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Background: Single-session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2 cm) to determine the safety of preoperative SRS at escalating doses., Methods: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose-limiting toxicity was defined as grade III or greater acute toxicity., Results: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21 Gy. The maximum tolerated dose of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%., Conclusions: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: In our center, five Gamma Knife proceduralists differed in opioid administration practices prior to Leksell frame removal, providing the opportunity to improve the care of patients with brain metastases by studying whether opioid medications improve pain scores and patient satisfaction during Gamma Knife treatment in a prospective, pseudorandomized fashion., Methods: We prospectively administered a questionnaire to patients undergoing Gamma Knife Radiosurgery for metastases between November, 2017 and July, 2018. Using multivariable methods, we assessed whether opioid pain medication administration influenced the change in pain scores after frame removal, and whether they influenced patient satisfaction on how often their pain was controlled, and their overall satisfaction., Results: We included 142 patients. Mean age was 65.2 ± 10.8 years and 52.7% were female. Morphine was the most commonly administered medication. Pain increases were greater around frame removal than placement. Opioids were not associated with any difference in the change in pain scores before and after frame removal, or patient satisfaction. Patients with higher pre-removal pain scores had smaller increases in pain scores after removal; they also had worse pain control and overall satisfaction with their treatment., Conclusion: Morphine administration prior to frame removal did not improve pain scores or pain control satisfaction. Absence of efficacy may be related to delayed onset of action, and stronger and faster-acting agents should be explored. Pre-removal pain scores were associated with decreased pain control and overall satisfaction, further identifying earlier and stronger pain treatment as a potential area for improvement., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18 F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions., Methods: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18 F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation., Results: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUV max statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUV mean (AUC = 0.875; p = 0.018), SUV peak (AUC = 0.813; p = 0.007), and SUV peak -to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUV max -to-normal-brain (p = 0.1) and SUV mean -to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2)., Conclusions: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18 F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: American Society of Radiation Oncology (ASTRO) has developed a guideline on appropriate radiation therapy for brain metastases. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations., Methods: "Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline" 2 was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations., Results: The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline, published May 6, 2022, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorses "Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline." 2 ., Recommendations: Within the guideline, stereotactic radiosurgery (SRS) is recommended for patients with Eastern Cooperative Oncology Group performance status of 0-2 and up to four intact brain metastases, and conditionally recommended for patients with up to 10 intact brain metastases. The guideline provides detailed dosing and fractionation recommendations on the basis of the size of the metastases. For patients with resected brain metastases, radiation therapy (SRS or whole-brain radiation therapy [WBRT]) is recommended to improve intracranial disease control; if there are limited additional brain metastases, SRS is recommended over WBRT. For patients with favorable prognosis and brain metastases ineligible for surgery and/or SRS, WBRT is recommended with hippocampal avoidance where possible and the addition of memantine is recommended. For patients with brain metastases, limiting the single-fraction V 12Gy to brain tissue to ≤ 10 cm 3 is conditionally recommended.Additional information is available at www.asco.org/neurooncology-guidelines.

Objective: Glioblastoma (GBM) is the most malignant form of astrocytoma. The average survival is 6-10 months in patients with recurrent GBM (rGBM). In this study, the authors evaluated the role of stereotactic radiosurgery (SRS) in patients with rGBMs., Methods: The authors performed a retrospective review of their brain tumor database (1997-2016). Overall survival (OS) and progression-free survival (PFS) after salvage SRS were the primary endpoints evaluated. Response to SRS was assessed using volumetric MR images., Results: Fifty-three patients with rGBM underwent salvage SRS targeting 75 lesions. The median tumor diameter and volume were 2.55 cm and 3.80 cm3, respectively. The median prescription dose was 18 Gy (range 12-24 Gy) and the homogeneity index was 1.90 (range 1.11-2.02). The median OS after salvage SRS was estimated to be 11.0 months (95% CI 7.1-12.2) and the median PFS after salvage SRS was 4.4 months (95% CI 3.7-5.0). A Karnofsky Performance Scale score ≥ 80 was independently associated with longer OS, while small tumor volume (< 15 cm3) and less homogeneous treatment plans (homogeneity index > 1.75) were both independently associated with longer OS (p = 0.007 and 0.03) and PFS (p = 0.01 and 0.002, respectively). Based on these factors, 2 prognostic groups were identified for PFS (5.4 vs 3.2 months), while 3 were identified for OS (median OS of 15.2 vs 10.5 vs 5.2 months)., Conclusions: SRS is associated with longer OS and/or PFS in patients with good performance status, small-volume tumor recurrences, and heterogeneous treatment plans. The authors propose a prognostic model to identify a cohort of rGBM patients who may benefit from SRS.

Background: Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival., Objective: To evaluate prognostic factors, which may predict early death (within 90 d) after SRS., Methods: A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices., Results: Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable., Conclusion: Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.

