Comparative evaluation of outcomes amongst different radiosurgery management paradigms for patients with large brain metastasis.

INTRODUCTION: This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS). METHODS: Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray's test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data. RESULTS: 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology. CONCLUSION: This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Management of Brain Metastases: A Review of Novel Therapies.

Brain metastases (BMs) represent the most common intracranial tumors in adults, and most commonly originate from lung, followed by breast, melanoma, kidney, and colorectal cancer. Management of BM is individualized based on the size and number of brain metastases, the extent of extracranial disease, the primary tumor subtype, neurological symptoms, and prior lines of therapy. Until recently, treatment strategies were limited to local therapies, like surgical resection and radiotherapy, the latter in the form of whole-brain radiotherapy or stereotactic radiosurgery. The next generation of local strategies includes laser interstitial thermal therapy, magnetic hyperthermic therapy, post-resection brachytherapy, and focused ultrasound. New targeted therapies and immunotherapies with documented intracranial activity have transformed clinical outcomes. Novel systemic therapies with intracranial utility include new anaplastic lymphoma kinase inhibitors like brigatinib and ensartinib; selective "rearranged during transfection" inhibitors like selpercatinib and pralsetinib; B-raf proto-oncogene inhibitors like encorafenib and vemurafenib; Kirsten rat sarcoma viral oncogene inhibitors like sotorasib and adagrasib; ROS1 gene rearrangement (ROS1) inhibitors, anti-neurotrophic tyrosine receptor kinase agents like larotrectinib and entrectinib; anti-human epidermal growth factor receptor 2/epidermal growth factor receptor exon 20 agent like poziotinib; and antibody-drug conjugates like trastuzumab-emtansine and trastuzumab-deruxtecan. This review highlights the modern multidisciplinary management of BM, emphasizing the integration of systemic and local therapies.

Genomic alterations associated with rapid progression of brain metastases.

OBJECTIVE: The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery. METHODS: This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses. RESULTS: The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3-85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence (RB1: OR 13.6, 95% CI 2.0-92.39, p = 0.008; and CTNNB1: OR 11.97, 95% CI 2.25-63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08-15.34, p = 0.039). CONCLUSIONS: Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.

OptImal Gamma kNife lIghTnIng sOlutioN (IGNITION) score to characterize the solution space of the Gamma Knife FIP optimizer for stereotactic radiosurgery.

OBJECTIVES: The objective of this study is to evaluate the user-defined optimization settings in the Fast Inverse Planning (FIP) optimizer in Leksell GammaPlan® and determine the parameters that result in the best stereotactic radiosurgery (SRS) plan quality for brain metastases, benign tumors, and arteriovenous malformations (AVMs). METHODS: Thirty patients with metastases and 30 with benign lesions-vestibular schwannoma, AVMs, pituitary adenoma, and meningioma-treated with SRS were evaluated. Each target was planned by varying the low dose (LD) and beam-on-time (BOT) penalties in increments of 0.1, from 0 to 1. The following plan quality metrics were recorded for each plan: Paddick conformity index (PCI), gradient index (GI), BOT, and maximum organ-at-risk (OAR) doses. A novel objective score matrix was calculated for each target using a linearly weighted combination of the aforementioned metrics. A histogram of optimal solutions containing the five best scores was extracted. RESULTS: A total of 7260 plans were analyzed with 121 plans per patient for the range of LD/BOT penalties. The ranges of PCI, GI, and BOT across all metastatic lesions were 0.58-0.97, 2.1-3.8, and 8.8-238 min, respectively, and were 0.13-0.97, 2.1-3.8, and 8.8-238 min, respectively, for benign lesions. The objective score matrix showed unique optimal solutions for metastatic lesions and benign lesions. Additionally, the plan metrics of the optimal solutions were significantly improved compared to the clinical plans for metastatic lesions with equivalent metrics for all other cases. CONCLUSION: In this study, FIP optimizer was evaluated to determine the optimal solution space to maximize PCI and minimize GI, BOT and OAR doses simultaneously for single metastatic/benign/non-neoplastic targets. The optimal solution chart was determined using a novel objective score which provides novice and expert planners a roadmap to generate the most optimal plans efficiently using FIP.

A study on inter-planner plan quality variability using a manual planning- or Lightning dose optimizer-approach for single brain lesions treated with the Gamma Knife® Icon™.

