Role Of Stereotactic Radiosurgery Research Articles

QLTI-03. REAL-WORLD PARADIGM FOR TREATMENT OF PRIMARY CNS LYMPHOMA PATIENTS IN CLINICAL PRACTICE

Abstract Although high-dose methotrexate (HD-MTX) is the foundation of induction therapy for primary CNS lymphoma (PCNSL), a gold-standard regimen has yet to be established. A 10-case-based survey, to assess the practice patterns at key decision-points in adult PCNSL management outside of clinical trials, was distributed through IPCG, HOVON, and AAN Neuro-Oncology Section. Eighty-five responses were collected from North American (N=42), European (N=33), Asian (N=7), and other countries (N=3) from neurologist neurooncologists (N=35), hem-onc neurooncologists (N=24), hematologist-oncologists (N=18), neurosurgeons (N=5), radiation-oncologist (N=2), and hematopathologist (N=1). The most common first-line induction regimen was R-MP+/-V: rituximab, HD-MTX, procarbazine, +/-vincristine (N=28) followed by MATRix: HD-MTX, cytarabine, thiotepa, rituximab (N=23), then R-MT: rituximab, HD-MTX, temozolomide (N=19). For elderly patients, R-MP+/-V remained most common (N=32). The majority preferred to omit intra-CSF chemotherapy (N=50). The most preferred consolidation after complete response was high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT, N=57), or high-dose cytarabine (N=17) in elderly patients. In cases of partial response, the most common approach was still HDC-ASCT (N=24). For stable disease, participants would move to various salvage chemotherapy (N=33), continue additional induction (N=39), or to move to radiotherapy (N=10). If early progression was noted, the most preferred approach was non-methotrexate chemotherapy (N=31). For recurrences after previous complete response and HDC-ASCT consolidation, the majority preferred to try chemotherapy before moving to radiotherapy in scenarios < 1 year (N=64) or > 1 year from consolidation (N=68), and even if the performance status was poor (N=57). Close to half (N=34) participants felt there is a role for stereotactic radiosurgery in various clinical settings. This survey noted clear consensus to use multi-drug MD-MTX based chemotherapy, and common induction regimens, however, highlighted a great variety of treatment preferences after first-line therapy even amongst disease experts through clinical consortiums, suggesting likely wider range of treatments and disease response in larger community settings.

Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: patient outcomes and lessons learned over a 3-decade single-center experience.

The role of stereotactic radiosurgery (SRS) in the management of intracranial dural arteriovenous fistula (dAVF) is unclear given the rarity of this lesion and the variability in treatment paradigms. This study describes a 3-decade experience with the SRS technique and its outcomes for patients with dAVF. The authors conducted a retrospective analysis of patients with dAVF who had undergone single-fraction SRS in the period from 1990 to 2021. The imaging modality initially used for targeting was angiography alone, then angiography plus MRI, and most recently MRI alone. Two hundred twenty-two patients underwent SRS alone (n = 56, 25%) or SRS plus embolization (n = 166, 75%), depending on the severity of symptoms or the presence of cortical venous drainage (CVD). Most patients were women (64%), and the median patient age was 60 years. Common presenting symptoms were pulsatile bruit (55%), visual change or chemosis (21%), headache (10%), and intracerebral hemorrhage (5%). The most frequent dAVF location was the transverse or sigmoid sinus (44%), followed by the cavernous sinus (24%), jugular bulb (9%), and torcula (5%). CVD was noted in 28% of cases, and venous ectasia in 5%. Borden dAVF types among the patients were I (72%), II (20%), and III (8%). Cognard dAVF types among the patients were I (44%), IIa (27%), IIb (5%), IIa+b (15%), III (4%), and IV (5%). The median SRS treatment volume was 7.6 cm3; the median margin and maximum doses were 18 and 36 Gy, respectively. Follow-up after SRS was available for 209 patients (median follow-up 31 months). Obliteration was noted in 75% of the patients (110/147) with follow-up vascular imaging; the median time to obliteration was 37 months. Multivariate analysis revealed that a cavernous sinus dAVF location was predictive of radiological obliteration (HR 1.86, 95% CI 1.08-3.18, p = 0.024). The absence of CVD was predictive of obliteration in subgroup analysis of non-cavernous sinus dAVF (HR 0.53, 95% CI 0.29-0.98, p = 0.04). Symptoms resolved in 86% of patients (160/185) with clinical follow-up. Twelve patients (5.4%) had complications related to angiography for SRS planning (n = 2, 0.9%), embolization (n = 3, 1.4%), post-SRS hemorrhage (n = 1, 0.5%), delayed sinus thrombosis (n = 1, 0.5%), radiation-induced tumors (n = 2, 0.9%), and chronic encapsulated expanding hematoma (n = 3, 1.4%). SRS alone or in conjunction with embolization provided obliteration and symptom relief for the majority of patients with dAVF, with a low rate of procedure-related morbidity. Patients are at risk for late radiation-related complications, which can require treatment many years after SRS.

