Adjuvant Stereotactic Radiosurgery Research Articles

Jugular Foramen Paragangliomas.

Paragangliomas are the most common tumors at jugular foramen and pose a great surgical challenge. Careful clinical history and physical examination must be performed to adequately evaluate neurological deficits and its chronologic evolution, also to delineate an overview of the patient performance status. Complete imaging evaluation including MRI and CT scans should be performed, and angiography is a must to depict tumor blood supply and sigmoid sinus/internal jugular vein patency. Screening for multifocal paragangliomas is advisable, with a whole-body imaging. Laboratory investigation of endocrine function of the tumor is necessary, and adrenergic tumors may be associated with synchronous lesions. Preoperative prepare with alpha-blockage is advisable in norepinephrine/epinephrine-secreting tumors; however, it is not advisable in exclusively dopamine-secreting neoplasms. Best surgical candidates are young otherwise healthy patients with smaller lesions; however, treatment should be individualized each case. Variations of infratemporal fossa approach are employed depending on extensions of the mass. Regarding facial nerve management, we avoid to expose or reroute it if there is preoperative function preservation and prefer to work around facial canal in way of a fallopian bridge technique. If there is preoperative facial nerve compromise, the mastoid segment of the nerve is exposed, and it may be grafted if invaded or just decompressed. A key point is to preserve the anteromedial wall of internal jugular vein if there is preoperative preservation of lower cranial nerves. Careful multilayer closure is essential to avoid at most cerebrospinal fluid leakage. Residual tumors may be reoperated if growing and presenting mass effect or be candidate for adjuvant stereotactic radiosurgery.

Is there an optimal time to administer postoperative stereotactic radiosurgery in patients with brain metastases? A systematic review of the literature and meta‐analysis

AbstractPostoperative stereotactic radiosurgery improves local tumor control in patients with metastatic brain cancer. However, the influence of timing on its therapeutic efficacy is unclear. In this study, we performed a meta‐analysis and systematic literature review examining publications that reported the timing of postoperative stereotactic radiosurgery (SRS) for patients with intracranial metastases. Our primary outcomes included median overall survival and rates of local and regional failure, while secondary outcomes examined the incidence of treatment‐related adverse events. Correlations between median SRS timing and these variables were assessed using linear regression and publication bias was appraised via Egger's test. Our study resulted in 22 articles comprising 1338 patients. The median timing of adjuvant SRS spanned 14.5 to 41 days. There was a significant negative study‐level correlation of median time to SRS with regional failure (p = 0.043, R2 = 0.32) but not with overall survival (p = 0.54, R2 = 0.03) or local failure (p = 0.16, R2 = 0.14). Additionally, there was significant heterogeneity within the reports (p<0.0001). In conclusion, our analysis demonstrated that postoperative SRS timing did not influence local failure rates which may in part be due to significant variability between individual study designs and patient demographics. Further research is warranted to elucidate the role of timing for postoperative SRS on oncologic outcomes.

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases

Adjuvant stereotactic radiosurgery (SRS) enhances the local control of resected brain metastases (BrM). However, the risks of local failure (LF) and potential for posttreatment adverse radiation effects (PTRE) after early postoperative adjuvant SRS have not yet been established. To evaluate whether adjuvant SRS delivered within a median of 14 days after surgery is associated with improved LF without a concomitant increase in PTRE. This prospective cohort study examines a clinical workflow (RapidRT) that was implemented from 2019 to 2022 to deliver SRS to surgical patients within a median of 14 days, ensuring all patients were treated within 30 days postoperatively. This prospective cohort was compared with a historical cohort (StanRT) of patients with BrM resected between 2013 and 2019 to assess the association of the RapidRT workflow with LF and PTRE. The 2 cohorts were combined to identify optimal SRS timing, with a median follow-up of 3.3 years for survivors. Timing of adjuvant SRS (14, 21, and 30 days postoperatively). LF and PTRE, according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria. There were 438 patients (265 [60.5%] female patients; 23 [5.3%] Asian, 27 [6.2%] Black, and 364 [83.1%] White patients) with a mean (SD) age of 62 (13) years; 377 were in the StanRT cohort and 61 in the RapidRT cohort. LF and PTRE rates at 1 year were not significantly different between RapidRT and StanRT cohorts. Timing of SRS was associated with radiographic PTRE. Patients receiving radiation within 14 days had the highest 1-year PTRE rate (18.08%; 95% CI, 8.31%-30.86%), and patients receiving radiation between 22 and 30 days had the lowest 1-year PTRE rate (4.10%; 95% CI, 1.52%-8.73%; P = .03). LF rates were highest for patients receiving radiation more than 30 days from surgery (10.65%; 95% CI, 6.90%-15.32%) but comparable for patients receiving radiation within 14 days, between 15 and 21 days, and between 22 and 30 days (≤14 days: 5.12%; 95% CI, 0.86%-15.60%; 15 to ≤21 days: 3.21%; 95% CI, 0.59%-9.99%; 22 to ≤30 days: 6.58%; 95% CI, 3.06%-11.94%; P = .20). In this cohort study of adjuvant SRS timing following surgical resection of BrM, the optimal timing for adjuvant SRS appears to be within 22 to 30 days following surgery. The findings of this study suggest that this timing allows for a balanced approach that minimizes the risks associated with LF and PTRE.