PURPOSE: The purpose of this study is to investigate inter-planner plan quality variability using a manual forward planning (MFP)- or fast inverse planning (FIP, Lightning)-approach for single brain lesions treated with the Gamma Knife® (GK) Icon™. METHODS: Thirty patients who were previously treated with GK stereotactic radiosurgery or radiotherapy were selected and divided into three groups (post-operative resection cavity, intact brain metastasis, and vestibular schwannoma [10 patients per group]). Clinical plans for the 30 patients were generated by multiple planners using FIP only (1), a combination of FIP and MFP (12), and MFP only (17). Three planners (Senior, Junior, and Novice) with varying experience levels re-planned the 30 patients using MFP and FIP (two plans per patient) with planning time limit of 60 min. Statistical analysis was performed to compare plan quality metrics (Paddick conformity index, gradient index, number of shots, prescription isodose line, target coverage, beam-on-time (BOT), and organs-at-risk doses) of MFP or FIP plans among three planners and to compare plan quality metrics between each planner's MFP/FIP plans and clinical plans. Variability in FIP parameter settings (BOT, low dose, and target max dose) and in planning time among the planners was also evaluated. RESULTS: Variations in plan quality metrics of FIP plans among three planners were smaller than those of MFP plans for all three groups. Junior's MFP plans were the most comparable to the clinical plans, whereas Senior's and Novice's MFP plans were superior and inferior, respectively. All three planners' FIP plans were comparable or superior to the clinical plans. Differences in FIP parameter settings among the planners were observed. Planning time was shorter and variations in planning time among the planners were smaller for FIP plans in all three groups. CONCLUSIONS: The FIP approach is less planner dependent and more time-honored than the MFP approach.

The safety profile of Tumor Treating Fields (TTFields) therapy in glioblastoma patients with ventriculoperitoneal shunts.

INTRODUCTION: Tumor Treating Fields (TTFields, 200 kHz) therapy is a noninvasive, locoregional cancer treatment approved for use in newly diagnosed glioblastoma (GBM), recurrent GBM, and malignant pleural mesothelioma. GBM patients with hydrocephalus may require implantation of a ventriculoperitoneal (VP) shunt, however, the current TTFields therapy label does not include the use of VP shunts in GBM patients due to insufficient safety data. This analysis evaluates the safety of TTFields therapy use in this population. METHODS: Unsolicited post-marketing global surveillance data from patients with GBM and a VP shunt (programmable/non-programmable) who received TTFields therapy between November 2012-April 2021 were retrospectively analyzed. Adverse events (AEs) were assessed using the Medical Dictionary for Regulatory Activities version 24.0. RESULTS: Overall, 156 patients with VP shunts were identified and included in this analysis. In total, 77% reported ≥ 1 AE; the most common TTFields therapy-related AEs were non-serious and localized, beneath-array skin AEs (43%). The incidence and categories of AEs were comparable between patients with or without VP shunts. Six patients with VP shunts experienced seven serious TTFields therapy-related AEs: skin erosion at the shunt site (n = 3); wound dehiscence at the shunt site (n = 2) and at the resection scar (n = 2). No shunt malfunctions were deemed related to TTFields therapy. CONCLUSIONS: In the real-world setting, TTFields therapy in GBM patients with VP shunts demonstrated good tolerability and a favorable safety profile. There was no evidence that TTFields therapy disrupted VP shunt effectiveness. These results suggest TTFields therapy may be safely used in patients with VP shunts.

Endovascular treatment of anterior cranial fossa dural arteriovenous fistula: a multicenter series.

PURPOSE: We report a multicenter experience using endovascular embolization as the first line approach for treatment of anterior cranial fossa (ACF) dural arteriovenous fistula (DAVF). METHODS: All patients with DAVFs located in the anterior cranial fossa who were treated with endovascular technique as a first line approach were included. Demographics, clinical presentation, angioarchitecture, strategy, complications, immediate angiographic, and follow-up results were included in the analysis. RESULTS: Twenty-three patients met the inclusion criteria (18 male and 5 female). Age ranged from 14 to 79 years (mean 53 years). Twelve patients presented with hemorrhage. Twenty-eight endovascular procedures were performed. The overall immediate angiographic cure rate after endovascular treatment was 82.6% (19/23 patients). The angiographic cure rate of the transvenous strategy was significantly superior to the transarterial strategy (p ≤ 0.001). There was 1 complication in 28 total procedures (3.6%). Angiographic follow-up was available in 21 out of the 23 patients with a mean of 25 months (range 2 to 108 months). In these 21 patients, the DAVF was completely cured in 20 (95%). At last follow-up, all patients had a modified Rankin scale (mRS) 0 to 2. CONCLUSION: Our experience suggests that endovascular treatment for ACF DAVFs has an acceptable safety profile with high rates of complete occlusion, particularly with transvenous approach. Whenever possible, transvenous approach should be preferred over transarterial approach as first line strategy.

