Gamma Knife Stereotactic Radiosurgery Research Articles

Deep learning for automatic segmentation of vestibular schwannoma: a retrospective study from multi-center routine MRI

Automatic segmentation of vestibular schwannoma (VS) from routine clinical MRI has potential to improve clinical workflow, facilitate treatment decisions, and assist patient management. Previous work demonstrated reliable automatic segmentation performance on datasets of standardized MRI images acquired for stereotactic surgery planning. However, diagnostic clinical datasets are generally more diverse and pose a larger challenge to automatic segmentation algorithms, especially when post-operative images are included. In this work, we show for the first time that automatic segmentation of VS on routine MRI datasets is also possible with high accuracy. We acquired and publicly release a curated multi-center routine clinical (MC-RC) dataset of 160 patients with a single sporadic VS. For each patient up to three longitudinal MRI exams with contrast-enhanced T1-weighted (ceT1w) (n = 124) and T2-weighted (T2w) (n = 363) images were included and the VS manually annotated. Segmentations were produced and verified in an iterative process: (1) initial segmentations by a specialized company; (2) review by one of three trained radiologists; and (3) validation by an expert team. Inter- and intra-observer reliability experiments were performed on a subset of the dataset. A state-of-the-art deep learning framework was used to train segmentation models for VS. Model performance was evaluated on a MC-RC hold-out testing set, another public VS datasets, and a partially public dataset. The generalizability and robustness of the VS deep learning segmentation models increased significantly when trained on the MC-RC dataset. Dice similarity coefficients (DSC) achieved by our model are comparable to those achieved by trained radiologists in the inter-observer experiment. On the MC-RC testing set, median DSCs were 86.2(9.5) for ceT1w, 89.4(7.0) for T2w, and 86.4(8.6) for combined ceT1w+T2w input images. On another public dataset acquired for Gamma Knife stereotactic radiosurgery our model achieved median DSCs of 95.3(2.9), 92.8(3.8), and 95.5(3.3), respectively. In contrast, models trained on the Gamma Knife dataset did not generalize well as illustrated by significant underperformance on the MC-RC routine MRI dataset, highlighting the importance of data variability in the development of robust VS segmentation models. The MC-RC dataset and all trained deep learning models were made available online.

Stereotactic Radiosurgery for Patients with Brain Metastases from Hepatopancreaticobiliary Cancers.

The role of stereotactic radiosurgery (SRS) for patients with brain metastases from hepatopancreaticobiliary (HPB) cancers has yet to be established. The authors present a single-institution experience of patients with HPB cancers who underwent SRS when their cancer spread to the brain. We surveyed our Gamma Knife SRS data base of 18,000 patients for the years 1987-2022. In total, 19 metastatic HPB cancer patients (13 male) with 76 brain metastases were identified. The median age at SRS was 61 years (range: 48-83). The primary cancer sites were hepatocellular carcinoma (HCC, 11 patients), cholangiocarcinoma (CCC, 2 patients), and pancreatic carcinoma (PCC, 6 patients). The median Karnofsky Performance Score (KPS) was 80 (range: 50-90). Two patients underwent pre-SRS whole-brain fractionated radiation therapy (WBRT) and eight patients underwent pre-SRS surgical resection. All SRS was delivered in single session. The median margin dose was 18 Gy (range: 15-20). The median cumulative tumor volume was 8.1 cc (range: 1.0-44.2). The median patient overall survival (OS) after SRS was 7 months (range 1-79 months). Four patients had documented local tumor progression after SRS at a median time of 8.5 months (range: 2-15) between SRS and progression. Out of 76 treated tumors, 72 tumors exhibited local control. The local tumor control rate per patient was 78.9%. The local tumor control per tumor was 94.7%. Four patients developed new brain metastases at a median of 6.5 months (range: 2-17) after SRS. No patient experienced adverse radiation effects (AREs). At the last follow-up, 18 patients had died, all from systemic disease progression. Metastatic spread to the brain from HPB cancers occurs late in the course of the primary disease. In this study, all deceased patients ultimately died from primary disease progression. SRS is a non-invasive strategy that maximally preserves quality of life, and our results reported favorable outcomes compared to the existing literature. SRS should be considered as one of the primary management strategies for patients with brain metastatic spread from HPB cancer.