Pachymeningeal disease: a systematic review and metanalysis.

Pachymeningeal disease (PMD) is a newly recognized pattern of brain metastasis (BrM) failure that specifically occurs following surgery with adjuvant stereotactic radiosurgery (SRS) and has unique prognostic implications relative to leptomeningeal disease (LMD). Here, we report its prevalence, prognostic implications, and associated risk factors. A literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses on PUBMED and Cochrane from January 2000 to June 2023. We identified 12 studies that included a total of 3992 BrM patients, 659 (16.5%) of whom developed meningeal disease (MD) following surgery plus adjuvant SRS, including either PMD or LMD. The mean prevalence of MD across studies was 20.9% (7.9-38.0%), with PMD accounting for 54.6% of this prevalence and LMD comprising the remaining 45.4%. Mean of the median overall survivals following diagnosis of PMD and LMD was 10.6 months and 3.7 months p = 0.007, respectively, a significant difference. Only 2 risk factors for PMD were reported in ≥ 2 studies and also identified as statistically significant per our meta-analysis: infratentorial location and controlled systemic disease status. While PMD has a superior prognosis to LMD, it is nevertheless a critical oncologic event associated with significant mortality and remains poorly recognized. PMD is predominantly observed in patients with controlled systemic disease status and infratentorial location. Future treatment strategies should focus on reducing surgical seeding and sterilizing surgical cavities.

Preoperative stereotactic radiosurgery as neoadjuvant therapy for resectable brain tumors.

Stereotactic radiosurgery (SRS) is a method of delivering conformal radiation, which allows minimal radiation damage to surrounding healthy tissues. Adjuvant radiation therapy has been shown to improve local control in a variety of intracranial neoplasms, such as brain metastases, gliomas, and benign tumors (i.e., meningioma, vestibular schwannoma, etc.). For brain metastases, adjuvant SRS specifically has demonstrated positive oncologic outcomes as well as preserving cognitive function when compared to conventional whole brain radiation therapy. However, as compared with neoadjuvant SRS, larger post-operative volumes and greater target volume uncertainty may come with an increased risk of local failure and treatment-related complications, such as radiation necrosis. In addition to its role in brain metastases, neoadjuvant SRS for high grade gliomas may enable dose escalation and increase immunogenic effects and serve a purpose in benign tumors for which one cannot achieve a gross total resection (GTR). Finally, although neoadjuvant SRS has historically been delivered with photon therapy, there are high LET radiation modalities such as carbon-ion therapy which may allow radiation damage to tissue and should be further studied if done in the neoadjuvant setting. In this review we discuss the evolving role of neoadjuvant radiosurgery in the treatment for brain metastases, gliomas, and benign etiologies. We also offer perspective on the evolving role of high LET radiation such as carbon-ion therapy. PubMed was systemically reviewed using the search terms "neoadjuvant radiosurgery", "brain metastasis", and "glioma". ' Clinicaltrials.gov ' was also reviewed to include ongoing phase III trials. This comprehensive review describes the evolving role for neoadjuvant SRS in the treatment for brain metastases, gliomas, and benign etiologies. We also discuss the potential role for high LET radiation in this setting such as carbon-ion radiotherapy. Early clinical data is very promising for neoadjuvant SRS in the setting of brain metastases. There are three ongoing phase III trials that will be more definitive in evaluating the potential benefits. While there is less data available for neoadjuvant SRS for gliomas, there remains a potential role, particularly to enable dose escalation and increase immunogenic effects.

