose prescripcion related to tumor size) to adjust the dose in situations of prior radiation or voluminous metastases.

6. Fractionated SRS: Used in 50% of cases, with an average dose of 24 Gy [18-30 Gy], especially in large metastases or those close to critical organs.

7. Use of V12 as a predictor of Radionecrosis: Used by 91.5% of respondents, but only 56.6% use it regardless of the total number of lesions.

8. Re-SRS for Recurrences: 41.51% prescribe the same dose initially used. 38.68% choose a lower dose, and 3.77% a higher dose.

9. Post-SRS Follow-up: Conducted every 3-6 months with MRI, being the common practice in 85% of cases.

Conclusions

SRS practice in Latin America shows variability that can be compared to that evidenced internationally in the literature.

The findings underscore the importance of generating internationally accepted protocols and regional consensus, to standardize SRS practice and ensure optimal outcomes for these patients.

Purpose) To examine the effectiveness of stereotactic radiation for intracranial solitary fibrous tumors, taking into account differences in modality. Background) Among solitary fibrous tumors, those that originate within the intracranial space often follow an aggressive course, and radiation treatment after surgery or for recurrent lesions is thought to play an important role. At our hospital, we use stereotactic radiosurgery (SRS) and hypo-fractionated stereotactic radiation therapy (SRT) using a Gamma Knife, or hyper-fractionated SRT using a Liniac, depending on the case. Methods) From April 2004 to September 2023, stereotactic radiation treatment was performed on 24 cases of intracranial solitary fibrous tumors. The average age of the patients at the time of first radiation treatment was 47.3 years. SRS or hypo-fractionated SRT using Gamma Knife was performed for small lesions, and hyper-fractionated SRT using Liniac was performed for large lesions and/or those were close to risk organs (16 cases using only Gamma Knife, only Linac hyper-fractionated SRT in 6 cases, Gamma knife and Linac hyper-fractionated SRT in 2 cases). The average lesion volume at the time of initial radiation treatment was 5.4 ml with Gamma Knife and 43.0 ml with Linac hyper-fractionated SRT. The irradiation doses were: Gamma Knife SRS with an average marginal dose of 16.4 Gy, Gamma Knife SRT with an average marginal dose of 31.2 Gy, and Linac hyper-fractionated SRT with an average marginal dose of 47.5 Gy in 15 -20 fractions. Results) An average follow-up period of 77.1 months was obtained. Progression-free survival rates were 94.7%, 60.9%, and 42.6%, respectively, at 1, 3, and 5 years after initial radiation treatment with Gamma Knife, and 100%, 83.3%, and 62.5%, respectively, with Linac hyper-fractionated SRT. At the time of final observation, 20 out of 24 patients were alive. Conclusion) Good control of the intracranial solitary fibrous tumor was obtained by performing stereotactic radiation taking into consideration the modality characteristics.

There has been a significant increase in the clinical utilization of stereotactic radiosurgery (SRS) for brain metastases (BM). Reducing the dose to the hippocampi in SRS holds promising implications for improved neurocognitive outcomes. HyperArc^® high-definition radiotherapy (HA)  is a single isocenter end-to-end solution for treating BM and other intracranial targets. This study aimed to evaluate dosimetric outcomes of patients receiving HA regarding factors that may impact symptomatic neurocognitive outcomes.

This is a retrospective study of patients who received HA treatment at selected Icon Cancer Centres in Australia between September 2018 and March 2022. Data included for analysis were previously uploaded to the HyperArc Registry (https://clinicaltrials.gov/study/NCT05270707), including demographics, target and organs at risk (OAR) dosimetry, primary tumour characteristics and patient outcomes (neurological symptoms and overall survival). Hippocampi were retrospectively contoured if not present in the original plan. Brain dose was defined as brain minus the total planning target volume (PTV). 

A total of 110 patients receiving 139 courses of radiation therapy were included for analysis. The median age at treatment was 67 years and tumor histology was predominantly non-small cell lung cancer, breast cancer or melanoma. The median number of treated metastases was four (interquartile range 3-6). Treatments were typically 24Gy/3# (n=83/139) and 30Gy/5# (n=35/139). Plans with a total PTV  >10 cm³ had significantly greater mean brain volume doses than PTV <10 cm³ (5.14 Gy vs. 2.14 Gy, p-value <0.001). Furthermore, the mean bilateral hippocampus dose exhibited a positive correlation with the total PTV. Plans with at least one target located within 2 cm of the hippocampi had markedly greater mean hippocampi doses compared to plans where all targets were greater than 2 cm from the hippocampi (4.83 Gy vs. 1.74 Gy, p-value <0.001). On multivariate analysis, the volume of the closest treated brain metastasis to the hippocampi was not predictive of hippocampal dose. Patients presenting with symptoms were more likely to have a greater disease volume (total PTV 23.86 cm³ vs. 17.15 cm³, p-value=0.001); however, the number of brain metastases was not predictive of symptoms. Patients with neurological symptoms at baseline were significantly more likely to experience neurological symptoms during follow-up (OR = 5.6, 95% CI 2.23-14.1).

Mean brain doses are correlated with total PTV. When the total PTV is greater than 10 cm³, the mean brain dose tends to be greater than 5 Gy. Hippocampi should be considered as organs at risk (OAR) and optimized in plans with targets

[Objective] We introduced the Leksell Gamma Knife Icon (ICON) in November 2016, and started fractionated irradiation for large metastatic brain tumors. In the present study, we investigated the efficacy of ICON in the treatment of large metastatic brain tumors. [Methods and Subjects] We included 178 patients who received ICON fractionated radiosurgery between December 1, 2016, and December 31, 2021, and who could be followed up for more than 1 year. [Results] The Gamma Knife fractionated irradiations were 30 Gy / 3 fx, 35 Gy / 5 fx, and 40-42 Gy / 8-10 fx. The number of patients divided into three groups by number of fractionations was 26, 94, and 58, respectively, and the mean volume of the irradiated object was 7.4 cm3, 11.8 cm3, and 25.2 m3, respectively. Median survival was 10.6 months overall and 16.6, 8.3, and 12.2 months for each fraction, respectively, with no significant differences. Kaplan-Meier analysis showed significantly longer MST in women, KPS ≥ 80, and primary breast and lung cancer, and these factors were significant in multivariate analysis. The overall cumulative recurrence rate was 6.9% at 1 year and 9.7% at 2 years. Competing risk analysis of the associated factors showed an increased recurrence rate for lesions larger than 14 cm3 in the five-fractionation group. The incidence of delayed radiation injury was 7.3% at 1 year and 9.7% at 2 years, with a trend toward higher incidence in the 3-fraction and 14 cm3 or greater groups, but the only significant factor was female gender. [Conclusion] With the introduction of ICON, effective and safe treatment of even large tumors is now possible. The number of cases that can be treated with gamma knife therapy is increasing, even in cases where craniotomy was previously considered an indication, and future treatment strategies for metastatic brain tumors should also be considered.

Surgical resection is used to treat brain metastases  may be associated with the risk of developing leptomeningeal disease (LMD). Stereotactic radiation therapy (SRT) is an effective strategy for the treatment of large brain metastases and may be an alternative to surgery or an adjuvant component.

Objective: To compare different techniques for the treatment of large brain metastases   examined rates and predictors of leptomeningeal disease.

Methods: 369 patients with large (≥2 cm in diameter) BMs  were underwent surgical treatment (S) alone (72 patients), or adjuvant SRT in hypofractionation (F) mode (126 patients), or neoadjuvant SRS (65 patients) or FSRT alone (106 patients) between 2011 and 2022. Among them were patients with non-small cell lung cancer (86), breast cancer (123), melanoma (59), kidney cancer (35), gastrointestinal cancer, (44)  and gynecologic cancer  (22) . Categorical baseline characteristics were compared using the χ2 test. LMD scores were assessed by the Kaplan-Meier (KM) method, and the log-rank test was used to compare subgroups.

Results: LMD was detected in 81 (21,9%) of 369 cases including 27.7%, 32.5%, 12.31% and 11.32% in S, S+FSRT, SRS+S and FSRT subgroups, respectively. The KM estimates of 12-month and 24-month LMD-free survival in the S, S+FSRT, SRS+S, and FSRT groups were 75.5% and 62%, 70.6% and 61.8%, 84% and 81%, 88.9% and 84.7%, respectively (P = 0.0031). The hazard ratio for developing LMD comparing with patients who received FSRT alone were 2.7(CI 1.42 to 5.23), 2.7 (CI 1.6 to 4.7), and 1.26 (CI 0.64 to 2.5) in the S, S+FSRT, and SRS+S groups. The 12-month LMD-free survival rates of large BMs in the non-small cell lung cancer, breast cancer, melanoma, kidney cancer, gastrointestinal cancer, and gynecologic cancer subgroups were 81.7%, 74%, 80.6%, 85.6%, 75.8%, and 63.8% respectively (P = 0.0388).

Conclusions: The risk of developing LMD depends on the primary focus, lower in the non-small cell lung cancer and kidney cancer subgroups. Surgery increase the risk of developing LMD compared to FSRT alone. SRS+S and FSRT have similar  low risk of developing LMD, and  may be the method of choice for patients with large BMs. 

Objective.

The impact of the stereotactic radiosurgery (SRS) prescription dose (PD) on local progression for small (≤ 1 cm) brain metastases was evaluated.

Methods.

An retrospective review was performed on 247 patients with brain metastases ≤ 1 cm (2070 tumors) who received  SRS with Gamma Knife  Icon between 2015 and 2022. Local progression were the primary end points. Each tumor was followed from the date of radiosurgery until one of the end points was reached or the last MRI follow-up. The median radiographic follow-up per lesion was 6,7 months.

Results. 

The median patient age was 57 years, and 58% of the patients were female. The most common primary pathology was breast cancer (36,8%) followed by non–small cell lung cancer (28,3%), melanoma (19%), renal cell carcinoma (12,5% %) and colorectal cancer (3,2%). The median tumor volume was 0,056 (95% CI 0,051–0,064) cm3. The PD for 1530 tumors (73,9%) was 24 Gy, for 233 tumors (11,2%) it was 22 Gy, and for 307 tumors (14,8%) it was 20 Gy.  

In total, 14 patients (5,6%) had local progression of 79 tumors (3,8%). The local progression for PD 24 Gy was in 61 tumors (3,9%), for PD 22 Gy it was in 6 tumors (2,6%) and for PD 20 Gy it was in 12 tumors (3,9%). In univariate analysis there was no statistical difference (P = 0,3532) in local progression for tumors with a dose of 24, 22 and 20 Gy. 

Conclusions. 

PD (within 20-24 Gy) is not an independent prognostic factor for local control of tumors smaller than 1 cm. Probably some pathologies and locations may also contribute to an increased risk of local progression. Further research is needed.

Objective.

Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain metastases with high local control rates. However, data about local re-irradiation in case of local failure after SRS are rare. We studied the effectiveness of treating local relapses with a repeated course of radiosurgery (re-SRS).

Methods.

We retrospectively evaluated patients with brain metastases treated with re-SRS for local tumor progression between 2015 and 2022. Patient and treatment characteristics as well as rates of tumor control and toxicity were analyzed.

Results

Overall, 110 locally recurrent brain metastases in 59 patients were irradiated with re-SRS. Median age at re-SRS was 53 years. The most common primary pathology was breast cancer (49,1%) followed by melanoma (22%), non–small cell lung cancer (16,9%), renal cell carcinoma (8,5% %) and colorectal cancer (3,4%). In the first SRS and in the re-SRS were treated with Gamma Knife. The median tumor volume for the first SRS and in the re-SRS was 0,82 and 1,43 cm3 respectively. Median prescription dose for the first SRS and in the re-SRS was 22 and 20 Gy respectively.

In total, 14 patients (23,7%) had local progression of 18 tumors (16,4%). The 1-year overall survival rate was 85,8% and the 1-year local control rate was 83,9%. The overall rate of radiological radio-necrosis was 28,2%.

Conclusions

A second course of SRS for locally recurrent brain metastases after prior local SRS appears to be feasible with acceptable toxicity and can be considered as treatment option for selected patients. Furthermore, further research is required to establish optimal fractionation regimens for repeat SRS in locally recurrent lesions.

INTRODUCTION:  Glioblastoma (GBM) are often relapse after preliminary removal with subsequent conventional radiation therapy, while often the optimal tactics for treating relapses has not been precisely determined. One of the option for the relapses of GBM relapses is  stereotactic radiotherapy with hypofractionation mode  (HFRT) .

OBJECT: To evaluate the role HFRT with GammaKnife (GK) in patients with recurrent of GBM after resection and fractionated radiation therapy (RT).

METHODS: From July 2018 till December 2023 at “Moscow GammaKnife Center”, which affiliated with Burdenko Neurosurgical Institute (National scientific research Center of neurosurgery named after N.N. Burdenko) 19 patients (8 males and 11 female) with recurrent of GBM was treated by HFRT with LGK Icon. Most patients were older than 55 years – 13 vs 6 pts. Median age at first GK procedure was 60 years (from 21 to 71). 18 patients underwent tumor repeat resection, chemoradiotherapy and adjuvant chemotherapy. One patient was treated without biopsy, after PT-CT with methionine for verification. The median time from initial surgery to GKRS was 17 months. 

RESULTS: The median target volume was 8.7 (from 2.2 to 72.2 cc) and the median dose to the tumor margin was 35 Gy (range 24-35 Gy) for 3 or 5 fractions. Total number of irradiated targets is 43. Average 19 patients followed at least 1 year (max 5 years). Progression-free survival after the initial GKRS was 68.4%, at 1 year. The distant tumor relapse rate despite RT and GKRS was 10.5% at 12 months respectively. Overall survival (OS) after HFRT was 65.5% at 1 year, and 2-year OS reaches 21.0%, respectively. Adverse radiation effects developed in 1 patient (5.2%).

CONCLUSIONS: HFRT by GK in different modes is the treatment of choice, along with reoperation, in patients with recurrent glioblastoma after initial combine treatment.

Abstract Background. One of the rare (1.5-2.5%) brain tumors is gliomas of the brain stem (BSG) in adults. At the time of detection of BSG, patients were about 30 years old, and the usually degree of malignancy of the disease was low (WHO grade I–II). The average life expectancy in adults varies from 30 to 40 months. Surgical treatment is not used in most cases, therefore radiation therapy is the main method of treatment

Objective. To evaluate the results of radiation therapy in adult patients with brain stem tumors and identify predictors of treatment effectiveness.

Material and methods. Radiation therapy was performed in 115 patients with brain stem tumors between 2005 and 2021. Patients under the age of 40 years (n=80), from 40 to 60 years (n=30) and older than 60 years (n=5). The average age was 34.45± 12,873. There were 67 men (58%) and 48 women (42%). Surgical intervention was performed in 44 (38.2%) people, while 71 (61.7%) did not. The functional state was assessed according to the Karnovsky index (IK). in IK 70% - 53 (46%), IK 80% - 45 (39.1%), IK 90% - 12 (10.4%) and IK 60% - 5 (4.5%). The average follow-up period after radiosurgery was 119.8 months. All patients received radiation therapy in the conventional mode, a single dose of 2 Gy, a total mean dose of 54 Gy.

Results. Radiation therapy for patients with brain stem tumors improved progression-free survival and overall survival. The overall cumulative survival rate at 12, 24, 36 and 60 months was 96.5%; 92.7%; 83.5% and 68.7%. The median disease-free survival was 43.47 months (95% CI from 30.5 to 56.4). The rate of disease-free survival for the research cohort of patients (total sample n=105) in the range of 12, 24.36 and 60 months was 79.5%; 72.4%; 58.9% and 38.4%, respectively. Significant factors influencing the outcome of treatment are: age, functional state and histological form of the tumor.

Conclusion.  Radiation therapy for adult patients with brain stem gliomas  in the standard fractionation mode at a total dose of 54 Gy is effective treatment method and is the method of choice for these patients.

Introduction: Stereotactic radiosurgery (SRS) has become a common treatment approach for small-to-medium size vestibular schwannomas.

Objective: To evaluate relationship between time (beam-on and treatment) and risk of hearing decline after stereotactic radiosurgery for vestibular schwannomas in patients with Gardner-Robertson (GR) baseline classes I and II.

Methods: This retrospective longitudinal single-center study included 213 patients with GR I and II treated between June 2010 and December 2019. Risk of passing from GR classes I and II (coded 0) to other classes III, IV, and V (coded 1) and the increase in pure tone average (continuous outcome) were evaluated using a mixed-effect regression model. Biologically effective dose (BED) was further assessed for an alpha/beta ratio of 2.47 (Gy2.47). The mean beam-on time was 36.3 ± 18.1 minutes (range 7.3-101.8). The mean treatment time was 38.8 ± 18.5 (range 9-106). The mean radiation dose rate was 2.8 ± 0.6 (1.7-3.8) Gy/minute. The mean BED received by the tumor was 57.1 ± 4.5 (42.7-66.3) Gy2.47.

Results: Binary outcome analysis revealed sex, dose rate, integral dose, time (beam-on time odds ratio 1.03, P = .03, 95% CI 1.00-1.06; treatment time ( P = .02) and BED ( P = .001) as relevant. The OR of 1.03 for the beam-on time implies a 3% hearing deterioration risk per minute, for 10 additional minutes, OR was 1.38 with a risk of 38% and for 20 minutes was 1.92 with a risk of 92% (P < .001). Fitted multivariable model included the sex, dose rate, and BED. Pure tone average analysis revealed age, integral dose received by tumor, isocenter number, time (beam-on time odds ratio 0.20, P = .001, 95% CI 0.083-0.33) and BED ( P = .005) as relevant.

Conclusion: Our analysis showed that risk of hearing decline was associated with male sex, higher radiation dose rate (cutoff 2.5 Gy/minute), higher integral dose received by the tumor, higher beam-on time ≥20 minutes, and lower BED. A BED Gy2.47 between 55 and 61 was considered as optimal for hearing preservation.