1134 A Call to Revise the Thirty-year-old SRS Dose Guidelines for Brain Metastases

INTRODUCTION: Stereotactic Radiosurgery (SRS) currently is the most widely used neurosurgical strategy for treatment of brain metastases. Many centers still rely on 30-year-old dose volume guidelines derived from RTOG 90-05. METHODS: Between 2014 and 2020 330 NSCLC patients (median age = 65 years) with 2910 brain metastases underwent Gamma knife SRS. The number of tumors treated per patient ranged from 1-56 and the total tumor cumulative volume ranged from .05 to 33.09 cc (median = 3.17). The median prescribed tumor margin dose was 18 Gy. RESULTS: Median overall survival after radiosurgery was 15.5 months. Radiological tumor progression was noted 66 out of 2910 tumors (2.27%) in 51 out of 330 patients (15.45%). Tumors were divided into 4 categories based on tumor volumes (<1.5 cc, 1.5-<5 cc, 5-<10 cc, and = 10cc). The effect of margin dose, and % tumor covered in 18 Gy, 20 Gy, and 24 Gy on local tumor control was analyzed for all 4 categories. In tumors with volumes >1.5 cc local tumor control was significantly better (P < 0.05) when =65% of the tumor volume received at least 24 Gy. No relationship was found between tumor control and 75, 90, and 100 % volumes receiving 18 or 20 Gy. CONCLUSIONS: In this study neither conformality of dose delivery nor tumor margin doses were the most important predictors of local tumor control as long as =65% of the tumor volume received at least 24 Gy. This finding can serve as a prescriptive guideline that allows margin doses below the RTOG guidelines, reduces reliance on strict conformality, and improves tumor control.

Uveal melanoma: the value of molecular genetic testing for early detection of metastatic disease. Clinical case

To date, the issue of not only timely diagnosis and treatment of patients with uveal melanoma (UM), but also the prediction of this pathology remains relevant. The technology of fine needle aspiration biopsy (FNAB) makes it possible to assess the risk of developing metastatic disease using tumor specimen in patients undergoing organ-preserving treatment by cytological and molecular genetic testing in the primary intraocular lesion. Here we present a case of newly identified locally advanced (T3a) UM, outline the possibilities of organ-preserving treatment using Gamma Knife stereotactic radiosurgery, and also demonstrate the feasibility of conducting a comprehensive prognostic testing on FNAB material, including cytological and molecular genetic and morphological prognostic factors. The results of this testing have made it possible to recommend a more frequent surveillance monitoring regime for metastatic disease, which ultimately led to the early detection of UM liver metastases, followed by their successful treatment.

Salvage Microsurgery Following Failed Primary Radiosurgery in Sporadic Vestibular Schwannoma

Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in the setting of microsurgical salvage for radiosurgical failure. To describe the clinical outcomes of salvage microsurgery following failed primary stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) among patients with sporadic vestibular schwannoma. This was a cohort study of adults (≥18 years old) with sporadic vestibular schwannoma who underwent salvage microsurgery following failed primary SRS/FSRT in 7 vestibular schwannoma treatment centers across the US and Norway. Data collection was performed between July 2022 and January 2023, with data analysis performed between January and July 2023. Salvage microsurgical tumor resection. Composite outcome of undergoing less than gross total resection (GTR) or experiencing long-term facial paresis. Among 126 patients, the median (IQR) age at time of salvage microsurgery was 62 (53-70) years, 69 (55%) were female, and 113 of 117 (97%) had tumors that extended into the cerebellopontine angle at time of salvage. Of 125 patients, 96 (76%) underwent primary gamma knife SRS, while 24 (19%) underwent linear accelerator-based SRS; the remaining patients underwent FSRT using other modalities. Postoperative cerebrospinal fluid leak was seen in 15 of 126 patients (12%), hydrocephalus in 8 (6%), symptomatic stroke in 7 (6%), and meningitis in 2 (2%). Each 1-mm increase in cerebellopontine angle tumor size was associated with a 13% increased likelihood of foregoing GTR (64 of 102 patients [63%]) or long-term postoperative House-Brackmann grade higher than I (48 of 102 patients [47%]) (odds ratio, 1.13; 95% CI, 1.04-1.23). Following salvage microsurgery, tumor growth-free survival rates at 1, 3, and 5 years were 97% (95% CI, 94%-100%), 93% (95% CI, 87%-99%), and 91% (95% CI, 84%-98%), respectively. In this cohort study, more than half of patients who received salvage microsurgery following primary SRS/FSRT underwent less than GTR or experienced some degree of facial paresis long term. These data suggest that the cumulative risk of developing facial paresis following primary SRS/FSRT by the end of the patient's journey with treatment approximates 2.5% to 7.5% when using published primary SRS/FSRT long-term tumor control rates.