P11.36.A TUMOR CONTROL AND FUNCTIONAL OUTCOME IN VESTIBULAR SCHWANNOMA - RESULTS FROM A DUAL-CENTER STUDY COMPARING MICROSURGERY AND GAMMA KNIFE RADIOSURGERY

Abstract BACKGROUND The level of evidence to provide treatment recommendations for vestibular schwannoma (VS) is low. Both Stereotactic Radiosurgery (SRS) and microsurgical resection (SURG) are available as treatment options for VS. There are very few direct comparative studies comparing both treatment modalities in large cohorts allowing detailed subgroup analysis. MATERIAL AND METHODS This is a retrospective dual-center cohort study. Data was retrospectively collected from two large centers involved in the treatment of solitary vestibular schwannomas for patients between 2005 und 2011 to enable follow-up of up to 10 years. Tumor size was classified by Koos Classification. Clinical state was reported by House and Brackmann (H&B) and Gardner-Robertson (G&R) scale (with H&B and G&R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. VS-associated symptoms like trigeminal affection, tinnitus, and vertigo/imbalance were also collected. RESULTS The study population included N=901 patients, who were treated in both centers. N=559 patients were treated by SRS, and 342 patients by SURG.Treatment-related functional deterioration (e.g. hearing and facial deterioration) was significantly more common in patients treated by SURG. The incidence of complications was similar in both groups (14% and 13%). Secondary VS-related symptoms like tinnitus, vertigo, imbalance and trigeminal symptoms were significantly improved by microsurgery, but not by SRS. This study reported an overall incidence of recurrence in SURG of only 4%, and 11% in SRS respectively. Tumor control was comparable in small tumors (Koos I and II) in both SRS and SURG. Patients treated by SRS had significantly smaller tumors (p<0.001). In large VS (Koos III and IV), SURG is superior to SRS considering tumor control with a risk reduction for incidence of recurrence. CONCLUSION SRS can achieve similar tumor control compared to SURG in smaller VS (Koos I-II) - with less severe postinterventional morbidities (hearing and facial function loss). In large VS (Koos III-IV), tumor control by SRS is inferior to SURG. Therefore, while SURG is increasing the risk for facial palsy, it reduces the risk for recurrence. Moreover, SURG may improve secondary VS symptoms (e.g. tinnitus, vertigo/imbalance and trigeminal symptoms), even in small VS. Our data on tumor control and tumor size in SRS and SURG suggest that if combination therapy is chosen, the residual tumor for adjuvant SRS should not exceed the size of Koos II.These figures should be considered when deciding on treatment modality.

Growth potential of small residual tumors after vestibular schwannoma surgery: comparison between remnants and the natural history of small tumors.

Due to the heterogeneous definitions of tumor regrowth and various tumor volume distributions, the nature of small remnants after vestibular schwannoma (VS) surgery and the appropriate timing of adjuvant stereotactic radiosurgery for these remnants remain unclear. In this study, the growth potential of small remnants (< 1 cm3) after VS surgery was compared with that of treatment-naïve (TN) small VSs. This retrospective single-center study included 44 patients with VS remnants following subtotal resection (STR) of a large VS (remnant group) and 75 patients with TN VS (< 1 cm3; TN group). A 20% change in tumor volume over the imaging interval indicated radiographic progression or regression. Tumor progression-free survival (TPFS) rates were estimated using the Kaplan-Meier method. In the remnant group, the mean preoperative tumor volume was 13.8 ± 9.0 cm3 and the mean tumor resection rate was 95% ± 5%. The mean tumor volume at the start of the observation period did not differ significantly between the two groups (remnant vs TN: 0.41 ± 0.29 vs 0.34 ± 0.28 cm3, p = 0.171). The median periods until tumor progression was detected were 15.1 (range 4.9-76.2) months and 44.7 (range 12.6-93.2) months in the TN and remnant groups, respectively. In the remnant group, the TPFS rates were 74% and 70% at 3 and 5 years after the surgery, respectively, compared with 59% and 47% in the TN group. The log-rank test demonstrated a significant difference (p = 0.008) in the TPFS rates between the two groups. Furthermore, 42 patients each from the remnant and TN groups were matched based on tumor volume. TPFS was significantly longer in the remnant group than in the TN group (3-year rates, 77% vs 62%; 5-year rates, 73% vs 51%; p = 0.02). In the remnant group, 18% of the tumor remnants demonstrated regression during follow-up, compared with 9% in the TN group, but this intergroup difference was not significant (p = 0.25). This study demonstrated that the growth potential of small VS remnants was lower than that of TN tumors. Observing for small remnants may be appropriate after STR of a large VS. Given the risk of tumor regrowth, careful observation using MRI should be mandatory during follow-up.