Background: Patients with single brain metastasis (SBM) have better outcomes after stereotactic radiosurgery (SRS). We analyzed our SRS database to evaluate possible prognostic factors in patients with SBM., Methods: A total of 584 patients with SBM were treated with SRS at our institution (2000-2012). Study end points were overall survival (OS), and distant and local intracranial progression-free survival (DPFS and LPFS, respectively). Multivariable analysis was performed to develop prognostic models., Results: Median OS was 10.8 months. A total of 196 patients (36.7%) had distant progression and 102 patients (19.2%) had local progression. New SBM prognostic indices (SPIs) were devised for OS, DPFS, and LPFS. Graded prognostic assessment, neurologic symptoms (P = 0.01), and tumor volume (P = 0.02) were independently associated with OS. The SPI for OS was defined: unfavorable (OS, 7.3 months), intermediate (OS, 10.6 months), and favorable (OS, 19.8 months). For DPFS, age (P = 0.0029), tumor volume (P = 0.0002), and previous whole-brain radiotherapy (P = 0.027) were prognostic and were used to define SPI for DPFS: favorable (6-month cumulative incidence failure [CIF], 10.9%), intermediate (6-month CIF, 16.7%), and unfavorable (6-month CIF, 26.0%) (P < 0.001). For LPFS, graded prognostic assessment (P = 0.0012) and tumor volume (P = 0.0004) were significant, and defined 2 groups in the LPFS SPI: unfavorable (6-month CIF, 12.3%) and favorable (6-month CIF, 6%) (P < 0.001)., Conclusions: This is the largest series of patients with SBM treated with SRS analyzed for OS, LPFS, and DPFS. SPI was devised for end points. Tumor volume had a significant association with all 3 end points. Neurologic symptoms, age, and previous whole-brain radiotherapy were also found to be prognostic., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

Little is known on the natural history, recurrence patterns, neurocognitive outcomes and prognostic factors associated with survival in long-term survivors (≥10 years) from brain metastasis (BM). In this study, the records of 1953 patients who underwent treatment for BM with a potential for ≥10 years of follow-up were reviewed. Cox regression analysis identified factors predictive for overall survival (OS). The median age at brain metastasis diagnosis was 60 years and the median OS was 6.4 months. The 1-year OS rate was 29.9, 12.1 % at 2 years, 3.0 % at 5 years, and 1.3 % at 10 years. On multivariable analysis, factors associated with worse OS included gender (males, HR 1.2), multiple brain metastases (HR 1.3), no surgery (HR 1.8), and no stereotactic radiosurgery (HR 1.8) (p < 0.0001 each). Fifty-six patients (2.9 %) survived ≥5 years; 23 patients (1.2 %) survived ≥10 years and the median survival for ≥10 year survivors was 18.5 years. Six of the 10-year survivors had an intracranial recurrence, five occurred within 11 years from the first treatment. Presence of a solitary lesion or single lesion at the time of brain metastasis diagnosis was associated with improved survival. Eight of the ≥10 year survivors (34.8 %) had no neurological symptoms at last follow-up; none of the 10-year survivors were documented to have a neurologic death. Our study demonstrates that patients with favorable prognostic features should undergo multimodality treatment. Albeit rare, patients who are alive 10 years after treatment for their brain metastases may be considered cured from their intracranial disease.

The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Object: The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS)., Methods: One hundred seventeen patients with VS underwent GKRS between January 1997 and February 2003. At the time of analysis, at least 5 years had passed since GKRS in all patients. The mean patient age was 60.9 years. The mean maximal tumor diameter was 1.77 ± 0.71 cm. The mean tumor volume was 1.95 ± 2.42 ml. Eighty-two percent of lesions received 1300 cGy and 14% received 1200 cGy. The median dose homogeneity ratio was 1.97 and the median dose conformality ratio was 1.78. Follow-up included MR imaging or CT scanning approximately every 6-12 months. Rates of progression to surgery were calculated using the Kaplan-Meier method., Results: Of the 117 patients in whom data were analyzed, 103 had follow-up MR or CT images and 14 patients were lost to follow-up. Fifty-three percent of patients had stable tumors and 37.9% had a radiographically documented response. Imaging-documented tumor progression was present in 8 patients (7.8%), but in 3 of these the lesion eventually stabilized. Only 5 patients required a neurosurgical intervention. The estimated 1-, 3-, and 5-year rates of progression to surgery were 1, 4.6, and 8.9%, respectively. One patient (1%) developed trigeminal neuropathy, 4 patients (5%) developed permanent facial neuropathy, 3 patients (4%) reported vertigo, and 7 patients (18%) had new gait imbalance following GKRS., Conclusions: Gamma Knife radiosurgery results in excellent local control rates with minimal toxicity for patients with VS. The authors recommend standardized follow-up to gain a better understanding of the long-term effects of GKRS.