Neurosurgery as an opportunity to correct symptoms of mental and behavioural disorders

Neurosurgical treatment for psychiatric disorders has a controversial history. This branch of neurosurgery called by developer of prefrontal leucotomy and Nobel prize laureate Egaz Moniz “psychosurgery”, was initially based not on scientific researches, but on enthusiasm of individuals and pressing social need. The outcome of psychosurgery regardless of its clinical benefits was the negative attitude of the broad masses and medical community, some countries have banned psychosurgery – the era of psychopharmacology has come. However, some patients suffering from severe course of the psychiatric disorder are resistant to conservative treatment.Over the last decades, the novel neuroimaging methods and neurobiological researches have considerably improved understanding of the pathogenesis of psychiatric disorders and scientific validity of the surgical intervention into the neural circuits. In this article, the main stages of the history of the psychiatric neurosurgery are briefly reviewed. Furthermore, the clinical and surgical considerations including the anatomic target localization, outcome and possible complications of the major operations which are still in practice are presented. The new neurosurgical techniques such as deep brain stimulation and gamma knife stereotactic radiosurgery were also considered. The part of the article is devoted to ethical, legal and terminological issues of psychiatric neurosurgery.

Cost of Treatment for Brain Metastases Using Data From a National Health Insurance Provider

In the United States, brain metastases (BMs) affect 10% to 20% of patients with cancer, presenting a significant health care challenge and necessitating intricate, high-cost treatments. Few studies have explored the comprehensive care cost for BMs, and none have used real insurance claims data. Partnering with a northeastern health care insurer, we investigated the true costs of various brain-directed radiation methods, aiming to shed light on treatment expenses, modalities, and their efficacy. We analyzed medical claims from Highmark Health-insured patients in Pennsylvania, Delware, West Virginia, and New York diagnosed with BMs (ICD-10 code C79.31) and treated with radiation from January 1, 2020 to July 1, 2022. Costs for radiation techniques were grouped by specific current procedural terminology claim codes. We subdivided costs into technical and physician components and separated hospital from freestanding costs for some modalities. From January 1, 2020 to July 1, 2022, 1048 Highmark Health members underwent treatment for BMs. Females (n = 592) significantly outnumbered males (n = 456), with an average age of 64.4 years. Each member had, on average, 5.309 claims costing $2015 per claim. Total cost totaled $10,697,749. Per-treatment analysis showed that hippocampal avoidance intensity modulated radiation therapy was the costliest treatment at $47,748, followed by stereotactic radiation therapy at $37,230, linear accelerator stereotactic radiosurgery (SRS) at $30,737, Gamma Knife SRS at $30,711, and whole-brain radiation therapy at $5225. Whole-brain radiation therapy was the least costly radiation technique. Similar per-treatment prices for Gamma Knife and linear accelerator SRS support their use in treating BMs. Stereotactic radiation therapy in general was costlier on a per-use basis than SRS, prompting further scrutiny on its frequent use. Hippocampal avoidance intensity modulated radiation therapy was the costliest radiation therapy on a per-use basis by a moderate amount, prompting further discussion about its comparative cost effectiveness against other radiation modalities. This study underscores the importance of multiple considerations in treating BMs, such as tumor control, survival, side effects, and costs.

O-01 Case report: Temozolomide treatment of refractory prolactinoma

Abstract Introduction Treatment of refractory prolactinoma is challenging. Temozolomide (TMZ), an oral chemotherapeutic agent, has been recommended as an effective drug for refractory pituitary adenomas or carcinomas. Clinical Case We report a 53-year-old male who presented with diplopia, left eye proptosis, conjunctival congestion, and headache. Magnetic resonance imaging (MRI) showed a macroadenoma 20×17 mm in diameter with compression of the optic chiasm and invasion of both cavernous sinuses. Hormonal evaluation revealed hyperprolactinemia of 2382 ug/L, 120x above the upper limit of normal (ULN), with central hypothyroidism and hypogonadism. Cabergoline was recommended as an initial treatment. Despite the maximum cabergoline dose of 1.5 g daily, tumor volume increased with visual disturbances and headaches. Prolactin (PRL) remained 60x above ULN so the patient underwent transsphenoidal surgery. Tumor histology was consistent with an atypical pituitary adenoma, positively stained for prolactin and sporadically for growth hormone, Ki-67 of 6.4%, no mitosis and negative p53. Postoperatively, the PRL level was still high (25x above ULN) with tumor remnants in both cavernous sinuses. Due to the tumor resistance to dopamine agonist treatment and uncomplete surgical resection, patient underwent stereotactic gamma knife radiosurgery (GK prescription dose 22 Gy, isodose 49%) simultaneously with TMZ treatment. After 2 cycles of TMZ (1. cycle TMZ 300mg/5days, 2. cycle TMZ 400 mg/5days), the PRL level decreased significantly (126 ug/L). The plan is to apply a total of 6 cycles of temozolomide. Conclusion Clinical evidence for the efficacy of TMZ in refractory prolactinoma remains limited, but early use of this agent may be helpful in some cases.