Brain and lung metastasis of uterine leiomyosarcoma: illustrative case.

Uterine leiomyosarcoma is a rare, extremely aggressive tumor with a high rate of metastasis. Five-year survival for individuals with metastatic disease is only 10%-15%. Metastases to the brain are exceptionally rare and are associated with poor survival. The authors report a case of uterine leiomyosarcoma that metastasized to the brain in a 51-year-old woman. A single lesion on magnetic resonance imaging was discovered in the right posterior temporo-occipital region 44 months after resection of the primary uterine tumor. The patient underwent a right occipital craniotomy with gross-total resection of the tumor and is receiving adjuvant stereotactic radiosurgery and chemotherapy with gemcitabine and docetaxel. At 8 months postresection, the patient remains alive and asymptomatic with no sign of recurrence. A literature review of prior reported cases was conducted to analyze patterns of approach to patient treatment and survival. The authors found an apparent survival benefit in patients receiving adjuvant radiation therapy.

Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery.

Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001). PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF.

Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.

The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.

Radiological Evolution of Fat Graft Used for Optic Neuropexy During Surgery for Parasellar Meningiomas.

Stereotactic radiosurgery (SRS) is an effective adjuvant therapy for residual tumor after subtotal resection of parasellar meningiomas. Fat graft placement between the optic nerve/chiasm and residual tumor (optic neuropexy [OPN]) allows for safe SRS therapy. To evaluate the radiological temporal profile of the fat graft after OPN, immediately after surgery and at 3, 6, and 12 months intervals, to elucidate the optimal time point of adjuvant SRS. A single-center, retrospective, cohort study of 23 patients after surgery for parasellar meningioma was conducted. Fat graft volume and MRI signal ratios were calculated. SRS dosimetric parameters (tumor/optic nerve) were measured at the time of SRS and compared with a hypothetical dosimetric plan based on an early postoperative MRI. Of 23 patients, 6 (26%) had gross total resection and 17 (74%) had subtotal resection. Fat grafts showed a progressive loss of volume and signal ratio over time. Radiosurgery was performed in 14 (82.3%; 8 hypofractionated radiosurgery and 6 single fraction). At 3 months, there is a loss of 46% of the fat volume and degradation of its tissue intensity, decreasing differentiation from tumor and nerve. The hypothetical treatment plan (performed on an early postoperative MRI) showed that single-fraction SRS would have been possible in 6 of the 8 hypofractionated cases. OPN is a technique that can be safely performed after resection of parasellar meningiomas. Because of the reduction of the fat volume and tissue differentiation between fat and tumor/nerves, adjuvant radiosurgery is better performed within the first 3 months after surgery.

Meningioma Presenting with Spontaneous Venous Intraparenchymal Hemorrhage

A 65-year-old woman with a known right-sided, dural-based lesion and metastatic pancreatic neuroendocrine tumor presented with multiple days of progressive lethargy and left-sided weakness culminating with obtundation and dilated pupils. Computed tomography demonstrated an acute right convexity subdural hematoma and a frontotemporal intraparenchymal hemorrhage with 1.3 cm of midline shift, uncal herniation, and an increase in size of now a hemorrhagic dural-based lesion. She underwent emergency hemicraniectomy for evacuation of subdural hematoma and resection of hemorrhagic meningioma with excellent postoperative result including improvement in midline shift and gross total resection of lesion. Pathology was consistent with a World Health Organization grade II meningioma with a chordoid component. She underwent adjuvant stereotactic radiosurgery and cranioplasty and made a full neurologic recovery. Identification of hemorrhagic meningioma as the underlying pathology causing multicompartmental hemorrhage is crucial. We recommend single-stage decompression with extraaxial clot evacuation and resection of the meningioma when feasible.