Melanoma brain metastasis with ependymal spread/metastases is uncommon. These cases are frequently classified together with leptomeningeal disease. However, the commonalities and differences in the underlying pathophysiology and clinical outcomes between these two types of spread are not clear. Very few reports on long term outcome and durable central nervous system (CNS) disease control have been reported in the literature. Here, we report a case of a 45 year-old Caucasian lady with BRAF-V600E mutant metastatic melanoma to the brain who had whole brain radiotherapy followed by two Gamma knife radiosurgery treatments for localized disease progression. She then developed extensive ependymal disease progression with no evidence of leptomeningeal spread. She was treated with a repeat course of whole brain radiotherapy and maintained on BRAF and MEK inhibitors with durable CNS disease control for more than a year. This study reviews the management of BRAF-V600E mutant melanoma with ependymal involvement. Management using radiation therapy with maintenance targeted therapy seems to be a reasonable approach to this challenging disease. [ABSTRACT FROM AUTHOR]

We reviewed our Gamma Knife® Radiosurgery case mix to evaluate practice pattern changes across a 10 year period of time. In 2011 we completed 384 procedures with 782 lesions targeted. The majority of the treatments were for malignant disease with metastases representing the largest subgroup (n=245; 63.8%), A total of 117 (30.4%) benign pathologies were treated with benign tumors (n=63; 16.4%), functional cases and AVMs (each n=27; 7%) representing the most common cases treated with the remainder of cases represented by a variety of other pathologies. All treatments were completed using the Perfexion™ system. By 2021, we doubled our case volume completing (n=778) procedures, however, nearly tripled the number of targets treated (n=2317). Metastases again represented the largest cohort (n= 617 cases;79.3%), 84 (10.8%) benign tumors, 19 (2.4%) functional cases and 15 (1.9%) AVMs. In 2021, all cases were completed using the GK ICON™ System and 193 cases (24.8%) were performed using mask-based immobilization. There were also 16 anesthesia cases. Approximately 50% of the treated patients were from Ohio and 50% came from out of state. The above data demonstrates a growing volume of cases treated with GK at a single institution across a decade, with metastases representing the dominant and expanding cohort of cases treated (63.8% vs 79.3%). The associated nearly tripling of lesions treated likely reflects a willingness to treat patient with a greater number of brain metastases per session. Further, 24.8% in 2021 were treated with mask-based immobilization reflecting a work-flow change and expanded capabilities compared to treatments in the previous decade. [ABSTRACT FROM AUTHOR]

Introduction: Gamma-Knife radiosurgery (GKRS) is a well-established treatment for brain metastases (BM). The imaging features of BM can variably have either homogeneous and heterogenous enhancement, or cystic-like appearances. These features can represent different biological behaviors concerning the treatment of these lesions. Cystic BM (cBM) are perceived to be more resistant to treatment than solid BM (sBM). In this study, we sought to compare the response rates and overall survival of patients with cBM relative to sBM after GKRS. Method: Patients treated for BM with GKRS over a 2-year interval (2016-2017) were evaluated. GKRS dosing was delivered per RTOG 90-05 according to our standard protocol. Patients were divided in 3 groups: those with cBM only, sBM only, and both cystic and solid BM (csBM). Kaplan-Meier analysis with the log-rank test was used to calculate and compare overall survival (OS) between groups. Local control was analyzed utilizing RECIST criteria at 3, 6, and 12 months. Chi-square analysis compared the response rate for cBM and sBM. Result: 73 patients (59% female) with a mean age 67 years (range: 43-91) were analyzed. The most frequent pathologies were lung (54%) and breast (18%). KPS was ≥70 in 66 patients (90%). Prior to GKRS treatment, 22% of patients received WBRT, 71% chemotherapy, 22% had prior surgery, and 16% received immunotherapy. No significant differences were found in the clinical characteristics between patient groups. Mean OS was 20 months (2-38, 95% CI) for the cBM patient group, 17 months (12-22, 95% CI) for sBM patient group and 13 months (7-19, 95% CI) for csBM patient group (p = .967). Of the 416 lesions evaluated, 15% (n=62) were cBM and 85% (n=354) were sBM.cBM were significantly larger than sBM (p < 0.0001) and therefore cBM received significantly lower doses of radiation (p 0.001). No other significant differences were found between cBM and sBM. Local control at 6 months was 92% for cBM and 89% for sBMs (p =.49). Conclusion: Despite a perceived worse prognosis, our results suggest that patients harboring cBM treated with GKRS achieve similar oncologic outcomes when compared with patients with sBM. cBM are usually larger than sBM and therefore these lesions may be treated with less radiation dose than their solid counterparts. Regardless, cBM and sBM are suitable stereotactic radiosurgery targets with comparable local control rates. [ABSTRACT FROM AUTHOR]