Smaller vestibular schwannomas (VS) can be managed with resection, stereotactic radiosurgery (SRS), or observation. The preferred management approach has been debated, however, particularly in older patients with serviceable hearing. This study assesses the safety and efficacy of observation versus SRS for Koos grade I/II VS in older adults, with aim to determine the optimal management strategy for this patient population. Multicenter data from patients aged 60 years and older with Koos grade I/II VS managed with observation and SRS was analyzed. Propensity score matching was conducted using patient characteristics, tumor size, and hearing assessments. Outcome measures of tumor control, serviceable hearing preservation (SHP), and neurologic function—including tinnitus, vestibulopathy, House-Brackmann grade, and trigeminal nerve function—were assessed per cohort. 51 matched patients with median age of 68 years comprised each group. 35 patients per cohort had ipsilateral serviceable hearing at presentation. Median follow-up was 39 months in the observation group versus 27 months in the SRS group (p=0.5). Tumor progression was significantly lower with SRS than with observation (2% versus 52.9%, p<0.001). 5-year tumor control rate was 100% in the SRS versus 43% in the observation (95% CI: 29-64%) group. 10-year tumor control rate was 90% in the SRS (95% CI: 73-100%) versus 20% in the observation (95% CI: 8.5-49%) group. At last follow-up, there was no significant difference in SHP rates between groups. Composite endpoints of tumor progression and/or worsened neurologic outcome demonstrated a significantly lower rate in the SRS (17.6%) versus observation (66.7%) cohort (p<0.001). Management with SRS in older patients with Koos grade I/II VS resulted in significantly superior tumor control rates, comparable hearing preservation rates, and significantly higher rates of favorable overall radiographic and neurologic outcomes than with observation alone. As compared to observation, SRS may be the preferred management option in this patient population.

Purpose: The biologically optimal time for brain metastasis (BrM) resection after pre-operative stereotactic radiosurgery (preSRS) is unclear. Emerging data suggests an immunological benefit with a longer interval to resection after preSRS. We conducted the first clinical trial to evaluate the feasibility of planned delayed resection (7-21 days) after preSRS. Methods: In this prospective single-centre, single-arm trial, patients with suspected BrMs suitable for preSRS and surgery were eligible. Surgery was scheduled 7-21 days after completion of preSRS (LINAC or GammaKnife-based) where possible. All patients referred to our neurosurgery service and multi-disciplinary meetings for suspected BrMs were screened. The primary endpoint was feasibility of delayed BrM resection after preSRS. Target accrual was 15 patients and the pre-defined feasibility threshold was ten patients (66%) receiving resection 7-21 days after preSRS completion. Secondary endpoints included adverse events (AEs), 6-month local control, and volume change following preSRS. Results: Between 01/2023 and 08/2024, 78 patients for resection of suspected BrMs were screened. The accrual target of 15 patients was met. Common reasons for preSRS ineligibility were lack of existing cancer diagnosis (44%) and size of tumour/peri-tumoural oedema (18%). Two patients refused surgery after preSRS. 14 brain lesions were resected, most commonly of melanoma histology (31%). Median lesion diameter and volume were 25mm (range 15-56mm) and 10.4cc (range 3.0-53.3cc). The most common dose-fractionation was 27Gy in 3 fractions (31%) and 81% of patients received fractionated preSRS. Median time from preSRS completion to resection was seven days (range 0–15 days). Nine lesions in eight patients (56%) were resected 7–21 days after preSRS. Reasons for earlier resection were logistical (n=2), miscellaneous surgeon/patient preferences (n=2), and medical (n=1, to expedite systemic therapy start). No histopathological diagnosis issues were encountered with delayed resection. At time of write-up, 13 patients had completed 6 months follow-up with no BrM local failure. Most common Grade 1-2 AEs were headache and fatigue (20% each), with no Grade >2 AEs. Conclusion: The pre-defined feasibility criterion for delayed resection after preSRS was not met, primarily due to logistical and preferential rather than medical reasons. Delayed resection was possible in more than half of patients with no early safety concerns.

Glioblastoma is the most common and aggressive primary brain tumour in adults. Standard treatment methods include surgical removal of cancer followed by chemotherapy and radiotherapy; however, effectiveness of therapy remains prohibited. This is primarily due to the tumour's heterogeneity and the limited accessibility through the blood-brain barrier. The development of a sensitive theranostic probe for the early detection of glioblastoma cells and drug transport is therefore crucial. Recent studies on glioblastoma imaging using Technetium-99m (99mTc) SPECT radiotracers show encouraging results for early-stage tumour visualisation. At the same time, temozolomide (TMZ) is the main drug used in chemotherapy. Based on the above the primary aim of this study is to develop an innovative theranostic molecule inspired by tetrofosmin. More specifically the compound bears two temozolomide elements and one chelating agent loaded in a triazine based multifunctional substrate designed for the concurrent targeted diagnosis and treatment of glioblastoma. The diagnostic function relies on a tetrofosmin derivative labeled with 99mTc, while the therapeutic component is provided by TMZ, also serving as the drug-transferring vehicle. Acknowledgements:This study has been supported by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: TAEDK-06189/T2EDK-0326, Acronym: Glioblastoma).

Glioblastoma (GBM) is a brain tumour that poses various challenges for its treatment. Its irregular morphology complicates the complete surgical resection, making the use of excel imaging agents necessary to achieve a more precise, real-time visualization during surgery. At the same time, the effectiveness of temozolomide (TMZ), the standard glioma treatment, is restricted by the presence of the blood–brain barrier (BBB) and blood–tumour barrier (BTB), which impede drug delivery to the brain. Angiopep-2, a peptide capable of crossing these barriers via receptor-mediated transcytosis (RMT), shows promise but faces limitations, including susceptibility to enzymatic degradation, the variable receptor-dependent efficiency and insufficient brain selectivity. This study presents the development of novel bioconjugates designed to address these challenges and improve glioma treatment. These bioconjugates incorporate peptide transporters for the targeted delivery of antitumor cargos, like TMZ, into the brain and are functionalized with chelating agents that bind terbium, lutetium or gallium-68 enabling both therapeutic and diagnostic applications. Preliminary cellular uptake experiments demonstrated efficient membrane penetration of the peptide carriers without cytotoxicity in T98 cell lines. Planned studies include monitoring the BBB penetration ability of the conjugates, as well as antitumor efficacy, and biodistribution of DOTA-radiolabelled conjugates in preclinical models. Concluding, the synthesized conjugates are anticipated to act as theranostics, allowing for both the treatment and the effectiveness of diagnostic imaging of glioma. Acknowledgements:This study has been supported by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: TAEDK-06189/T2EDK-0326, Acronym: Glioblastoma).

Effective treatment of cancer, especially in challenging cases like glioblastoma, mainly depends on the utilization of specific tools that can identify and accumulate into cancer cells while maintaining cytotoxic properties. This approach facilitates an initial diagnosis followed by targeted toxicity to cancer cells via chemotherapy and/or radiation. Real-time monitoring of these interactions shed light into the mechanisms of action, as well as valuable data for assessing treatment response and evaluating the efficacy of preclinical anticancer drugs. Herein, a promising cyanine-based probe with a positive charge, designed for mitochondrial targeting due to the overexpression of mitochondria in glioma cells, and fluorescence in the rear infrared, is presented. This probe is strategically designed to enable the study of mitochondrial metabolism in two axes. The first one relies on fluorescence intensity increasing in response to rising environmental viscosity and the second one in its fluorescence responds to specific metabolites. Additionally, a glucose moiety has been incorporated into the molecule to facilitate preferential uptake by cancer cells through GLUT receptors. Another crucial feature of this probe is its integrated chelating substituent, which enables binding to the Auger-emitting radioisotope Terbium-161 (161Tb). 161Tb binding not only facilitates the receiving of high-quality SPECT imaging but also imparts therapeutic potential to the molecule through β-particle and Auger electron emissions. Therefore, we have designed, synthesized, and characterized a multifunctional theranostic tool that enables dual imaging capabilities (FL-SPECT) at both preclinical and clinical levels, while through irradiation this tool can enhance cytotoxicity specifically in targeted cancer cells. Acknowledgements This study has been supported by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: TAEDK-06189/T2EDK-0326, Acronym: Glioblastoma).

One of the most common and aggressive forms of cancer is Glioblastoma. Being a form of brain cancer, imaging and treatment options are limited. Recent research about the chelating agent DOTA shows that DOTA-conjugated compounds can be used in imaging and targeted radiotherapy. Herein, we designed and synthesized three novel napthalimide based compounds conjugated with DOTA that can be promising theragnostic agents. Naphthalimide’s fluorescence and the radiation of the conjugated radiometal Terbium-161 (161Tb)enable these compounds to function as dual imaging probes that selectively target cancer cells. Additionally, the ability of naphthalimide to intercalate DNA increases cytotoxicity and improves their therapeutic properties against glioma cells. Acknowledgements This study has been supported by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: TAEDK-06189/T2EDK-0326, Acronym: Glioblastoma).

Glioma belongs to the category of primary brain tumors that stem from the glial cells. Amongst them the worst of all is glioblastoma, with a median survival rate of 14,6 months post-diagnosis. The main problem for traditional therapies is that not enough drug reaches the target, due to insufficient crossing of the BBB. To address these challenges, a novel peptide-carrier was developed based on an existing peptide already known in literature for its ability to interact with glioma specific surface receptors as also for its BBB penetrating properties. Several strategic modifications were made in order to enhance its stability, efficacy and functionality, turning it into a multifunctional theragnostic agent. Key modifications included the replacement of several amino acids that could be cleaved by proteases with other hydrophobic, non-natural to the human body amino acid residues to enhance the peptide’s stability, while preserving those that were crucotaial for the interaction with the surface receptors on the targeted tumor site. Further modification was the addition of another peptide consisting of 5 amino acids to the sequence, also already known to interact with specific proteolytic enzymes and surface receptors that are overexpressed on tumor sites and can help them facilitate intracellular delivery of the cargoes. The peptide so far was functionalized to carry two cytotoxic agents, one on its BBB permeability site and another onto the site designed for specific proteolytic cleavage and receptor-mediated endocytosis. Last, was the addition of a chelating agent known as DOTA, which is capable of binding Terbium-161 (161Tb). 161Tb provides therapeutic benefits since it emits Auger electrons and beta particles, while its gamma radiation supports diagnostic imaging. This multifunctional theragnostic agent, which offers improved BBB penetrating properties, enhanced stability, tumor specific delivery of therapeutics and real-time imaging capabilities, is expected to be a significant advancement in glioblastoma treatment. Acknowledgements This study has been supported by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: TAEDK-06189/T2EDK-0326, Acronym: Glioblastoma).

Meningiomas constitute the most frequent central nervous system tumor in adults. SPECT and PET, may provide the metabolic profile of these tumors. Herewith, we performed the first meta-analysis of SPECT for the prediction of meningioma grade. This systematic review and meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The MEDLINE, Scopus and Cochrane databases were systematically searched. The search yielded 93 results from the Medline (n=46), Scopus (n=44) and Cochrane (n=3) databases, which were screened by title and abstract. Twelve articles were retrieved for full-text review. After excluding the studies that did not include patients with meningioma, did not provide data for tumor grade and also did not allow the calculation of diagnostic accuracy, four cohort studies and no randomized trials were considered eligible for the quantitative analysis. The pooled sensitivity was 90% (95% CI: 72%-97%) and the pooled specificity was 91% (95% CI: 67%-98%). The diagnostic odds ratio was 87.95 (95% CI: 9.2-834.4), the positive likelihood ratio was 9.71 (95% CI: 2.24-42.15) and the negative likelihood ratio was 0.11 (95% CI: 0.03-0.36). Based on the results so far SPECT has high sensitivity and specificity for the detection of meningioma grade. Acknowledgement This program is co-financed by the European Union (European Social Fund- ESF) and Greece through the Operational Programme “Human Resources and Social Cohesion”, “ΕΣΠΑ 2021-2027”, in the context of the project “Support for Internationalization Activities of the University of Ioannina, Neurosurgery Novel Advancements”– MIS: 6004807.