Utilization of neoadjuvant stereotactic radiosurgery for the treatment of brain metastases requiring surgical resection: a topic review.

Following surgical resection of brain metastases (BMs), adjuvant stereotactic radiosurgery (SRS) has become the standard of care post-operative cavity irradiation. Recent studies, however, have demonstrated that with the current sequence of surgery and radiation, risk of leptomeningeal disease (LMD) and radiation necrosis (RN) remains high. Pre-operative, or neoadjuvant, SRS (nSRS) has been proposed as an alternative treatment strategy which not only minimizes local recurrence (LR) but also LMD and RN. It is thought that nSRS sterilizes the tumor, allowing for minimal spillage of viable tumor cells during resection, creating less favorable conditions for LMD. Furthermore, nSRS allows for easier contouring and decreased margin irradiation during planning and treatment, respectively, diminishing the risk of symptomatic RN. While nSRS has already been adopted for treating other extra-cranial tumors, its role in treating BMs is yet to be defined. We aim to summarize recent studies in nSRS usage for BMs and the rationale of this treatment strategy. We performed a search for articles regarding nSRS for BMs published in PubMed from 2018 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized a total of 14 retrospective reviews, case series, dose/timing studies, and ongoing Phase II & III clinical trials. In this review, we describe the findings of current studies and identify prospective clinical trials with the aim of understanding the efficacy of nSRS over current treatment standards. Herein, we also discuss the theoretical advantages and limitations of nSRS (both biologic and clinical) to help guide future clinical investigations.

SURG-03. SURGICAL MANAGEMENT OF BRAIN METASTASIS FROM OVARIAN CANCER: A SYSTEMATIC REVIEW AND CASE SERIES

Abstract INTRODUCTION Ovarian cancer is a rare cause of brain metastasis requiring neurosurgical intervention. Management strategies vary and prognostic factors are not well known. OBJECTIVE We aim to systematically review the literature on management and outcomes of ovarian cancer brain metastasis and compare it with our experience. METHODS Systematic review was performed using PRISMA guidelines. Databases were sourced from inception to April 2022. Study selection was based on predetermined inclusion/exclusion criteria. A simultaneous retrospective analysis was performed on patients from our institution who underwent evaluation and treatment for metastatic intracranial lesions of ovarian origin. RESULTS Literature search generated 214 articles. Twelve were ultimately selected, representing 428 brain metastasis (BM) patients from ovarian cancer. Patients age from 27-80 years. The interval from cancer diagnosis to BM ranged from 0 – 226.2 months. Surgical resection (SR), stereotactic radiosurgery (SRS), and whole-brain radiotherapy were the most frequently used treatment modalities. Individual patients’ overall survival following BM diagnosis ranged from 0 – 173 months. For our institutional analysis, 9 patients were included with median age of 56 years. Median interval from diagnosis to BM was 51 months. Four patients were treated with SR and adjuvant SRS. Two patients had SR and SRS with additional extraventricular drain placement. Two patients had SR only, and one received only SRS. Median radiation dose received was 20 Gy. For those who experienced progression, median progression-free survival was 14 months. One patient exhibited no progression at the time of analysis. Three patients were alive at the time of analysis with two others lost to follow-up. CONCLUSION brain metastases following ovarian cancer are a rare outcome carrying a poor prognosis. Multimodal therapies, specifically SR and SRS, correlate with increased survival. Further study is needed to better guide optimal management, with particular attention to the benefits of resection with targeted adjuvant radiation.

Adjuvant versus on-progression Gamma Knife radiosurgery for residual nonfunctioning pituitary adenomas: a matched-cohort analysis.

Radiological progression occurs in 50%-60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consensus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs. This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ; treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deterioration were analyzed. Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor control was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55-4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6-12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = -0.8%, p > 0.99) or visual deficits (RD = -2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01). SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormonal/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progression could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS.