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.

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.

Stereotactic radiosurgery and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitors, or conventional chemotherapy for the management of melanoma brain metastases

BackgroundImmunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and various systemic therapies. MethodsPatients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1+CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. Comparisons between groups were made for overall survival (OS), distant MBM control, local MBM, systemic progression-free survival (sPFS), and neurotoxicity. ResultsIn total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 and 2020 were identified. On MVA, treatment with anti-PD1+anti-CTLA-4, anti-PD-1, and BRAF/MEK-i improved distant intracranial control over conventional chemotherapy. No significant differences were noted in local control (LC) between groups (p = 0.78). Kaplan–Meier OS at 12 months for anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, and conventional chemotherapy was 68%, 59%, 45%, 62%, 21%, and 15%, respectively (p = <0.0001). The sPFS rates at 12 months were 57%, 53%, 42%, 45%, 14%, and 6% (p = <0.0001). No significant differences were noted in rates of radiation necrosis (p = 0.93). ConclusionsThis is among the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in OS, distant MBM control, and sPFS by systemic therapy. No differences in LC or radiation necrosis risk were noted.

Stereotactic Radiosurgery for Brain Metastases in Patients With Small Cell Lung Cancer

Treatment of small cell lung cancer (SCLC) with brain metastatic disease has traditionally involved whole brain radiation therapy (WBRT). The role of stereotactic radiosurgery (SRS) is unclear. Our study was a retrospective review of an SRS database evaluating patients with SCLC who received SRS. A total of 70 patients and 337 treated brain metastases (BM) were analyzed. Forty-five patients had previous WBRT. The median number of treated BM was 4 (range, 1-29). Median survival was 4.9 months (range, 0.70-23.9). The number of treated BM was correlated with survival; patients with fewer BM had improved overall survival (P < .021). The number of treated BM was associated with different brain failure rates; 1-year central nervous system control rates were 39.2% for 1 to 2 BM, 27.6% for 3 to 5 BM, and 0% for >5 treated BM. Patients with previous WBRT had worse brain failure rates (P < .040). For patients without previous WBRT, the 1-year distant brain failure rate was 48%, and median time to distant failure was 15.3 months. SRS for SCLC in patients with <5 BM appears to offer acceptable control rates. Patients with >5 BM have high rates of subsequent brain failure and are not ideal candidates for SRS.

Single-Session Gamma Knife Radiosurgery for Patients With 20 or More Brain Metastases.