Introduction: Gammaknife radiosurgery (GKRS) is one of the main options for the management of small to medium vestibular schwannomas (VSs) due to its high tumor control rate and low morbidity. When failure occurs, microsurgical removal is generally advised. Yet, surgery is deemed as more challenging, after initial treatment by GKRS. We report our own experience of repeat GKRS using of historical cohort for VSs.

Methods: Were included patients with sporadic VS treated by GKRS in Marseille from July 1992 to December 2017 and who benefited from a second GKRS in our center after initial failure.

Outcomes: 81 patients were included in the study. Median marginal dose was 12 Gy at both GKRS. Follow-up after GKRS 2 was available for 72 patients (9 patients lost to follow-up). Median follow-up after GKRS2 was 56 months. Tumor control GKRS2 was achieved in 92.9% with no patients requiring a further microsurgical resection. Hearing preservation was 61.9% (13/21 patients). No patient experienced persistent facial nerve deficit. New persistent TN was observed in 1.4%, and hemifacial spasm in 1.4%. A ventriculoperitoneal shunt was required in 7%, all after GKRS2. No patients experienced malignant transformation or adverse radiation effect.

Conclusion: We report the largest series of patients managed by repeat GKRS for VS after initial failure. The management of these patients is challenging and requires a multidisciplinary team. GKRS is as safe and effective in case of retreatment compared to a first treatment. This option should be proposed before surgical resection when the clinical condition of the patient and the tumor volume is still compatible. 

Fractionated Radiotherapy for Meningiomas Using the Mask System of Leksell Gamma Knife Icon
Yuta Oi, Gaku Fujiwara, Takuya Kawabe, Manabu Sato
Maizuru Medical Center, Rakusai Shimizu Hospital

Objectives:
The Leksell Gamma Knife Icon has facilitated the implementation of novel immobilization techniques utilizing mask fixation and the option of fractionated treatment.

Methods:
We conducted a retrospective analysis involving 176 patients (209 instances) diagnosed with meningiomas who underwent fractionated radiotherapy using the mask system of Leksell Gamma Knife Icon over the initial 6-year period at Rakusai Shimizu Hospital. A fractionated schedule was applied in cases where tumor volume exceeded 5.0 ml, instances of recurrence, or when the lesion was located in eloquent areas. The reasons for selecting a fractionated schedule (including duplications) were categorized as follows: large volume (122 instances), proximity to eloquent areas (108 instances), and recurrence (45 instances). To enhance precision, we reduced the upper limit of the HDMM system from 1.5mm to 0.5mm near eloquent areas. Of the 112 patients, 112 underwent surgical resection. Tumors were classified according to the WHO classification system, with Grade I representing 116 cases, and Grade II and III combined representing 60 cases. Ninety-two tumors were located in the skull base, while 84 were in non-skull base areas. The median tumor volume was 7.6 mL (IQR: 3.3-13.3). Median marginal doses were 30Gy in ten fractions for Grade I and 37 Gy for Grade II and III.

Results:
The median follow-up period was 21.5 months (range 0.6-69.5). Throughout this period, 10 patients deceased, with seven deaths attributed to neurological causes. Poor local control rates were 3%/4%/11%/15% at 6/12/24/36 months post-treatment for Grade I and 16%/22%/35%/41% for Grade II and III, respectively. Neurological function preservation rates were 98%/96%/92%/92% at 6/12/24/36 months post-treatment for Grade I and 80%/72%/64%/54% for Grade II and III, respectively. Serious complications occurred in only 1%/1%/2%/5% of patients at 6/12/24/36 months post-treatment for Grade I and 3%/3%/7%/7% for Grade II and III, respectively.

Conclusions:
While acknowledging the limitations of these findings due to the relatively short follow-up periods, survival rates, local control rates, and qualitative survival rates among patients unsuitable for stereotactic radiosurgery – particularly those with large, recurrent, or lesions in eloquent sites – were observed within acceptable ranges.

Introduction:

Brain arteriovenous malformations (AVMs) are rare conditions with an annual rupture rate between 2-4%.

Depending on the depth at which they are located, the rupture rate can reach up to 33% in deep lesions

associated with venous drainage. After a rupture there is a 50% probability of suffering neurological

deficits, which are fatal in up to 10% of cases. Radiosurgery with gamma knife is an alternative in those

lesions smallers (<3.5cm), complex or with high surgical risk, achieving obliteration that prevents rupture

and secondary hemorrhage.

Materials and methos:

Retrospective descriptive study of patients with arteriovenous malformations treated with single-dose

radiosurgery in our Gammaknife unit at Virgen de las Nieves University Hospital, Granada, from

November 2022 to October 2023

Results:

A total of 28 patients with a median age of 47 years (18-72) have been treated. 45% were women and

55% men. 3 of them were previously treated with CR and 2 with surgery. The most common clinical

presentation was hemorrhage (46%) and seizures (25%). 86% were <3cm, 11% 3-6cm and 3% > 6cm.

Located in eloquent area 35%. Deep 25%. Median follow-up of 5 months.

Spetzler-martin score: 1 (33%), 2 (33%), 3a (6%), 3b (17%) and 4 (11.1%). Median tumor volume 0.7

(0.04-6.6). Coverage dose 18Gy. Median coverage isodose 58% (47.7-98.3). Median selectivity 0.6

(0.28-0.99). Median Gradient 2.86 (0.8-9.29). Paddick Index median 0.61 (0.14-2.58). Acute toxicity:

perinidal edema G1 21%.

Conclusions:

Radiosurgical treatment with Gammaknife for AVMs is a safe treatment, with a low acute toxicity profile. It

is necessary to obtain greater follow-up to quantify the obliteration rate of the lesions as well as the

probability of bleeding in the latency period between treatment and obliteration.

Introduction

Stereotactic radiosurgery (SRS) is a common option for patients with intracranial meningiomas. Major contraindications to SRS include large tumor volume and critical location (e.g. perioptic). One strategy to expand the treatment envelope of SRS Is to deliver radiation over several fractions. The data on the durability of tumor control and optimal fractionation regimen are limited. Our goal is to clarify these questions through a multi-institution collaborative study.

Methods

We reviewed consecutive patients with meningioma who underwent multi-session radiosurgery at NYU Langone Health (New York, USA; Gamma Knife = 25) and University Health Network (UHN, Toronto, Canada; Gamma Knife = 9, LINAC = 4). Patients were selected for multi-session radiosurgery either due to larger tumor volume and or critical locations. Comparisons of overall survival between cohorts were done using a Cox proportional hazards model.

Results

38 consecutive patients were identified with mean age of 62.9 years and female-to-male ratio of 25:13. 44 tumors in total underwent irradiation spanning all WHO grades. Most commonly, tumors were located in the convexity (n = 14, 32%). 13 patients had previous EBRT while 5 had prior SRS. The mean gross tumor volume was 7.1 (range 0.02 - 64) cm³. The most common fractionation schemes were 20-25 Gy over 5 fractions, followed by 21 Gy over 3 fractions. 

The median follow-up was 26.8 months. The overall median survival was 68.5 (95% CI 36.3 - NA) months, with 3 and 5 year survival at 69.8% and 50.9%. Meningiomas with unknown grade or WHO grade 1 were associated with improved survival (p = 0.026). The median survival of these low grade meningiomas was not reached. The 3 and 5 year local control rates of all tumors were 70.4% and 60.3%. Again, WHO grade was associated with tumor control (p = 0.022). The 3 and 5 year local control rates of low grade meningiomas were both 91.7%. 

13 (34%) patients experienced an improvement in symptoms or neurologic deficits after SRS. 6 (16%) patients experienced adverse radiation effects of worsening seizures or neurologic deficits.

Conclusion

Hypofractionated SRS results in durable local tumor control in WHO grade 1 or suspected grade 1 meningiomas. Limitations to the study are the small size and heterogeneous tumor and treatment characteristics in the sample population. Our next step will investigate the relationship of volume, pathology markers, and dosing regimen to tumor control and adverse radiation effects. 

Background/Objective: Varian’s HyperArc (HA) radiosurgery-specific solution offers highly conformal dose distributions, allowing for the fractionated stereotactic radiotherapy (fSRT) treatment planning of benign brain tumours. These tumours are commonly located in deep-seated eloquent positions overlapping with or near critical optical and neural structures, requiring highly skilled dosimetrists and significant time resources within busy clinical environments. This project aimed to significantly enhance fSRT treatment planning for benign, deep-seated brain tumours by integrating an innovative and novel knowledge-based planning (KBP) prediction model using Varian’s Rapid Plan (RP) solution (KBP-RP). This work presents the robust quality assurance methodology used to refine the model through qualitative, quantitative, and iterative processes to reduce dose significantly and time-efficiently to organs-at-risk (OARs) while maintaining or improving planning target volume (PTV).  

Methods: 51 clinical fSRT patients treated on a Varian Edge HDMLC MV-6FFF LINAC using HA ranging from 5 to 37 fractions between January 2020 and December 2023 were shortlisted in the preliminary KBP model. A qualitative review of OAR contouring and geometrical OAR-PTV relationships was documented for each patient to ensure complexity robustness. A Preliminary noncoplanar HA-specific KBP model was then generated and retrospectively applied to 11 clinical fSRT Plan(_Clinical) patients and compared to the new optimised plans using the preliminary KBP model Plan(KBP_prelim). We evaluated the R50%, Brain-GTV V5, V18, V24 and the maximum dose (D_max) to the Brainstem, Optic Chiasm, Left Optic Nerve, and Right Optic Nerve to determine the consistent efficacy of the KBP model. Any Plan(KBP_prelim) that did not meet the mandatory PTV parameters was reoptimised to ensure clinical suitability.  

Results: Plan(_Clinical) and Plan(KBP_prelim) were compared for each of the 11 fSRT patients; there was a reduction in the Brainstem D_max of 14.1%, while the Optic Chiasm, Left Optic Nerve and Right Optic Nerve all had a reduction of 13.9%, 22.9% and 18.8%, respectively. Plan(KBP_prelim) also demonstrated a R50% reduction of 6.40%, while the Brain-GTV V5, V18 and V24 was reduced by 8%, 7.6% and 8.20%, respectively.  

Conclusion: Integrating a refined KBP-RP prediction model with HA technology substantially reduces OAR sparing while maintaining or improving target coverage for deep-seated brain tumours treated with fSRT. This synergy improves patient outcomes and clinical efficiency through personalised, machine-learned treatment planning. A second stage of the study is now in progress – comparing a further refined second KBP-RP model against the clinical and initial KBP-RP, comparing 19 OARs on all 51 treatment plans trained into the model.  

Purpose 

            Pituitary tumors patients treated with fractionated stereotactic radiation therapy were studied to determine overall survival (OS), progression-free survival (PFS), factors that influence them and complications derived.

Materials and Methods

From 1997 to 2021, 102 patients have been treated with an average age of 55 years (18-81). An extensive database has been created.

Patients treated with cones until 2008, at which time they began to be treated with micromultilaminae and probability of doing IMRT.

The dosimetry was carried out with the planners Iplan‍® of Brainlab until 2016 and later a combination between Elements‍® (contouring) and Eclipse®‍ (dosimetry). The prescribed dose and fractionation was (45-62.1Gy) in 16-31 fractions [one patient 14 Gy in one fx]. With an average volume of planning or PTV: 6.81cc (0.32-11.27).

Tumor types found at similar frequencies: hormone-producing (55.68%) and non-producer (44.32%) adenomas. Being the most manifested growth hormone.

Most common symptom was visual deficit (35.63% of the cases).

Most patients had previous surgeries (93%).

Results

OS and PFS have been studied with a high mean follow-up, up to 15-20 years. OS at 5 years 0.87; tumor PFS at 5 years 0.82; hormonal PFS at 5 years 0.28. Post-radiotherapy ophthalmopathy only 1.4%; post surgery plus radiotherapy 8.8%; ophthalmopathy due to surgery 39.71% and without visual toxicity 50%;

Conclusion

Patients with good prognostic; no direct influence of age or tumor type was found.

The radiotherapeutic effect seems to achieve a great control of the tumor size or volume while the hormonal control is low but easily corrected with substitutive treatment.

Fractionated stereotaxic radiotherapy is safe, with low acute and long-term toxicity including visual or hormonal

The great heterogeneity of the base gives rise to more studies that could also be necessary.

Objective: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes.

Methods: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose.

Results: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047).

Conclusions: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

Optic nerve sheath meningiomas (ONSM) are rare entity which irreversibly leads to vision loss. Treatment options are observation, microsurgery, or standard fractionated radiotherapy. None of these approaches are optimal. With the increasingly available frameless radiosurgery, the possibility of precise radiation is established using a multisession treatment with doses below the tolerance dose of the optic nerve, and sufficient to achieve local control of the disease with no side effects.

Multisession radiosurgey was offered to five patients with ONSM (four females). Patient age ranged from 43 to 73 years (mean 54 years). The diagnosis was based on MR neuroimaging. The tumor originated from the orbital segment of the optic nerve in three patients, from the canalicular segment in one and one patient had bilateral ONSM. The patients underwent thin-slice (1.00- mm-thick) CT scanning and volumetric MR imaging. The median pretreatment tumor volume was 1.96 mL (range, 0.5-5.6 mL). One patient was treated using the Cyberknife S7 machine, four were treated with Linac-based SRS with the Varian Edge RapidArc technique. An 80% prescribed isodose of 25 Gy was delivered in 5 sessions of 5 Gy. Patients were evaluated for tumor growth control and visual function. Mean follow-up duration was 16 months (6 to 25 months) and consisted of MR imaging and visual field and acuity examinations. On MR no changes in lesion size were observed in four patients and minimal regression in one. Visual function was stable in two and improved in three patients. No patients had worsening of visual function. No radiation-induced toxicities were observed. Furthermore, we made a dosimetric comparison between Cyberknife and LINAC-based stereotactic radiosurgery. Both techniques yielded good gross tumor volume coverage and organs at risk sparing. The conformity index was better in RapidArc (1.13 ± 0.35) compared to CyberKnife (1.48 ± 0.43). RapidArc also had a better dose gradient index (73.47 ± 27.98) compared to CyberKnife (55.76 ± 23.94). CyberKnife demonstrated lower maximum doses to some organs at risk such as lens, optic nerve and eye, and RapidArc delivered lower doses for chiasm. For normal brain tissues, V12Gy was lower with RapidArc (3.17 ± 9.69) compared to CyberKnife (5.49 cc ± 10.40).  Tretment time was lower for RapidArc. Conclusion: Multisession radiosurgery for ONSMs is safe and effective. The results from our series, in terms of growth control, visual function improvement, and toxicity, are promising without significant differences between Linac-based and Cyberknife techniques. Further investigations are warranted.

Background: Chondromyxoid fibromas (CMFs) are benign tumors and exceedingly rare in the sellar region. Radical excision is often technically impossible because of their local invasiveness and the presence of complex neurovascular structures. The role of gamma knife radiosurgery (GKRS) as an adjuvant or primary treatment for CMFs in this area has not been reported to date. The goal of this study was to investigate whether GKRS is an effective and safe treatment modality for CMFs in the sellar region.

Methods: Between December 2014 and August 2019, 3 patients haboring CMFs were treated using a Leksell Gamma Knife Perfexion at Gamma Knife Center of Huashan Hospital. Of these, 2 with definitive histopathologic diagnoses after surgery, 1 was diagnosed mainly based on his corresponding MR images and clinical presentation. There were 2 male and 1 female patients with a median age of 39 (range, 36-46) years old. The median tumor volume was 14.26 (range, 4.63-21.76) ml at initial GKRS treatments. Patients received a median prescription dose of 12 (range, 9.5-14) Gy directed to the 48%-50% isodose line (median, 50%).

Results: The median follow-up period after GKRS was 47 (range, 33-60) months. At last follow-up, we report no cases of failure in GKRS for CMFs in the sellar region. All three patients demonstrated a significant reduction in tumor volume. The median tumor volume reduction was 38.99% (range, 9.72%-47.24%) after GKRS treatments compared with the pre-GKRS volume. Post-GKRS clinical improvement was achieved in all three patients (100%). No radiation-induced neurological deficits or delayed complications secondary to GKRS were observed during the follow-up period.

Conclusions: This is the first report to address GKRS for CMFs in the sellar region. Our study showed that GKRS is a useful and safe therapeutic method for CMFs in the sellar region as both a primary and adjuvant treatment. Further studies with long-term follow-up and larger numbers of cases are necessary to optimize the treatment conditions and verify the benefit of this treatment.

Meningiomas are the most common CNS tumors. Recently, an increasing amount of data has emerged regarding the influence of genetic factors on the progression of the disease. Moreover, patients who exhibit biallelic inactivation of Nf2 and Nf2-inactivated schwannomatosis have shown a diminished response to radiation treatment. Additionally, this particular group of patients has a higher incidence of developing meningiomatosis.

In order to study the molecular genetic characteristics of various tumors in nf2-associated schwannomatosis patients (neurofibromatosis type II), a targeted sequencing panel of genes was created. The panel was designed based on the molecular relationships of merlin and also took into consideration known targets of targeted therapy. The selected target genes included mtor, egfr, vegf, map2k1, map2k2, akt1, igf1, kit, erbb2, erbb4, pik3ca, pak1, and pak2. A total of 80 samples were sequenced from 23 patients, including 10 patients with sporadic meningiomas and 13 patients with nf2-inactivated schwannomas and meningiomas. The average number of mapped reads was 1,463,189, with an average coverage of 1447x. 

A total of 740 unique genetic variants were identified, categorized as benign (204), pathogenic (46), variants of unclear clinical significance (477), and artifact (13). The most common pathogenic variants were found in the genes AKT1, EGFR, and ERBB2. It is interesting to note that in the literature, variants in the ERBB2 gene in schwannomatosis patients are primarily described for transitional tumors (schwannoma/neurofibroma) that are usually painful. However, in our sample, variants in this gene were found in vestibular schwannoma and meningioma cells with equal frequency, and none of the cases presented with a pain syndrome such as trigeminal pain. 