Meningiomas are usually benign, slow growing neoplasms that arise from meningothelial cells and constitute the most common primary central nervous system (CNS) tumors. They can be observed or preferentially treated with gross total resection or radiosurgery showing similar and good outcomes. Meningiomas with complicated histology or in compromising locations have proven to show more symptoms, but there are no specific predictors of spreading capacity, with reports that show a frequency of metastasis of about 1%. We present the case of a previously healthy woman, that presented with lung lesions that turned out to be metastatic spread of a benign meningioma. A previously healthy, 64-year-old female came into our consult due to abnormal findings on a chest computed tomography(CT) scan during a SARS COV-2 infection follow up. She had no oncologic family history and had a light past smoking habit, with no other relevant medical background. From the beginning, she denied respiratory symptoms, aside from a mild SARS COV-2 infection in the previous month, and didn´t presented any neurological symptoms, weight loss or fever. Chest CT scan revealed a nodule located in the left inferior lobe and another one in the cardiophrenic angle, adjacent to the left cardiac atrium. In sight of a high suspicion of malignancy, we solicitated an 18-Fluorodeoxyglucose (18-FDG)positron emission tomography (PET-CT) scan which reported a 29 x 16 mm extra-axial, solid lesion in the left posterior cranial fossa, exhibiting remodeling of the inner surface of the occipital bone associated to increased metabolism (SUVmax: 8.7); 28x22 mm subpleural solid nodule in the medial segment of the right middle lobe, reaching the pericardium, with an inner calcification (SUVmax:4.5); 21 x 15 mm solid nodule in the left antero-medial basal segment (SUVmax: 3.7) [Figure 1]. MRI was also performed, noting a T1 isointense, T2 and FLAIR hetegeneous area located in the subdural region on the left occipital bone, showing homogeneous intense contrast enhancement and noticeable bone involvement [Figure 2], with approximate dimensions of 22.8 x 24.2 x 25.4 mm, compatible with a meningioma. As of those findings, the patient underwent a CT-guided lung biopsy that reported a mesenchymal lesion consistent with a lung meningioma.We approached the patient about the oddity of the diagnosis and offered a surgical resection of the lesions to confirm it, however she decided to have only the lung ones resected.

Background Stereotactic radiosurgery (SRS) for vestibular schwannoma can lead to irreversible hearing loss, mainly due to irradiation-induced damage to the nearby inner ear. Currently, no preventive or therapeutic options exist, highlighting the need for the development and experimental testing of novel treatments. To enable this research, we developed a protocol for inducing unilateral hearing loss in mice through targeted unilateral cochlear irradiation. Methods We used 6-week-old C57BL/6J mice to administer precise unilateral irradiation in the vicinity of the cochlea using a Leksell Gamma Knife Icon device. The precision and reproducibility of the targeted area were ensured through radiological imaging for each mouse using the integrated cone beam CT scan and co-registering these images with MRI and CT mouse atlas images. To ensure meaningful translational data, we placed a single isocenter lateral to the cochlea with the 80% isodose line passing through the medial edge of the cochlea to deliver 8 (n=3), 16 (n=5), 24 (n=8), and 32 (n=8) Gy. Hearing was assessed using auditory brainstem responses. Results In all experimental groups, the irradiation dose received by the non-irradiated cochlea was less than 15% of that received by the irradiated cochlea. In the 32 Gy group, irradiation of the cochlea yielded significant unilateral hearing loss at 22.6 and 32 kHz on day 7 and to a greater degree on day 28. Similar but less pronounced effects were observed in the 24 Gy group. No hearing loss was detected in the 8 and 16 Gy groups. The histological analysis corroborated these functional changes. In the 32 Gy group, quantification analysis of the outer hair cells (OHC) found a loss, only in the irradiated cochlea, of an average of 44% and 14% at the cochlea frequency regions of 45 and 32 kHz, respectively. In the same experimental group, counts of CtBP2-positive puncta per inner hair cell (IHC) yielded an average reduction of 35% at the irradiated cochlea when compared to the non-irradiated cochlea at both the basal and apical turns. Comparable yet less marked histological findings were noted in the 24 Gy group. Conclusions Targeted near-cochlear irradiation in mice induces unilateral dose-dependent high-frequency hearing loss associated with OHC loss and a reduction of CtBP2-positive puncta per IHC. This model provides a valuable tool for exploring the radiobiological mechanisms underlying SRS-induced hearing loss and for testing potential radioprotective agents.

Introduction and Objectives: The Leksell Gamma Knife lightning is a novel dose optimization software generating superior treatment plans by using large number of isocenters (2-3 times higher compare to the previous plans) often with very short beam on times (less than 0.5 min). Thus issue of end effects and verification of dose delivery by End-to-end test becoming more important. Methods and materials: The PTW 31010 ion chamber and a Solid Water phantom were used for end effects assessment. The 16 mm collimator, 15 Gy to 50% and all isocenters positioned at the center of the phantom (100, 100, 100) were used. Multiple plans consisting of 1-50 shots were generated and delivered for the same prescription and the absorbed dose measured. Corresponding beam on time varied from 10.2 minutes for 1 shot to 0.2 minute for 50 shots. End-to end tests or dosimetry audits for Lightning were performed by two institutions: National Radiation Protection Institute, Prague, Czech Republic (NRPI) and The MD Anderson Dosimetry Laboratory (MDADL), Houston, USA. Measurements were made in two phantoms: 1) adapted anthropomorphic Alderson Head phantom (NRPI) and 2) Stereotactic Radiosurgery Head phantom from MDADL. Mean dose in two spots was measured by Exradin W1 plastic scintillator detector in the NRPI phantom. Gafchromic EBT3 film was positioned between two layers of the phantom. The MDADL head phantom consisted of imaging insert with nylon ball target for treatment planning imaging and then the insert was exchanged to a dosimetry insert with two TLDs and two Gafchromic films. Results: It was observed that the absorbed dose decreases with increasing number of isocenters for end effects measurement showing that the effect is slightly “overcompensated”. Deviation in dose between one and fifty shots was -0,75%. Deviation in mean dose measured by W1 detector in two positions in the NRPI phantom was -2.9 % and -0.7 %, respectively. Gamma passing rate for absolute dose distribution measured by film was 99.1 % (4 %/3 mm) and 98.5 % (3% / 3 mm). Deviation in mean dose measured by two TLD capsules in the MDADL phantom was 0.45 % and -0.04 %, respectively. And gamma passing rate for absolute dose distribution measured by two films was 100 % and 99% for (5 %/3 mm). Conclusion: End effect is measurable and is overcompensated by the software. End-to-end tests showed good agreement between planned and delivered dose for both absolute point dose and 2D dose distribution.

Purpose/Objectives: Radiosurgical treatment of trigeminal neuralgia (TN) is the most common procedure in functional radiosurgery in order to modulate refractory pain. The aim of this study is to describe the clinical results and dosimetric parameters of the first series of patients with TN treated with ZAP-X gyroscopic frameless radiosurgery (GRS), an innovative, frameless radiosurgical device. Material/Methods: 30 patients with TN received GRS between February 2023 and January 2025. Treatment plans were developed delivering a maximum dose of 90 Gy in a target that covered a 5-mm segment of the trigeminal nerve in the retrogasserian location using a single isocenter (5 mm collimator). Clinical and treatment information were analyzed with specific focus on demographic characteristics, etiology, previous treatments, Barrow Institute (BNI) Pain Intensity Scale before and after GRS (pain relief response), the time to pain relief, the rate of complications and recurrences. Results: 30 patients (21 females and 9 males) with a median age of 66 years (range 31-92 years) underwent GRS for refractory TN. Half of the series (15 patients) had not an established etiology (idiopathic), 6 patients developed the TN after a dental procedure, 4 patients related to benign tumors with nerve compression, 3 patients had multiple sclerosis, one patient developed TN after a meloplasty and one patient after trigeminal herpes zoster. Median time from first diagnosis to GRS was 4 years (range 6 months – 18 years). All patients had received a first therapeutic pharmacological line, 15 patients received at least a radiofrequency thermocoagulation, 7 patients received nerve blocks, 4 patients were treated with botox injection and 2 patients had a previous radiosurgery. Median BNI Pain Intensity Scale before GRS was IV (range IIIa-V). Median treatment time was 37 minutes using a median of 221 beams. Median V12 and V10 of the brainstem were 0.04cc (range 0-0.16cc) and 0.07cc (range 0-0.24cc), respectively. Median BNI Pain Intensity Scale after GRS was II (range I-VI) with 80% of patients reporting no pain or occasional pain without medication. Median time to pain relief was 15 days (range 1-60 days). 5 patients (16,6%) presented ipsilateral facial hypesthesia after GRS. 10% of patients presented with recurrent pain 2 to 6 months after GRS. Conclusion: GRS is a precise tool for the treatment of TN showing safety and effectiveness in the first series of patients reported so far.

Title SMART (TROG 23.02): a multi-centre prospective trial of single versus multi-fraction preoperative radiosurgery for patients with brain metastases Background: Preoperative radiosurgery (PreOp-SRS) for brain metastases (BM) is increasingly utilised supported by large multi-institution retrospective and prospective non-randomised reports with results from recruiting phase III trials awaited. Most of the prospective protocols and reported data involves single fraction PreOp-SRS. Retrospective results suggest that multi fraction PreOp-SRS may have some benefits compared with single fraction PreOp-SRS Objective: The study will prospectively compare single- and multi-fraction PreOp-SRS for BM in a randomised fashion evaluating if multi fraction PreOp-SRS results in higher local control (LC) rates than single fraction PreOp-SRS Methods: SMART is a randomised phase II prospective clinical trial sponsored by the Trans-Tasman Radiation Oncology Group (TROG). Up to 73 patients with histologically confirmed primary cancer diagnosis and radiologically confirmed BM who have been recommended surgery for up to two BM will be eligible. Exclusion criteria include index lesion > 4cm, neurological symptoms mandating emergency surgery, prior whole brain radiotherapy or SRS to the index BM(s) or presence of leptomeningeal disease (LMD). Eligible patients will be randomised to single fraction (15-20Gy) or 3 fraction (24 or 27 Gy) PreOp-SRS followed by surgical resection of the BM ideally within 7 days up to maximum 14 days after SRS. All patients will undergo Magnetic Resonance Imaging (MRI) of the brain within 1 day after surgery then reviewed clinically and with MRI 3 monthly for 12 months. A 2:1 randomisation will be performed using the method of minimisation to optimise balance between the stratification factors and desired allocation ratio. Primary endpoint will be measured as cavity LC at 12 months after surgery. Secondary endpoints include overall survival, neurological death, LMD, adverse events and QOL Discussion: PreOp- SRS is increasingly utilised however evidence for the most optimal fractionation schedule from prospective randomised trials is lacking. Retrospective data suggest that the therapeutic ratio may be improved when 3 fraction SRS is delivered. This will be the first prospective randomised study to compare single fraction with multi fraction PreOp-SRS. Seed funding has been obtained allowing the opening of the study in a select number of centres in 2025

Background Gamma knife stereotactic radiosurgery (GKRS) is recognized as an effective and safe alternative treatment for skull base tumors and trigeminal neuralgia. This study aims to evaluate the efficacy of targeting both tumor and trigeminal nerve in a single procedure for patients with benign tumor-related trigeminal neuralgia. Methods A retrospective study was conducted on 44 patients with benign tumor-related trigeminal neuralgia who underwent GKRS targeting both tumor and trigeminal nerve in a single procedure between December 2016 and December 2022. The cohort included 30 meningiomas, 9 vestibular schwannomas, and 5 trigeminal schwannomas. The median tumor volume was 3.62 mL (range: 0.14–20.74 mL). The median radiation dose was 12–13.4 Gy for the tumors and 88.9 Gy (range: 85–90 Gy) at the 100% isodose line for the trigeminal nerve. The facial pain before and after GKRS was assessed using the Barrow Neurological Institute (BNI) pain intensity scale. Results Following GKRS, 38 patients (86.4%) experienced significant pain improvement, with a median latency period of 2 months (range: 0.3–12 months). Sixteen patients (36.4%) experienced a relapse at a median time of 6 months (range: 1–30 months) post-GKRS. After a median follow-up time of 31.9 months (12.1–77.3 months), 22 patients (50.0%) continued to experience durable pain relief. Fourteen patients (31.8%) developed GKRS-related complications, most of which fully resolved, except in 3 patients (6.8%) who experienced permanent facial hypoesthesia. Tumor control rate was 86.2%. Conclusions GKRS targeting both the tumor and trigeminal nerve in a single session demonstrated favorable outcomes in terms of pain relief and tumor control in patients with benign tumor-related trigeminal neuralgia.