Stereotactic radiosurgery (SRS) is a widely accepted treatment modality for brain metastases. The role of SRS in patients with higher numbers of metastases remains controversial. To define outcomes in patients with ≥20 brain metastases managed using single-session SRS. This single-institution retrospective cohort study studied 75 patients (26 non-small-cell lung cancer, 21 small-cell lung cancer, 14 breast cancer, and 14 melanoma) undergoing single-session SRS. The median number of tumors per patient was 24, and the median cumulative tumor volume was 3.70 cc. The median margin dose prescribed to each individual tumor was 16 Gy. The median integral cranial dose was 5492 mJ. The median beam on time was 160 minutes. Univariate and multivariate analyses were performed with significance set at P < .05. The median overall survival after SRS was 8.8 months (patients with non-small-cell lung cancer), 4.6 months (patients with small-cell lung cancer), 11.3 months (patients with breast cancer), and 4.1 months (patients with melanoma). Primary cancer type, number of brain metastases, and concurrent immunotherapy were significant factors in predicting survival. Local tumor control rate per patient was 97.3% and 94.6% at 6 and 12 months after SRS, respectively. Thirty-six patients underwent additional SRS for new tumor development with a median time after SRS of 5 months. Three patients experienced adverse radiation events. Single-session SRS is a well-tolerated palliative treatment option even in patients with ≥20 brain metastases, achieving local control rate >90% with low risks of neurotoxicity while continuing concurrent systemic oncological care.

Trends in Stereotactic Radiosurgery for Intracranial and Spinal Pathologies: Analysis of the Top 100 Most Cited Articles.

There is a plethora of papers on the role of stereotactic radiosurgery (SRS) in various benign and malignant intracranial tumors, and it is possible to overlook the most important and landmark studies. Thus, the necessity of citation analysis arises, which reviews the most cited articles and recognizes the impact made by these articles. Utilizing the 100 most cited articles describing the use of SRS for intracranial and spinal pathologies, this article aims to provide meaningful information regarding the historical trends and recent directions in which this field is headed. We performed a search of the Web of Science database using the keywords "stereotactic radiosurgery," "gamma knife," "GKRS," "gamma knife radiosurgery," "LINAC," and "Cyberknife" on May 14, 2022. Our search retrieved a total of 30,652 articles published between the years 1968 and 2017. The top 100 cited articles were arranged in descending order based on citation count (CC) and citation per year (CY). The journal with the largest number of publications as well as citation count was the International Journal of Radiation Oncology Biology Physics (n = 33), followed by Journal of Neurosurgery (n = 25). The most cited article was authored by Andrews, which was published in 2004 in The Lancet (1699 CC, 89.42 CY). Flickinger, with 25 papers and 7635 total citations, was the author with the highest impact. Lunsford, with 25 publications and total citations of 7615, was a close second. The USA was the leading country with the maximum number of total citations (n = 23,054). Ninety-two articles described the use of SRS for intracranial pathologies (metastases, n = 38; AVM, n = 16; vestibular schwannoma, n = 9; meningioma, n = 8; trigeminal neuralgia, n = 6; sellar lesion, n = 2; glioma, n = 2; functional, n = 1; and procedure related, n = 10). Eight studies describing spinal radiosurgery were included, out of which four were on spinal metastases. Citation analyses of the top 100 articles revealed that the focus of research in the field of SRS started with functional neurosurgery and progressed to benign intracranial tumors and AVMs. More recently, central nervous system (CNS) metastases have received the maximum attention with 38 articles, including 14 randomized controlled trials finding a place in the top 100 cited articles. Presently, the use of SRS is concentrated in developed countries. Efforts need to be made for more widespread use in developing nations to bring the maximum possible benefits of this focused noninvasive treatment to a wider population.

Role of Stereotactic Radiosurgery for Cavernous Sinus Hemangiomas - An Individual Patient Data-Based Meta-Analysis.