Advocacy for Epilepsy Surgery in Africa: Moroccan Experience of 132 Cases

In Africa, epilepsy is a real burden. Temporal lobe epilepsy is the most common drug-resistant focal epilepsy disorder, and temporal lobectomy are the most common effective treatment on patients with drug-resistant epilepsy. We aim to highlight the Moroccan experience in epilepsy surgery and to ascertain its long-term outcome. Through the results of surgical treatment in our series, we expect to raise awareness of the need of epilepsy surgery in Africa and contribute to its development. We present a retrospective study of 132 patients who underwent surgery for epilepsy from January 2005 to December 2021 at our institution. The presurgical evaluation was based on clinical screening, interictal EEG, VEEG, neuropsychological tests, MRI and Pet Scan in some cases. Data are presented as the median and ranges. For all analyses, P-values < 0.05 were considered statistically significant. Our series includes 132 patients (69 males, 52.27%), median age at surgery was 24 years (range: 1-64). One hundred -fifteen patients (87%) were operated for temporal lobe epilepsy, among them, 98 (85%) had anterior temporal lobectomy, and 17 (15%) had a lesionectomy. Seventeen patients (13%) were operated for extratemporal epilepsy, among them, 4 had lesionectomy, 7 functional hemispherotomy, and 5 patients had Gamma Knife Stereotactic Radiosurgery. Our postoperative outcomes 3 months after surgery found 113 patients (85.6%), seizure-free (Engel I), 16 Engel II (12.1%), and 3 Engel III (2.3 %) in temporal lobe epilepsy. In extratemporal lobe epilepsy, 12 (70.5%) were Engel I, seizure-free, 4 Engel II (23.5%) and 1 Engel III (6%). These results confirm that a majority of patients with drug-resistant epilepsy may benefit from surgical treatment without submitting to preoperative invasive explorations. This should help develop epilepsy surgery widely in Africa.

Utility of 68Ga-DOTATATE PET-MRI for Gamma Knife® stereotactic radiosurgery treatment planning for meningioma.

To investigate the impact of adding 68Ga-DOTATATE PET/MRI to standard MRI for target volume delineation in Gamma Knife® stereotactic radiosurgery (GKSRS) for meningioma. Seventeen patients with 18 lesions undergoing GKSRS for WHO grade 1 meningioma were enrolled in a prospective study. All patients underwent pre-treatment 68Ga-DOTATATE PET/MRI examination in addition to standard procedures. Five clinicians independently contoured the gross tumour volume (GTV) based on standard MRI (GTVMRI) and PET/MRI (GTVPET/MRI) on separate occasions. Interobserver agreement was evaluated using Cohen's Kappa statistic (CKS), Dice similarity coefficient (DC), and Hausdorff distance (HD). Statistical analysis was performed with paired t-test and Wilcoxon signed rank test. The addition of PET/MRI significantly increased GTV contour volume (mean GTVPET/MRI 3.59 cm3 versus mean GTVMRI 3.18 cm3, P = .008). Using the treating clinician's pre-treatment GTVMRI as the reference, median CKS (87.2 vs 77.5, P = .006) and DC (87.2 vs 77.4, P = .006) were significantly lower, and median HD (25.2 vs 31.0, P = .001) was significantly higher with the addition of PET/MRI. No significant difference was observed in interobserver contouring reproducibility between GTVMRI and GTVPET/MRI. The addition of 68Ga-DOTATATE PET/MRI for target volume delineation in GKSRS for meningioma is associated with an increase in GTV volume and greater interobserver variation. PET/MRI did not affect interobserver contouring reproducibility. This study provides novel insights into the impact of 68Ga-DOTATATE PET/MRI on GTV delineation and interobserver agreement in meningioma GKSRS, highlighting its potential for improving GKSRS treatment accuracy.

The Role of Stereotactic Radiosurgery in Patients With Brain Metastases From Colorectal Cancers.