Rationale: Intracranial metastases are the most common malignancies, thereby representing the most frequent neurological complication of systemic cancer. Brain metastases (BM) are found in up to 40% of all cancer patients and impact their quality of life and survival. Stereotactic radiosurgery (SRS), which delivers high doses of radiation focally to the tumor, is the preferred treatment for these patients. The main challenges with SRS include determining whether the tumor is responding early after the treatment, and managing radiation-induced late effects as it’s difficult to differentiate radiation-induced changes from tumor progression using conventional MRI. Purpose: The purpose of this work was to determine the predictive value of saturation transfer MRI in brain metastasis treated with SRS. Saturation transfer MRI has been used to assess BM in the past. This study is the first in the literature to probe the efficacy of this method at higher magnetic field. Patients: 17 patients with BM were recruited in the study and were scanned at 7 Tesla MRI system (GE) at minimum 3 time points: pretreatment, one week and one month post. Methods: Saturation transfer spectra were collected in two different regimes: Chemical Exchange Saturation Transfer (CEST,at radiofrequency power, RF of 0.52 μT and low frequency offsets) and Magnetization Transfer (MT – RF of 1 and 3 μT and high frequency). In addition, T1 and T2 relaxation were also measured. Multiparametric maps were calculated from relaxation and saturation data and yielded quantitative MRI CEST and MT parameters. These parameters were compared between lesions that were successfully treated (group A,tumors shrank within one month) and the ones for which treatment failed (group B). Results: 9 out of 17 lesions were treated successfully. Significant differences between groups were observed for two MRI parameters: Magnetization Transfer Ratio (MTR) at -3.5ppm (Amide Proton Transfer,APT) and MT exchange rate constant. Both parameters at baseline were approximately two times lower for group A than group B. Moreover, for group B, both APT and MT parameters decreased slightly after treatment while APT for group A increased after one week of treatment and MT exchange for this group remained unchanged. Conclusion: Saturation transfer metrics, specifically APT and MT exchange have a potential to predict the outcome of SRS in BM. Moreover, their changes during or post treatment may serve as a biomarker of treatment success.

Female, at the age of 15 underwent surgery for a Breslow 2 mm Clarck III cutaneous melanoma on the right arm with 1 mm margin. Sentinel lymph node biopsy was performed in the right axilla with negative results in 3 resected lymph nodes. Two years late, she had a seizure, was studied and multiples metastases were observed (lung, adrenal, liver, spleen and brain). A brain MRI was performed and 7 lesions were seen. After a few days, treatment with immunotherapy began (ipilimumab 3 mg/kg and nivolumab 1 mg/kg). Two weeks later she presented pain in the right hypochondrium and fever. Elevation of liver enzymes x10 was evident. Infectious and immunological causes were ruled out and it was assumed to be moderate toxic hepatitis related to the systemic treatment received. She was hospitalized, received more steroids and showed improvement. Then she received brain fractionated radiosurgery with ALE and Frame-less system, 2 isocenter, 5 fractions of 6 Gy. The 7 known brain lesions were treated. After that she received the second cycle of monoclonal antibodies and 21 days later the third cycle. Liver enzymes rose again (GOT x10 and GPT x25). She received corticosteroid treatment, managing to normalize everything within a month. The option of a new treatment attempt with monoclonal antibodies was rejected. A month later, she had a new seizure episode that required increasing the dose of the anticonvulsant and steroids. The control brain MRI showed a considerable decrease in the size of the treated lesions and no new lesions were described. The lesions showed enhancement with intravenous contrast, and were surrounded by little edema. After a few days she received only one cycle of nivolumab and 2 weeks later she again had elevated liver enzymes. Treatment with steroids was started and the liver condition resolved after a month. 16-month post brain radiosurgery, in the brain MRI, lesions were no longer seen or described, achieving complete cerebral response. An FDG PET CT SCAN was also done and no highlight areas were described. She has currently been free of illness for a year. Conclusion: Melanoma-related brain metastases are a real challenge for fractionated brain stereotaxic radiosurgery. Monoclonal antibodies today are the best therapy that can be offered to a patient with this diagnosis and this extent of the disease. Not only the description of the Abscopal effect but also the most recent publications explain and demonstrates this synergy

Stereotactic radiosurgery (SRS) is an effective treatment of trigeminal neuralgia (TN). Variations in dose delivery rate associated with total treatment time have been reported to affect the biological effectiveness of cobalt-based radiosurgery. In this study, we aimed to quantify the range of treatment delivery times in CyberKnife radiosurgery (CKRS) for TN and investigate its impact on the treatments’ bio-efficacy using the concept of biological effective dose (BED). Treatment data of patients undergone CKRS for TN were retrospectively reviewed from the participating centers. Planning details were extracted from XML files stored in the CK database following treatment completion. For each case, time-resolved dose and dose-rate distributions were calculated per beam for every voxel comprising the target and brainstem using a ray tracing-based dose calculation algorithm developed in-house. BED distributions accounting for sublethal damage repair effects (BED_SRE) were obtained for both the target and brainstem along the lines described in Moutsatsos et al 2022 (Phys Med Biol 2022, 67, 135004). Studied variables included treatment delivery time, beam-on-time, target volume, prescription dose, maximum, minimum, average, and integral taget doses, as well as corresponding BED_SRE data. Planning data of 199 patients were evaluated and statistical analysis results are summarized in Table 1. The median age of patient cohort was 67 years, with a male to female ratio of 9/11. 56% of the patients had right and 44% left trigeminal neuralgia. Treatment was delivered using CK system models equipped with linear accelerators of nominal output rates of 800 and 1000 MU/min. A median dose of 60 Gy was prescribed at the periphery of the delineated nerve, having a median volume of 22 mm3. The median maximum and minimum dose values were 71.4 Gy and 59 Gy, respectively. All treatment plans used the 5 mm fixed cone. A median treatment delivery time of 43 min (range: 27 – 97 min) with median bean-on-time equal to 27 min (range: 17 – 42 min) was recorded. A strong linear correlation between integral BED_SRE and integral dose was found (Figure 1). Treatment delivery time varied significantly among the different plans, ranging from 27 min to nearly 97 min for the same physical dose of 60 Gy. This variation correspondingly affected the BED_SRE delivered to the target. The Integral Dose data can be used to estimate the Integral BED_SRE using the proposed linear function.

Purpose: Leksell Gamma Plan (LGP) Fast Inverse Planning (FIP) optimizer, known as Lightning, was introduced in 2020. Since then, Lightning has been shown to generate plans with metrics comparable to or better than manually optimized plans with reduced planning time and inter-planner variability. After rigorous testing, Lightning was adopted clinically at our institution in 2021. The objective of this study is to retrospectively review the patterns of Lightning use at our institution. Methods: 1,858 lesions (mean vol=0.903cc, [0.001cc,38.298cc]) planned and treated with LGP (v11.3.2) from March 2022 to December 2023 were analyzed. Planning techniques, target coverage, and Paddick conformity index (PCI) for each lesion were tracked from the clinical plans. Planning techniques included Lightning only (LT), Lightning with manual tweaks (LT-MT), and Manual planning (MP). Lightning plans were reviewed visually and when necessary, modified by adding shots, adjusting prescription isodose line, shot position, weight, or sector collimator size to achieve the desired dose distribution. LT-MT and MP lesions were replanned using similar parameters with Lightning LGP(v11.4.2) only. Differences in target coverage and PCI between the clinical plans and Lightning replans were recorded. Wilcoxon signed rank test (p <0.05) was performed to establish significance. Results: Of 1,858 total lesions, 1,314 lesions (70.7%) were clinically planned using Lightning and 1,227(93.4%) of these were manually tweaked. When compared to the LT replans, 90.1% of LT-MT group showed improvements in coverage(47.1%), PCI(18.2%), or both coverage and PCI (24.8%). In contrast, 9.9% of the LT-MT showed similar or worse coverage or PCI compared to LT replans. In the manually planned 544 lesions (29.3%), 94.5% showed increased coverage (35.1%), PCI (17.1%), or both (42.3%), compared to LT replans while 5.5% showed similar or worse coverage or PCI. Mean improvement in coverage and PCI were 0.30±0.30%, p< 0.01 and 0.05±0.04,p<0.01 for LT-MT, respectively and 0.40±1.40%,p<0.01 and 0.08±0.07,p<0.01 for MP, respectively when compared to LT replans. Conclusion: Lightning was widely utilized in our institution, although many of the Lightning plans benefited from manual tweaks resulting in improved coverage or PCI in >90% of plans. More than 90% of manual plans also showed improved coverage or PCI when compared to LT replans, indicating that in certain conditions manual planning may still outperform Lightning.

Brain metastases are associated with a worse prognosis and considered a major cause of cancer morbidity and mortality. Objectives - The use of stereotactic radiosurgery and fractionated stereotactic radiotherapy to determine response rates in patients diagnosed with different histological types of primary tumors with brain metastases. Methods - In this pilot study, 21 patients aged 38 to 82 (median age 69) were treated with linear accelerator-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) for brain metastases secondary from lung, breast, colon adenocarcinoma, malignant melanoma, sarcoma and seminoma. These patients were treated from January to December 2022. Patients were treated with a median dose of 24 Gy (range 15 to 30 Gy) in 3 fractions (range 1 to 5). Median follow-up after SRS or fSRT was 7 months (range 1–36 months). Results - Complete response was achieved in 22% of patients with breast cancer, lung cancer, sarcoma and seminoma, with no statistical difference between histologies. Partial response was achieved in 22% of patients with lung cancer and malignant melanoma, also with no statistical difference between groups. In the remaining patients (56%) brain metastases stabilized (17%), remained unchanged in 28% of patients, and progressed in 11% of patients, regardless of the histological type of the primary tumor. Conclusion - In our pilot study, we were unable to determine which histological type of primary tumor with brain metastases had the greatest benefit from SRS or fSRT.