Cavernous sinus haemangiomas (CSHs) are rare vascular malformations arising from the micro-circulation of the cavernous sinus. The current treatment options are micro-surgical excision of CSH, stereotactic radiosurgery (SRS), and fractionated radiation therapy (FRT). We conducted a meta-analysis assessing the effect and complications of SRS in CSH and compared the pooled results after surgical excision of CSH. The aim of the study is to provide valuable insight into the role of SRS in the treatment of CSHs. The literature search revealed a total of 21 articles with 199 patients who met our inclusion criteria, and these were analyzed for this study. There were 138 (69.3%) female and 61 (30.7%) male patients. The mean age at the time of radiosurgery was 48.4 ± 14.9 years. The mean tumor volume at the time of SRS was 17.4 cm3 (range 0.3-138 cm3). Fifty (25%) patients had undergone surgery before SRS, whereas 149 (75%) patients received standalone SRS. A total of 186 (93.5%) patients were treated by gamma knife radiosurgery (GKRS), whereas 13 got treated by Cyberknife. The mean tumor volume in CK-F, GKRS, and GKRS-F groups was 36.6 ± 26.3, 15.4 ± 18.4, and 86.0 ± 19.5 cm3, respectively. The mean marginal dose was 21.8 ± 2.9 Gy, 14.0 ± 1.9 Gy, and 25 ± 0.0 Gy in CK-F, GKRS, and GKRS-F groups, respectively. The mean marginal dose of SRS was 14.6 ± 2.9 Gy. The mean follow-up period after SRS was 35.8 ± 31.6 months. Significant clinical improvement was seen in 106 patients out of 116 (91.4%) after SRS with remarkable shrinkage, 22 patients out of 27 (81.5%) with minimal shrinkage, and nine patients out of 13 (69.2%) with stationary tumor shrinkage. The sixth cranial nerve (CN6) was the most commonly involved nerve in 73 patients (36.7%). 30/65 (89%) experienced an improvement in the abducent nerve function following SRS. 115/120 (95.8%) patients primary treated with SRS experienced clinical improvement, whereas the rest of the five patients remained clinically stable. Radiosurgery SRS is a safe and effective option in patients with CSHs and resulted in more than 50% decrease in tumor volume in 72.4% of the patients.

Role of Stereotactic Radiosurgery in the Management of Dural AV Fistula.

Dural arteriovenous fistulas (DAVFs) are a relatively rare intracranial vascular malformation. The various treatment options for DAVFs include observation, compression therapy, endovascular therapy, radiosurgery, or surgery. A combination of these therapies may also be used. The treatment choice for DAVFs depends on the type of fistula, the severity of symptoms, DAVF angioarchitecture, and the efficacy and safety of treatments. The use of stereotactic radiosurgery (SRS) in DAVFs started in the late 1970s. There is a delay before the fistula gets obliterated after SRS and there is a risk of hemorrhage from the fistula till the fistula gets obliterated. Initial reports described the role of SRS in small DAVFs without severe symptoms, which were inaccessible by endovascular or surgical measures or in combination with embolization in larger DAVFs. SRS can be appropriate for indirect cavernous sinus DAVF fistulas (Barrow type B, C, and D). Borden types II and III and Cognard types IIb-V DAVFs have a high risk of hemorrhage and are traditionally considered less favorable to be treated with SRS as immediate treatment is required to decrease the risk of hemorrhage. However, recently SRS has been tried in these high-grade DAVF as a monotherapy. Factors that have a positive impact on the obliteration rates of DAVF following SRS are the location of DAVF with the cavernous sinus DAVF having much better obliteration rates than DAVF located at other locations, Borden Type I or Cognard Types III or IV DAVFs, absence of CVD, hemorrhage at the time of initial presentation, and target volume lesser than 1.5 mL.

Role of Stereotactic Radiosurgery in Glial Tumors.