Furthermore, while only one driver mutation was found in all samples of sporadic meningiomas in one patient, different gene variants were detected in patients with schwannomatosis, suggesting the need to inhibit previous stages of the signaling pathway. Despite the successful use of VEGF inhibitors to control the growth of vestibular schwannomas and ependymomas in schwannomatosis patients, variants in this gene were only identified in patients with sporadic meningiomas. Nonetheless, these findings also demonstrate the potential use of drugs from this group for some patients with sporadic meningiomas if surgery is not feasible or if the response to radiation treatment is poor.

Introduction: Vestibular schwannoma (SV) is a benign intra or extra-canalicular lesion, which tumor control with radiosurgery is challenged by the choice of an adequate dose and fraccion.

Main objective: To choose different fractionation and equivalent dose, according to the size and proximity of SV to the brain stem. 

Materials and methods: A retrospective analysis was conducted with patients having at least 6 months of follow-up. Nine patients (2016-2023) were treated with five fractions of SRS for a Koos III-IV vestibular schwannoma. Five patients had undergone prior surgery before SRS treatment . SRS was delivered using Linac Novalis Tx or TrueBeam Stx, iPlan v4.5 or Elements Cranial v1.5. Frequency and intensity of tinnitus, dizziness, facial paresis, spasms and trigeminal nerve pain were recorded, before and after SRS, in person or by survey. 

Results: The median tumor volume at the time of SRS was 9.7 cc (4.38-22). Initial symptoms were: 3 anacusis, 2 hypoacusis, 2 tinnitus, 3 dizziness, 2 facial paresis. With a mean follow-up of 34,2 months (6-84), functional hearing was preserved and the intensity and frequency of dizziness were reduced. In resonance imaging 6 had shrinking tumors, 1 showed growth and 2 had stable tumor. 

Conclusions: Fractionation according to tumor size and contact with the brain stem makes it possible to respect the tolerance dose with significant reduction of dizziness and preservation of functional hearing.

Objective: 

Gamma Knife radiosurgery is commonly used in the multimodal management of patients with pituitary adenomas. Regarding the radiation exposure of risk structures such as the optic nerve or the optic chiasm, a safety distance of two millimeters is often considered as crucial in treatment planning. Moreover, varying levels of radiation tolerance have been reported in the literature for organs at risk in close proximity to the pituitary adenoma. The aim of this study is to evaluate the effect of different radiation doses on the critical structures via the endocrinological, ophthalmological and neurological outcome.

Methods:

A retrospective analysis of 139 patients with pituitary adenomas, who underwent at least one Gamma Knife radiosurgical treatment between 2000 and 2022, was performed. The radiation dose to the defined critical structures as well as the minimal distance between the pituitary adenoma and these structures were measured with the Elekta Planning System. 

Results:

The majority of the study population (134/139, 96%) underwent a previous surgical removal of the pituitary adenoma. The pituitary adenomas were hormone-active in 92/139 (66%) patients. The median treatment volume was 4.6 cm3 (0.5-16.7). In 3/139 (2%) patients, a compression of the optic chiasm or optic nerve could be observed. 

Of 130/139 (94%) with available pre-radiosurgical planning data, the maximal radiation doses on the optic chiasm were 6.2 Gy (1.5-16.3). After Gamma Knife radiosurgical treatment, the majority of patients (95%) with radiological follow-up had a decreased tumor volume. Furthermore, the majority of the patients (96%) did not have any worsening of the ophthalmological deficits. 

Conclusion:

Radiosurgical treatment is a safe therapy option for pituitary adenoma patients without worsening of ophthalmological deficits. 

Objective:

Gamma Knife SRS is an established technique in the treatment of Brain AVM,s. However radiosurgery for AVM is still associated with a risk of developing new neurological deficits, which may be permanent. We report our experience with integrating stereotactic diffusion tensor imaging (DTI) tractography into treatment planning for Gamma Knife SRS for Arteriovenous Malformations.

Methods:

Stereotactic DTI studies were performed in 37 (41 treatments) patients who underwent GKRS for AVM over a four year period.

Age range 18-77 years Female 14pts : Male 23 pts.

Marginal dose 18-25 Gy, 6 retreatments, 5 staged treatments, 26 primary treatments 90-99% coverage, TV 0.057 – 15.9cc

DTI images were obtained at the time of standard GKRS protocol MRI (T1 and T2 weighted) for treatment, with the patient's head secured by a Leksell stereotactic frame. DTI was performed with diffusion gradients in 32 directions and coregistered with the volumetric T1-weighted study. DTI post-processing by means of commercially available software allowed tensor computation and the creation of directionally encoded color, apparent diffusion coefficient & fractional anisotropy mapped sequences. The visualized critical tracts were exported as a structural volume and integrated into GammaPlan as an “organ at risk” during during shot planning and subjected to dosimetry.

Results:

DTI allowed visualisation & dosimetry of eloquent white fibre tracts during treatment planning.

The Optic Radiation was most frequenty involved in 26 cases, Cortiso-Spinal Tract in 12 cases and the Arcuate Fasiculus in 6 cases.

The 12 Gy Vol ranged from 0.221 – 45.65 cc. One patient with mesial temporal AVM developed delayed worsening of a pre-existing hemianopia & another with AVM required steroids for cerebral swelling, One patient died of natural causes during the follow up period.

No other neurological deficits due to radiation were recorded at follow-up.  

Conclusions:

Stereotactic Tractography represents a promising tool for preventing GK-SRS complications by reduction in radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts & further increase our knowledge of critical cerebral structure radiation tolerances to better improve the therapeutic potential and safety of SRS for AVMs.

Brain Tumour Surgery in the Context of Evolution in Radiosurgery

Objective: 

highlight brain tumour patient selection for radiosurgery vs. surgery in the two most frequent brain tumour types: metastasis and meningioma.

Review up-to-date surgical and radiosurgical techniques.

Introduction: 

The use of GKRS in brain metastasis and meningioma has increased worldwide, with high-impact evidence on its safety and efficiency with new modern techniques.

The variations in international standards widened the gap where, in some places, GKRS is overused and, in some places, not applied to brain tumors. In this presentation, I will try to review the current evidence and up-to-date techniques.

Methods: 

updated literature review on GKRS in meningioma and brain metastasis (solitary)

a retrospective review of some surgical cases.

Results:

The grey zone is wide when it comes to patient selection for surgery vs. radiosurgery for the two most common brain tumours.

GKRS in brain metastasis can be used as a standalone option or before surgical resection and in the resection cavity. Tumour size, number of metastases, primary tumour origin, systemic disease, and KPI are very important factors in decision-making.

Surgical resection of brain metastasis, either enbloc or piecemeal removal Enbloc resection has shown some superiority.

GKRS in meningioma offers an excellent option as a standalone option or for a residual tumour after surgery with evidence of progression. Tumour size, the presence of a neurological deficit, and meningioma grade are crucial in decision-making. Fractionated GKRS offers a safe option for tumours with close proximity to ctrical structures like the optic pathway and brain stem.

Surgical resection should aim for Simpson grade zero when possible, and the key surgical steps include devascularization of the tumour first, followed by central debluking and degloving from the surroding neurovascular structures and brain. Minimally invasive approaches, including navigational-guided craniotomies, keyhole approaches, and endcscopic approaches, should be applied when feasible.

Conclusion: 

Radiosurgery for meningioma and brain metastasis is an important aspect of management. A multidisciplinary approach is preferred to achieve better outcomes.

Introduction: Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs.

Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions.

Methods:We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded.

Results:Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24-233). Median tumour volume was 6.2 cc (+/-7), and the median marginal dose was 14 Gy (+/-3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6-233). Permanent morbidity occurred in 5.9% of cases at last follow-up.

Conclusions: Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

Estimation of the minimum value for the gradient index (GI) in Vestibular Schwannomas planning considering the sphericity degree using Leksell Gamma Plan^â

Authors: Saraiva, C. W. C.; Folador, B. C. F.; Da Rosa, L. A. R.; Gorgulho, A. A.; De Salles, A. A.;

Introduction: The sphericity degree is defined as a measure of how similar the shape of an irregular volume (V) is to that of a sphere. In vestivular schwannoma treatments, the volumes can vary significantly, as well as the sphericity degree. In addition to these geometric characteristics, its proximity to the cochlea requires a high dose falloff. Therefore, estimating a minimum possible value for these plans helps to identify a metric for the evaluate the quality of the plan obtained. 

Methodologia: For the sphericity degree, the equation used was, j = (V_TV / V_{sphere circ})^1/3 where V_TV is the irregular target volume and V_{sphere circ} is the volume of the smallest sphere that circumscribes the target volume (TV).

To calculate the gradient index, the ratio between the volume of the isodose of 50% of the prescription and the volume of the prescription isodose is used. These volumes were obtained from the Leksell Gamma Plan planning system.

To evaluate dose falloffs, plans called reference plans were carried out using the TPS, Leksell Gamma Plan® (LGP), version 10.0. These reference plans were defined using the following steps: (i) calculate the diameter d_eq, of an equivalent sphere – a sphere that has a volume equal to the volume of the target; (ii) delineate this sphere within a Alderson® anthropomorphic phantom head; (iii) define this equivalent sphere as the target volume in the TPS LGP; (iv) define planning parameters; With these results, it was possible to evaluate, in a comparative way, the GI obtained in the treatment plans with the GI obtained in the reference plans.

Results and discussion: The average value of the sphericity degree obtained was 0.69±0,10, with the lowest value equal to 0.50 and the highest value equal to 0.9. Regarding the evaluation of the gradient index, it was possible to observe that this parameter, under the reference conditions (spherical target volume, anthropomorphic phantom phantom), assumes values lower than 3, thus corroborating the GI = 3 metric. Thus, the minimum values for the gradient index ranged from 2.44 to 2.90.

Skull base perioptic meningiomas are challenging for stereotactic radiosurgery (SRS). The therapeutic window between tumor control and normal tissue complication is extremely narrow in these tumors, especially of large volume and/or in close proximity to the optic apparatus (OA). To minimize the risk of radiation toxicity, we optimized our SRS plans in terms of both steeper dose fall-off and dose-volume constraints for OA and delivered hypofractionation treatment.  

Thirty-one patients had been treated with hypofractionated SRS using the CyberKnife for perioptic meningiomas > 10 cm³ in volume (median 18.9 cm³). Tumor locations were cavernous sinus (n=7), petroclival (n=6), and tentorial edge (n=6). Optimization in SRS planning was carried in two aspects: 1) for steeper dose fall-off, multiple virtual shells outside the target were introduced and appropriate dose limits (formulated from our own Gamma Knife data) were applied; and 2) to minimize the risk of optic neuropathy, dose-volume constraints for OA (from AAPM TG101) were applied. SRS was delivered in five daily fractions with a median cumulative dose 27.8 Gy.

With a median follow-up of 33 months, tumor control was achieved in 28 of 31 patients (90.3%). Treatment response on MRI included partial response (volume decrease > 20%) in 17 patients, stable in 11, and progression (volume increase > 20%) in 3. Neurological symptoms improved in 10 patients, unchanged in 20, and worsened in 1.

Our current results show a promising role of hypofractionated SRS with optimization in steeper dose fall-off and dose-volume constraints for OA for large-sized skull base perioptic megningiomas in terms of both tumor control and neurological outcomes.

Central AVMs are challenging group of vascular  Malformations. Radiosurgery alone or in combination with endovascular approach seems to be the best available treatment modality right now. However there is inherent risk of edema and radiation necrosis risk involved.

We reviewed our patients with central AVM with a minimum follow up of 2 years retrospectively. The machine learning deep neural network applied to look for risk factors for adverse reactions in these cases.

A total of 35 patients receiving primary Gamma knife were included in the study. They were divided into pure thalamic, thalamo peduncular and brainstem lesions. 

It was observed that the trickiest lesions are those located in thalamopeduncular area and low dose staged Gamma knife is the best approach.

Purpose: This study aimed to evaluate the dosimetric accuracy of Cyberknife (CK) for benign perioptic tumor using patient-specific head phantom.

Methods: A patient specific head phantom was fabricated using a 3D-printer to ensure dosimetric equivalence with the actual target regions of a benign perioptic tumor case treated via Cyberknife radiosurgery. A head phantom quality assurance (QA) plan was produced using the original CK contour set encompassing the target and optic nerve. The head phantom, equipped with Gafchromic EBT3 film, was subjected to irradiation using the Cyberknife 6D skull tracking method. The dose distributions calculated by the MultiPlan Treatment Planning System (version 5.6) were compared to the measurements obtained through film dosimetry using the gamma analysis method. The CK treatment manipulator utilized 6D corrections data obtained from orthogonal X-ray images to automatically deliver radiation to the displaced position of the target. To access the accuracy of the 6D skull tracking, the couch table was adjusted by translating it by 1-5mm and rotating it by 1 degree prior to beam delivery, and the resulting beam irradiation was examined.

Results: All cases achieved passing rates that exceeded the acceptable threshold of 80% and 90% for the 2%/1 mm and 2%/2 mm criteria, respectively. Among the ten cases (case 1 - 10) with less than 2 mm shift and 1 degree rotation, the calculated gamma index with pass criteria of 2%/1 mm and 2%/2 mm averaged at 84.71 ± 1.73% and 94.12 ± 0.75%, respectively. For the other two cases (case 11 and case 12) with a 5 mm shift in both the right and left directions, the average gamma pass rates using the same criteria were 81.09 ± 0.74% and 91.03 ± 0.21%, respectively.

Conclusions: Dosimetric verification using patient-specific head phantom was successfully implemented as an evaluation method for CK perioptic tumor radiosurgery delivery with 6D skull tracking system.  

Introduction: Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium-sized vestibular schwannoma (VS). Its use in the treatment of large tumors, however, is still being debated.

Objectives:  To assess the potential role of SRS in larger VS.

Materials and Methods: Between 2016 and 2023, 35 patients diagnosed with unilateral VS greater than 25mm, underwent SRS.  A total dose prescribed to the tumor volume ranged 11-35Gy in 1-5 fraction, delivered with linear accelerator with image-guided radiotherapy (IGRT) system.  Acute and chronic toxicity was evaluated according to the International Criteria for Adverse Events (CTCAEv4.0).  In the statistical analysis, Pearson chi-square test, was used. 

Results: The median follow-up was 36 months (6-50 months), median age 50 years (20-77), 58% of the patients had prior surgery, median irradiated tumor volume (GTV) 8 cc. (2-45cc), 86% of patients were Koss 3 and 14% Koss 4.

At the first planned imaging follow-up at 6 months, tumors 30% were slightly expanded with central radionecrosis, 52% were stable in size, and 18% were smaller. In the last follow-up none presented tumor regrowth after radiosurgery.

As regards the evolution of related symptoms post SRS treatment, hearing loss was observed in all patients, tinnitus increased from 31% to 35% (p=0.17). Decreases in vertigo from 58% to 31% (p=0.05), and facial neuropathy from 46% to 12 % (p=0.0006).  Two (6%) patients developed temporary symptomatic trigeminal sensory dysfunction developed, and in 1(3%) patient mild facial weakness. These patients had a previous resection or postsurgical neurological dysfunction.

Conclusions: although microsurgical treatment remains the primary management choice, in selected patients with low comorbidities, most larger vestibular schwannomas without significant mass effect can be managed satisfactorily with SRS. 

Introduction:

In Cavernous Malformations, recurrent haemorrhage is common after an initial bleed. Rates of recurrent haemorrhage in supratentorial and brainstem lesions are 5% and 21% per year, respectively and can be associated with devastating consequences. The aim of this retrospective study is to highlight the efficacy of Gamma Knife Surgery (GKS) in managing Cavernous Malformations. 

Methods:

Data from 11 symptomatic cavernous malformation patients undergoing GKS at Hospital Universiti Kebangsaan Malaysia (HUKM) from the beginning of 2020 to 2023. The patient’s treatment plan and case notes were retrospectively reviewed. The mean and median cavernoma volumes before GKS treatment were 2140mm³ and 1222mm³  respectively (range: 850mm³ – 1156mm³). The median tumour margin dose was 14Gy (range 12Gy – 16Gy). Median follow up was 12 months (range: 6 – 21 months).

Results:

Among the 11 patients, two experienced at least one episode of pre-GKS seizure. Post-GKS, mean and median cavernoma volumes dropped to 1263mm³ (59% reduction) and 889mm³ (73% reduction), respectively. Five patients showed no change in size. There were no recurrent haemorrhages, seizures, or radiation adverse effects during the 11 person-years of follow up. 

Conclusion:

GKS demonstrated significant clinical improvement in all 11 symptomatic patients. No recurrent haemorrhages or seizures were observed. A comprehensive evaluation through a systematic review with a larger sample size is warranted.

Abstract

Purpose: Skull base meningiomas represent a very challenging pathology due to relatively difficult surgical access. In contrast, stereotactic radiosurgery (SRS) proved to be an effective and more secure treatment technique based on the greater accuracy in delivering precise focused radiation into the target, sparing at the same time healthy surrounding tissues.

Methods and results: Our study, based on almost 20 years of experience in delivering SRS treatments using various models of Leksell Gamma-Knife units, reports a high tumor control rate for complex-shaped skull base meningiomas close to critical structures. We retrospectively evaluated the risk factors and complications after high-dose irradiation in patients undergoing single-fraction radiosurgery combined with clinical imaging criteria established using MRI scans (in T1 weighted imaging with gadolinium and the edema in T2 weighted sequences).