Introduction: For large brain metastasis (≥2cm), staged stereotactic radiosurgery (SSRS) is used to improve control rates over single fraction SRS alone. However, perfusion MRI metrics measured throughout treatments and their association with local failure (LF) and radiation necrosis (RN) risk have yet to be evaluated. Methods: Patients treated with SSRS (15Gy per session) with perfusion imaging from 2017-2023 were included. Primary endpoints were disease control (DC, stable disease, partial and complete response) and development of RN, recorded on a per-lesion basis. Tumor volume (TV) (cc) and mean relative-cerebral-blood-volume (rCBVmean) were extracted from MRI scans (baseline (before 1st SSRS), interim (before 2nd SSRS), post-treatment (8 weeks after 2nd SSRS)). Comparisons were made between DC vs. LF and RN vs. RN-free cohorts using Kruskal-Wallis, statistical significance at p<0.05. Results: 30 patients (39 lesions) met inclusion criteria. Median TV: 5.6cc.(range: 1.2-27.8cc.) with primary histology of lung (47.5%) and breast (20.0%) cancer. 5.2% had LF, while 20.5% developed RN, with median times to LF and RN of 6.5 (R: 2-11) and 8.5 (R:4–54) months, respectively. For DC vs. LF, median interim change in TV (ΔTV) was -53.2% [-61.4% to -31.6%] vs.+14.17% [-71.8% to 100.2%] p=0.70 and post-treatment ΔTV was -43.7% [-64.8% to -24.9%] vs. -42.2% [-47.39% to -37.1%], p =0.95. Similarly, for RN vs. RN-free cohorts, interim ΔTV was -27.6% [-53.0% to -15.7%] vs.-56.0% [-67.0% to -37.0%] p=0.05 and post-treatment ΔTV was -25.1% [-44.0% to -0.3%] vs.-47.4% [-65.5% to -30.5%], p=0.06. Median-rCBVmean for DC vs. LF: Baseline:2.47 [1.8 to 4.17] vs. 2.62 [2.47 to 2.77], p=0.82; Interim:1.77 [1.24 to 2.36] vs.1.49 [1.15 to 1.82], p=0.59; Post-treatment:1.41[1.08 to 2.16] vs.0.71[0.68 to 0.73], p=0.06. For RN vs. RN-free lesions, median-rCBVmean: Baseline: RN:2.34 [1.89 to 2.73] vs. RN-free:2.54 [1.91 to 4.58], p=0.31; Interim: RN:1.82 [1.44 to 2.06] vs RN-free:1.74[1.20 to 2.46], p=0.93; Post-treatment: RN:1.26[0.93 to 1.57] vs. RN-free:1.41[1.07 to 2.20], p=0.50. Conclusions: Lesions that developed RN exhibited less TV reduction on the interim MRI scan. Although rCBVmean decreased with treatment in most lesions, no clear correlation with clinical outcomes was observed. Larger studies incorporating refined perfusion analysis and advanced imaging techniques, such as novel PET tracers, are necessary to further clarify the prognostic value of these metrics.

PURPOSE: Predicting local failure (LF), distant intracranial failure (DIF), and Radiation necrosis (RN) after stereotactic radiosurgery (SRS) requires consideration of numerous variables. The study objective was to evaluate machine-learning (ML) algorithms to accurately predict LF, DIF, or RN using relevant patient, disease-specific, and treatment-related factors. METHODS: Patients with small brain metastases (≤2 cm max dimension) treated with single fraction SRS (20-24Gy) between 2017-2021 were included. Key variables used were age, gender, race, Karnofsky Performance Status (KPS), pathology, # of lesions, Paddick conformity index (PCI), target max dose, max dimension(cm), and post-SRS systemic therapy (immunotherapy, targeted therapy, or chemotherapy). Python’s ML library SciKit Learn was used to evaluate ML algorithms including logistic regression (LR), support vector machines (SVM), and random forest (RF) to predict the risk of LF, DIF, and RN (independently). A stratified 5-fold internal cross-validation 80%/20% training/test split with GridSearch was used to identify optimal hyperparameters for each metric evaluating the model at the lesion-level. Jaccard index (JI), F1-score (F1), and accuracy (acc) averaged across the folds for the training set and once for the test set were measured. RESULTS: Data from 1566 brain metastases in 235 patients were included. Median age was 64 years (R:18-90) and 64% were female. Median KPS was 90 (R:50-100) and median # of lesions/patient was 9 (R:1-28). The RF model achieved the highest performance for DIF [acc=0.91, F1=0.94, JI=0.86] and LF [acc=0.94, F1=0.61, JI=0.43]. For RN, all models achieved similar acc (0.96) however, had low F1 and JI (JI=0.07-0.13 & F1=0.13-0.24), indicating that the models struggled to correctly identify the minority class (RN+), resulting in poor performance metrics despite high acc scores (Training:45 RN+/1207 RN-; Testing:11 RN+/303 RN-). Top 5 important features from RF model F1, for DIF were # of lesions, age, target max dose, PCI, and KPS and LF were # of lesions, target max dose, prescription isodose, and GTV size. CONCLUSION: ML models demonstrated superior classification for DIF treated with SRS and contemporary systemic therapies, largely due to the greater number of DIF events. Limited data for LF and RN led to high acc but lower F1, underscoring the need for larger, more balanced datasets to enhance predictive accuracy in future clinical applications.

Purpose/Objective: Our department performs radiosurgery on multiple targets of reduced dimensions in a single isocenter (SRS-SIMT). This work aims to implement the off-Axis Winston-Lutz (OAWL) test on the department’s linear accelerators to measure delivery accuracy with different gantry, collimator and couch rotations (GCC). The goals are to 1) evaluate if the deviation between the radiative and mechanical isocenter for different targets (isocentric and off-axis) is less than 1mm (tolerance); 2) find out if it is necessary to establish a limit on the target-isocenter distance for clinical plans; 3) select the most suitable accelerator for SIMT plans; 4) study the sensitivity of the OAWL. Material/Methods: Tested linacs were 1) Varian Edge HD-MLC (2014), 2) Varian TrueBeam HD-MLC (2012) 3) Varian TrueBeam Millenium 120MLC (2018). The MultiMet-WL SunNuclear® phantom was used (Fig.1a). It contains an isocentric target and five off-axis targets distanced up to 7 cm from the isocenter. The phantom was irradiated, over the MV imager, using the manufacturer's OAWL test with 15 different GCC combinations. The MV images were collected (Fig.1b) and analyzed in MultiMet-WLQA-v2 software. Sensitivity tests, with translational errors in the positioning of the phantom from 0.5 mm to 2 mm and rotational errors between 0.5º and 2.0º in GCC rotations, were irradiated and the respective images analyzed using the same software. Results: In seven months, the original OAWL test was run 21 times. The average field-target coincidence deviations for all targets and GCC combinations are shown in Fig.1c. The isocenter had a lower average deviation (0.39±0.21 mm) than the off-axis targets (0.49±0.25 mm). Linac1 showed smaller deviations (Fig.2a), and the overall maximum deviation found was 1.28 mm. Deviations greater than 1.0 mm were 1.9% in Linac1 and Linac2 and 3.2% in Linac2, located at more than 5.8 cm from the isocenter. Forty-five sensitivity tests were carried out. The introduced errors were detected in all linacs, the deviation from the field-target coincidence increased with the magnitude of the error and the off-axis targets presented a greater deviation compared to the isocentric target for same error (Fig.2b). Conclusion: A smaller tolerance (< 1mm) could be applied at the isocenter than off-axis. The tests allowed us to choose the most accurate linac (Linac1) to perform SRS-SIMT.

Background: Essential & Parkinsonian tremors significantly impair quality of life. Gamma Knife radiosurgery (GKRS) has been used to ablate the ventral intermediate nucleus (VIM) of the thalamus but traditionally requires rigid head-frame placement & long treatment times. This report examines a frameless, linear accelerator (LINAC)-based, virtual cone radiosurgery technique for thalamotomy. Methods: In this prospective, single-center, open-label trial, 40 patients with medically refractory tremor (36 with essential tremor & 4 with tremor-dominant Parkinson’s disease) underwent unilateral LINAC-based thalamotomy using a thermoplastic mask for immobilization. The isocenter was placed at the classical VIM location per Guiot’s diagram & shifted posteromedially if needed to ensure internal capsule dmax <26Gy. The primary outcome was percentage improvement in contralateral tremor severity per the Fahn-Tolosa-Marin (FTM) scale at 3, 6, & ≥12 months. Secondary outcomes included safety, patient satisfaction, & quality of life. Adverse events were prospectively collected & graded using the Common Terminology Criteria for Adverse Events (CTCAE). Wilcoxon signed-rank tests compared pre- vs. post-treatment scores, & linear mixed-effects models assessed tremor changes over time. Results: With a median follow-up of 26 months, 90% of participants achieved ≥10% improvement in global FTM score at 6 months (p<0.001). The mean decrease in total FTM score was 54.6% (SD 25.0%). Four patients (10%) experienced significant neurological side effects (dysarthria, focal hemiparesis) requiring medical therapy; these events emerged around 6 months post-treatment & generally improved with steroids or bevacizumab. Transient paresthesias were the most common minor side effect. Among the 4 patients with Parkinsonian tremor, similar tremor improvement was observed, though baseline severity was lower. A durable contralateral tremor reduction was noted compared to MR-guided focal ultrasound. Conclusions: Frameless, coneless LINAC-based thalamotomy is a safe & effective alternative to traditional frame-based or ultrasound-based procedures for medically refractory tremor. Its noninvasive thermoplastic mask setup & shorter treatment time may improve patient comfort & accessibility. Larger randomized studies, ideally with blinded tremor assessments, are needed to confirm these findings. Work is ongoing to enhance outcomes using personalized connectomic & tractography-based planning.

Aim: Worldwide, 3D magnetization-prepared rapid gradient-echo (MPRAGE) sequences are widely used to diagnose and monitor patients with brain metastases (BM). Recent data suggest that 3D spin-echo (SPACE) imaging provides better detection and visualization, particularly for small BMs. We hypothesize that earlier and more precise detection of BM using SPACE imaging, along with accurate treatment, may positively impact patient prognosis and reduce treatment-related toxicity. Methods: We evaluated intact BM comparing post-contrast T1-MPRAGE with T1-SPACE images in 51 patients with respect to the following; 1) tumor-enhancement contrast rate, contrast-to-noise ratio and visual prominence, 2) tumor volume (TV) delineation of the 3D “target” objects created for radiosurgery planning, 3) comparison of radiosurgery plans generated based on MPRAGE or SPACE. Results: An experienced neuroradiologist identified 188 BM in 51 patients in both imaging. The senior radiation oncology resident correctly detected 178 (94.6%) brain metastases on T1-SPACE and 155 (82.4%) on T1-MPRAGE. The contrast ratio (p<0,001; mean; 122,89 ±67,73 vs 67,72 ±43.48) and contrast-to-noise ratio (p<0,001; mean; 31,56 ±16,49 vs 21,76 ±14,37) values of the lesions were found to be statistically higher on T1-SPACE. In the qualitative assessment of images, T1-SPACE was assessed as higher frequency of excellent visual image quality (58% vs 6%), while good and poor image ratings were less common. The TV was found to be larger on T1-MPRAGE MRI (mean; 4,57 ±3,11 vs 4,79 ±3,13 cc). On the radiosurgery plan comparison, Brain V12Gy (mean; 5,72 ±3,35 vs 6,00 ±3,42 cc) and V10Gy (mean; 7,96 ±4,65 vs 8,30 ±4,71 cc) was significantly smaller with T1-SPACE. Contrary, gradient index was significantly higher with T1-SPACE planning (3,11 ±0,33 vs 3,03 ±0,26). There was no difference in brainstem Dmax and V10Gy between the radiosurgical plans. Conclusion: T1-SPACE may be superior in detecting BM. Since the final number of brain metastases can influence the decision between radiosurgery or whole-brain radiotherapy, and undetected metastases on MRI may later complicate the distinction between distant intracranial recurrence and progression of existing metastases, T1-SPACE could offer a clinical advantage. With improved visual image quality and contrast, T1-SPACE may enhance TV delineation, potentially impacting plan quality—particularly in relation to radiation necrosis risk surrogates such as V12Gy and V10Gy.