Glial tumors are a relatively new indication for stereotactic radiosurgery (SRS). Traditionally, SRS has been considered to be an inadequate treatment for glial tumors as these are diffuse tumors, but SRS is a highly focused treatment. Tumor delineation can be challenging given the diffuse nature of the gliomas. It has been recommended to include the T2/fluid-attenuated inversion recovery (FLAIR) altered signal intensity areas in addition to the contrast enhancing part in the treatment plan of glioblastoma in order to increase the coverage. Some have recommended to include 5 mm margins to cover up for the diffusely infiltrative nature of the glioblastoma. The most common indication of SRS in patients with glioblastoma multiforme is tumor recurrence. SRS has also been used as a boost to the residual tumor or tumor bed after surgical excision before conventional radiotherapy. The addition of bevacizumab has been recently tried along with SRS in patients with recurrent glioblastoma to decrease radiation toxicity. Besides, SRS has also been used in patients with low-grade gliomas following recurrence. Brainstem gliomas, which are usually low-grade gliomas, are another indication for SRS. Outcomes following the use of SRS are comparable with external beam radiotherapy in brainstem gliomas, whereas the risks of radiation-induced complications is less. SRS has also been used in other glial tumors such as gangliogliomas and ependymomas.

Stereotactic Radiosurgery and Anti-PD-1 + CTLA-4 Therapy, Anti-PD-1 Therapy, Anti-CTLA-4 Therapy, BRAF/MEK Inhibitors, BRAF Inhibitor, or Conventional Chemotherapy for the Management of Melanoma Brain Metastases

<h3>Purpose/Objective(s)</h3> Immunotherapy and targeted BRAF/MEK inhibition have revolutionized the systemic management of advanced melanoma with sustained intracranial responses noted in prospective clinical trials. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAF inhibitor, or conventional chemotherapy. <h3>Materials/Methods</h3> Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. The assigned regimen was the last course of systemic treatment to avoid the effects of multiple systemic agents influencing clinical end points. The primary endpoint was distant MBM control with secondary endpoints of local MBM control (defined as a sustained less than >20% volume increase on follow-up MRIs) and OS from SRS. <h3>Results</h3> In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 to 2020 were identified: Median SRS dose was 24 Gy (range: 15-24 Gy) all in a single fraction. Median follow-up using the reverse Kaplan-Meier (KM) method was 41.8 months. No significant differences were noted in age (p=0.10), gender (p=0.47), Karnofsky Performance Scale (KPS) (p=0.27), treated gross tumor volume (p=0.07), number of MBM treated per patient (0.08), or Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) (p=0.28) between groups. Twelve-month KM OS rates by DS-GPA were 17%, 33%, 54%, and 69% for scores 0-1, 1.5-2, 2.5-3, 3.5-4, respectively (p=<0.001). Twelve-month KM distant MBM control rates were 42%, 63%, 24%, 44%, 23%, and 16% (p=<0.001) for SRS with anti-PD-1 + CTLA-4, anti-PD-1, anti-CTLA-4, BRAF/MEK inhibitors (i), BRAF-i, or chemotherapy, respectively. The 12-month KM local MBM control rates were 86%, 77%, 79%, 85%, 87%, and 57% (p=<0.001). Twelve-month OS rates from SRS diagnosis were 68%, 59%, 45%, 62%, 21%, and 15% (p=<0.001). On multivariate analysis (MVA), 2-5 MBM (HR 1.72, 95% CI: 1.1-42.7, p=0.02) and >5 MBM being treated (HR 2.65, 95% CI: 1.65-4.25, p=<0.001) was associated with worse distant MBM control. Treatment with anti-PD-1 therapy (HR 0.24, 95% CI:0.14-0.41, p=0.0009) was associated with improved distant MBM control. MVA also showed, treatment with anti-PD-1 (HR 0.27, 95% CI: 0.17-0.41, P=0.0007) and anti-PD-1 + CTLA-4 (HR 0.29, 95% CI: 0.15-0.53, p=0.01) were both associated with increased OS. The rates of symptomatic radiation necrosis were 2%, 2%, 1%, 1%, 2%, and 3% (p=0.93). <h3>Conclusion</h3> To our knowledge, this is the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in distant MBM control as well as OS by systemic therapy.