The mean volume of the tumors was 18.6 cubic centimeters (only tumors with a volume in excess of 15 cubic centimeters were included in the study). The median administered marginal dose was 12.5 Gy. Mean imaging follow-up was 112 months. Tumor control rate was not influenced by sex, age, tumor site, neurological status of the patient or irradiated volume, even though larger meningiomas are associated with poor long-term local control in most published series.

The long-term follow-up data indicates tumor control in 88,5% of patients after 10 years, with low incidence of complications.

Conclusions: Current practice shows a slight potential increase in the incidence of meningiomas, the superiority of the individual techniques needing to be confirmed in prospective and methodologically rigorous studies with at least 20 years of follow-up.

Intracranial Paragangliomas are rare neuroendocrine tumors arising from paraganglia, and given the morbidity and mortality associated with surgical treatment, is a great challenge for Neurosurgery. The use of Radiosurgery is a alternativ to surgey,  with excellent results, but the lack of long-term follow-up still left in doubt its effectivenes.

OBJECTIVE: To present the results of local lesion control and toxicity in a series of patients undergoing treatment with exclusive use of focal ionizing radiation, be it Radiosurgery (RS), Fractionated Stereotactic Radiotherapy (FSRxT) or Hypofractionated Stereotactic Radiotherapy (HFSRxT) and who were followed for a minimum of 60 months after treatment.

MATERIAL AND METHODS: A retrospective analysis in the medical records of our hospital, selecting patients with intracranial Paragangliomas who underwent SR, FSRxT or HSRxT) between 2000 and 2023. A Linear Accelerator (LINAC) was used associated with Micro-Multileaf collimators and dedicated software. To enter the study, these patients had a minimum follow-up of 60 months. We evaluated local control as well as treatment toxicity.

RESULTS: Among 2930 patients treated, 32 patients were selected. With a mean follow-up of 85 months, 68% of patients had a reduction of the lesion when compared to treatment and 32% maintained stability of the lesion. No patient followed had progression of the disease, but 1,  that had bilateral lesion, and the untreated lesion progressed 3 years later, when it was treated there and subsequently reduced its volume. No patient presented clinical worsening associated with toxicity in the brain tissue or cranial nerves involved.

CONCLUSION: Treatment with the use of focal ionizing radiation, whether SR, FSRxT or HSRxT, is an extremely safe and effective procedure in the management of paragangliomas regardless of their volume. Even in giant tumors should be the first therapeutic option and surgery should be limited to selected cases

Background: Silent corticotroph pituitary adenomas (SCAs)/ neuroendocrine tumors (PitNETs), exhibit heightened clinical aggression, predisposing them to higher recurrence rates and reduced treatment responsiveness compared to other subtypes. These patients often require comprehensive treatment, and Cyberknife radiosurgery (CKRS) may become a vital postoperative therapy for relapse.

Objective: This study aimed to investigate the efficacy and safety of Cyberknife radiosurgery in recurrent aggressive PitNETs. 

Methods: We conducted a retrospective study involving patients who experienced postoperative recurrence and were treated with CKRS at our medical center. We present patient outcomes encompassing alterations in tumor size assessed through radiological evaluations, along with recorded adverse events such as newly diagnosed visual impairment and pituitary dysfunction.

Results: Fourteen patients underwent CKRS between 2017 and 2023. All patients received a pathological diagnosis confirming PitNETs characterized by positive immunohistochemistry for t-pit or ACTH markers. Among the series, 50%(n=7) patients underwent dose-staged CKRS, whereas the remaining received fractionated CKRS. The median fractionation regimen encompassed 3, with varying ranges from 2 to 5. Single-dose parameters ranged from 4 to 10.2Gy. The mean tumor volume before treatment was 16.39cc. The average follow-up period was 27.1 months, 95%CI [14.5, 39.7]. Following a 5-year post-CKRS, one patient demonstrated complete remission(CR), and no recurrence to date. 50%(n=7) of total patients had partial response (PR). In a specific case, the tumor volume exhibited an increase 4 months after CKRS, leading to a surgical intervention. The tumor response was quite similar between patients who underwent 2-staged CKRS and all other patients. Notably, the subgroup that underwent staged CKRS presented with larger tumor volumes(P=0.05). None of the patients developed newly onset pituitary dysfunction or visual defect following CKRS.

Conclusion: Fractioned CyberKnife radiosurgery demonstrates effective tumor control for aggressive pituitary tumors experiencing postoperative recurrences, representing a safe and promising therapeutic option. Staged CKRS is considered viable when dealing with large lesions or those in close proximity to critical organs.

Background: The optimal postoperative management of WHO grade 2 meningiomas is controversial, because target definition is difficult with standard-of-care contrast-enhanced MRI.

Patients with subtotal resections are generally offered either radiotherapy or radiosurgery. We evaluated the local control (LC) probability following [68Ga]-DOTATATE PET/MRI guided radiosurgery in patients with subtotally resected WHO grade 2 meningiomas.

Methods: In this institutional review board-approved, HIPAA compliant study, patients with a history of clinically suspected or pathology-proven meningioma were prospectively enrolled into a registry after undergoing DOTATATE PET/MRI. Seventeen consecutive patients with biopsy-proven WHO grade 2 meningiomas were identified from the registry for further analysis. Patients underwent [68Ga]-DOTATATE PET/MRI with concurrent contrast-enhanced brain tumor protocol MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI series were fused to a simulation CT for radiosurgery planning. 16/17 (94%) patients received fractionated radiosurgery while 1 patient (6%) received single-fraction radiosurgery. The residual meningioma gross target volume (GTV) was identified from both the post-contrast T1-weighted MRI and the [68Ga]-DOTATATE PET. The PET GTV was defined as having a SUV ratio (SUVR) in reference to the superior sagittal sinus blood pool of 3 or greater. A 1.0 mm isotropic planning target volume (PTV) margin was added to the combined PET/MRI GTV. Postoperative radiosurgical treatments were (Gy/fractions, N (patients) listed in parentheses): 35/5 (N = 10), 30/5 (N = 4), 25/5 (N = 1), 28.5/3 (N = 1), 18/1 (N = 1). Follow-up contrast-enhanced MRI was performed per standard-of-care and the development of new nodular contrast enhancement on surveillance MRI was defined as progression based on RANO criteria and confirmed with DOTATATE PET.

Results: The mean age was 56 (range 39-75) months and the mean follow-up time after radiosurgery was 25 (range 5-48) months. 10/17 patients (59%) were female. 11/17 patients (65%) achieved LC after [68Ga]-DOTATATE PET/MRI-guided radiosurgery for their biopsy-proven WHO grade 2 meningiomas. Six patients (35%) had progression after [68Ga]-DOTATATE PET/MRI guided radiosurgery and underwent a second course of [68Ga]-DOTATATE PET/MRI guided salvage radiosurgery. Five of these six patients (83%) achieved LC after salvage radiosurgery. Thus, 16/17 patients (94%) achieved LC after 1 or 2 sessions of PET/MRI-guided radiosurgery. One of the six patients who progressed (17%) had multiple recurrences treated with additional courses of radiosurgery and [177Lu]-DOTATATE radionuclide therapy.

Conclusions: An excellent overall rate of tumor control is achievable (when salvage radiosurgery is included) with the addition of [68Ga]-DOTATATE PET to MRI-based radiosurgery planning for WHO grade 2 meningiomas.

Background: Somatostatin receptor 2 (SSTR2) is a highly sensitive and specific meningioma biomarker that can be imaged with [68Ga]-DOTATATE. [68Ga]-DOTATATE PET/MRI has demonstrated clinical utility for meningioma diagnosis, surgical and radiation planning, however its effect on clinical outcomes is less well understood. The management of gross-totally-resected (GTR) WHO grade 2 meningiomas is controversial, with ongoing randomized clinical trials mounted to determine the benefits of postoperative fractionated irradiation of the resection cavity versus active surveillance. We hypothesized that the determination of GTR by DOTATATE PET/MRI would increase the progression-free-survival (PFS) probability in patients subsequently managed with active surveillance compared to historical data of patients with GTR determined by MRI alone.  

Methods: 27 consecutive patients enrolled into our prospective observational registry met inclusion criteria of (1) WHO-2 meningioma, (2) postoperative brain PET/MRI or PET/CT (with contemporaneous brain MRI) demonstrating GTR, (3) postoperative management with active surveillance only. Postoperatively, patients were followed with serial standard-of-care MRI. Recurrences were determined using RANO criteria and Kaplan-Meier analyses were performed to determine PFS probabilities.

Results: 27 subjects met inclusion criteria. MRI follow-up data were available for a mean of 17 (range: 3-49) months. We found PFS of 100% at 2.5 years and 80% at 4 years.

Conclusions: We found that DOTATATE PET/MRI-determined GTR and subsequent active surveillance resulted in excellent PFS in patients with WHO grade 2 meningiomas. Our findings suggest that DOTATATE PET/MRI can increase the diagnostic certainty of a GTR in WHO grade 2 meningioma compared to MRI alone, thereby increasing the PFS probability for patients subsequently managed with active surveillance. DOTATATE PET/MRI thus has the potential of changing clinical practice and outcomes in this patient population.

Background: 

Cerebral meningiomas represent approximately 40% of primary brain tumors. They can present challenges in managent requiring combination of treatment modalities such as endovascular embolization, surgery and radiosurgery. Gamma Knife radiosurgery has proven successful as a non-invasive high precision treatment tool for complex cases not amenable to surgery.

Objective: 

To evaluate the safety and effectiveness of Gamma Knife radiosurgery for intracranial meningiomas focusing on the single center experience of the Puerto Rico Medical Center.

Methods: 

Retrospective review of 148 patients with 158 brain meningiomas treated with single fraction (N=132) and dose-fractionated (N=16) Gamma Knife radiosurgery from 2010 to 2022. Treatment efficacy was evaluated based on tumor volume reduction or stabilization rates. Procedure safety was assessed based on frequency and severity of adverse radiation effects. Follow-up ranged from 2 months to 10 years.

Results: 

Tumor control was adequate as evidenced by tumor volume reduction and/or stabilization in the majority of cases. Adverse effects were similar to those reported in the literature, consisting of peritumoral adverse radiation effects that responded to short course of steroids and seizure medications when indicated.

Conclusion: 

Gamma Knife radiosurgery for cerebral meningiomas represents a safe and effective alternative for either simple or complex cases. Tumor control rates were adequate as evidenced by tumor volume reduction and/or stabilization with minimal adverse effects that were manageable with medications. Dose fractionation shows promising results for cases with high tumor volumes or close to eloquent areas.

Objective: The contemporary approach to treating cerebral arteriovenous malformations (AVMs) integrates microsurgery, embolization, and stereotactic radiosurgery (SRS). While single-fraction SRS is the standard for AVM treatment, challenges arise with large AVMs (>10 cc), particularly in eloquent brain areas, where the required high doses (18-24 Gy) may pose safety concerns. Hypofractinateded radiosurgery emerges as a solution to reduce radiation exposure to critical structures while ensuring effective AVM obliteration. This study aims to assess the safety and efficacy of hypofractinated SRS for large AVMs based on our clinical experience.

Methods: From 2016 to 2022, 10 patients (7 women, 3 men) with large AVMs (>10 cc) underwent stereotactic radiosurgery using the CyberKnife M6 at SRC Sigulda, Latvia. Among them, 8 had a history of AVM-related hemorrhage. 6 patients underwent endovascular AVM obliteration using Onyx, with incomplete nidus shutdown or recanalization. Symptoms included headaches (9 patients), seizures (5 patients), and sensory/motor deficiencies (4 patients). SRS comprised single-fraction CyberKnife at 20 Gy for 3 patients and hypofractionated SRS (2 fractions, total dose 24 Gy) for 7 patients.

Results: Patients received post-treatment assessments at 6, 12, and 24 months, involving magnetic resonance imaging (MRI) and MRI angiography. Digital subtraction angiography (DSA) was performed for four patients at the 24-month mark. 5 patients (2 from single-fraction SRS, 3 from hypofractionated dose-staged SRS) displayed complete AVM obliteration. All patients maintained stable clinical conditions without signs of post-radiation toxicity (grade 2-3). 2 patients experienced recurring AVM bleeding six months post-treatment.

Conclusions: Dose-staged SRS emerges as a safe strategy for treating large AVMs, particularly in eloquent brain regions, with minimal risks of post-radiation toxicity and hemorrhage post-SRS. However, achieving statistically reliable levels of obliteration warrants ongoing observation and research.

Introduction: Stereotactic radiosurgery (SRS) stands as a crucial therapeutic avenue for individuals grappling with cavernous sinus meningiomas (CSM). This clinical study delves into a retrospective examination of the efficacy of SRS in treating CSM, employing diverse radiosurgical techniques.

Materials and Methods: Thirty-two patients (10 males, 22 females) with CSM underwent stereotactic radiosurgery using the "Trilogy + BrainLab" linear accelerator (LINAC). Tumor volumes ranged from 2.8 cc to 20.9 cc (median, 9.1 cc). In the LINAC group, 75% of patients received SRS exclusively, while 25% underwent prior surgery. Additionally, 13 patients (6 males, 7 females) underwent CyberKnife (CK) SRS, with a median tumor volume of 13.6 cc. In the CK SRS group, 30.7% of patients had undergone surgery before. Marginal doses for LINAC SRS ranged from 11 Gy to 12.5 Gy (median, 12.1 Gy), while CK SRS utilized doses of 18-25 Gy in 3-5 fractions. The median follow-up duration was 42 months (range, 30-60 months).

Results: Follow-up assessments revealed a reduction in tumor size in 46.8% of LINAC patients, with no further growth observed in 53.2% of cases. In the CK group, 38.4% experienced a decrease in tumor size, while 53.8% maintained a stable tumor size. Improvement in neurological condition was noted in 35.5% of patients in both groups, with no worsening observed in the remaining 64.4%. None of the patients reported post-radiation toxicity of grade 2-3.

Conclusions: SRS emerges as an effective treatment modality for CSM, demonstrating comparable outcomes across various radiosurgical techniques. Whether utilizing LINAC or CK, SRS provides robust tumor control with no discernible difference in the quality of life outcomes for patients with CSM

Introduction: 

In the present study, we systematically review the literature describing outcomes of CyberKnife radiosurgery (CKRS) for vestibular schwannoma (VS), with particular focus on tumor control, hearing preservation, and dosing schema. 

Methods: 

We queried the three databases to identify all primary retrospective studies reporting local tumor control and hearing preservation rates following CKRS for VS. Studies meeting inclusion/exclusion criteria were reviewed to extract data on treatment paradigms, hearing outcomes, and local control. Pooled random effects meta-analysis of long-term tumor control and hearing preservation rates were performed.

Results:

Fifteen studies were included in the final analysis. In aggregate the studies comprised 2,018 treated patients (mean age 60.2 years; 52% female), of whom 64 had neurofibromatosis type 2 (NF-2) and the remaining had sporadic lesions. Three hundred nine patients had undergone prior treatment – surgical resection and/or radiosurgery and mean follow-up for the entire cohort was 40.0 months. Dosing paradigms varied across included studies without any identifiable trends in total dose, marginal dose, or fractionation schema over the range of years studied. Marginal dose ranged from 1.9-25.78 Gy. Published schema ranged from 1-5 fractions, and dose and fraction regimens described in studies published prior to 2014 and those published thereafter appeared comparable. Isodose lines were reported in 13/15 studies and ranged from 55%-95%. Average local control across all studies was 96.0% (95% CI: 95%-98%) with no significant difference in control rates being noted between the pre-2014 (OR 0.96; 95% CI [0.94, 0.99]) and post-2014 cohorts (OR 0.96; 95% CI [0.95, 0.98]. As demonstrated by the funnel plot for tumor control, asymmetry is readily apparent, suggesting the potential for publication bias. Additionally, the I² was 57% (p<0.001), suggesting the potential for significant heterogeneity across studies. Hearing outcomes were measured using the Gardner-Robertson classification system in 8 studies and the American Academy of Otorhinolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification system in seven. For patients with serviceable pre-treatment, 73% had preserved hearing at last follow-up (95% CI 66%-81%). Significant heterogeneity was noted between studies in hearing preservation rates (I²=89%, p<0.001). Comparison of outcomes between the pre-2014 (OR 0.82; 95% CI [0.74, 0.90]) and the post-2014 era (OR 0.66; 95% CI [0.55, 0.79]) showed a non-significantly higher rate of hearing preservation than the pre-2014 cohort.

Conclusions:

The present meta-analysis shows CyberKnife radiosurgery offers high rates of local control and hearing preservation in patients undergoing SRS for vestibular schwannomas. 

68 patients with newly diagnosed Vestibular Schwannoma (VS) between 2013 and 2016 were randomized to upfront Gamma Knife Radiosurgery (GKRS) or conservative management (wait-and-see approach). Patients in the GKRS-group were given a state-of the art VS-treatment with Gamma Knife Perfexion or Icon at Karolinska University Hospital with a dose prescription of 12 Gy and optimization of dose to organs at risk, coverage and selectivity. All patients in both groups received 1-, 2-, 3- and 5-year follow-up with T1-weighted FSPGR images of 1mm slice thickness by the latest General Electric MRI system. Tumor volumes were identified on all images by experienced GK-users. All follow-up images were discussed in a multi-disciplinary committee and patients in the conservative group with significant tumor-growth were scheduled for a GKRS-treatment. Differences in tumor volume dynamics between the two groups at each follow-up was analyzed using Wilcoxon Rank Sum Test.

35 patients were randomized to GKRS whereas 33 patients to the conservative group. Both groups were balanced with respect to age, gender and tumor volume at baseline. 15 patients in the latter group had significant tumor growth on follow-up imaging which disqualified them from further conservative treatment: 11 of these at 1-year, 3 at 2-year and 1 at 3-year follow-up, respectively. Average change in volume (compared to baseline) for the GKRS-group was 6%, -11%, -14% and -24%, at 1-, 2-, 3- and 5-years, respectively, whereas the volume dynamics in the conservative group was 91%, 32%, 17% and -1%. Significant difference in the follow-up tumour-volumes between the groups was identified for all follow-up periods: p-values 0.0001, 0.0002, 0.0054 and 0.0398 for 1-, 2-, 3- and 5-year follow-up, respectively.