The role of stereotactic radiosurgery (SRS) in patients with brain metastases (BMs) from colorectal cancers (CRCs) has not been established. The authors present a single-institution experience of patients with CRC who underwent SRS with metastatic brain spread. We retrospectively analyzed 111 patients with metastatic CRC (64 female, 57.7%), with 449 BMs treated with Gamma Knife SRS between 2000 and 2022. The median age during SRS was 63 years (range: 28-86), and the median Karnofsky Performance Scale was 80 (range: 60-100). The primary sites were colon (85 patients, 76.6%) and rectal (26 patients, 23.4%). Three patients underwent hypofractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27-30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 13-20). The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (88.3%) patients expired at last follow-up and 15 patients (15.3%) died related to progressive intracranial disease. A Karnofsky Performance Scale of <80 at SRS presentation ( P = .02, hazard ratio [HR]: 0.6, 95% CI: 0.4-0.9) and no previous surgical resection ( P < .01, HR: 0.4, 95% CI: 0.3-0.7) were associated with inferior overall survival using multivariate analysis. Seventeen patients (15.3%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.4%) developed new BMs at a median of 5 months (range: 2-26) between SRS and new tumor detection. Less than three BMs at SRS presentation ( P = .02, HR: 2.6, 95% CI: 1.2-5.6) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.4%. SRS effectively controls BMs from CRC with low risk of treatment-related toxicity. During follow-up, the development of additional metastases can be safely treated by repeat SRS.

RADT-10. BRAINSTEM METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY: MASKED VS. FRAMED IMMOBILIZATION

Abstract BACKGROUND Patients with brainstem metastases (BSM) have minimal surgical options due to high-risk anatomy. To review our efficacy treating BSM using Gamma Knife stereotactic radiosurgery (GK SRS), we compared results based on the utilization of mask-fixation (MF) or frame-fixation (FF). METHODS Data were retrospectively collected for 32 patients. Follow-up data for 49 lesions were analyzed for local control rate (LCR) and objective response rate (ORR). RESULTS Primary cancers included lung, breast, and melanoma; most lesions were pontine. MF was used in 18 patients. Average tumor volume was 0.99 cm3 (0.005 – 13.3 cm3). 39 lesions were treated with single fraction 16 Gy. 10 lesions were treated in 3-5 fractions with mean dose of 22.5 Gy. Mean follow-up was 14.2 months (1.2 - 48.2 months). 1-year LCR was 94.7%. ORR at last follow-up did not differ between MF vs. FF (p = .81). Average reduction of lesion volume at 6 and 12 months did not differ between MF vs. FF (64% vs 45%, p = .77; 70% vs 77%, p = .78). Failure occurred in a pontine colorectal cancer metastasis mask-immobilized for treatment with 14 Gy. CONCLUSIONS SRS for BSM achieved high LCR despite variability in tumor size and histology with no significant difference between MF vs. FF. Although trials have historically excluded patients with BSM, our data support SRS as a safe and efficacious treatment. This is the first study showing that MF provides equivalent, successful outcomes when compared to FF for patients with BSM.

METASTASES-01 OUTCOME OF BRAIN METASTASES TREATED WITH GAMMA KNIFE STEREOTACTIC RADIOSURGERY (GKSR): COHORT RETROSPECTIVE STUDY ON 205 CASES

Abstract BACKGROUND Brain metastases (BMs) are the most common expansive intracranial lesions in adults. Approximately 50% of patients diagnosed with new brain metastases have more than one brain metastasis at the time of diagnosis. OBJECTIVE We report our experience of brain metastases treated with GKSR and evaluate the outcome. METHODS Patients treated by Gamma Knife stereotactic radiosurgery (GKSR) in our institution between 2008 and 2021 for BM were recorded retrospectively. RESULTS A total of 205 patients (56.6% females) were included, with a median age of 59 (25-83) years old. Breast (n=85, 42.5%) and lung (n=76, 38%) were the common original locations for the primary tumors (Table 1). There were 103 patients (50.3%) with single BM and 102 patients (49.7%) with multiple BM⩾2. The median number of multiple BM treated was 4 (2-43). The overall mean survival time was 6.00(95% CI, 5.07-6.93) months for all BM. The median percentage of tumor control after radiosurgery treatment was 65% (20-99) over the median follow-up time of 6.00(3-84) months. In the overall population, the 1-year OS rate was 37.55%, the 2-year OS rate was 25.12%, and the 5-year OS was 18.51%. The mean survival time among patients with BM was higher in those with multiple BM than those with single BM ([10 (95%CI 6.67-13.33) months vs 5(4.21-5.70) months, P (0.03)]). Retreatment, tumor stability (control), and progression influence the overall survival of BM, whether single or multiple (P&amp;lt;0.001). CONCLUSION Stereotaxic Radiosurgery provides good results in terms of Overall survival and better Quality of Life for BM, whether single or multiple. Stability and retreatment influenced the overall survival of BM.