The Role of Stereotactic Radiosurgery in the Treatment of Large Brain Metastases

Stereotactic radiosurgery is a modern treatment modality for patients with intracranial metastases. However, it has long been acknowledged that radiosurgery of large tumors results in limited efficacy and increased rate of complications. There have been still debates on the need of combination of radiosurgery and open surgery for intracranial metastases and the sequence of these modalities. The next question is about the proper treatment for metastases that could not be resected. There is a paucity of data describing the relationship between radiosurgical options and radiobiological effect, in particular how prescribed dose, type of fractionation, volume of irradiated tumor and morphology of cancer are related. The information presented in this review highlights opportunities of stereotactic radiosurgery for treatment of patients with large intracranial metastases in combination with open surgery as well as a stand-alone method when using hypofractionation regimen.

The role of stereotactic radiosurgery in the multidisciplinary management of pituitary metastases

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

P14.03.B Glutamate excitotoxicity in brain metastases from lung, breast, and melanoma treated with stereotactic radiosurgery

Abstract Background Brain metastases (BM) are the most frequent neoplasm in the central nervous system (CNS) and primary tumors frequently involved are melanoma, lung cancer and breast cancer. CNS localisation is associated with poor prognosis, and stereotactic radiosurgery (SRS) represents a treatment option for patients with a good performance status. Glutamate (Glu) is a neurotransmitter which plays a facilitating role in carcinogenesis and progression of malignant tumors, as well as in excitotoxicity. Glu efflux from the brain is regulated by scavengers glutamic oxaloacetic transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH), with aspartate and lactate as catabolites. Glu efflux from the brain seems to be impaired in advanced-stage cancers, resulting in increased blood Glu levels where scavengers exert a protective role. Our hypothesis is that serum Glu and scavengers’ levels are related to neuroinvasion and treatment response in patients with BM and may represent potential biomarkers for BM course and prognosis. Material and Methods Serum Glu scavengers (GOT1, GPT and LDH), serum Glu, aspartate and lactate levels are collected in included patients treated and grouped in A) BM group of patients affected by BM from lung or breast cancer or melanoma, treated with SRS; B) Control-1 group of patients affected by lung cancer, breast cancer or melanoma but without BM and C) Control-2 group of patients with benign intracranial lesions (meningiomas, acoustic schwannomas) treated with SRS.In A) and C) serum metabolites and scavengers will be analyzed before and after SRS treatment (at 3, 6, 9 months) while in B) analyzed once. Blood levels in A) and C) help in identifying differences related to malignancy, the role of SRS and the association with disease control, while blood levels in A) and B) help in detecting differences related to BMs. Exclusion criteria are surgical or previous radiosurgical treatment for BM. This study has received Institutional Ethical Committee approval on 3rd August 2020 (Project NCH04-2020, Clinicaltrials.gov identifier: NCT04785521). Preliminary results Comparison between BM group (n = 32) and Control-1 (n=18) revealed a significant difference in LDH (271.93 vs 217.56 U/L; p 0.041) and lactate (1.86 vs 1.34 mmol/L, p = 0.022) and a trend towards significance in glutamate (103.43 vs 73.74 µmol/L, p = 0.07). Comparison between BM group (n=32) and Control-2 (n = 37) revealed a difference in LDH (271.93 vs 210.89 U/L; p &amp;lt; 0.001), lactate (1.86 vs 1.24 mmol/L; p &amp;lt; 0.001), aspartate (16.36 vs 10.22 µmol/L, p 0.006) and glutamate levels (123 vs 103 µmol/L, p = 0.052). Conclusion The present study is the first one addressing serum glutamate and scavenger levels in patients with BM. If the hypothesis will be confirmed, new targets in glutamate signalling pathway could be identified to define new therapeutic strategies in this challenging disease.

The role of stereotactic radiosurgery in the management of petroclival meningioma: a systematic review.