This randomized controlled study shows that there is a strong statistical difference in the follow-up tumour-volume between the two groups. This significance weakens with increasing follow-up time (by increasing p-values) which is assumed to be due to reduction of the conservative group by patients with fast tumours growth (consisting of 45% of the initially conservative group) leading to a selected group of slow- and non-growing tumours. This work also demonstrates that newly diagnosed VS can be seen as a mixture of three groups with respect to tumour-growth: 45% fast-growing tumours, 33% slow/negligibly-growing tumours and 21% with negative tumour-growth (average -34%) at 5-year follow-up. Developing means to identify the projected tumour-growth of newly diagnosed VS can potentially have an impact on treatment selection, treatment time guarantee and follow-up duration.

BACKGROUND: The difference in tumor control rate after stereotactic radiosurgery (SRS) between neurofibromatosis type-2-associated vestibular schwannomas (NF2-VSs) and sporadic vestibular schwannomas (S-VSs) has been debated and is yet to be completely elucidated. To address this issue, the Korean Gamma Knife Radiosurgery Society conducted the first nationwide, multicenter, retrospective study (KGKRS-21-001).

METHODS: A total of 4,718 patients treated with SRS for VSs were enrolled from 13 nationwide institutes. NF2-VS cases were matched with S-VS cases at a ratio of 1:1 using propensity scores for age, tumor volume, and marginal dose. After matching, 122 cases in each group of NF2-VS and S-VS were selected and analyzed.

RESULTS: There were no statistically significant differences in age, tumor volume, or marginal dose between the NF2-VS and S-VS groups. The overall matched cohort analysis showed that the tumor control rates at 1, 3, and 10 years after SRS were 93.3%, 87.7%, and 80.7%, respectively. The difference in tumor control rates between the two matched cohorts was not statistically significant (p=0.63). In the subgroup analysis of NF2-VSs, age ≤20 years was a significant negative factor related to tumor control (p<0.001). However, there was no significant difference in tumor control with respect to age in the S-VS cohort (p=0.78).

CONCLUSION: There was no difference in tumor control between NF2-VSs and S-VSs after SRS. However, patients younger than 20 years of age, especially in the NF2-VS cohort, showed significantly poorer tumor control after SRS compared with older patients.

Introduction

The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding cochlear nerve damage by transient volume expansion of VSs after radiosurgery and radiation-induced cochlear damage. This study aimed to investigate whether there is a specific patient population that can achieve definite hearing preservation after SRS for VSs.

Methods

A total of 40 consecutive patients with sporadic unilateral intracanalicular VSs and serviceable hearing (Gardner-Roberson [G-R] class I or II) were treated with SRS from 2009 to 2023. This is a retrospective study. Survival analysis with Cox regression for hearing deterioration was performed.

Results

The median age was 55 years old. The median tumor volume was 0.089 cm³ and the median marginal dose was 12.0 Gy. Nonserviceable hearing deterioration occurred in 9 patients (24.3%), with a median onset of 11.9 months after SRS. The actuarial rates of serviceable hearing preservation were 86%, 82%, and 70% at 1, 2, and 3 years after SRS, respectively. A marginal dose >12 Gy, tumor volume >0.15 cm³, and baseline pure tone average >30 dB increased the risk of nonserviceable hearing deterioration with significant hazard ratios. There were 13 patients with petit VSs whose tumor volume was smaller than 0.05 cm³, and 11 of them were treated by a 4-mm single shot with a marginal dose of 12 Gy. None of the 13 patients had nonserviceable hearing deterioration.

Conclusions

Petit VSs that can be treated with 4-mm single or double shots with a marginal dose of 12 Gy may achieve hearing preservation after SRS. 

Objective Gamma knife radiosurgery(GKRS) has been recommended as a reasonable primary and adjuvant treatment modality for cavernous sinus hemangiomas(CaSHs). Single session radiosurgery may be contraindicated if tumors are adjacent to the optic pathways for the substantial risk of visual complication. This study was conducted to evaluate the efficacy and safety of dose-staged GKRS for perioptic CaSHs.

Methods From March 2018 to September 2020, 11 patients haboring CaSHs adjacent to the optic pathways received dose-staged GKRS treatment at Gamma Knife Center of Huashan Hospital. 10 patients were diagnosed according to clinical symptoms and classic MR images of CaSH, and only 1 patient had received transsphenoidal microsurgery before staged GKRS. There were 1 male and 10 female patients with a median age of 40 (range, 27~72) years old. The median tumor volume was 15.09 cm³ (range, 5.54~31.00 cm³). All of the enrolled patients underwent 2-dose-stage GKRS, and the median interval between the two GKRS treatments was 8 months (range 3~9 months). For the first stage GKRS procedure, the median isodose line was 45% (range 40%~50%), and the median marginal dose was 8.8 Gy (range 8~10 Gy). For the second GKRS treatment, the median isodose line was 46% (range 40%~52%), and the median marginal dose to the CaSHs was also 8.8 Gy (range 8~10 Gy).

Results The median follow-up duration was 40 months (range 25~60 months). The median tumor volume reduction was 64.2% (range, 20.3%~85.3%) at second-stage GKRS compared with the first-stage GKRS volume. At last follow-up, tumor control was achieved in all 11 patients and the median tumor shrinkage was 83.0% (range 70.6%~92.5%) compared to the pre-GKRS volume. Post-GKRS clinical improvement or stability was reported in 90.9% (n=10). No patient showed clinical deterioration. No radiation-induced optic neuropathy or neurological deficits were detected after staged GKRS.

Conclusions Dose-staged GKRS is an effective and safe alternative to either surgery or fractionated radiotherapy for perioptic CaSHs that are unsuitable for single session radiosurgery.

Single-session radiosurgery has to be suggested for patients with non-functioning adenomas who are not suitable for medical surgery or when a residual lesion is present. Multisession radiosurgery may be useful for larger adenomas or those located near the optic pathways. However, due to the absence of long-term tumor control data, the suitability of this treatment schedule has to be confirmed. The aim of this study is to examine the safety and efficacy of multisesion radiosurgery in this setting.

The present is an exploratory study, focusing on patients with residual/recurrent non-functioning pituitary adenomas who have been evaluated at our institution. Patients fulfilling the inclusion criteria (no prior cranial irradiation, absence of pregnancy, no contraindications for MRI or CT scans, and the ability to provide informed consent) are enrolled and treated with hypofractionated radiosurgery using CyberKnife technology (Accuray).

The primary end-point of the study is to assess early and delayed toxicity concerning cranial nerves and pituitary function post-treatment. Secondary end-points are late toxicities, local control, and evaluation of patients' quality of life (QoL).

From September 2020 to September 2023, 21 patients underwent multisession radiosurgery for pituitary adenomas. All patients received a total dose of 25 Gy delivered in 5 fractions over 5 consecutive days. At the time of treatment, the average age was 52 years (range 20-74 years, median 55 years).

The treated lesions had a mean volume of 10 cc (range 0.5-33 cc, median 6 cc). The mean value of the maximum point dose to the chiasm varied from 6 to 32 Gy. The mean value of the maxiumum and the mean doses to the pituitary gland, when identifiable, were 24 Gy (range 14-31 Gy) and 19 Gy (range 6-28 Gy), respectively.

Following a mean follow-up period of 32 months (range 6-36 months), 1 patient experienced transient dysphagia and dysphonia, which was successfully treated with low-dose oral dexamethasone, and 4 patients required minor adjustments in their substitutive hormonal therapy. Overall, visual function was generally maintained, and none of the treated tumors showed progression during the follow-up period.

While awaiting a more extended period of observation, the current study provides support for the safety of multisession radiosurgery and suggests its efficacy in the short term.

BACKGROUND: The purpose of intracranial arteriovenous malformations (AVMs) treatment is to prevent bleeding or subsequent hemorrhage with complete obliteration. For large, difficult-to-treat AVMs, multimodal approaches including surgery, endovascular embolization, and gamma knife radiosurgery (GKRS) are frequently used.

OBJECTIVE: To analyze the outcomes of AVMs treated with single-session, neoadjuvant, and adjuvant embolization GKRS. METHODS: We retrospectively reviewed a database of 453 patients with AVMs who underwent GKRS between January 2007 and December 2017 at our facility. The obliteration rate, incidence of latent period bleeding, cyst formation, and radiation-induced changes were compared among the 3 groups, neoadjuvant-embolized, adjuvant-embolized, nonembolized group. In addition, the variables predicting AVM obliteration and complications were investigated.

RESULTS: A total of 228 patients were enrolled in this study. The neoadjuvant-embolized, adjuvant-embolized, and nonembolized groups comprised 29 (12.7%), 19 (8.3%), and 180 (78.9%) patients, respectively. Significant differences were detected among the 3 groups in the history of previous hemorrhage and the presence of aneurysms (P < .0001). Multivariate Cox regression analyses revealed a significant inverse correlation between neoadjuvant embolization and obliteration occurring 36 months after GKRS (hazard ratio, 0.326; P = .006).

CONCLUSION: GKRS with either neoadjuvant or adjuvant embolization is a beneficial approach for the treatment of AVMs with highly complex angioarchitectures that are at risk for hemorrhage during the latency period. Embolization before GKRS may be a negative predictive factor for late-stage obliteration (>36 months). To confirm our conclusions, further studies involving a larger number of patients and continuous follow-up are necessary.

Background:

68Ga-DOTATATE PET-CT is useful in identifying somatostatin receptor (SSTR), which can help create a physiologic image of the extent of meningioma involvement and allow for a clearer determination of appropriate planning with observation, surgery or radiation therapy. 68Ga-DOTATATE PET-CT is able to detect and identify meningiomas with a sensitivity of 81% and specificity of 90%.  We have examined a series of fifteen cases in which this test was useful and affected the final patient treatment.  We have grouped these in to five indications to allow for further evaluation of this technology for treatment of meningiomas.

Methods:

Fifteen individual cases using 68Ga-DOTATATE PET-CT in meningiomas management were reviewed.  Upon reviewing these case studies, they were grouped into one of five categories. These categories were based the use and role 68Ga-DOTATATE PET-CT had on the meningiomas case. 

Results:

Meningioma management was affected by 1) Detection of new primary meningioma at a new anatomic Site, 2) Clarification of scar versus recurrence in a previously treated region. 3) Treatment planning for radiosurgery or surgical resection 4) Diagnoses of metastasis versus meningioma 5) Extent of disease demonstrating etiology of atypical facial pain. Seven of the fifteen cases used 68Ga-DOTATATE PET-CT to detect a new origin of meningioma not detected by MRI. The PET/CT scan directly allowed for management decision of gamma knife radiosurgery, proton therapy or re-resection of the second region. In Three cases, 68Ga-DOTATATE PET-CT was used to gain clarity of whether a site was a scar or a recurrence in the same location of prior therapy.  Two of these could be observed and the other one was appropriate for further treatment.  In three other cases, 68Ga-DOTATATE PET-CT was able to be used in planning treatment for either surgical or radiation therapy tumor volume.  For one unique case, we were able to use 68Ga-DOTATATE PET-CT in the diagnoses of metastasis versus meningioma, and allowed for detection of a meningioma instead of a breast cancer metastasis.  Another novel case allowed for 68Ga-DOTATATE PET-CT to delineate the extent of a meningioma extension into the infratemporal fossa as the cause of atypical facial pain.  

Conclusions:

68Ga-DOTATATE PET-CT in these fifteen cases identified five novel methods and uses in meningioma cases. The role of 68Ga-DOTATATE PET-CT is helpful in the multidisciplinary management of meningioma treatment.  

Introduction: Craniotomy is the gold standard treatment for meningiomas (MGMs) of medium size or larger, but there is often concern about postoperative deterioration of performance status (PS) in elderly patients. Stereotactic radiosurgery is considered as the next best option, but it is known that gamma knife radiosurgery (GKS) with single fraction has a poor local control rate for medium-sized MGMs with a tumor volume of more than 10 ml. The latest GKS systems allow fractionated radiotherapy with mask fixation, and appropriate radiosurgical techniques are now being explored for medium-sized or larger tumors. In this study, we retrospectively examined the preliminary results of hypofractionated GKS (fGKS) for medium-sized MGMs in elderly patients and discussed the significance of this strategy.

Methods: Five patients aged 75 years or older with neuroradiological diagnosis of MGM and tumor volume >10 ml who underwent fGKS were included. The age ranged from 75-89 (median 81) years, KPS 80-90 (median 80), tumor volume 10.5-18.0 (median 17.0) ml, and were localized in 2 cerebellopontine angle, 2 sphenoidal ridge, and 1 parasagittal. Three (60%) were symptomatic (visual impairment 2, dizziness 1). Each of these cases was treated with a prescription dose of 24-25 Gy/5 fractions.

Results: The follow-up period after fGKS ranged from 22-40 (median 30) months, and all patients were alive, with a tumor local control rate of 80% (4/5 patients). Tumor volume at the final neuroimaging evaluation was generally well reduced compared to at the time of fGKS, ranging from -66% to +49% (median -30%) in all but one case. In one case, the tumor grew after 6 months of fGKS and required craniotomy, and pathology showed a slightly elevated Ki-67 labeling index of 5-7%. Neurological symptoms in the three symptomatic patients improved in one, remained unchanged in two, and there were no adverse events associated with fGKS.

Conclusions: Although the results are preliminary, fGKS may be useful and safe for the maintenance of PS in elderly patients with medium-sized or larger MGMs. This suggests that fGKS may be a treatment option, especially in elderly patients with MGMs that are increasing in volume but who are hesitant to undergo craniotomy. Further experience with this strategy is needed in the future.

Radiosurgical hypophysectomy has shown promising results and is being investigated as a potential alternative to traditional surgical methods for managing drug-resistant pain in cancer patients. all the described clinical cases, irradiation  was carried out on Gamma-knife. We proposed irradiation on the Cyber Knife in our pilot study

As of now, the prospective pilot study including  three women who were trated for cancer-related pain syndrome between 2020 and 2023. It is important to note that all patients primarily experienced somatic oncological pain syndrome. All patients were assessed for pain with a 100mm visual analogue scale. Moreover, an assessment for  potential endocrine disorders was conducted in all patients both before and after the procedure on a monthly basis.

When performing hypophysectomy using the CyberKnife device, a 5 mm collimator is utilized to ensure maximum radiation selectivity and a high dose gradient outside the target area. During the planning and optimization of the dose distribution, our goal is to cover the entire junction area of the pituitary gland and the stem with the highest doses (100-160 Gy). To achieve this, a target ball with a diameter of approximately 4 mm is positioned in the specified area. In addition, we aim to cover 40-50% of the pituitary gland volume with a dose of 80 Gy, and 2/3 of the pituitary gland volume with a dose of 60 Gy. Furthermore, more than 95% of the pituitary gland volume receives a dose greater than 40 Gy.

To ensure that the target coating remains undisturbed, we optimize the dose loads on critical structures. Typically, the brain stem receives no more than 14 Gy per 90.03 cm3. The dose per 5% (0.035 cm3) of the chiasm can be reduced to 9.3-14.0 Gy, depending on the relative positioning of the target and the chiasm. Other visual pathways generally receive a dose of no more than 10-12 Gy per 5% volume.

The treatment was well-tolerated, with no observed exacerbation of neurological symptoms or radiation toxicity. 

In all cases, an analgesic effect was observed. Although none of the patients were able to completely discontinue painkillers, they all managed to reduce their dose of morphine by 30-50%. Additionally, the frequency of pain breakthroughs decreased for all patients. There was no observed decrease in any of the cases. However, within three months, two patients died from  the underlying disease.

Introduction

Gamma Knife Radiosurgery (GKRS) for trigeminal neuralgia (TN) is effective well established treatment. Treatment effectivness and adverse effects highly depends on fine details of planning protocols not formalized in abstract dosimetric values. That’s why reproduction of treatment results with the other radiotherapy devices including CyberKnife (CK) is not straightforward task.

Materials and methods

42 patients with TN was treated using Gamma Knife (GK). For all patients: Dmax=90 Gy produced with one 4 mm short at 7.5 mm from Brainstem. Integral dose to TN was controlled not increasing with blocking. Proactive follow up was available in 21 patients.

In parallel at the Burdenko Neurosurgery Institute (NSI) 37 patients with TN was treated using CK. GK technique was imitate on planning: 4 mm spheric target was generate at the same position. Proactive follow up was available only in 13 patients.

Results

Resulting BNI pain intensity scale was I-III and IV-V in 15 (71%) and 6 (29%) cases in GK series vs 9 (69%) and 4 (31%) cases respectively in CK series. Numbness or burning appears in 1 and 2 patients respectively in GK series (total 14% adverse events) and 3 and 2 patients respectively in CK series (total 38%). 

Treatment efficiency was the same in GK and CK series but adverse event appears much more often after CK. 

Discussion

We propose 2 reasons for such results. First one is the fact that GK dose fall fast from point of Dmax and has cone-like dose spatial distribution. CK dose was flat on all 4 mm sphere (60-70 Gy on 95% of volume), and has truncated cone-like dose spatial distribution. As result total energy released in TN noticeably less in GK than CK. Other reason is difference in calculation algorithm – GK TMR10 algorithm doesn’t take into account tissues densities in contrast with CK. As results GK plans shows dose larger on few percent than real dose.

Conclusion

TN RS with GK and CK has the same efficiency, but adverse event appears much more often after CK. The reduce Dmax in CK cases by 5-10% compared to GK may be reasonable.

Purpose: to present a curious case of an adult affected by recurrent ependymoma, treated on two occasions with radiosurgery using Gamma Knife.