Changes in the Symptomatic Burden of High Koos Grade Vestibular Schwannomas Following Definitive and Adjuvant Stereotactic Radiosurgery

<h3>Purpose/Objective(s)</h3> Emerging literature suggests definitive SRS is an option for large vestibular schwannomas with brainstem compression. We investigate our institutional experience of SRS on the Gamma Knife platform (GKRS) in both the definitive and post-operative settings and report control and morbidity outcomes. <h3>Materials/Methods</h3> An IRB-approved institutional database compiled clinical, radiographic, and treatment planning data for Koos grade 3-4 vestibular schwannomas treated by GKRS in our institution from March 2014 to January 2021 with minimum of 6-month follow-up, stratified by definitive (GKRS-D cohort) vs. adjuvant (GKRS-A cohort) treatment approaches. Baseline symptoms per CTCAE definitions were recorded for all patients prior to SRS (pre-SRS) and after SRS (post-SRS). For the adjuvant cohort, pre-operative symptoms were also recorded (pre-op). Hearing function was excluded due to inconsistent availability of audiometric records. Outcomes of tumor control, treatment toxicity, and changes in individual and aggregate symptomatic burdens as sums of relevant CTCAE grades (aggregate impairment; AI) were analyzed. AI was tested for association with definitive vs. adjuvant treatment parameters on presentation and post treatment. <h3>Results</h3> 34 patients were identified, of whom 19 were GKRS-D and 15 GKRS-A. Tumor control rates were 100% with median follow-up 34.2 months for GKRS-D (range: 6-74) and 48.6 months for GKRS-A (range: 6-84). Rates of brainstem necrosis or prolonged steroid use were 0%. No patients required shunt placement or developed clinical hydrocephalus post-GKRS. GKRS-A had greater symptom burden both at pre-op presentation and pre-GKRS than GKRS-D (AI 3.73 vs 2.11, p=0.017; AI 3.40 vs. 2.11, p=0.093). Symptom burden improved following treatment in both groups (mean AI Δ = -1.13 and -0.47 for GKRS-A and GKRS-D, p=0.243). In the GKRS-A cohort, symptom burden improved both with surgical intervention (mean Δ = -0.33), and following GKRS (mean Δ = -0.80.) Following definitive GKRS, 6 subjects had improvement in AI (mean Δ = -2.00), 3 subjects had worsening in AI (mean Δ = +1.00), and 10 subjects had no change. 1 subject had improvement in CNVII weakness (Δ = -2.00) and the remainder had no change. Following subtotal resection and adjuvant GKRS, 11 subjects had improvement in AI (mean Δ = -2.09) and 4 had worsening in AI (mean Δ = +1.50). 1 subject had improvement in CNVII weakness (Δ = -1.00), 6 had worsening (mean Δ = -1.33), and 8 had no change. <h3>Conclusion</h3> In well-selected patients with Koos grade 3 or 4 vestibular schwannomas, definitive SRS without surgical decompression has demonstrated excellent local control and minimal toxicity, with significant numbers of patients demonstrating an improvement in their baseline symptoms post-treatment. We increasingly select surgical intervention based on pre-treatment clinical symptoms rather than tumor volume or Koos grade alone. Larger prospective data are needed to confirm our experience.

Integrated Multidisciplinary Brain Metastasis Care Reduces Patient Visits and Shortens Time to Adjuvant Irradiation.