Delayed Imaging Changes 18 Months or Longer After Stereotactic Radiosurgery for Brain Metastases: Necrosis or Progression

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

Survival and Radiation Dose Differences Between Single Versus Multi-Session Gamma Knife Stereotactic Radiosurgery in Patients Treated for Multiple (≥10) Brain Metastases.

To explore whether treatment with multiple Gamma Knife sessions (mGK) resulted in different survival outcomes or cumulative radiation doses compared to single session Gamma Knife (sGK) in patients who have been treated for ≥10 brain metastases (BMs). Thirty-five patients with ≥10 BMs treated with Gamma Knife stereotactic radiosurgery (GK SRS) were identified and separated into sGK vs. mGK cohorts. Survival outcomes and dosimetry data were compared between the two groups. Recursive partitioning analysis (RPA) classes were used to further stratify patients. mGK patients survived longer from the first GK treatment (p<0.009). By RPA class, patients with class 1 had a prolonged survival from BM diagnosis than those in classes 2 and 3 (p=0.004). However, survival was not significantly different between the classes from the first GK treatment (p=0.089). Stratified by mGK vs. sGK and RPA classes, sGK patients in RPA class 1 had the longest survival from BM diagnosis but the worst survival from GK treatment. mGK patients in any RPA class had the best survival from the first GK treatment. For patients with RPA class 2+3, mGK was associated with longer survival from both BM diagnosis and first treatment. Statistical but not clinical differences between the mGK vs. sGK groups were observed in the max dose to the targets and cochlea, and the V40Gy whole brain dose. mGK may be beneficial if GK is initiated early at first BM diagnosis vs. sGK initiated late. Future research is required to confirm these findings and explore additional areas of interest, such as quality-of-life and economic considerations.

Role of Genetics and Surgical Interventions for the Management of Cerebral Cavernous Malformations (CMM).

Cerebral cavernous malformations (CCMs) are comprised of tissue matter within the brain possessing anomalous vascular architecture. In totality, the dilated appearance of the cavernomatakes on a mulberry-like shape contributed by the shape and relation to vascular and capillary elements. Analyzing its pathophysiology along with its molecular and genetic pathways plays a vital role in whether or not a patient receives GKRS, medical management, or Surgery, the most invasive of procedures. To avoid neurological trauma, microsurgical resection of cavernomas canbe guided by the novel clinical application of a 3D Slicer with Sina/MosoCam. When cavernomas present in deep lesions with poor accessibility, gamma knife stereotactic radiosurgery (GKSR) is recommended. For asymptomatic and non-multilobal lesions, medical and symptom management is deemed standard, such as antiepileptic therapy. The two-hit hypothesis serves to explain the mutations in three key genes that are most pertinent to the progression of cavernomas: CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10. Various exon deletions and frameshift mutations can cause dysfunction in vascular structure through loss and gain of function mutations. MEKK3 and KLF2/4 are involved in a protein kinase signaling cycle that promotes abnormal angiogenesis and cavernoma formation. In terms of potential treatments, RhoKinase inhibitors have shown to decrease endothelial to mesenchymal transition and CCM lesion development in mice models. All in all, understanding the research behind the molecular genetics in CCMs can foster personalized medicine and potentially create new neurosurgical and medicative treatments.

Long-Term Outcomes of Non-Vestibular Cranial Nerve Schwannomas Treated with Fractionated Stereotactic Radiotherapy and Stereotactic Radiosurgery