Material and methods: this is a single case reported in our center of a 36 years old male with no relevant medical history, diagnosed in 2015 with WHO grade II ependymoma. He was treated by subtotal resection and adjuvant radiotherapy to the tumor rest, 54Gy in 30 fractions. It remained stable until 2020, when he presented a local recurrence within the field of radiotherapy that was treated with surgery. In 2021, the initial tumor rest grew up and underwent successful surgical salvage. In 2022, the disease progressed with nodules in the posterior fossa, and radiosurgical treatment with Gamma Knife was performed. On 11/22/2022 he received 12Gy in a single fraction on the 5 lesions, with a volume of 0.067-0.486cc. The main organ at risk was the brainstem, which received >10Gy in a volume of 0.094cc and >12Gy in 0.019cc. During follow-up, the treated lesions responded and decreased in size but a new nodule appeared outside the previous treatment field, so a new treatment with Gamma Knife was decided, administering 16Gy in a single fraction on 11/7/2023 to a tumor volume of 0.12cc. All organs at risk were respected.

Results: tolerance to treatment with radiosurgery was excellent, presenting only acute toxicity consisting of grade 1 headache that resolved with first step analgesia, without presenting late toxicity for the moment. After more than one year of follow-up, the five lesions initially treated have achieved a response consisting of a decrease in size. The last lesion is still pending reevaluation. Eight years after diagnosis, the patient remains clinically stable and maintains a good quality of life.

Conclusions: ependymomas are an infrequent group of glial tumors specially uncommon in adults, where outcome datas are limited. Ependymomas are associated with significant risk of recurrence and long-term prognosis for these patients is poor. Due to the location and recurrent nature of the lesions, their treatment is still a real challenge today. This case is an example of the safety and effectiveness of treament with radiosurgery using Gamma Knife, even in the context of a second re-irradiation, allowing multiple consecutive treatments to be administered.

Objective

Trigeminal neuralgia (TN) is a well-known facial pain disease that has been shown to have difficult control with high recurrence rates after medication, surgical decompression (MVD) and ablation. Gamma Knife Radiosurgery (GKRS) is a treatment modality where a focused high-dose radiation is delivered to the trigeminal nerve. It has become the best treatment alternative after MVD for uncontrollable pain and the main option after failure or recurrence. It has a response rate of 76-92%, with a durability that can reach 4.9 years, with recurrence rate of 30-40%. We present the result of a 24-years’ experience with repeated GKRS for hard-to-treat TN.

Methods

A single-institution retrospective analysis, from 1998 to 2023, of TN cases treated with GKRS and their need for re-treatments for pain control. Indications for re-treatment were: uncontrolled pain; controlled pain with medication but intolerable side-effects; recurrence after initial response; no pain improvement after treatment; patient choice of GKRS over other treatment modalities. All patients were evaluated on BNI pain scale prior and after each treatment, pain characterization between typical and atypical, evaluation of TN type, time interval between treatments, prescription dose and reported side-effects.

Results

Of the 206 patients treated with GKRS, 51 (24,8%) needed additional GKRS, of those, 8 (15,7%) needed 3 treatments for pain control. No patients were treated more than 3 times. Of the retreated patients, 20 were Type II, 10 being secondary to MS and the others due to tumor compression. One patient with MS and 1 with tumor compression needed 3 GKRS. Only 2 patients initially presented with atypical pain but 7 changed from typical to atypical after the first GKRS and 8 after the second. No patients presented this change after the third procedure. The time interval between the first and second treatment had a median of 3 years and between the second and third of 6 years. After the first treatment, BNI improved from a median of 4 to 3b, the same results were noted with the second treatment and, after the third, it improved from 4 to 2. The median doses were 72Gy, 66.5Gy and 70Gy respectively. No adverse radiation effects were reported.

Conclusion

GKRS has been used for TN since its development and has had its use increased as a primary or secondary treatment option. We report a 24-year experience of a single high-volume center that shows the visibility, efficiency, and safety of repeating GKRS for hard-to-treat TN.

Objectives: The thalamus plays a key role as a brain relay, significantly influencing motor and sensory signals through cortical-subcortical pathways. Targeting and lesioning the posterior part of the central lateral nucleus (CLp) in the thalamus is thought to affect pain in multiple ways; however, thalamic subregions are not clearly visible using standard MRI techniques. As a result, CLp targeting methods depend on indirect techniques, which often fail to consider individual differences in anatomy. Therefore, standardizing this targeting process is critical for improving treatment planning. This technical study evaluated the integration of thalamic nuclei segmentation in Gamma Knife treatment planning for chronic pain.

Methods: Ten healthy participants without structural abnormalities underwent T1-weighted high-resolution structural MRI, and subcortical segmentation was performed using FreeSurfer software (version 7.4.1). Detailed segmentation was performed with a probabilistic atlas of the thalamic nuclei built with histological data. Label images were then converted into a DICOM form as 3D label objects, and these objects, along with the associated T1-weighted image, were imported into GammaPlan. A single 4-mm isocenter was placed on the CLp using an indirect targeting method based on stereotactic brain atlases.

Results: The data from 10 participants (5 males, 5 females, aged between 25 and 60 years) were analyzed. All segmentations were confirmed to accurately delineate the subregions of the thalamus. In cases with atypical thalamic structures and where the indirect coordinates alone would have been less reliable, the pre-segmented thalamic maps provided a critical visual reference. 

Conclusions: Our observations suggest that incorporating thalamic segmentation into the radiosurgical planning process could be a valuable tool in enhancing the accuracy of indirect targeting methods. This is particularly relevant in patients with anatomical variations, where deviations from standard thalamic morphology could otherwise lead to inaccuracies in targeting.

Background

Sphenoorbital meningioma (SOM) is a unique and uncommon subset of skull base meningiomas. Optic nerve involvement and visual impairment are not uncommon. For tumors in close contact with the optic nerves, it is very difficult both to preserve vision and inhibit tumor progression by remaining within safe dose ranges, especially for single fraction stereotactic radiosurgery (SRS). To achieve this, it is essential to perform radiosurgical planning with the utmost caution. We report radiosurgical planning, implementation, and the long-term results of SRS to manage a SOM surrounding the optic nerve.

Methods

In January 2011, a 54-year-old woman was examined in another center for headache and referred to our outpatient clinic for SRS after being diagnosed with SOM. Her neurologic examination, including normal visual acuity and visual field, was unremarkable. Magnetic resonance imaging (MRI) revealed a left SOM surrounding the left optic nerve. Stereotactic radiosurgery was performed using a Leksell G frame (Elekta, Sweden), MRI-guided dose planning, and the 4C model Gamma Knife unit. Radiosurgical planning was carefully tailored to spare the left optic nerve. The tumor was treated with a 10 Gy prescription dose to 50% isodose line.

Results

The patient’s postoperative course was uncomplicated, and her headaches gradually improved over the course of the next 6 months. MRI showed tumor volume regression at 12 months. Twelve years after radiosurgery the patient is symptom free and has not had any further progression of tumor.

Discussion

The main goal in both surgical and radiosurgical treatment of perioptic tumors is to manage the tumor without causing or increasing vision loss. A crucial step in SRS is the evaluation of treatment plans, which affects the features of the plan chosen for treatment and, subsequently, how radiotherapy patients are treated. The process involves creating a detailed map of the target area, determining the optimal radiation dose and delivery technique, and considering patient-specific factors such as anatomy and any previous treatments. Accurate planning helps maximize the therapeutic benefit and minimize the risk of adverse effects.

Conclusion

SRS provides a minimally invasive treatment option as an alternative to surgical resection, particularly for tumors that are challenging to access, close to vital structures, and patients with contraindications to surgery. This case demonstrates the unique technical importance of radiosurgical planning in managing a challenging neurosurgical task with long-term effectiveness and safety.

Introduction

Sphenopalatine ganglion is a target for Leksell gamma knife (LGK) radiosurgery in cluster headache in patients who failed conservative treatment. Only a few studies present this therapeutic approach and outcomes are inconsistent. The target identification and treatment parameters are still unclear. The aim of this study is to analyze data from patients with cluster headache who underwent LGK radiosurgery treatment and evaluate the efficacy and safety of this therapeutic approach.

Methods:

We enrolled 36 patients (15M, 21F; mean age 48y) with diagnosed cluster headaches. All patients underwent a radiosurgical irradiation of sphenopalatine ganglion using the Leksell gamma knife (model C, Perfexion, and ICON).  We used a single 4mm shot, and the mean Dmax was 85.3Gy (80-90Gy).

Results

The pain reduction was achieved in 24 patients (66%) and the intensity of pain was reduced to 42% of the previous pain level on average. The mean time to pain reduction was 53 days (3-180). In 12 patients (50%) the effect was temporary, and the mean time to recurrence was 22 months (1-120). In 5 patients with pain recurrence, repeated Leksell gamma knife treatment was done with no longtime lasting effect. The mean follow-up was 35 months. No adverse event was observed.

Conclusion

Leksell gamma knife irradiation of the sphenopalatine ganglion is a safe and effective method for pain reduction in cluster headache.  Two-thirds of patients experienced pain reduction; in one-third, the pain reduction was permanent.

Treating brainstem metastases can be challenging for the multidisciplinary team involved.

Due to its location, surgery is not an option. Therefore, radiation is the best solution in these cases, with the concern of potential toxicity in such a sensitive structure. The goal of treatment is to ensure safety and efficacy while preserving the patient's quality of life.

In October 2022, the first patient with a diagnosis of brainstem metastasis was treated by a dedicated group of stereotactic radiosurgery in our department, which began its clinical activity in 2021.

We presented a case of a 59-year-old male patient who had a solitary brainstem metastasis from non-small cell lung cancer without any other extracranial disease. The patient presented with diplopia and occipital headache as initial symptoms, which were controlled with steroids. The diagnostic MRI conducted in September 2022 showed a solitary lesion localized in the midbrain with a large dimension of 10.4 mm with marginal oedema.

He had an ECOG-Performance Status score of 0. In addition, the Neurologic Assessment in Neuro-Oncology Scale and the Mini-Mental State Examination were performed. The Lung Ds-Graded Prognostic Assessment (Lung-molGPA) calculated an estimated median survival of 26.5 months.

The patient underwent fractionated stereotactic radiosurgery in October 2022. The immobilization device used was an open mask for surface image-guided radiation, in accordance with our institution's protocol. Planning involved fine slice CT scans (1mm) and MRI (1mm) with contrast injection. Geometric distortion correction was applied during the MRI planning process. A GTV of 0.25cc and a PTV margin of 1mm were delineated, along with critical organs at risk. Constraints were based on the recommendations of the American Association of Physicists in Medicine Task Group 101.

The total prescribed dose was 21 Gy administered in 3 fractions. The maximum dose to the brainstem was 25 Gy (in GTV: 119.9%), with a maximum of 23 Gy in the brainstem minus PTV. Treatment was delivered using volumetric modulated arc therapy on a linac. Plan evaluation parameters included Paddick conformity index, conformity index, selectivity index, homogeneity index, and gradient measure, with values of 0.93, 1.07, 0.77, 0.15, and 0.34, respectively.

No toxicity has been observed during or after treatment thus far, and the patient is no longer receiving steroid therapy. In October 2023, the patient underwent an MRI which showed a complete response after 12 months of treatment. Serial MRIs are being conducted every 2 months as per institutional protocol for follow-up.

Background:

   Microvascular decompression of the trigeminal nerve is an effective procedure for treating patients with trigeminal neuralgia (TGN). However, vertebrobasilar decompression involves technical difficulties and demonstrates a higher risk of minor trigeminal hypesthesia/hypalgesia, transient diplopia, and hearing loss. Stereotactic radiosurgery (SRS), mainly using Gamma Knife (GK), has been an effective alternative treatment for TGN. Few studies reported the treatment results of SRS for TGN caused by vertebrobasilar compression. This report presents the treatment results of GK-SRS in four TGN cases.

Materials and Methods:

   GK-SRS was performed for TGN due to vertebrobasilar compression in four patients, including two males and two females, aged 67-90 years. The maximum dose of 80 Gy was delivered at the retrogasserian portion of the ipsilateral trigeminal nerve root.

Results:

   All four cases with TGN achieved relief in 4-10 months after GK-SRS. However, TGN recurred 41 months after GK-SRS in one of the four cases. A second GK-SRS at the root entry zone at a maximum dose of 70 Gy relieved pain again 10 days after the second GK-SRS. TGN in another case among the four partially recurred in 3 years but did not deteriorate until the patient died from old age 62 months after GK-SRS. The other three cases, including the one with repeat GK-SRS, were alive with complete TGN remission at the end of follow-up of 20-52 months. GK-SRS-related adverse effects were not observed in any case.

Conclusions:

   GK-SRS was a safe and effective treatment in all four TGN cases due to vertebral artery-basilar artery compression, although a second treatment session was added again for pain recurrence in one of the four cases.

Background: Gamma Knife stereotactic radiosurgery (GK-SRS) is considered for treatment of disabling pharmacoresistant tremor in various movement disorders mainly as unilateral Vim-thalamotomy. Advantageously, GK-SRS may be performed in patients with severe concomitant diseases or requiring constant anticoagulants, and in patients with implanted neurostimulator. Its limitation is impossibility of neurophysiological control and intraoperative testing of clinical and side effects, as well as delay in their appearance.

Objective: To study efficacy and safety of GK-SRS unilateral Vim-thalamotomy in patients with different tremor.

Methods: 12 patients underwent GK-SRS (Parkinson’s disease – 9 patients, post-stroke tremor – 1, essential tremor – 1, post-traumatic tremor – 1). Mean age was 66.4±14.3 years. In 3 PD-patients, GK-SRS was performed aiming additional tremor management after previous stereotactic interventions (radiofrequency Vim-thalamotomy on the other side, STN-DBS with remaining tremor on dominant side, and explantation of Vim-DBS). Tremor severity in patients with parkinsonism was assessed by UPDRS-subtests, in other cases – by Fahn‐Tolosa‐Marin CRST-subtests. Radiation dose was 130Gy.

Results: In PD-group, outcome was assessed in 7 patients. In short-term follow-up (0.5–1 year), tremor reduction in the contralateral extremities according to UPDRS-subtests was >50% in 4 patients, >25% – in 2 patients, and <25% – in 1 patient. At the same time, functional improvement was observed in 71%. In 5 PD-patients, long-term follow-up was available (1.5–5 years) demonstrating stable GK-SRS effect on tremor. Upon further observation, most PD-patients showed gradual increase in severity of motor and/or non-motor PD-symptoms due to disease progression, which had a negative impact on daily living activities.

In a patient with levodopa-responsive post-stroke tremor, a significant decrease in tremor severity was observed approaching 60% by 6 months after GK-SRS and 90-100% in long-term follow-up until 9 years. Levodopa equivalent daily dose was reduced from 2650 to 250mg.

In a patient with ET, one year after GK-SRS, severity of postural and kinetic tremor in the contralateral arm decreased moderately (25% according to FTM-CRST), accompanied by some improvement in function.

In a patient with post-traumatic tremor, improvement was 58% (FTM-CRST) by the second year.

There were no side effects associated with GK-SRS.

Conclusion: Outcomes of GK-SRS thalamotomy are heterogeneous. Most patients receive meaningful reduction in tremor severity without marked side effects. 20-30% of patients may have insufficient clinical effect. This may be due to inability of direct Vim visualization, lack of neurophysiological verification of the target and intraoperative testing, and presence of hypo- and hyperresponders to radiosurgical intervention.

INTRODUCTION: The aim of this study is to present the methodology and the results of a truly Patient-Specific Quality Assurance (PSQA) process via the RTsafe-PseudopatientTM service (RTsafe P.C.) for a challenging Stereotactic Radiosurgery (SRS) treatment of a multiple brain cavernomas case. The treatment was implemented at the Neuro Spinal Hospital, Dubai, UAE using CyberKnife M6 (Accuray Inc.).
MATERIALS AND METHODS: A female patient with multiple brain cavernomas was treated with CyberKnife robotic radiosurgery in our center. Planning CT with 1mm slice thickness was co-registered with T1 with contrast and T2 MRI scans to identify four deep seated, surgically unrespectable, cavernomas. Treatment plans were devised employing fixed collimators (5mm, 7.5mm) for four brain cavernomas. A RTsafe - PseudopatientTM patient-specific head phantom was built by RTsafe P.C., (Athens, Greece) for the selected patient, using as input the patient’s anonymized planning CT scan. The patient's head replica, filled with polymer gel as a 3D dosimeter, was precisely positioned using the same immobilization devices used for the patient's actual setup. PSQA plans were executed using the 6d skull tracking method as in the actual delivery on the patient. Subsequently, a T2 MRI scan of the phantom was obtained (1.5T Aero SIEMENS) 24 hours post-irradiation. Polymerization degree after irradiation is proportional to the dose delivered at each point of gel’s volume. The phantom's MRI scan and the calculated GelDose were registered with the patient's DICOMRT dataset. PSQA was assessed through 3D Gamma Index analysis with passing criteria of DTA(1.5mm)/DD(2%)/DT=1%.
RESULTS: Evaluation was conducted for four targets, revealing a mean GI passing rate of 97.3% (min=95.9%, max=98.6%). This indicates a high level of dosimetric and 3D spatial accuracy of dose delivery, ensuring the safety and effectiveness of the treatment
DISCUSSION:  Verification of dose distributions on 3D printed patient's anatomy is achieved through 3D dosimetry employing the Polymer Gel Dosimeter. This method ensures submillimeter spatial and dosimetric accuracy, making it particularly well-suited for Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT). The Polymer Gel Dosimeter exhibits no directional dependence, offering consistent and reliable results from all angles. Moreover, plans are summed on the gel phantom enabling comprehensive assessment of the total dose distribution in the treatment of multiple lesions. This summation approach provides a holistic view, enabling effective verification of the overall dose delivery across various treatment targets.