Redistributing Central Target Dose Hot Spots for Hypofractionated Radiosurgery of Large Brain Tumors: A Proof-of-Principle Study.

OBJECTIVE: The present proof-of-principle study investigated radiobiological effects of redistributing central target dose hot spots across different treatment fractions during hypofractionated stereotactic radiosurgery (HSRS) of large intracranial tumors. METHODS: Redistribution of central target dose hot spots during HSRS was simulated, and its effects were evaluated in eight cases of brain metastases. To assess dose variations in the target across N number of treatment fractions, a generalized biologically effective dose (gBED) was formulated. The gBED enhancement ratio was defined as the ratio of gBED in the tested treatment plan (with central target dose hot spot redistributions across fractions) to gBED in the conventional treatment plan (without central target dose hot spot redistributions). RESULTS: At a median α value of 0.3/Gy, the tested treatment plans resulted in average gBED increases of 15.6 ± 3.5% and 8.3 ± 1.8% for α/ß ratios of 2 and 10 Gy, respectively. In comparison with conventional treatment plans, the differences in the Paddick conformity index and gradient index did not exceed 2%. CONCLUSION: Redistributing central target dose hot spots across different treatment fractions during HSRS may be considered promising for enhancing gBED in the target. It may be beneficial for management of large intracranial neoplasms; thus, it warrants further clinical testing.

Feasibility and Significance of Dose Adaptation via Linear Couch Translations to Correct for Rotational Shifts During Frameless Brain Radiosurgery with the Gamma Knife Icon™.

OBJECTIVE: The present study aimed to examine the technical feasibility and effectiveness of adapting the radiation dose distributions with three-dimensional (3D) linear couch translations in contrast to full six-dimensional couch maneuvers to correct for rotational shifts during frameless radiosurgical treatment with the Gamma Knife Icon™ (Elekta AB; Stockholm, Sweden). METHODS: The original magnetic resonance images used for radiosurgery treatment planning (15 targets) were digitally processed to simulate rotational shifts of ±1, ±2, ±3, ±5, and ±10 degrees in the transverse plane and imported back into Leksell GammaPlan® (Elekta AB), creating "uncorrected" treatment plans. In addition, geometrically optimized 3D translation shifts were consequently applied to each isocenter in all "uncorrected" treatment plans to account for systematically introduced rotational shifts and to produce "corrected" treatment plans. The differences in the dose distribution between the original treatment plans and the "uncorrected" and "corrected" treatment plans were calculated and compared at each rotational shift position. RESULTS: The "uncorrected" treatment plans resulted in a significant deterioration in target coverage (by 8-72%) and selectivity (by 2-42%), with some targets being missed completely with rotations of ±3 or more degrees. In contrast, in all "corrected" treatment plans, the average decreases in target coverage and selectivity were only 1% (maximum values 4-5%). CONCLUSION: Applications of 3D linear couch translations successfully overcome gross uncertainties in dose distributions caused by up to ±10 degrees of rotational shifts in a target. As a result, rapid dose adaptation with 3D couch translations is unique and effective for frameless radiosurgery with the Gamma Knife Icon™.

Impact of the Skull Size on the Normal Brain Radiation Dose During Gamma Knife Radiosurgery: Results of a Pilot Study.

OBJECTIVE: The objective of the present study was evaluation of the interrelationships between changes in the skull size and variations in the normal brain radiation dose during Gamma Knife surgery (GKS). METHODS: With use of systematic modeling within Leksell GammaPlan® (Elekta AB; Stockholm, Sweden) in each of 15 analyzed cases, the skull was "expanded" and "contracted" by variation of its measurement values from 0 to ±3 cm. The mean normal brain radiation dose was then computed for each variant of the adjusted skull size and compared with the original treatment plan. Variations in the maximum point dose delivered to selected critical anatomical structures were also investigated. RESULTS: With changes in the skull radius within ±3 cm, the maximum absolute deviation in the mean normal brain radiation dose was 0.8%. As the skull radius increased, the mean normal brain radiation dose also increased linearly (confidence level >99%) with a positive slope of 0.2% per centimeter of radius length change. The maximum point dose deviations in all evaluated critical anatomical structures did not exceed 0.5%, with an overall trend toward a dose increase in parallel with an increase in the skull radius. CONCLUSION: The small skull size of pediatric patients may be associated with dosimetric advantages in terms of normal brain sparing during GKS.