Trigeminal neuralgia (TN) presents a therapeutic challenge when pharmacotherapy fails. While Gamma Knife (GK) and CyberKnife (CK) radiosurgery are established modalities, direct comparisons of their clinical efficacy, toxicity, and dosimetric profiles remain limited. This study evaluates outcomes and technical nuances of GK and CK in TN management to guide personalized treatment decisions. We analyzed 117 patients with refractory classical and idiopathic TN treated between 2007–2024: 57 with GK (single 4-mm isocenter, median prescription dose 90 Gy) and 60 with CK (single fraction, median maximum dose 85 Gy). Primary endpoints included pain relief (Barrow Neurological Institute [BNI] Pain Intensity Scale) and durability (freedom from recurrence). Secondary endpoints were complications (facial numbness, anesthesia dolorosa) and dosimetric parameters. At median follow-up of 25 months (GK) and 36 months (CK), GK achieved higher rates of good pain relief (BNI I–III) at 6 months (76,9% vs 70%, p=0.04) and faster time-to effect (median 3 weeks vs median 13 weeks, p=0.028). Recurrence at 2 years was higher with Gamma-knife treatment (GK 34,7% vs. CK 15,6%). CK correlated with higher rates of facial numbness (32% vs. 14, 2%). No cases of anesthesia dolorosa were identified in either group. A method for dosimetric comparison of treatment plans for GK and CK was developed. To equate the planning features of different types of radiation therapy instruments, treatment plans were uploaded to an independent planning system where the comparison was performed. The aim of this method is to verify the different treatment methods for trigeminal neuralgia and to develop the same method for the two types of instruments. Comparison of doses delivered to brainstem, root entry zone, the length of cisternal part of TN, dose delivery in comparison to centro-periphereal junction location were also analyzed. The study underscores the importance of direct comparisons between GK and CK in managing TN. While GK offers faster and higher-magnitude pain relief with tolerable sensory toxicity, CK demonstrates lower recurrence rates but higher incidences of facial numbness. Dosimetry comparison studies are essential for refining our understanding of the strengths and limitations of each approach, ultimately reinforcing stereotactic radiosurgery (SRS) as a versatile and effective tool in TN management.

Objective: Solitary fibrous tumors (SFTs) constitute rare intracranial mesenchymal neoplasms with a high recurrence potential. Gamma Knife Radiosurgery (GKRS) has emerged as an effective adjunctive therapy for residual or recurrent intracranial and orbital disease following surgical resection. This study assesses the clinical and radiological outcomes of seven patients treated with GKRS at a single center, with particular emphasis on early tumor control and symptomatic response. Methods: Seven patients (mean age 35.1 years; range 10–60), including one pediatric case, underwent GKRS for histologically confirmed intracranial or orbital SFTs/HPCs or recurrent meningioma at the Dow Gamma Knife Radiosurgery Center, DUHS, Karachi, between February 2023 and February 2025. All patients had undergone prior single or multiple surgical resections, with varying degrees of conventional radiotherapy. GKRS was delivered in single or fractionated sessions (range: 13-14Gy in a single session and 25 Gy in five sessions for fractionated sessions, delivered at 50% isodose). Clinical and radiological follow-up was conducted using MRI brain with contrast at 3-6 monthly intervals. Results: At a median follow-up of 12.5 months (range 3–24 months), six of seven patients (85.7%) demonstrated radiographic regression of treated lesions. One patient exhibited disease progression at 17 months, necessitating consideration for re-treatment. Notably, a 10-year-old girl with orbital hemangiopericytoma and prior right eye enucleation received fractionated GKSRS (25 Gy in 5 fractions) and exhibited excellent clinical and radiologic response. Follow up MRI at 6 months revealed significant regression of the orbital lesion and the patient exhibited near-complete resolution of proptosis. Clinical improvements across the cohort included resolution of seizures, improved vision, reduced headaches, and functional gains. No radiosurgery-related complications were reported. The estimated 1-year progression-free survival (PFS) rate was 85.7%, and overall short-term survival remained 100%. No patient developed extracranial metastases. Conclusion: GKSRS appears to be an effective and safe modality for the treatment of residual or recurrent soft tissue sarcomas (SFTs) and hemangiopericytomas (HPCs), offering high short-term tumor control and symptomatic improvement in both adult and pediatric populations.

INTRODUCTION RN represents the most assessed late complication of brain SRT, resulting from RT-induced vascular changes. Its incidence depends on dosimetric and clinical factors. RN management includes observation, corticosteroids (CCS) or bevacizumab. We report the results from a mono-institutional case series of RN patients (pts) treated with bevacizumab. MATERIALS AND METHODS Pts with heterogeneous primary tumors who developed RN following Gammaknife Radiosurgery (GKRS) or Cyberknife (CK) for metastatic or recurrent brain disease and who received Bevacizumab were retrospectively collected. Dose, fractionation, RN site, prior RT and concurrent systemic therapies were recorded. Clinical data included symptoms, CCS use and Bevacizumab administration (dose, cycles, discontinuation). Radiological and clinical responses were assessed. RESULTS 19 patients (male:n=10; female:n=9) treated with SRT (August 2019- September 2024) were reported (Fig.1). Median age at diagnosis was 53.5 years (23-72). Primary tumors were NSCLC (n=7), CNS (n=6), SCLC (n=2), breast (n=2), cervix (n=1) and melanoma (n=1). GKRS (n=12, 63%) was mostly delivered as 24 Gy in single fraction (42%), while CK (n=7, 37%) as 25 Gy/5 fractions (43%). GKRS was prescribed to 50% isodose line, CK to 80%. RN, predominantly left-sided (58%), occurred supratentorially in 89% (n=17); 2 cases were infratentorial. 53% had prior RT (CNS tumor bed: n=5; WBRT: n=3; SRT: n=2). Median time to RN onset was 13.29 months (0.93-63.46); concomitant systemic therapy was given in 53% pts (immunotherapy:n=2; antibody-drug conjugate:n=1; targeted-therapy: n=3; chemotherapy: n=4). RN was detected by MRI in 18/19 cases and 53% developed symptoms. CCS were administered in 68%, most commonly dexamethasone 4 mg (50%). All pts started Bevacizumab (5 mg/kg q14) for a median number of 4 cycles (1-11). Median time from RN onset and Bevacizumab start was 1.1 months (0.5-3.93). No adverse events were reported; 2 discontinued due to progressive disease. Radiological response occurred (Fig.1) in 80% at a median time of 3.21 months (1.33-12.2), while 44.4% of symptomatic patients had clinical benefit at a median of 2.52 months (2.1-2.76). After a median follow-up of 8.18 months, 63% were alive. CONCLUSION Our series supports bevacizumab (5 mg/kg for 4-6 cycles) for RN patients, regardless of symptoms and CCS use. Key limitations include the lack of randomized data and a standardized efficacy assessment.

Introduction Optic nerve sheath meningioma is a rare tumor of predominantly adult age patients, including those with II neurofibromatosis, accompanied by decreased visual function and exophthalmos. Possible treatment options: dynamic observation, surgical resection or optic canal decompression, radiation therapy, and a combination of these methods. Radiation therapy can be recommended for patients with intact visual functions, no severe exophthalmos and trophic eye lesions. The classic fractionation mode is used as standard. In this study we present our experience of applying hypofractionated radiosurgery mode for optic nerve sheath meningiomas. Materials and methods 18 patients with optic nerve sheath meningiomas underwent hypofractionated radiosurgery on CyberKnife or Novalis between March 2010 and May 2020. Single focal dose was 5.5 Gy in 5 fractions up to total focal dose of 27.5 Gy. The sample enrolled 16 adults with median age 51 years; IQR 21 (range 25 – 70 years) and two children aged 8 and 14 years. The median tumor volume was 1.5 cm3 (range 0.34 to 6.49 cm3). Results Median follow-up was 57 months (range 11 to 102 months; IQR 49). Tumor growth control was achieved in all patients, partial response (≥40% volume decrease) was observed in 5 (27.8%) patients. There was no deterioration in visual function in any patient; improvement in visual acuity was noted in 6/14 (42.9%) cases. Visual field improvement was observed in 5 (62.5%) of 8 patients who initially had the ability to assess visual fields. After irradiation, exophtalmos size decreased by ≥ 1 mm in 7 (50%) out of 14 patients. Conclusion Stereotactic radiosurgery for optic nerve sheath meningioma in hypofractionated mode (5 fractions with 5.5 Gy) can be an effective and safe method of radiation exposure. Tumor growth control was achieved in all patients, and there was no deterioration in visual functions.

Purpose: To validate and compare the survival prediction performance of prognostic indices (RPA, BSBM, GPA, ds-GPA, SIR) in patients with brain metastases treated with SRS and/or WBRT. Introduction: Brain metastases occur in 20–40% of cancer patients, leading to reduced survival and cognitive decline¹. Advances in cancer therapies have extended survival, increasing brain metastasis incidence². This highlights the need for reliable prognostic models to support individualized treatment². The rise of SRS and molecular-targeted therapies has exposed limitations of traditional models, encouraging development of new indices incorporating molecular data¹˒³. Materials and Methods: This retrospective study included 116 patients treated with SRS or WBRT between 2020 and 2024. WBRT was delivered as 30 Gy in 10–12 fractions; SRS as 27–30 Gy in 3–5 fractions. Prognostic scores were calculated per original definitions; patients with prior cranial RT or surgery were excluded³⁻⁵. The primary endpoint was overall survival (OS). Cox regression and Kaplan–Meier analyses assessed prognostic factors and survival. Predictive power at 6 and 12 months was evaluated using ROC curves and AUC values. SPSS v20.0 was used; p<0.05 was considered significant. Results: Median age was 59; 59.5% were male. Lung cancer was the most common primary (68.1%). Among NSCLC patients, 73.4% had adenocarcinoma; 38 showed PD-L1 positivity and 4 had EGFR mutations. KPS ≤70, brain metastasis number, primary tumor type, and extracranial metastases were independently associated with OS (Table 1). Median OS ranged from 4–24 months by ds-GPA and 3–13 months by RPA (Figure 2). In the full cohort, BSBM and ds-GPA had the best predictive performance (AUCs: 0.930/0.899 and 0.892/0.931). In the SRS-only group, GPA and ds-GPA performed best (GPA: 0.984/0.910; ds-GPA: 0.949/0.843; Figure 2). Conclusion: All indices significantly stratified survival. BSBM was simple and effective, while ds-GPA offered more detailed evaluation. Its performance was limited in patients without targeted therapies. As SRS and molecular treatments become standard, accurate prognostic models are increasingly vital for personalized care. Future models should better integrate molecular and systemic factors.

Introduction: Epilepsy in the eloquent cortex may present several issues owing to the critical role of these brain areas, such as language, motor skills, and sensory processing. Moreover, surgical interventions in these areas are quite complex for balancing between controlling seizures and preserving essential neurological functions. Surgical resection of the epileptogenic zone in the eloquent cortex seems to have a high risk of postoperative neurological deficits, such as speech impairment, paralysis, or sensory loss. Case presentation: The patient is an 18-year-old male, right-handed, known case of refractory epilepsy, who came to the neurology ward with a chief complaint of abnormal movement. His head suddenly turned to the left and became motionless. Besides, there was some increase in the tone of his extremities, which is prominent in his left hand. Additionally, in his ictal Electroencephalography (EEG), signals started as 20hz low voltage fast activity in left frontal max F3, F7 that evolved to 4hz high voltage spike and wave. Right frontal involvement occurred after 0.5 seconds, and spreading to the right temporal area was revealed after one second. The seizure lasted about 12 seconds. At the end of his seizure, there was evidence of bradycardia. There was a postictal left frontal spike and wave. Also, his brain magnetic resonance imaging (MRI) showed cortical high signal intensity with Gary white matter junction blurring in the posterior of left middle frontal gyrus junction with inferior frontal gyrus suggestive of focal cortical dysplasia (FCD) type 2a. Furthermore, owing to the suspicion of FCD in his frontal lobe, fMRI was performed. His fMRI depicted the activation area Broca’s is close to the mentioned lesion on the left side. Hence, since the lesion is located near Broca's area, and traditional surgical resection might have a high risk of neurological deficits, the patient is a candidate for Gamma Knife radiosurgery. The Gamma Knife protocol of 24 Gy at 50% isodose applied for him. The fixation was done with the G frame and the beam on time was about 120 minutes. As a consequence, 4 months after radiosurgery the frequency of his seizure decreased significantly. Also, it is worth mentioning, that the patient did not show any side effects except losing hair at the site of irradiation. Conclusion: Gamma Knife radiosurgery seems to be a suitable choice for treating FCD Type 2a in the eloquent cortex due to its precision and non-invasive nature.