Petroclival meningioma (PM) is a challenging neuro oncology case and stereotactic radiosurgery (SRS) is proposed as one treatment option. This systematic review aimed to examine the role of SRS in treating PM cases. We constructed a systematic review using the PRISMA guidelines using peer-reviewed English literature until 16 February 2022 from EuroPMC and PubMed. We used the terms petroclival meningioma, clival meningioma, apex petrous meningioma, spheno petroclival meningioma, stereotactic radiosurgery, radiosurgery, CyberKnife, Gamma Knife, linear accelerator, LINAC, and radiotherapy. 10 out of 266 studies were chosen for this systematic review, two of which are case reports. The study comprised 719 patients, 73.7% of whom were female (n = 530) and had a median age of 56.99years (18-90years). At the time of diagnosis, the median tumor volume was 6.07 cm3 (0.13-64.9 cm3). The tumors were frequently located near the petroclival junction (83.6%, n = 598). Following SRS, the median follow-up was 64.52months (3-252months). 46.5% of 719 PMs exhibited a decrease in tumor size. 46% and 7.5% showed no change and increase in tumor volume, respectively. At the last radiographic follow-up (7-21.2years), tumor control with a median of 98.8% (85-100%). Complications occurred in 6% of patients, with hydrocephalus (2.2%) as the prevalent complication.The use of SRS as a primary treatment for petroclival cases was not associated with increased complication rate RR 0.62 (95% CI [0.11, 3.59], p = 0.59) but statistically correlated with clinical failure clinical failure RR 0.56 (95% CI [0.32, 0.98], p = 0.04). We found a low number of complications following SRS intervention and has been effectively controlling tumor progression.

Stereotactic Radiosurgery for pituitary adenomas: A review of literature.

Stereotactic radiosurgery (SRS) is a choice of treatment for pituitary adenomas (PA), particularly for residual or recurrent disease, apart from surgery. It has a progression free survival and endocrine remission rate comparable to surgery, with fewer side effects, making it an ideal tool for dealing with PA. In this review, we have discussed the role of SRS for primary as well as post-operative residual/ recurrent PA, and have assessed its safety and outcomes.

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas—A Multicenter Analysis and Review of the Literature

Simple SummaryMeningiomas represent the most common central nervous system (CNS) tumor. Despite their often benign nature, a tumor location in direct proximity to vital brain structures may lead to significant morbidity. This is the case for foramen magnum meningiomas (FMMs) as they grow at the skull base, next to the brain stem and foramen magnum. Surgical resection represents the mainstay of FMM treatments. In patients unsuitable for surgery, with tumor recurrences or tumor remnants after surgery, non-invasive treatment modalities may play a crucial role in patient management. Reports and studies on stereotactic radiosurgery (SRS) for the treatment of FMMs are scarce. This multicenter analysis reported the outcome data of 62 patients with FMMs. SRS achieved a high local tumor control and demonstrated a favorable safety profile. These results are in agreement with previous findings. SRS should be considered for selected FMM patients.Background: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. Methods: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. Results: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. Conclusions: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.

A Case Report Of Cerebral Arterio Venous Malformation Treated With Frameless Stereotactic Radiosurgery

Central nervous system Arterio-venous-malformations (AVM) are relatively rare developmental anom-alies in both paediatric and adult populations. It is although not very rare to treat these AVM’s with radiosur-gery. There has been multiple case series published in literature about the possible treatment options and role of Stereotactic radiosurgery (SRS). Gamma Knife, Cyber knife, Linac based SRS and Proton beam radiosurgery are different options used for the delivery of SRS. We intend to present a case of cerebral AVM in an adult pa-tient, successfully treated with Linac based SRS using simplified setup techniques and advanced planning sys-tem. Keywords: Case report, Stereotactic Radio Surgery , Arterio-Venous-Malformations , Acuros, Radiotherapy

Commentary: The Role of Stereotactic Radiosurgery in the Management of Brain Metastases From a Health-Economic Perspective: A Systematic Review.

Haider, Sameah A MBA, MD; Shank, Christopher D MD, MBA; Walters, Beverly C MD, MSc, FRCSC Author Information