Non-vestibular cranial nerve schwannomas (NVCNS) are rare tumors that account for approximately 10% of cranial nerve schwannomas. They are commonly treated with radiation therapy (XRT) due to their location often precluding safe resection. We examined the long-term outcomes of NVCNS treated with XRT as primary management and for post-operative salvage. We conducted a retrospective review of patients with NVCNS treated with fractionated stereotactic radiation therapy (FSRT) or Gamma Knife Stereotactic Radiosurgery (GK-SRS) from 1996 to 2018 at our institution. We examined patient demographics, cranial nerve (CN) involvement, CN function pre-/post-XRT, treatment volume (TV), toxicity, surgery pre-XRT, and local control. Kaplan-Meier analysis was performed for evaluation of local control. We identified 66 patients (38 female, 28 male) with NVCNS, a portion of whom had tumors involving more than one cranial nerve. Forty-six (69.7%) were treated with FSRT (median dose 50.4 Gy in 1.8 Gy/fraction; range 45-54 Gy), and 20 (30.3%) with GK-SRS (median dose 12 Gy; range 12-15 Gy). Median follow-up time was 92.5 months (5-306). Median Karnofsky Performance Status was 90 (70-100). Median age at start of XRT was 45 years old (15-92). Prior to XRT, 34.8% (23) of patients had surgical resection, with median time from surgery to XRT of 4.25 months (0.5-130 months). Median treatment volume was 4.72 cc (0.26-29). The cranial nerve most commonly involved was CN V (48.4%), followed by CN X (15.2%), CN VII (13.6%), CN VI (6.1%), CN XII (6.1%), CN III (6.1%), and CN IX (3%). Twenty-nine (43.9%) patients experienced grade 1 acute toxicity during treatment. Six (9%) patients experienced grade 1 chronic toxicity. No grade 2 or higher acute or chronic toxicity was observed. No significant difference in rates of acute or chronic toxicity was observed between patients treated with GK-SRS vs. FSRT. Post-XRT, 37 patients (56.1%) had improvement in CN function/symptom, 24 patients (36.3%) had stable function/symptoms, and 5 patients (7.6%) had worsening function/symptoms. Local control at one and five years was 100%. In-field recurrence was observed in one patient (1.5%), at 9 years post-XRT. For salvage this patient was treated with a second course of FSRT to the recurrent tumor. Our large institutional series with long term follow up showed excellent local control of NVCNS treated with FSRT or GK-SRS both for primary management and post-operative salvage. Treatment is well tolerated, with high rates of preservation or improvement of CN function, and minimal acute and chronic toxicity.

Clinical Outcomes and Patterns of Failure in Patients with High-Risk Atypical Meningioma Treated with Single Fraction vs. Hypofractionated Gamma Knife Radiosurgery

The recently completed RTOG 0539 supports fractionated radiation therapy for patients categorized as having intermediate (3 yr PFS 93.8%) or high-risk (3 yr LC 68.9%) meningiomas. Stereotactic radiosurgery (SRS) has not been widely established in the treatment of WHO grade 2 atypical meningiomas given concern that there is a greater risk of microscopic infiltration and therefore requires larger margins than safely achievable with SRS. We look to review a consecutive cohort of patients at our institution who have been diagnosed with atypical meningioma treated with either single fraction Gamma Knife SRS (GK-sfSRS) or hypofractionated Gamma Knife SRS (GK-hfSRS). We review both control rates and patterns of failure. Patients diagnosed with intermediate or high-risk WHO grade 2 meningioma per RTOG 0539 classification, without a history of prior radiation (RT) and treated with either GK-sfSRS or GK-hfSRS between 2014 to 2021 at our institution, were included. Patient charts were reviewed, and follow-up data were analyzed for local control (LC) and failure patterns. Local failure was defined as tumor recurrence within the prescription isodose line, marginal was ≤5 mm outside the prescription isodose line, and distant was >5 mm outside of the prescription isodose line Primary outcome was LC, and secondary outcomes were overall survival (OS) and progression free survival (PFS). We identified 47 pathologically confirmed WHO grade 2 meningiomas in 27 patients. 33 lesions were treated with GK-sfSRS and 14 lesions with GK-hfSRS. 6 lesions were intermediate risk, and 41 were high-risk per RTOG 0539. With a median follow up of 36 months (range 2-86 mo), the 3yr LC was 82.7%, PFS was 83.1%, and OS was 96.3%. A total of 4 patients with 8 lesions failed treatment - all with high-risk disease. All failures were local (4) or marginal (4). The 4 local failures were all from a single patient with 4 distinct meningiomas that were treated with GK-sfSRS without surgical resection. The 4 marginal failures were all in patients treated with GK-sfSRS. There were no failures in patients treated with GK-hfSRS. Our institutional data for patients with atypical meningiomas treated with radiosurgical techniques compare favorably to the patients treated with EBRT in RTOG 0539, though longer follow-up is needed to confirm these findings. Outside of one patient, no patients developed recurrence within the prescription volume. There were 4 tumors with marginal failures, suggesting that additional dural margins than what were prescribed may be meaningful. At our institution, we are increasingly moving to hypofractionated radiosurgery with 5 mm of dural margin when using radiosurgical techniques for high-risk atypical meningioma. However, longer term follow-up is needed to validate the use of radiosurgical techniques in atypical meningioma.