Treatment of glomus tumors with cyberknife. INTRODUCTION Glomus tumors, also known as paragangliomas, are benign, slowgrowing tumors, originating from neuroectodermal tissues. They are highly vascular lesions and arise from the capillary and precapillary blood vessels, located along the tympanic branch of glossopharyngeal nerve (Jacobson's nerve). It occur predominantly in women, and are typically diagnosed between the fifth and sixth decade of life. Clinical aspects present as pulsatile tinnitus followed by conductive hearing loss, otalgia, and aural fullness. METHERIALS AND METHODS From January 2003 to December 2023, 51 patients (42 females and 10 males) affected by tympanojugular glomangioma were treated with CyberKnife at our Center. The age ranged from 32 to 85 years (m: 59.7, M: 62). The average lesion volume treated was 4457 mm3 (median: 2660 mm3) while the range: 91-29331 mm3. Four patients showed multicentric lesions. Six patients underwent 2 treatments and three underwent 3 treatments. while the maximum treatment doses delivered were between 16 and 27.5 Gy (average 21.3 Gy). The isodoses between 75-80%. In particular, a maximum dose of 22.5 Gy was used on 18 patients (34%). As regards fractionation, the majority of patients, 34/51, underwent three fractions while 6 underwent a single session. No re-treatment was performed less than three years after the previous one. The FU has a range of 5-150 months for a total of 2796 months of observation (average: 65). 43 patients underwent FU, 7 patients did not show up for checks while one died from senectus. Radiological FU was scheduled at 6-12-18-24-30 and 36 months after treatment; 38 patients underwent checks with thin-layer contrast-enhanced MRI while the other 5 underwent high-definition contrast-enhanced CT due to no indication for MRI. RESULTS In 43 patients observed, 6 (14%) presented initial disease progression (PD). However, only one actually showed full-blown disease progression while five were re-treated. 27 patients (63%) experienced disease stabilization with a single treatment (SD) while 8/43 patients (23%) experienced disease dimensional regression (RD), 2 of which after retreatment. As regards the clinical aspect, 19 patients showed a clear regression of the initial symptoms, 8 showed new symptoms (not serious and/or debilitating) while 2 underwent progression (hearing loss and tinnitus). The remainder remained neurologically quo-ante.

Aims SRS treatment planning is based on multimodal imaging, as the co-registration of Magnetic Resonance Imaging (MRI) and CT images, to improve the accuracy of targets definition, but MRI data may contain geometric distortions that could affect precision of co-registration and consequently, the accuracy of Gross Tumor Volume (GTV) delineation. We analyzed the impact of MRI-related distortion in SRS planning for patients with brain mets. Materials and Methods Our analysis included seven delineated GTVs. MRI data (THRIVE and MPRAGE sequences) were corrected using Cranial Distortion Correction (CDC) protocol (Brainlab, Elements), which elastically deform MRI images on patient CT (MR CDC), to reduce intra-cranial distortions. A radiation oncologist contoured GTVs on MRI set and this set was rigidly fused with contrast-enhanced CT; the same radiation oncologist re-contoured GTVs on MR CDC, obtained with fusion of no-contrast-enhanced CT. GTVs’ comparison was realized mapping contours on CT scans, with and without contrast agent. Geometrical agreement between GTVs was evaluated comparing changes in target volume with paired t-test. Furthermore, displacement grid in MR CDC and Dice Similarity Coefficient between GTVs on the two set were calculated (poor agreement 0.41-0.60, medium agreement 0.61-0-80, satisfactory agreement 0.81-1.00). Results Median GTV corrected volume was 0.24 cc (range 0.04-1.13 cc). Difference in volume were negligible, thought the contours obtained from MR CDC set tend to be larger, with a median percentage change of all GTVs around 16 %. The lesions contured on the THRIVE sequence, exibiths a better agreement with the ones contured on the MR CDC: no notable shift arise from the evaluation of the distorsion field in CDC, with DICE 0.85, 0.85. 0.75, and 0.71; while the lesions contured on the MPRAGE show displacement in the distortion field up to 3mm, in particular for GTV in the anterior region, with DICE respectively 0.47, 0.67 and 0.57. The risk of target missing due to distorsion is primarly influenced by displacement than target size (p-value<0.001), also because the magnitude of distorsion depends on distance from tomograph isocenter. Conclusions MRI distortion, though visually subtle, has significant implication in SRS planning. Regular utilization of a suitable MRI sequence, distortion corrected MRI algorithm and its revision is recommended for SRS planning, to reduce volumetric miss of SRS GTV.

Introduction: Brain metastases are manually identified during stereotactic radiosurgery (SRS) treatment planning, a process that is time-consuming, challenging, and prone to inter-practitioner variability. Advanced software tools can assist in lesion detection and segmentation, potentially improving efficiency and accuracy. This study evaluates the performance of an automated contouring tool across various demographic and clinical characteristics in patients with brain metastases treated with SRS. Materials and Methods: We retrospectively selected 15 patients with brain metastases who underwent initial SRS. Axial T1-weighted Gadolinium-enhanced magnetic resonance (MR) images were extracted and processed using Elements SmartBrush (Brainlab, Munich, Germany). A lesion was considered "detected" if the software-generated contour overlapped with the physician-defined ground-truth contour. Newly identified lesions were reviewed by an expert physician. Performance was assessed using Dice similarity coefficient (DSC), Hausdorff distance (HD), false positive count (FP), and sensitivity (%). Results: We analysed 15 patients with 110 brain metastases with a median number of 7 (ranging between 1 and 24) treated with SRS. The median tumour size was 0.85cc (SD 1.81cc) for the doctor while 0.68cc (range 1.68cc) for the software. The detection sensitivity was 87% (96 lesions) and 3 new lesions were found by the software with 5 lesions being false positives. Regarding contouring we found a means DSC of 0.78, a mean HD of 0.97. Conclusion: In this study, Elements SmartBrush, a software tool for tumour segmentation, showed promising results in segmenting brain tumours and detecting the lesions with limited false positives. Even though human expertise remains critical, automated software offers potential to improve the efficiency of lesion management.

Single center clinical experience with Cyberknife radiosurgery for skull base meningiomas Objectives and Purposes The aim of this retrospective study is to evaluate the efficacy in local control and tolerance of radiosurgery (single RS or hypofractionated HRS doses) for the treatment of skull base meningiomas Material and methods We analysed the treatment of 30 patients diagnosed with skull base meningiomas treated with CyberKnife Radiosurgery between March 2020 and February 2024. Planning was performed using CT-plan with termoplastic inmobilization mask registered with brain nuclear magnetic resonance using T1-weighted MRI with contrast and fat saturation (useful in skull base tumors, orbital lesions, or surgical beds) and high-resolution T2-weighted MRI (useful in cisternal segments of cranial nerves, cavernous sinuses or Meckel's cave). All contours are reviewed by a dedicated neuroradiologist. In resected or unresected grade 1 meningiomas, the GTV = PTV. In grade 2 meningiomas, a margin of 1-5 mm was applied, according to international contouring guidelines. Results Out of 30 patients, 22 women and 8 men. Mean age 62 years old (39-87). Most common locations were: pontocerebellar angle (14p), cavernous sinus (6p), optic nerve (4p) and others (6p). 13 patients had undergone previous surgery. 83% (25p) received a total dose of 25-30Gy in 5 fractions, 17% (5p) single fraction (14-18Gy). Mean lesion volume 10cc .For the 5 fractions scheme: mean maximum dose (Dmax) in PTV was 46.04 Gy,, mean Dmax in visual pathway 30.67Gy, pituitary 36.69Gy and brainstem 30.50Gy. For 1 fraction scheme: mean Dmax in PTV was 20.96 Gy, mean Dmax in visual pathway 7.46Gy, pituitary 7.97 Gy and brainstem 9.84 Gy.Mean conformation index of 1.3.With a median follow-up of 24 months (3-59) for 26 p who underwent the first control RMI, 100% patients achieved radiological stability. Acute toxicity was reported in 46% of patients presenting minor grade 2 toxicity, most frequently mild transient headache and asthenia. Chronic toxicity was evaluated for 26p, 26% presented minor grade 2 headache (6), neurological deterioration (1) and tinnitus (1). No cases of stroke or cranial nerve palsy were reported. Radiologic radionecrosis occurred in 1 asymptomatic patient. Conclusions Our clinical experience using Cyberknife RS or HRS for skull-base meningiomas shows that these schemes are safe, effective, and helpfull for patients who are rarely candidates for complete resection.

Introduction N.N. Burdenko Neurosurgical Center is equipped with CyberKnife, GammaKnife, and two TrueBeam STx systems. This study aimed to evaluate the capabilities of each modality in delivering localized conformal irradiation for multiple brain lesions. Seven irradiation methods were compared, considering the equipment and dose optimization techniques. Materials and Methods Nine patients with multiple brain lesions (≥ 4) were selected, totaling 57 targets (TV=0.05–2.61 cm3). All patients were treated with the CyberKnife. CT scans with target and critical structures contours in DICOM were transferred from the MultiPlan to GammaPlan, Eclipse, Monaco and Precision. Then, radiosurgery plans were created for GammaKnife, TrueBeam, Versa HD and CyberKnife, respectively. On all LINACs, the average doses ​​in TV were the same. On the GammaKnife, the dose to 98–100% of the TV was equal to the same dose characteristic on the CyberKnife. Given the high probability of re-treatment, the medical physicist sought to minimize doses to brain tissue. Dose distributions were analyzed in MIM and Excel, focusing on comparison of their characteristics. The doses in targets were optimized in accordance with the irradiation methodology approved in the department and were identical. The following dose indices in normal tissues were estimated: GI50, V10, V12. Conformity indexes were also analyzed: CIRTOG, PCI. Their dependence on the volume and number of lesions was studied. Results GI50 (fig. 1): • Cone collimators provide the lowest GI values ​​(GammaKnife – 2.9, CyberKnife – 7.2, versus TrueBeam 12.7). • Significant differences were observed for TV < 0.7 cm3 while minimal for TV > 2 cm3 • For GammaKnife, the GI was independent of tumor number and volume • For MLC-based systems, GI increases significantly for lesions > 6 V12: • Cone collimators achieved the lowest V12, especially at TV < 0.2 cm3 (GammaKnife – 0.27, CyberKnife – 0.54, versus TrueBeam –1.23) • Collimator type had negligible impact for TV > 2 cm3 PCI: • CyberKnife - the best conformity ​​spatially for TV < 0.7 cm3 (0.69). • ​​GammaKnife - the worst conformity ​​(0.5). Conclusions Cone collimators allow significantly more effective than MLC (up to 4–5 times) in reducing doses outside the target, particularly for small lesions (TV < 0.7 cm3) and cases with > 6 lesions. HyperArc, an automated radiosurgery planning option, performed worse than manual VMAT in most analyzed indicators.