INTRODUCTION

Severely impaired patients with obsessive and compulsive disorder (OCD) may remain refractory to medical and behavioral treatments. These patients may benefit anterior capsulotomy using radiosurgery. We evaluated the safety and efficacy of Cyberknife radiosurgery in intractable patients with OCD.

METHODS

At our center, we treated 20 consecutive patients with intractable OCD using Cyberknife Robotic Radiosurgery between February 2014 and June 2022. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Beck Anxiety Scale and Beck Depression Scale were used before the treatment and in the follow-up. Bilateral radiosurgical capsulotomies were performed using targets at the midputaminal point of the anterior limb of the internal capsule. Median prescription dose to the target margin was 80 Gy (range, 70-95 Gy) for each side. 

RESULTS

Median follow-up time was 55 months, ranging 12 to 100 months. In three patients, a second treatment was performed due to lack of bilateral lesions 7,8 and 10 months after initial procedure. Patients tolerated the procedure well without significant acute adverse events. Two patients developed edema and cyst formation on one side that required medical treatment but not surgical intervention. Thirteen patients (65%) showed marked clinical improvement which is defined as at least 35% reduction in Y-BOCS score.

CONCLUSIONS

Bilateral anterior capsulotomy using Cyberknife radiosurgery may be a safe and effective treatment in patients with intractable OCD.

Introduction:

Meningiomas are the most common dural masses, but other neoplastic lesions can sometimes mimic them. In these cases, because of differential diagnostic difficulties, inappropriate findings can lead to inadequate medical treatment. Here, we present the case of our patient, whose initial medical investigations led to a failed result.  

Patient's history

A 66-year-old female with a former 14-year oncologically stable breast cancer history applied for medical examination because of dizziness, severe headache, and left-sided facial pain. After one month, complete peripheral facial paresis appeared without hearing complaints. Imaging revealed a left-sided parasellar mass with a tiny contrast-enhancing tissue in the internal auditory canal. That last was diagnosed as an en-plaque propagation of the parasellar tumor that could be a meningioma. Contrary to the first opinion of the radiologist, and due to the cancer history, we were convinced that the visible lesions were not else than leptomeningeal dissemination of the cancer. Complete oncological restaging was initiated, including staging CTs, lab tests, and liquor screening. To our surprise, at that time, no tumor was found outside the intracranial space, so we accepted the diagnosis of meningioma that the radiologist had suggested before. 

Treatment:

Stereotactic irradiation of tumor mass was performed with a 13Gy at 50% marginal dose. 

Result:

Follow-up MRI was performed after 3 and 6 months. The regression of the lesion was visible, but clinically there was no improvement. 

The headache was almost uncontrollable, and generally, the patient had poor general conditions. Several lab tests, lumbar puncture, and staging CTs were repeated, but with negative results. So observation and general medication were continued. Further MRI after 2 months showed a remarkable change. Strong leptomeningeal contrast enhancement appeared with some leptomeningeal nodules. An open-skull biopsy was performed. This was the first examination that could verify our initial suspicion. So the diagnosis after the histology was modified to leptomeningeal dissemination of previous breast cancer that was mimicking meningioma. After several months, the patient passed away. Finally, the autopsy confirmed the highly disseminated cancer disease, but no intracerebral metastasis was found, only dural lesions. 

Conclusion:

Considering the results of the initial investigations, which suggested a meningioma, stereotaxic radiosurgery seemed to be an appropriate choice. We could not recommend whole brain irradiation at the beginning, since leptomeningeal dissemination could not be verified by any procedure at that time.

However, in the case of leptomeningeal dissemination, whole-brain irradiation would have been the only right choice.

Introduction

Radiosurgery Cingulotomy is underutilized for refractory neuropathic pain (RNP). We reviewed three patients of RNP with allodynia and dysesthesias treated with bilateral Icon Gamma-Cingulotomy (IGKCi) who had failed multiple pain surgeries.

Methods

IGKCi used double 4mm shots of 120 Gy on each side. Coordinates were 7mm from midline, 7mm above the roof of the lateral ventricles for the first shot, and 20-25mm posterior to the lateral ventricles anterior wall. Tractography by artificial intelligence (Brainlab-Elements, Germany) turned into objects transported to the Gamma-Plan (Elekta, Sweden) demonstrated the cingulate gyros span, defining the site of the second shot. Sided-by-side anteroposterior shots center distance offset decreased the high dose to branches of the anterior cerebral arteries.

Results

Patient one, a 53-year-old woman had left V2-V3 trigeminal neuralgia (TN) for 15 years. This is after microvascular decompression (MVD), balloon compression (BC), upper cervical dorsal column stimulation (SCS-trial), and deep brain stimulation (DBS). Her RNP involved the left hemi-cranium. Dependence on high opioid doses and frequent visits to the emergency room (ER) led to bilateral IGKCi. Additionally, she received 90 Gy to the root entry zone of the left trigeminal nerve on the same day. She stopped opioids and visits to the ER three months after the procedure, she developed asymmetric radiation reaction with edema without symptomatic repercussion. At 18 months follow-up, her visual digital scale for pain (VAS) fell from 10 to 2. Patient two, a 56-year-old woman, with tetraparesis since she was 14 months. She underwent numerous spine deformities and renal surgeries. Her RNP involved her legs and lower back, she also complained of generalized body pain. She did not accept traditional neuromodulation techniques, opting for bilateral IGKCi. At four months follow-up she stopped opioids, her pain improved more on the right side, persisting on the left, VAS fell from 10 to 5. She continues working as a librarian. Patient three was a 36-year-old woman with left TN, failure of MVD, balloon compression, and DBS. She also developed RNP. She required an intensive care unit for pain control and had multiple admissions through the ER. At nine months follow-up after IGKCi she stopped regular use of opioids and hospital admissions. She reports a VAS decrease from 10 to 7.

Conclusion

Neuromodulation using IGKCi maximal dose of 120 Gy, aided by tractography placing double shots on each cingulum affords a substantial decrease of pain and need for opioids.

Introduction

GammaKnife radiosurgery (GKRS) is a valuable modality for the treatment of trigeminal neuralgia. However, the durability of response and the factors predicting response remain somewhat unclear. 

Methods

This study was a retrospective analysis of a prospectively maintained database spanning the years 1998-2022 (inclusive). Demographic and medical details were obtained from the electronic medical records (EMR). Plan parameters, dose delivered, morphometric data pertaining to the nerve and brainstem, etc. were obtained from the imaging sequences in Gamma Plan. Follow up details were also obtained from the EMR. Differences between patients who responded and those who did not were analyzed.

Results

A total of 206 patients were treated over the study period; 155 patients had received single treatments and 51 had received more than 1 treatment for the same side. The right side was more commonly affected than the left (58% vs 42%) and women were more frequently affected than men (68% vs 31%). For patients who had received a single GKRS treatment, the mean follow up was 908 (±1218) days. At last follow up, 61.5% had significant pain relief and 19.3% had adequate pain relief; overall 71% were pain free, on or off drugs, after treatment. Based on any change in BNI scores at last follow up, 85% responded to treatment, 11% did not respond and 4% were worse off than before GKRS. More men (90%) than women (76.5%) had pain relief (p=0.03). The mean weight and BMI were higher for those who responded to GKRS than those who did not. The presence or absence of a conflict did not affect response to GKRS. However, patients with venous conflicts were more likely to respond to GKRS (88%) than those with arterial conflicts (80%) or both (54%, p=0.016). The site of shot placement (nerve vs conflict) did not affect response rates, nor did the dose to the root entry zone. For patients who required multiple treatments, those with right sided pain were more likely to respond (93%) than those with left side pain (72%). Optimal visualization of the affected nerve led to better pain free rates (p=0.04).

Conclusions

GKRS for trigeminal neuralgia results in a good response rate with more than 70% of the patients being pain free, on or off drugs. Various modifiable and non-modifiable factors could influence the outcome of GKRS for trigeminal neuralgia. 

Introduction

Radiation treatment plans for essential tremor (ET) are executed in two steps: defining the ACPC line and then, applying linear shifts from the PC point. 25-30% ACPC length anterior, 11-15 mm lateral and 2-4 mm superior, aiming for the ventralis intermediate nucleus (VIM) and establishing the target coordinate.

Objective

Verify the capability of Brainlab Elements Trajectory to automatically define the Anterior Commissure – Posterior Commissure (ACPC) line in T1 MRI in ET treatment cases.

Method

We analyzed data from 13 essential tremor cases treated in a Leksell Gamma Knife Icon (LGKI). The plans were created using Elekta Gammaplan (GP), with the ACPC line defined in a T1 MRI by the attending neurosurgeon and double-checked by the attending radiation oncologist. From the PC point, shifts were applied to reach the treatment target. Two shots were placed in the same coordinate, 4 mm collimators open with two sectors closed each [2,6 (Left cases) or 4,8 (Right cases) and 7,3 (both cases)] to generate a more shaped isodose of 50%. The Diffusion Tensor Imaging (DTI) MRI with 32 directions sequence was used to define the pyramidal tract (PT) as an OAR in Brainlab Elements Fiber Tracking, the VIM was also defined by Brainlab Elements, and the structures exported do GP.

In Brainlab Elements Trajectory, the same T1 MRI sequences were loaded and the ACPC line was defined automatically by the software without any adjustments. The same shifts from the reference plan, in mm, were applied from PC point setting a new target. Shots were adjusted to the new coordinate.

Results

Elements sets a shorter ACPC line (23,0 ± 1,5 mm) than the experts (25,9 ± 1,6 mm). In terms of distance from the target to the center of mass of the VIM, the software could match the experts’ result (2,7 ± 1,4 mm) with an average of (2,8 ± 1,1 mm). Dose in the PT were also comparable, 10,7 ± 4,8 Gy for experts and 9,4 ± 4,1 Gy for the software. Mean dose to VIM of 37,0 ± 10,4 Gy for experts and 40,6 ± 12,4 Gy for Elements and V_{70 Gy} in VIM of 33,2 ± 12,9 Gy for experts and 29,2 ± 18,9 Gy for Elements.

Conclusion

Elements is capable of auto define an ACPC line. With a 12% shorter ACPC line there was not statistically significance difference in any other dosimetric or geometric parameter analyzed.

Background

Close to 100 million people worldwide suffer the sequelae of severe trauma or hereditary impairment of the brain or spinal cord, with spasticity and related pain being a common long-term complication in survivors. Conventional surgical treatments are effective but available to a limited number of patients.

Aim

A novel non-invasive treatment for spasticity, stereotactic radiosurgery (SRS) of the sensory component of selected nerve roots, is here reported. This treatment is the radiosurgical equivalent of selective dorsal rhizotomy, a procedure of well-known efficacy.

Methods

Four patients with refractory spasticity and related pain associated with trauma or injury to the brain and/or spinal cord underwent stereotactic irradiation of selected cervical or lumbar roots. Treatment was delivered to the post-ganglionic sensory segment of cervical roots or to the dorsolateral sensory region of lumbar roots. Selection of irradiated roots was based on somatotopic distribution of spasticity and related pain as well as EMG findings. Pre- and post-procedure spasticity and pain levels were assessed with Modified Ashworth Scale (MAS) and Visual Analogue Score (VAS).

Results

The treatment was well tolerated. Marked symptomatic relief of spasticity and pain was found in all patients. After 2 years, median reduction of MAS score was 50%. Mean reduction of MAS & VAS were, respectively, 43.7% & 64.3%.

Conclusions

SRS of spinal nerve roots appears to be a safe, effective, and noninvasive treatment for patients with spasticity & pain caused by brain or spinal cord injury. This technique provides a useful option for the treatment of a wide variety of patients suffering from long-term sequelae of neurological injury and can broadly expand the ability to treat patients currently orphaned of treatment.  

Given the treatment’s remarkable results, we developed and have initiated a randomized, sham-controlled clinical trial to assess the efficacy of the treatment in the most rigorous fashion possible. Twenty-two patients will be randomized to treatment vs sham with blinding of the patient and raters. The trial is powered for an 80% power of detecting 50% reduction in MAS, the primary outcome. Secondary outcomes include adverse events and quality of life. At the time of submission, 3 patients have enrolled.

Introduction.

Oncological abdominal pain due to celiac plexus compression or infiltration, is often severe and difficult to treat with current approaches including opioid analgesics, nerve block or neurolysis, chemotherapy and conventional radiation therapy. Emerging no invasive treatment modalities such as Stereotactic Body Radiation Therapy for the celiac plexus are being studied in order to treat this complex pain syndrome.

Methods.

Patients with classic celiac abdominal pain (Visual Analogue Scale >5) and decreased in the quality of life related to oncological malignancies, even with the optimal use of opioids and estimated survival of at least 30 days were included. All patients were simulated in 3D CT scan using ALTA® Qfix with vacuum bag, abdominal compression, and oral contrast. Two millimeters slice thickness images were acquired from T8 to L5-S1 vertebral space and transferred to TPS(Eclipse®). Celiac plexus was contoured (anterolateral aspect of aorta) from T12 to L2 plus/minus adjacent tumor. Organs at risk and constraints were based upon AAPM Task group 101. The primary endpoints were reduction of pain (>50%) before 3 weeks (best case scenario before 72 hours) and quality of life (QoL) improvement.

Results.

From October 2022 to July 2023, 4 patients were treated (75% pancreatic cancer, 25% gallbladder) with ring gantry lineal accelerator (HALCYON™). Mean age= 68 years {59-80}.  Prescribed dose was 25Gy/1 fraction (3 patients) and 45Gy/5 fractions (1 patient) to the celiac plexus, using uniform dose technique. Adjacent tumor was treated in 3 patients. Mean celiac plexus volume= 28.8cc {22.31-39.58}, Mean tumor volume= 36.6cc {20.68-51.59}.  Volumetric Arc Therapy (RapidArc®) with 6 MV energy plans were calculated to deliver SBRT. Due to Halcyon™ monitor units (UM) it was necessary to use 8 to 15 arcs. Mean treatment time=11.28 minutes {5-16.74}. Mean follow up=8 weeks {4-13}. All patients had relief of pain ≥ 50% before 72 hours post treatment and QoL improvement.

Conclusions.

This first experience in Central America using SBRT to the celiac plexus, demonstrated that this treatment modality is feasible and safe for palliative treatment in oncological abdominal pain, with early response observed in the decrease of pain probably associated to the neuromodulation effect.

Background: Gamma capsulotomy is an established neurosurgical procedure for refractory psychiatric disorders. However, radionecrosis is a serious complication associated with this intervention. This report presents a rare case of severe, steroid-refractory bilateral radionecrosis in a 26-year-old male patient following bilateral ventral anterior limb internal gamma capsulotomy, which showed a remarkable response to Boswellia serrata. Boswellia serrata is a traditional herbal extract with potent anti-inflammatory properties, and has recently gained attention for its potential role in mitigating radiation-induced cerebral edema and radionecrosis in oncological treatments. Here we showcase its effect in a non-oncologic treatment.

Case Description: The patient, a 26-year-old male with a history of severe obsessive compulsive disorder, underwent bilateral ventral anterior limb internal gamma capsulotomy (80Gy @ 50%IDL, bilaterally). Post-procedure, his OCD improved (YBOCS 33 -> 28) but he developed severe bilateral radionecrosis. Initial management with steroids failed to yield any improvement, and caused severe weight gain and hallucinations in the patient.

Intervention and Outcome: Given the challenges with conventional steroid therapy, the patient was commenced on oral Boswellia serrata 2400mg BID. Subsequent imaging revealed significant improvement and then complete resolution of radionecrosis, leaving only intended gliosis at the site of the prescription isodose line. No significant side effects of Boswellia serrata were observed during the treatment course.

Discussion: This case highlights the potential efficacy of Boswellia serrata in managing severe, steroid-refractory radionecrosis post-neurosurgical interventions. The positive outcome in this case suggests the need for further exploration into alternative treatments like Boswellia serrata, especially in cases where conventional therapies fail or are not viable.

Conclusion: Boswellia serrata can be a viable alternative for treating steroid-refractory radionecrosis following functional radiosurgical procedures. This case underscores the importance of considering novel therapeutic approaches in complex clinical scenarios. Further studies are warranted to establish its efficacy and safety profile in a broader patient population.

Background and Objectives

Trigeminal Neuralgia (TN) affects about 2% of multiple sclerosis (MS) patients and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for TN did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS.

Methods

We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the BNI Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio.

Results

258 patients - 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS were included from 14 institutions. 84.6% of patients achieved initial pain relief, with a median time of one month. 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months PPMS, SPMS 8.1 months (p=0.424). Achieving BNI-I after SRS was a predictor for longer periods without recurrence (p=0.028). Analyzing pain control at last available follow up, and comparing to RRMS, PPMS was less likely to have pain control (OR = 0.389; 95% CI 0.153-0.986; p=0.047) and SPMS was more likely (OR=2.0; 95% CI 0.967-4.136; p=0.062).

A subgroup of 149 patients did not have other procedures apart from SRS. Median times to recurrence in this group were: 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log rank, p = 0.045).

Conclusion

This study is the first to investigate the relationship between MS subtypes and pain control following SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.

Background

Glioblastoma (GBM) is the most common primary brain tumor with poor patient prognosis. Spinal leptomeningeal metastasis has been rarely reported, with long intervals between the initial discovery of the primary tumor in the brain and eventual spine metastasis.

Observations

Here, the authors present the case of a 51-year-old male presenting with seven days of severe headache, nausea, and vomiting. Magnetic resonance imaging of the brain and spine demonstrated a contrast-enhancing mass in the pineal region, along with spinal metastases to T8, T12, and L5. Initial frozen-section diagnosis led to treatment strategy for medulloblastoma, but further molecular analysis revealed characteristics of IDH-wild type, grade 4 GBM. CyberKnife radiosurgery was utilized for treatment of the pineal tumor and the three spinal metastases at T8, T12, and L5. Concurrent use of radiosurgery, craniospinal radiation, and chemotherapy helped with overall stability of the pineal mass. 