Frameless Linear Accelerator (LINAC) Based Radiosurgery (SRS) vs. Framed Gamma Knife SRS for Idiopathic Trigeminal Neuralgia (TN)

Stereotactic radiosurgery (SRS) is an effective treatment for idiopathic trigeminal neuralgia (TN). Conventional treatment is done through frame-based solution due to small target and high radiation dose. More recently, LINAC based frameless SRS technique has been established as a patient friendly alternative. Herein we compared our single institution experience of LINAC based frameless SRS vs frame-based gamma knife SRS for TN. The hypothesis is LINAC based frameless SRS can provide equivalent dosimetric and clinical outcome as compared frame-based gamma knife treatment. Patients with idiopathic TN who received SRS treatment (LINAC based frameless treatment or Gamma knife framed treatment) at our institution from 2015-2022 were included. A minimum follow up of 1 year was required. Patient data was extracted from electronic medical records and radiation treatment planning system. Pain intensity was evaluated utilizing a modified 0-4 Barrow Neurological Institute (BNI) pain intensity score, and then dichotomized where BNI score 0-2 represented response to treatment and BNI score 3-4 represented no response. Statistical analysis was conducted with a linear regression model accounting for race, gender, prior pain, pain distribution including laterality and branch involvement, medication regimen at time of treatment, previous radiation treatment, and prior procedures. Response was then compared between both modalities overall and within each sub-group with chi-square testing and linear regression. A total of 81 patients were identified, 14 patients were excluded due to lack of adequate follow-up, leaving 67 for analysis. 12 (17.9%) were male and, 55 (82.1%) were female. All patients were managed with medication prior to SRS treatment. 5 (7.5%) had rhizotomy and 13 (19.4) had microvascular decompression, and 8 (11.9%) had previous gamma-knife radiosurgery prior to SRS treatment at our institution. Of the 67 patients, 23 (34.3%) received frame-based gamma knife SRS, 44(65.7%) received frameless LINAC treatment. 58 (86.6%) radiation naïve patients received 90 Gy in 1 fraction, while out of the 9 who had previously had intracranial radiation treatment 7 (10.4%) received 70 Gy and 2 (3%) received 80 Gy all prescribed to 100% isodose line. All patients were treated with 4 mm cone. There was no significant difference in brainstem dose between these two techniques. Between LINAC-based or Gamma Knife modalities rate of pain control (77.3 % vs 82.6 %, respectively, p = 0.61) as well as toxicity in facial numbness (31.8% vs 21.7%, respectively, p = 0.38) showed no statistical difference. There was no statistically significant signal (p > 0.05) detected within the subgroups analyzed. The linear regression model also showed no significant difference. LINAC based frameless SRS provides comparable dosimetry and pain control for TN as compared to frame-based gamma knife treatment. It is a patient friendly solution for patients with TN.

Pentoxifylline and Vitamin E Can Restrict Radiation Necrosis via Vascular Pathways, Experimental Study in an Animal Model

Radiation necrosis is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have previously been shown to be effective in the treatment of radiation necrosis in the published literature, but there are no data on the prophylactic use of these molecules or, more importantly, whether prophylaxis is required. The iatrogenic radiation necrosis model included 50 Sprague-Dawley rats of both sexes. There were seven treatment subgroups established. Gamma-Plan 8.32 was used to plan after magnetic resonance (MR) scans were performed in a specially designed frame. The injection doses used in the treatment groups were vitamin E (30 mg/kg/day in a single dose) and pentoxifylline (50 mg/kg/day in two doses). Control MR scans were performed at the end of a 16-week treatment, and the subjects were decapitated for pathological evaluations. The intensity of HIF-1α immunoreactivity is statistically significantly lower in the therapeutic vitamin E, prophylactic pentoxifylline and vitamin E, and therapeutic pentoxifylline and vitamin E groups than in the other groups. Similarly, the intensity of VEGF immunoreactivity was reduced in the therapeutic vitamin E and prophylactic pentoxifylline and vitamin E treatment modality groups. When compared with other groups, the therapeutic pentoxifylline group had significantly fewer VEGF-immunoreactive cells in the peri-necrotic area, with an accompanying decreased contrast enhancement pattern. Both vitamin E and pentoxifylline are effective for the treatment and/or restriction of radiation necrosis, either alone or in combination. The use of these molecules as a preventive measure did not outperform the therapeutic treatment.