Background: Surgical resection of WHO grade 2 meningioma can be curative. [68Ga]-DOTATATE PET imaging is more sensitive than gadolinium-enhanced MRI for detection of residual meningioma following surgery. We explored the progression-free survival prospects of patients who had undergone an radiographically complete resection of a WHO grade 2 meningioma as assessed by both MRI and [68Ga]-DOTATATE PET. Materials & Methods: Our institutional registry was queried for patients who had undergone resection of a WHO Grade 2 meningioma and who had both postoperative high-resolution gadolinium-enhanced MRI and postoperative [68Ga]-DOTATATE scans which were declared negative for any residual meningioma. A total of 30 consecutive patients were identified, all of whom had elected to have active surveillance over conventional fractionated radiotherapy to the resection bed. Follow-up for all patients included contrast-enhanced MRI scans to monitor for any progression in the resection bed. The Response Assessment in Neuro-Oncology (RANO) criteria were used to calculate a Kaplan-Meier progression-free survival (PFS) curve (Figure 1). Results: The average pre-operative RANO two-dimensional size product was 11.5 cm2 (range 3.0-28.6 cm2). Half of the tumors arose from a skull base location (n=15; 50%). Nine patients had tumors located along the convexity (30%) and six had tumors arising from the falx (20%). All but 3 patients (10%) underwent craniotomy for resection, and those 3 individuals had endoscopic endonasal resections. The mean MRI follow-up data duration was for 23 months. There was a 30-month PFS rate of 100%, at which time a single patient progressed and was treated with salvage radiosurgery. The PFS rate was 83.3% at the time of maximum follow-up (5 years). Conclusion: For patients with WHO Grade 2 meningiomas with an apparent gross total resection on postoperative MRI, the completeness of surgical resection can be confirmed with [68Ga]-DOTATATE imaging. The high negative predictive value of this additional imaging permits the avoidance of partial brain irradiation for this subset of patients and preserves all radiation options for any possible tumor recurrence that may be detected on surveillance.

Background and purpose: Paraspinal involvement has been consistently reported as a predictor of local failure post-stereotactic body radiotherapy (SBRT) for spinal metastases. We aim to investigate the characteristics of paraspinal disease and their impact on outcomes. Materials and methods: Patients who underwent SBRT for spinal metastases with paraspinal involvement, identified from a single-institutional prospective database, were retrospectively reviewed. Those with prior radiation/surgery were excluded. The treated clinical target volume (CTV) was segmented into the paraspinal (CTV_PS), neuroforaminal (CTV_NF), epidural (CTV_EP) and osseous (CTV_bone) components. The extent of extraosseous disease was classified according to involvement of rib, neuroforamina, and muscle. Volume and dosimetric parameters were collected and dichotomised using recursive binary partitioning. The outcomes of interest were cumulative incidence of local failure (LF), overall survival (OS), and re-irradiation rates (ReRT). Results: There were 125 treated spinal sites in 114 patients included in the study. The 12-month and 24-month cumulative incidences of LF were 19.5% (95%CI=12.6-27.4%) and 29.8% (95%CI=21.4-38.7%). The 12-month cumulative incidence of LF were 12.0% (95% CI=5.9-20.5%) and 36.3% (95%CI=20.2-52.6%) in patients with CTV_PS<42.9cc and >42.9cc (P<0.001), respectively. On multivariable analyses (MVA), CTV_PS volume independently predicted for LF (HR=2.3;95%CI=1.13-4.83;P=0.02) for risk of LF compared to CTV_PS <42.9cc. The 12-month and 24-month OS were 56.1% (95%CI=46.5-64.7%) and 41.2% (95%CI=32.3-50.1%), respectively. ECOG performance status and oligometastatic state were associated with OS on MVA. The 12-month and 24-month of ReRT were 7.3% (95%CI=3.4-13.3%) and 16.5% (95%CI=10.2-24.1%), respectively. Conclusion: Spinal metastases with high-volume paraspinal involvement were associated with increased risk of LF following SBRT and strategies to optimize outcomes are required.

Introduction Radiotherapy has a known role in the treatment of symptomatic spinal bone metastases, but its use with ablative purpose remains controversial. The aim of our study is to evaluate efficacy and toxicity of stereotactic body radiotherapy (SBRT) in treating spinal oligometastases. Methods A series of spinal oligometastatic patients was treated between 2018 and 2023. The clinical target volume was defined according to Cox contouring guidelines. When feasible, a simultaneous integrated boost (SIB) was administered to the site of the macroscopic disease. The primary end-point was local control (LC). Secondary objectives were toxicity, distant progression-free survival (DPFS) and overall survival (OS). The following covariates were evaluated: SIB, biologically effective dose, hystology, number of metastases, and association with systemic therapy. Results One hundred-fifty two (152) spinal oligometastases in 120 patients were treated. Median follow-up was 22 months. Median dose was 24 Gy (range 21-30) delivered in 3 (3-5) fractions. SIB was administered in 33 metastases (21.7%). One-, and 2-year LC was 92.1% and 90%. Moreover, SIB resulted in a significantly improved 2-year LC (p= 0.037). Fourteen (9.2%) metastases locally relapsed. One- and 2-years OS were 94.8% and 90% respectively. One- and 2-years DPFS were 47.8% and 30.8% respectively, with a median DPFS of 11 months. Oligometastatic prostate cancer patients showed better PMFS (p=0.03) and DPFS (p=0.008) than other hystologies. Conclusions Spinal SBRT is effective in treating spinal oligometastases. Dose boost could be safely administered to improve significantly LC. Prostate cancer patients showed better outcomes.

Local failure (LF) after spine-SBRT for metastases has no standard salvage treatment. We investigated our institutional experience using salvage 30Gy in 10fx IMRT to involved vertebral levels with a 40Gy dose-escalated spinal simultaneous integrated boost (SSIB) to gross disease, herein referred to as “salvage-SSIB.” Patients who received prior spine-SBRT in 1-5 fractions from C1-L5, experienced LF, and subsequently received salvage-SSIB between 2010-2023 with at least 1 MRI spine follow-up were included on this IRB-approved analysis. LF was defined per SPINO criteria. Freedom-from-local-failure (FFLF) was calculated from salvage-SSIB to LF or last MRI spine follow-up. Overall survival (OS) was calculated from salvage-SSIB to death or last visit. The Kaplan-Meier method was used to estimate 1- and 2-year event rates. Univariable analysis was performed with the log-rank test to explore factors associated with FFLF after salvage-SSIB. Thirty-five patients met inclusion criteria. Median age at salvage-SSIB was 64 years (range, 35-86); 54% were female. The most common histologies were renal cell carcinoma (31%) and sarcoma (14%); 71% were considered radioresistant. Initial spine-SBRT was post-operative in 17% and dose was 24Gy/1fx (42.9%), 24-27Gy/3fx (25.7%), 16-18Gy/1fx (17.1%), or 30-40Gy/5fx (14.3%). Median time from initial spine-SBRT to salvage-SSIB was 24 months (range, 6-98 months). Post-SBRT recurrence, patients had a component of epidural disease in 63%, paraspinal disease in 14%, or both in 9%; 22% had bone only disease. Fourteen (40%) patients had salvage surgery preceding salvage-SSIB. Median number of salvage-SSIB treated vertebral levels was 3 (range, 1-7). Median maximal dose to spinal cord and cauda equina were 30.09Gy (range, 8-35) and 31.19Gy (range, 13-37), respectively. Following salvage-SSIB, median imaging follow-up was 14 months (range, 2-55 months). Eight (23%) patients experienced LF. FFLF at 1- and 2-years were 80% and 64%, respectively. OS at 1- and 2-years were 75% and 51%, respectively. The most common site of failure was epidural (n=6, 75%). On univariable analysis, there was no association between FFLF and histology, epidural/paraspinal disease, or salvage spine surgery, although limited events preclude meaningful interpretation. Salvage-SSIB is a reasonable treatment option following LF after spine-SBRT. Further dosimetric and toxicity analyses with longer follow-up are required to optimize this treatment technique.

Introduction: The localization of target location of Spine Stereotactic Body Radiotherapy (SBRT) is clinically satisfied the high precise margin requirement when focusing on the spinal region for the rigid characteristic of the bony structure. Current Linear accelerator provides onboard imaging system at in vivo recording the treatment delivery exit dose. With this feature, the detail dose delivery perturbation could possibly be investigated. In this study, a permutational combination method was utilized to analyze the information of surrounding organs at risk contribution to the variation of exiting dose recorded images. Methods and Materials: A spine Stereotactic body radiotherapy was accomplished with TrueBeam Linac in 3 fractions. After on-board Cone Beam Computer Tomography(CBCT )images were taken and utilized for treatment target alignments, the doses were delivered, and three images were recorded with electronic portal imaging device (EPID). The permutational combination of these three images were compared with the organs at risks surrounding the spinal prescription treatment volume (PTV). These surrounded organs were Cauda equina, bowel bag, right and left kidney and liver. These organs at risk contours were attained by online registration of fractionated CBCT images with plan CT and transferred to different CBCT image sets. Comparison was used to evaluate the exit dose recorded image and these organs at risk Hounsfield unit (HU) standard deviation. Results: in permutational combination order, the percentage difference of HU standard deviations in right kidney, left kidney, cauda equina, bowel bag, liver and PTV were 19%, 2%, 8%, 2%, 8%, and 1% in between fraction 1 and fraction 2; 30%, 25%, 9%, 4%, 4% and 2% in between fraction 1 and fraction 3; and 13%, 23%, 0%, 6%, 5% and 1% in between fraction 2 and fraction 3. And in corresponding order, the EPID recorded dose fluence images showed Gamma passed rates were 91.1%, 89.9%, and 100% at 2% dose difference and 2.0mm distance to agreement settings. Conclusion and discussion. A permutational combination method was employed to study the variation of exit dose difference related to CBCT images. And the correlation may be displayed by the organ at risk Hounsfield unit standard deviation, which could provide clinical rational for treatment tactic selections. Further study including recruiting more clinical cases and reciprocal transfer model analysis of the effect in exiting dose variations.

Purpose: To evaluate dosimetric accuracy of Brainlab Elements (BLE) 4.0 treatment planning system (TPS) for linac based SRS and spine SBRT treatments. Methods: RTsafe cranial and thoracic phantoms with incorporated inhomogeneities that simulate tissue, bone, and air is utilized for this end-to-end testing. The phantoms were imaged on CT and treatment plans were generated on BLE 4.0 TPS to simulate cranial stereotactic radiosurgery (SRS) and spinal stereotactic body radiation therapy (SBRT) treatments. For the cranial SRS, two distinct plan geometries were created with the difference being in the target size. The smallest target measures 0.08cc and the larger target measures 32.61cc. For Spinal SBRT, three distinct plans were generated: uniform irradiation, simultaneous integrated boost (SIB) and avoidance structure plan to simulate clinical scenarios of sharp dose gradients within target. The SIB volume and avoidance structures were planned such that the volumes coincided with the measurement volume. Each of these plans were generated with 6MV and 6FFF beam and calculated separately with pencil beam (PB) and Monte Carlo (MC) dose calculation algorithm. These plans were delivered on Elekta Versa HD Linac. Prior to treatment delivery the phantom was localized using BL dynamic Exactrac localization system in order to ensure spatial integrity. Exradin® A16 micro ion-chamber was used to measure the delivered dose in each of these geometries. A comparison was made between the calculated dose and measured dose for each of these configurations. Results: For the cranial irradiation, the discrepancies between the PB and MC methods are noticeable in the smaller target sizes. PB shows larger difference (-5.9%) in 6FFF configuration and MC showed higher discrepancy (8.2%) in 6MV beam. For larger target sizes, the differences between PB and MC calculation methods are minimal for both 6MV and 6FFF beams, indicating that the methods perform similarly under these conditions. For the spinal irradiation, PB method shows higher percentage difference than MC in all scenarios (average difference for PB being 6.3% and that for MC being 1.83% across various plans). The differences between PB and MC are more pronounced for avoidance setting with PB overestimating the dose significantly (14.3%). Conclusion: BLE TPS supports high dosimetric accuracy for SRS and Spine SBRT deliveries and MC appears to provide more accurate dose prediction across different geometries.