Lessons

Glioblastoma has the potential to show metastatic spread at time of diagnosis. Spinal imaging should be considered in patients with clinical suspicion of leptomeningeal spread. Furthermore, CyberKnife radiosurgery should be considered in treatment options and planning for late-stage glioblastoma. Molecular analysis should be confirmed following pathological diagnosis to finetune treatment strategies.

Background

Secondary trigeminal neuralgia occurs in up to 15% of patients, with multiple sclerosis being one of the identified possible causes. The natural progression of the disease often leads to refractory control of symptoms, requiring specialized procedures due to medical treatment failure.

Lovo et al. published a case series in May 2022, treating eight patients with radiosurgery for severe trigeminal neuralgia pain crisis. The affected trigeminal nerve received a dose of 80 to 90 Gy, and an additional target was defined in the contralateral centromedian nucleus of the thalamus, receiving a dose of 120 to 140 Gy. A 25% complete pain resolution rate at 24 hours and an 87.5% pain improvement rate >50% at 48 hours post-treatment were reported. No adverse events were reported in a median follow-up of 135 days.

Case summary

A 45-year-old male with a 15-year history of diagnosed multiple sclerosis treated with natalizumab presented with a 5-year history of severe right-sided trigeminal neuralgia pain episodes.

The patient had previously been managed with neuromodulators and microvascular decompression surgery, achieving partial control.

In October 2022, the pain worsened, with daily refractory pain paroxysms rated as 10/10 on the visual analog scale (VAS). The case was discussed in the radiosurgery unit, and it was decided to offer SRS treatment using the CyberKnife M6 system with dual targeting. The patient received 90 Gy to the retrogasserian zone of the affected trigeminal nerve and 120 Gy to the contralateral centromedian nucleus of the thalamus in a single session.

Following treatment, the patient was monitored using the VAS. At 24 hours: VAS 6/10; at 72 hours: VAS 3/10; at 8 days post-treatment: VAS 0/10. The patient was contacted by phone every 3 months, with the latest update in January 2024 confirming continued pain relief and no need for neuromodulators. The patient has been pain-free for 14 months until now, with no toxicities reported.

Conclusion

Dual-target SRS may be considered for complex mechanisms of refractory pain, as seen in our patient with a demyelinating disease. We propose that the effect of radioneuromodulation is an excellent mechanism for improving pain and quality of life. However, further clinical trials are needed.

Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing.  Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being “reversible”, deep brain stimulation (DBS) of the Ventral Intermediate Nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by High-Intensity Focused Ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a “second look”. While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this technical study, we compare the dosimetric profiles of three major radiosurgical platforms(Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS) for the treatment of ET. Treatment plans were generated for all three platforms, utilizing a uniform sample patient. The respective treatment plans are shown in figures 1-3.  The volume receiving 5 Gy (V_5Gy), 10 Gy (V_10Gy), and 12 Gy (V_12Gy ) is reported as well as the gradient index (V50%/V100%), and V35% which is the volume receiving half of prescription dose. These parameters allow us to make uniform comparisons across the platform. These dosimetric parameters are summarized in table 1 with indication of collimator size and energy used. In general, GRS and Gamma Knife were shown to have the best dosimetric profiles for VIM lesioning, which is mainly the result of lower beam energy and smaller collimators that are utilized by these platforms. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

Introduction: Chronic, refractory orofacial pain, persistent, concomitant, continuous (PCC) pain in primary trigeminal neuralgia or derived from tumors, deafferentation pain from surgery, destructive or lesioning procedures such as radiofrequency, failed radiosurgery or usually a combination of various techniques, can have a devastating effect on patients and care givers. Radiosurgery to the medial structures of the thalamus has been used for oncological pain and non-oncological pain over the years, specially to the centromedian and parafascicular complex region. Radiomodulation effect can be understood as a substantial (more than 50%), quick pain response (hours to days) after treatment that cannot be explained by lesion formation due to the brief time span after treatment.

Methods: We present our experience in forty-six patients that have been treated with radiosurgery from Nov 2016 to Dec 2023 to the contralateral medial structures of the thalamus alone (10), in combination with the ipsilateral trigeminal nerve to the pain (34) and in two cases bilateral irradiation of the thalamus. Doses to the thalamus have varied from 90 to 140 Gy and 80 to 90 Gy to the nerve.

Results: Radiomodulation effect was noticed in 60% of those patients treated unilaterally with single target to the thalamus, overall success rate defined by visual analogue score of less than 50% and Barrow Neurological Institute BNI less than IIIb was 50% at last follow-up. In the 34 patients treated by dual strategy to the nerve and contralateral thalamus radiomodultaion effect was seen in 21 (62%) at last follow up 73% were improved. On the two patients with bilateral irradiation of the thalamus both experienced radiomudulatory effect, one remains pain free at one year and the other one has a 70% pain relief at 2 months. Facial numbness has been close to 30% for those treated to the nerve only. 

Conclusions: Radiosurgery of central structures of the thalamus has been proven to be a safe alternative to obtain pain relief in most refractory patients experiencing complex trigeminal pain and other orofacial pain.

Radiomodulation effect in pain is a phenomenon occurring at a timespan to brief to be explained by lesioning of the nerve or other central pain, pathway structures. It may be transitory in nature, with pain relapses that are usually better tolerated and less intense than the original pain. 

There is a need for more clinical trials and longer follow upto validate the success rate of radiosurgery in this subgroup of patients.

Breast cancer is the 5th cause of cancer-related mortality, with metastatic disease developing at the time of diagnosis in 20-30%, with leptomeningeal metastasis in only 5-8% of cases.

Objective: To describe a clinical case with multimodal and multidisciplinary management in a patient with HER-2 clinical stage 4 breast cancer, with liver and leptomeningeal metastases, using radiosurgery and intrathecal chemotherapy as part of the treatment.

Case report: A 53 year old female patient, upon self-examination detecting a mass in the right breast, went to a specialist who initiated an oncological study protocol, finding an additional tumor in the liver, confirmed by PET/CT. A radical and simple mastectomy were performed in the right and left breast, respectively, and histopathology confirmed HER-2/neu, positive 3+, p53 positive breast cancer. She was initially treated with chemotherapy with a regimen of Pertuzumab, Trastuzumab and Docetaxel, every 15 days for 7 months, and subsequently treated with Pertuzumab and trastuzumab every 15 days for 9 months and then TDM1 every 15 days to date.

The patient had stable breast and liver cancer disease during the first 20 months after the diagnosis. Then, she presented cerebellar syndrome, and leptomeningeal metastases were found by cranial MRI. Whole brain radiotherapy (WBRT) was used to treat these metastases. The patient's symptoms improved, and lesions were not observed by MRI 3 months after WBRT. 15 months later, the patient presented mild ataxia, and in the control brain MRI scan reactivation of the leptomeningeal disease was observed at the infratentorial level. At this point, a lumbar puncture was performed, with cerebrospinal fluid positive for neoplasic cells. An Ommaya catheter was fixed to deliver intrathecal treatment with Methotrexate/Dexamethasome/Trastuzumab. The patient improved, but required walking assistance. 12 months after catheter placement, the patient presented infratentorial reactivation of 5 solid lesions in the cerebellum and cerebellar vermis, which were then treated with radiosurgery. Systemic and intrathecal chemotherapy is still underway. 4 years after diagnosis, patient is currently stable, with moderate gait ataxia.

Conclusion: Although there is still no defined strategy for patients with leptomeningeal metastasis, in this patient, the treatment with radiosurgery, combined with systemic and intrathecal chemotherapy, has been beneficial in terms of quality of life and prolonged survival. Radiosurgery appears to be an effective treatment for solid lesions, offering tumor control and increased survival.

Stereoteactic radiosurgery was developed with the aim of providing non-invasive treatment in neurosurgical pathologies, including functional pathologies such as essential tremor and tremor associated with Parkinson's disease where the ventral intermediate nucleus of thalamus has been used as a target with proven success.

Although most treatments have been reported with gamma knife, radiosurgery with LINAC has also shown successful results.

Between March and April of this year at the Puebla Specialties Hospital of the IMSS, radiosurgical treatment was carried out on 5 patients with Parkinson's disease refractory to pharmacological medical treatment, all with different forms of presentation from spastic to kinetic.

The dose used of 75 to 85 Gy was given in a single session randomly, with monthly monitoring maintained until now. Although the initial period to assess the effects of radiosurgery treatment is 8 to 10 months, at 6 months we have observed an improvement of at least 60% in terms of control of involuntary movements of patients, likewise these benefits have been manifested in neurological tests such as UPDRS, Hoehn-Yahr and Scwarb-England.

In subsequent months, close monitoring will continue, waiting for greater improvement with the combination of pharmacological medical treatment and waiting for the average effect time of radiosurgery.

Background:

Endolymphatic sac tumors are a very rare type of tumors located in the petrous portion of the temporal bone. They can occur sporadically or be associated with Von Hippel-Lindau syndrome, causing symptoms depending on the structures invaded by the tumor. Typically, it presents with neurosensory hearing loss, vertigo, and facial paralysis. The standard management is surgical resection; however, due to the challenging location, complete resection is often difficult. Therefore, radiosurgery could be an option for local control and symptom remission.

Case:

This involves a 27-year-old male who, in 2019, experienced sudden-onset central vertigo, making ambulation impossible. Additionally, he had decreased hearing, prompting him to seek an ENT specialist who ordered a brain MRI. The MRI revealed a poorly defined tumor of the left endolymphatic sac measuring 27x18x26mm in its anteroposterior, lateral, and cranial-caudal axes, with extension towards the jugular vein. Given these findings, the patient underwent embolization and surgical resection.

Three months after the procedure, in March 2019, a follow-up simple and contrasted ear MRI showed a residual tumor adjacent to the jugular vein gulf, measuring approximately 8x10x8mm. The patient was then referred to our center to assess the residual tumor for radiosurgery.

In June 2020, simulation was performed using a simple and contrasted brain MRI and we contoured the residual tumor. A prescription of 16 Gy/1Fx was given to the 84% isodose curve using CyberKnife, with a treatment duration of 28 minutes.

Currently, the patient is under follow-up with simple and contrasted brain MRI, demonstraiting tumor stability.  The patient continues with daily activities without experiencing any symptoms.

In conclusion, based on this case report, the patient with this rare tumor benefited from a multidisciplinary approach. Given the challenge of achieving complete resection, receiving radiosurgery has yielded excellent results over a 3-year follow-up. Continued documentation of such cases is essential for a clearer understanding of treatment outcomes.

Introduction. Severe tremor can have a devastating impact on a patient’s quality of life. Deep brain stimulation (DBS) and radiofrequency thermocoagulation (RFT) are established therapeutic options for tremor reduction. In our clinic, we offer patients that are ineligible to these invasive surgical procedures Gamma Knife radiosurgery (GKRS) as a last resort option. Here we evaluate the clinical efficacy of these procedures and seek for ways to optimize GKRS.

Materials and methods. Data were retrospectively retrieved from patient records between 2013 and 2022 in a single center. Initial target for all procedures was the ventral intermediate nucleus of the thalamus. Patient-reported tremor outcome and satisfaction were conjointly classified on a 4-point Likert-scale. Adverse effects (AE) were recorded, including balance impairment, dysarthria, sensorimotor decline, infection, or hemorrhage with clinical deterioration. For all patients a Leksell frame was used for stereotaxy. DBS and RFT were performed awake to optimize targeting. For GKRS, a single 4 mm shot with a prescription dose of 130 Gy was used; planning was done on a T1-weighted MR image.

Results. 198 treatments were performed in 178 patients: 98 for GKRS, 62 for DBS and 38 for RFT. Most common diagnoses were essential tremor (n=98) and Parkinson’s disease (n=79). Mean age of the GKRS patients was significantly higher than for DBS and RFT (respectively 78 versus 67 and 69 years). Proportion of patients that was satisfied with their treatment outcome was highest for DBS (87%), followed by RFT (74%) and GKRS (52%). Incidence of AE was lowest in the GKRS group (1%). Dysarthria was more present in DBS patients, whereas sensorimotor impairments was more present in the RFT group.

Conclusion. GKRS treatment is a very safe and reasonably effective tremor treatment in selected patients, but is in our series still less effective than current invasive methods DBS and RFT. We acknowledge the obvious limitations of our current retrospective and qualitative approach. However, as DBS and RFT study results are in line with those of the literature, we think conclusions are valid. The lower GKRS treatment outcome may be explained by the fact that during DBS and RFT usually multiple targets are identified, frequently also in the subthalamic white matter, indicating significant interindividual variability. Recently, we incorporated new MRI techniques in our GKRS protocol to better visualize the hypothalamic region (FGATIR) and to image thalamodentate fibers. Further studies should assess whether this personalization can increase efficacy of GKRS for tremor.

Purpose

Ventricular tachycardia (VT) in patients with structural heart disease is associated with reduced quality of life and poor prognosis. Therapeutic options include medication, anti-tachycardia pacing or shock by implantable cardiac devices and catheter-based ablation of heart arrhythmogenic substrates. STereotactic Arrhythmia Radioablation (STAR) tested in a phase I/II trial by Robinson and colleagues offers a novel approach.

Materials and Methods

Dosimetric and clinical data from a retrospective series of 5 high-risk patients with VT refractory to catheter ablation and medication, treated with STAR are reported from a single referral center.

The clinical target volume (CTV) was defined to encompass the arrhythmogenic substrate by a team of a radiation oncologists and treating electrophysiologists, based on clinical and electro-anatomical information derived from CT scan and catheter ablation maps. An internal target volume (ITV) was added to CTV to compensate for heart and respiratory movement. The planning target volume (PTV) was then defined by adding an isotropic margin of 2-3 mm to the ITV.

Volumetric Modulated Arc Therapy (VMAT) plans were generated, optimized, and delivered using a TrueBeam^TM (Varian Medical System) linear accelerator employing both cone beam CT and surface-guided radiotherapy for real-time image guidance.

The prescription dose to the PTV was 25 Gy in 1 fraction.

Results

Mean CTV, ITV and PTV volumes, were 141.1cc, 187.7cc, 298.1cc, respectively. Mean heart volume was 1740.6 cc. The main dosimetric data are summarized in Table 1(A).

All 5 patients completed STAR procedure and treatment. There were no acute treatment-related adverse events. Clinical and treatment-efficacy data are summarized in Table 1(B). STAR significantly reduced or abrogated arrythmia at a median time of 24 weeks (range 4-48) post-treatment. Patient n.1 and n.3 showed a remarkable reduction of VT episodes at 4- and 8-weeks post-treatment, respectively. Patients n.2, n.4 and n.5 were free of VT episodes at 6-months post-treatment.

At a median follow-up time of 11 months (range 1-19), 2/5 patients are alive (patient n.2 and n.4), both free of VT events at 1-year post-treatment. Patient n.1 died due to complication after cardiac transplantation, patients n.3 due to sepsis and multiorgan failure and patient n.5 due to COVID pneumonia, at 11-, 1- and 5-months post-STAR, respectively.

Conclusion

These data suggest that LINAC-based STAR is a safe and effective treatment option in high-risk patients with VT refractory to catheter ablation and medication. Results from large prospective studies will define optimal patient selection and inform about long-term outcomes.

Background: One approach to treating medically refractory tremor is radiosurgical thalamotomy, which ablates aberrant cerebello-thalamo-cortical circuitry by targeting the dentato-rubro-thalamic tract (DRTT) within the ventral intermediate nucleus (VIM) of the thalamus We report on the accuracy and precision of frameless, MLC-based linear accelerator radiosurgery using a thermoplastic mask and optical surface imaging for intra-fraction motion monitoring.

Methods: 40 patients, diagnosed with either essential tremor or Parkinsonian tremor, underwent unilateral SRS thalamotomy on an Edge linear accelerator (Varian Medical Systems, Palo Alto, CA) on an IRB-approved clinical trial (ClinicalTrials.gov Identifier: NCT03305588). In each patient, the VIM was identified using stereotactic reference coordinates and automated scripting. Scripted treatment planning was done in Eclipse (Varian Medical Systems) with 1 mm dose calculation grid size on a treatment planning CT having 0.8 mm slice spacing. Patients were immobilized using the non-invasive Encompass SRS Immobilization system (CQ Medical, Avondale, PA). Treatment encompassed a single dose of 135Gy (Dmax) delivered using our previously described MLC-based 4.5mm-equivalent virtual cone technique. Patient position was monitored real-time using optical surface imaging with either AlignRT (VisionRT, London, UK) or IDENTIFY (Varian Medical Systems). 3D high-resolution (0.8 mm) T1-post Gadolinium-contrast MPRAGE imaging was obtained 3 and 6 months post-treatment on a 3T PRISMA MRI scanner (Siemens Healthineers, Erlangen, Germany) and was co-registered to the high-resolution pre-treatment T1 MPRAGE 3T image using a two-stage linear registration (rigid followed by affine). The enhancing lesion was segmented using a semi-automated, threshold-based method. The center-of-gravity (COG) of the lesion and the planned 50% isodose (67.5Gy virtual cone) volume were compared.

Results: At the time of analysis, post-treatment imaging data was available for 33/40 patients.  The analysis showed a mean 3D Euclidean distance of 0.9 mm between the centroids of the enhancing lesion and the 50% isodose volume. Detailed measurements of the X, Y, and Z offsets of the lesion centroids from the treatment isocenter were recorded (Figure 1), with their respective mean and standard deviation values: 0.2 ± 0.4, 0.5 ± 0.4, and 0.0 ± 0.7 mm for X, Y, and Z, respectively. 

Conclusion: Our findings indicate that frameless, mask-based linear-accelerator radiosurgical thalamotomy provides high-level accuracy and precision in lesioning the intended target within the thalamus. Our work demonstrates planning and delivery accuracy comparable to that reported for traditional frame-based radiosurgery.