Timely surgical cavity stereotactic radiosurgery (SRS) is an important adjuvant to brain metastasis resection, with earlier treatment associated with less frequent recurrence. The logistical complexity of treatment organization, however, has resulted in suboptimal start times postsurgically. We implemented a process improvement approach to reduce the time from surgery to adjuvant irradiation of resected brain metastases. A multidisciplinary working group used process mapping to identify opportunities to reduce visits and shorten treatment times. The care delivery process was modified to streamline perioperative SRS preparation with (1) early patient identification, (2) preoperative intrateam communication, and (3) consolidation of required steps. Plan-Do-Study-Act cycles were used for process improvement. The surgery-to-SRS initiation time interval was the primary outcome. Secondary outcomes included the number of associated patient encounters. After implementation, the median (interquartile range) interval from surgery to SRS was reduced 48% from 27 (21-34) to 14 days (13-17; P < .001). The rate of surgical cavity SRS within 30 days increased from 64% (n = 63 of 98) to 97% (n = 60 of 62; P < .001). The median (interquartile range) number of CNS-associated encounters between resection and SRS decreased from 5 (4-6) to 4 (3-5; P < .001). The proportion of patients who had > 1 magnetic resonance imaging/computed tomography between surgery and SRS decreased from 45% (44 of 98) to 13% (8 of 62; P < .001). The time from surgery to systemic therapy resumption/initiation among patients treated within 90 days postoperatively decreased from 35 (24-48) to 32 days (23-40; P = .074). There were no wound complications in either group. Adjuvant SRS latency and treatment-associated encounters were significantly reduced after care-coordination implementation. This approach reduces patient and health care system burden and can be applied to other scenarios where early postoperative SRS administration is critical.

CLRM-12 TITLE: STEREOTACTIC RADIOSURGERY (ADJUVANT OR NEOADJUVANT) COMPARED TO HIPPOCAMPAL AVOIDANCE WHOLE BRAIN RADIATION THERAPY WITH SIMULTANEOUS INTEGRATED BOOST FOR LIMITED BRAIN METASTASES (SRS-CHART): PHASE III OPEN-LABEL PARALLEL-GROUP RANDOMIZED CONTROLLED TRIAL

BACKGROUNDSurgery is indicated for large or symptomatic lesions in patients with limited brain metastasis (BM), followed by adjuvant stereotactic radiosurgery (A-SRS) to the cavity. Emerging evidence suggests promising role of neoadjuvant SRS (NA-SRS) before surgery with potentially lesser risk of leptomeningeal disease (LMD) and radionecrosis (RN). Hippocampal avoidance whole brain radiotherapy (HA-WBRT) results in better neurocognitive outcomes than standard WBRT, and use of simultaneous integrated boost (SIB) to surgical cavity can improve the local control. Absence of high-quality evidence forms the basis of current study comparing these three treatment strategies. OBJECTIVESPrimary endpoint is 1-year event-free survival (EFS) a composite endpoint comprising any local failure, LMD, DBF, symptomatic RN, or death as events. Other endpoints include individual endpoints and longitudinal neuro-cognitive function and quality-of-life assessment. METHODSTarget population includes adults with newly diagnosed BM (≤3 lesions) with life expectancy >1 year and one target lesion needing surgery. Patients will be randomized (1:1:1) to A-SRS (control arm) or one of two test arms (NA-SRS or HA-WBRT-SIB). In A-SRS arm, patients will receive single fraction (16-20Gy) or hypofractionated-SRS (24-27Gy/3 fractions or 30-32.5Gy/5 fractions) based on volume and location of cavity and other intact BM. In the test arms, patients will be allocated to either NA-SRS group (single/multi-fraction) followed by surgery within 2 weeks or HA-WBRT (30Gy/10 fractions) with SIB to cavity plus other intact BM (40-50Gy/10 fractions) combined with memantine within 6 weeks of surgery. A sample size of 168 patients is required to prove the superiority of test arms individually compared to the control arm with assumption of 1-year EFS of 43% versus 25% with a hazard ratio of 0.6 (two-sided alpha=0.05, power=80%, and 15% attrition rate). DISCUSSIONThe study will generate level 1 evidence investigating the role of NA-SRS or HA-WBRT-SIB compared to A-SRS in limited brain metastases.