Purpose: Radiation myelitis (RM) is the most dreaded complication of stereotactic ablative radiotherapy (SABR) for the spine. We investigated radiation-induced radiculo-plexopathy (RIRP) in patients who underwent SABR for spinal metastases. Materials and Methods: Patients who received SABR for metastatic spine tumors arising in C3 to T1 and T12 to S2 vertebrae from 2013 to 2023 were analyzed. Medical records and images were retrospectively reviewed. RIRP was defined as a motor power decrease by MRC grade 2 or greater in the myotome of the spine treated by SABR that was not caused by local progression or RM. In addition to the spinal cord and cauda equina, neural foramina that is either included within or adjacent to target volumes were designated as organs at risk. While 407 neural foramina were contoured, only those with a maximum EQD2 (a/b ration=2) greater than 45 Gy were included for dosimetric analysis. The Cox proportional hazard model was used to identify risk factors for RIRP. Results: Of 132 patients with spinal metastases, 168 C1-T1 and T12 to S3 spine segments were treated with SABR. The median follow-up was 9.5 months. Twenty-four local recurrences occurred (14.3%, 24/168). No cases of radiation myelitis were observed, and one case of radiation-induced cauda equina syndrome was identified. Overall, 20 SABR cases in 12 patients were identified to have decreased motor power by 2+ grades. Of these, 7 spine segments in 6 patients showed bilateral limb weakness. Detailed analysis revealed that none of these motor weaknesses were caused by local progression or RM. The crude incidence of RIRP was 11.9% (20/168) in 12 patients. The incidence of bilateral RIRP was 4.2% (7/168). The planning target volume and the maximum dose to neural foramina were significantly associated with the occurrence of RIRP (p<0.001). Conclusions: In contrast to RM or radiation-induced cauda equina syndrome, RIRP occurs more frequently after spinal SABR. Neural foramina may serve as provisional surrogate organs at risk for RIRP. Further studies are necessary to characterize RIRP and relevant dosimetric constraints.

Stereoteactic radiosurgery was developed with the aim of providing non-invasive treatment in neurosurgical pathologies, including functional pathologies such as essential tremor associated with Parkinson's disease where the ventral intermediate nucleus of thalamus has been used as a target with proven success. Most treatments have been reported with gamma knife, radiosurgery with LINAC have also shown successful results. Objetives: Between March and April of 2023 at Puebla Specialties Hospital of the IMSS, radiosurgical treatment was carried out on 5 patients with Parkinson's disease refractory to pharmacological treatment, all with different forms of presentation from spastic to kinetic. Methods: The patients were treated with radiosurgery through LINAC using dose of 75 to 85 Gy in a single session randomly, with monthly monitoring maintained during 6 months. The initial period to asssess the effects of treatment was at 6 month with an improvement in control of involuntary movements of at least 70% asessed by neurological tests such as UPDRS, Hoehn-Yahr and Scwarb-England. Results: treatment of radiosurgery with LINAC in tremor associated with Parkinson's disease is an effective option. Conclusions: In our Medical Centter with the combination of pharmacological medical has observen improvement in quality of life for patients. Dose escalation is expected in subsequent months in relation to the chosen patient.

Introduction: This historical review explores the development of early stereotactic devices, the challenges faced in the pre-CT era, and the gradual refinement of techniques that laid the foundation for modern practices. Methods: We reviewed articles on the history of stereotactic neurosurgery and consulted original works by the inventors of radiosurgery. Results: Stereotactic treatment depends on high precision. There are precursors to stereotaxis in many countries. In older textbooks, there is a lack of description of head fixation. Swift understood the need for more precision and constructed in 1905 the first stereoscopic instrument for "excitation and electrolysis" in the brain of animals. British surgeon Clarke patented it in 1914. EA Spiegel was the first to use stereotactic treatment in humans. Starting in the 1930ies in Philadelphia, he collaborated for many decades with HT Wycis. They published a ground-breaking article in 1947 in Science, describing an adapted "stereotaxic technic" that "permits one to insert a wire or a cannula accurately into a desired subcortical area with minimal injury." They aimed to reduce the crude prefrontal lobotomies that resulted in undesirable personality changes. To target the thalamus, anatomical landmarks were visualized using pneumoencephalography. The limiting factors in the pre-CT era were anatomical considerations, complicated by variations in the human skull and brain. Spiegel and Wycis published their brain atlas in 1952. The landmarks used were the calcified pineal gland, the third ventricle, and the posterior commissure. In 1949, Leskell published about his "stereotaxic apparatus for intracerebral surgery" and in 1951 his paper on stereotactic radiosurgery using radiotherapy. Always an inventor, he identified a relatively constant distance between the commisures and mapped the third ventricle. He also invented the stereotacic frame system, which allows for the isocentric reach of any intracranial target. Based on this concept and after testing several other radiation approaches, he introduced the multisource Cobalt-based Gamma knife in a 1968 publication, which was the founding of modern radiosurgery. Conclusion: Stereotactic neurosurgery has evolved remarkably from experimental procedures in animals to minimally invasive techniques in humans. Owing to the efforts of clinicians and scientists, stereotactic radiosurgery allows for more precise and less traumatic treatment of neurological disorders.

Aim: Radiosensitizers (RS) are structures that increase the effect of radiation in the tissue they are located in. Nanoparticles are frequently used for radiosensitizing purposes today, and studies report promising results (1). We have previously produced and presented a system containing %5 radiosensitizer nanoparticles(RSNs) that we predicted could also have a fiducial function and it called `nanofiducial´ (NF)(2). This system had released RSN for three days. In this study, Houndsfield Unit(HU) values of the a nanofiducials are presented. And also NFs that loaded with twice as much (from 5% to 10%) radiosensitizer nanoparticles are presented. We would like to discuss the importance of low Houndsfield Unit (HU) values in nanofiber-based systems for tracking systems and multifuctional nanofiducials. Methods: AGuIXs(NH TherAguix,France) are used as a radiosensitizer nanoparticles in the study. AGuIXs are nanoparticles containing gadolinium and can increase the effect of radiation up to 2.3 times (3). For controlled release of AGuIX, a nanofiber substructure has been produced. A mixture of tetrahydrofuran(THF) and dimethylformamide(DMF) were used as the polymer solvent. Most RT applications are based on Computed Tomography (CT) and the HU values of the fiducials used for tumor tracking are important. In this study, NF was synthesized in two forms, both 5% and 10%, and their HU values were calculated. Results: NFs containing 5% AGuIX, 10% AGuIX and no AGuIX are produced in the Pharmaceutical Technology Research Laboratory of Hacettepe University, Faculty of Pharmacy. NFs placed between a 1 cm thick tissue equivalent bolus in Ankara Bilkent City Hospital Radiation Oncology Clinic (GE Discovery RT CT Simulator) and CT images are obtained with 1 mm slice thickness. NFs appeared hypodense on CT images (Figure 2). The mean HU values of nanomaterials containing “AGuIX-free”, “AGuIX-containing 5%” and “AGuIX-containing 10%” are measured as follows: -94.7 (STD 22.0), -68.9 (STD 12.3); -48.2(STD 12.3); respectively. Conclusions: We would like to discuss the effect and necessity of multifunctional fiducals with this research. Instead of bulky materials as fiducials, materials that have a combination of effects can be produced. In this research, the structure containing radiosensitizer loaded into the nanofiber system and which we predict can have a fiducial function is presented with HU values and it is desired to discuss it before animal experiments.

Purpose: Phantom-based pre-treatment verification is not possible for online adaptive plans, because of the patient is lying on the treatment table during this type of radiation therapy. Currently, patient-specific QA (PSQA) relies on a secondary independent dose calculation of the treatment plan. We aim to analyze the dosimetric accuracy of the type of online adaptive SBRT plans delivered for prostate treatment in our department. Methods and Materials. Prostate SBRT with five fractions is performed at our institution using an online adaptive method previously described (Pract Radiat Oncol. 2022 Mar-Apr;12(2):e144-e152). To analyze the dosimetric accuracy of the delivered adaptive plans, 75 treated patients were randomly selected from our database. For each one, two adaptive plans were randomly chosen (150 adaptive plans were collected). Post-treatment experimental verifications of these plans were performed using the Varian Portal Dosimetry tool. Measured arc fluence was compared against the corresponding fluence predicted by the Varian PDIP v. 16 algorithm (Fig. 1). The agreement between measured and predicted fluences was investigated for each arc using a 2D gamma index analysis. Gamma passing rates (GPRs) were computed using two criteria: 1) the 3%(global)/2 mm criteria recommended by the AAPM TG-218 report (Med Phys. 2018 Apr;45(4):e53-e83), and 2) the stricter 2%(local)/2 mm gamma index criteria, both criteria using an exclusion threshold set to 10% of the maximum value. The AAPM TG-218 report establishes universal tolerance and action limits of GPR greater than 95% and 90%, respectively. Results: With the 3%(global)/2 mm gamma index criteria, all plans passed the PSQA universal tolerance limit ≥ 95.0% (mean ± SD: 99.7% ± 0.5%; range: 95.7%-100%). With the 2%(local)/2 mm criteria, 6% of plans reported GPRs < 95%, whereas all plans passed the PSQA universal action limit ≥ 90.0% (mean ± SD: 97.8% ± 1.7%; range: 90.5%-100%). Conclusions Portal dosimetry measurements revealed that the deliverability of the adaptive plans met the universal tolerance limit ≥ 95% adviced by the AAPM TG-218 report for the 3%(global)/2 mm criteria. With the more demanding 2%(local)/2 mm criteria, all plans passed the PSQA universal action limit recommended by that report for the less strict 3%(global)/2 mm criteria. These results, based on the retrospective analysis of a sample of 150 adaptive plans, ensure the dosimetric accuracy of our adaptive SBRT technique for prostate cancer.

Introduction: The use of radiosurgery in various nervous system disorders has experienced a progressive increase, attributed to its ability to deliver radiation with millimeter precision, preserving the functionality of the regions adjacent to the lesion. In this context, the so-called "differential clinical effect" described by Regis has been described, suggesting a neuromodulatory mechanism of radiation observed in patients with epilepsy secondary to arteriovenous malformations (AVMs), who present significant clinical improvement without evidence of volumetric resolution of the lesion in imaging studies. However, this phenomenon has not been described in detail in other pathologies. The following job analyzes this effect in two cases unrelated to AVMs. Presentation: The first case corresponds to a 24-year-old man diagnosed with a perimedullary arteriovenous fistula from T8-L2, who presented with weakness in the lower extremities and loss of sphincter control. The second case describes a 32-year-old patient diagnosed with meningioma in the T10 segment, causing motor and sensory deficits, receiving treatment with RS at a rate of 21 grays (gy) in 3 sessions and 15 gy single sessions, respectively. Both presented a sudden improvement in clinical status despite no volumetric changes being observed in imaging studies during the post-treatment evaluation (3 months after). Discussion: Regis was one of the first to propose radiotherapy as a neuromodulatory treatment. In his study, he exposed a group of rats to a single dose of 50 Gy at a single isocenter, observing a selective disruption of catecholaminergic transmission without affecting GABAergic transmission. These findings have led us to hypothesize that radiation can exert a neuromodulatory effect through its biological action on the neuronal environment in the periphery of various conditions other than AVMs without disrupting the function of the underlying cortex, thus promoting its structural and functional remodeling. Consequently, the cessation of symptoms, termed the "differential clinical effect," after radiation therapy could be directly related to this radiation-induced biological effect. Conclusion: The excellent clinical response observed after radiosurgery without the need for radical change in the lesion suggests the potential neuromodulatory effect of radiation could be extended to other conditions, so further basic research is proposed to evaluate this phenomenon.