CLRM-20 IDENTIFYING RISK FACTORS AND ANALYZING SURVIVAL FOLLOWING PACHYMENINGEAL FAILURE

OBJECTIVENeurosurgery (NS) is an essential modality for large brain metastases (BM). As an adjuvant treatment, stereotactic radiosurgery (SRS) reduces neurocognitive toxicity without affecting post-treatment overall survival (OS) compared to whole brain radiation therapy. Pachymeningeal failure (PMF) beyond the SRS field is a relatively newly described entity, distinct from classical leptomeningeal failure (LMF), and unique to postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS+SRS. METHODSWe reviewed a prospective registry (2009 to 2020) and identified all patients treated with NS+SRS. Clinical, radiological, pathological and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model and differences between cohorts were measured using the Fine-Gray method. RESULTS144 Patients were identified. Median age was 62 (23-90). PMF occurred in 22.2% (32/144) patients). Univariate analysis indicated female gender (HR 2.65, p=0.013), higher GPA status (HR 2.4, p<0.001), absence of prior radiation therapy (HR N/A, p=0.018), controlled extracranial disease (CED) (HR 3.46, p=0.0038), and contact with the pia/dura (HR 3.30, p=0.0053) as risk factors for PMF. Piecemeal (vs En-bloc) resection also trended towards correlation (HR 2.07, p=0.054). Multivariate Analysis identified contact with pia/dura (HR 3.51, p=0.0053), piecemeal resection (HR 2.38, p=0.027), and CED (HR 3.97, p=0.0016) as significant correlates to PMF. PMF correlated with reduced OS (HR 2.90, p<0.001) but was improved compared to patients who developed LMF (HR 10.15, p= p<0.001). CONCLUSIONSPMF is an underrecognized phenomenon that correlates with pre-operative pia/dura contact and piecemeal resection in patients treated with NS+SRS for BM. While less morbid than LMF, it is a critical event that deserves increased vigilance and analysis.

Genomic analysis and clinical correlations of non-small cell lung cancer (NSCLC) brain metastasis (BM).

2008 Background: Approximately 30% of patients with NSCLC present with BM, and up to 50% of patients ultimately develop BM. While modern NSCLC-directed agents yield excellent systemic response, most patients require focal treatment. Prior reports of BM genomics have been limited by low numbers, missing clinical data, and lack of matched specimens. Here, we report the largest cohort to date of molecularly profiled NSCLC BM samples with clinical correlates. Methods: Clinical data and outcomes for 244 patients with NSCLC and resected BM were identified, and BM samples were assessed with one of four versions (341, 410, 468, 505) of MSK-IMPACT, a custom FDA-approved next generation sequencing-based tumor sequencing assay. 51 (20.9%) patients had matched primary site tissue, and 44 (18%) patients had matched tissue from another metastatic site or CSF. Genomic alterations were filtered for driver variants using OncoKB. Results: Median age was 66 years (range 31-91), and median follow-up was 2.3 years (IQR 1.3-4.3). Adenocarcinoma was the most common histology (183, 78%). Half presented with a single BM, and 121 (51%) patients were treatment naive. Most (197, 83%) received adjuvant stereotactic radiosurgery (SRS) to the resection site and 28% received SRS to additional BM. After resection, 130 (55.1%) had CNS progression, often regional (54, 42%). SRS to new BMs (32%) was the most common salvage treatment. Median overall survival from BM diagnosis was 2.5 years (95%CI 2.1-3.2). Median CNS-progression-free survival was 1.2 years (95%CI 0.9-1.4). The most frequently altered genes in BM samples were TP53 (72%), CDKN2A (34%), KRAS (31%), KEAP1 (26%), and EGFR (21%). CDKN2A was more frequently altered in BM samples when compared to NSCLC primary samples (34% vs 14%, p = 0.003, q = 0.034). With regard to overrepresented gene sets, cell cycle pathway alterations were enriched in BM (56% vs 31%, p = 0.002, q = 0.022). BM samples had a significantly higher fraction of genome altered relative to the primary samples (p &lt; 0.0001, q &lt; 0.0001). After grouping patients based on type of CNS progression, we found that EGFR alterations were enriched in patients with leptomeningeal failures when compared to both patients without progression (42% vs 18%, p = 0.03, q = 0.93) and to patients with either local or regional progression (42% vs 19%, p = 0.03, q = 0.9). Conclusions: In the largest-ever assembled cohort of genomically-profiled NSCLC BM, we found significant enrichment for CDKN2A and cell cycle pathway alterations in BM compared to extracranial disease, as well as a higher fraction of genome altered, in BMs compared to matched primary tumor controls. We also observed EGFR alteration enrichment in patients who develop LMD, suggesting specific biologic underpinnings driving patterns of CNS failure. Further investigation into the role of systemic therapy and time course will elucidate potential mechanisms for CNS failure in patients with NSCLC.