Multidisciplinary Frontotemporal Orbitozygomatic Craniotomy for Spheno-orbital Meningiomas: Ophthalmic and Orbital Outcomes.

PURPOSE: Advances in surgical approaches have improved access for total or near-total resection of spheno-orbital meningiomas (SOM). Herein, the outcomes of multidisciplinary resection and reconstruction of SOM via frontotemporal orbitozygomatic craniotomy at a single institution are evaluated. METHODS: A retrospective chart review was performed of all patients with SOM who underwent joint neurosurgical and oculofacial plastic resection via frontotemporal orbitozygomatic craniotomy between January 1999 and December 2018. Demographic data, clinical presentation, risk factors for meningioma, radiographic imaging, pathology results, postoperative outcomes, and surgical complications were reviewed. The outcome measures assessed included visual acuity, pupillary function, color vision, ocular motility, visual fields, and proptosis. RESULTS: A total of 48 patients were identified having had multidisciplinary frontotemporal orbitozygomatic craniotomy for SOM of which 43 met inclusion criteria. A mean follow-up period of 23.9 ± 20.4 months (range 1-60) was observed. There were 35 patients who underwent primary resection and 8 patients who had prior surgical resection. The main presenting complaints were proptosis (88%), headache (44%), and reduced vision (12%). Gross total resection was achieved in 15 patients (35%) while near-total or subtotal resection was achieved in the remainder. Histologic analysis revealed World Health Organization grade I meningioma in 72% of tumors, grade II in 23%, and grade III in 5%. Mean visual acuity (Logarithm of the Minimum Angle of Resolution) improved from 0.24 ± 0.46 preoperatively to 0.09 ± 0.13 postoperatively (p = 0.03). Surgery improved proptosis, with a reduction in mean Hertel exophthalmometry from 22.37 ± 3.78 mm to 17.91 ± 3.84 mm (p < 0.001), of which 80% had no residual proptosis or developed subsequent recurrence. Exophthalmic index calculated by radiologic evaluation also improved from a mean preoperative value of 1.32 ± 0.19 to 1.12 ± 0.13 at the 6-month interval after surgery (p < 0.001). Before surgery, 19 (45%) patients had a relative afferent pupillary reaction with improvement in 9 (24%) after surgery. Of the 14 (33%) patients with preoperative ocular motility deficit, 7 (16%) had resolution of ocular motility deficit postoperatively. The most common surgical complications were temporalis muscle atrophy with temporal hollowing (14%), wound infection (7%), neurogenic strabismus secondary to trochlear nerve palsy (5%), restrictive strabismus (5%), and aponeurotic blepharoptosis (5%). CONCLUSIONS: Multidisciplinary frontotemporal orbitozygomatic for resection of SOM is a safe and effective means of tumor removal. It can provide improved visual acuity and proptosis metrics, as well as relief of optic neuropathy and ocular motility deficits.

Outcomes of sinonasal mucosal melanomas with endoscopic and open resection: a retrospective cohort study.

PURPOSE: To compare the outcomes of Sinonasal Mucosal Melanomas (SNMM) treated with endoscopic and open resection. METHODS: A retrospective case review of 20 patients with SNMM treated surgically at UCSF. Kaplan-Meier analyses were calculated to determine outcome differences in endoscopic vs. open resections. RESULTS: From 2005 to 2014, 20 cases of SNMM were confirmed and treated at UCSF. All cases underwent surgical resection, with 10 cases by open resection and 10 cases by endoscopic resection. Using Kaplan-Meier analyses, the open resection group had a 1-year survival of 30% whereas endoscopic resection group was 80% (p = 0.032). Endoscopic resection showed improved survival at all time points after surgery compared to open resection. CONCLUSION: SNMM is a rare and aggressive tumor that is associated with low survival rates. In this small case series, endoscopic resection had improved survival outcomes compared to open resection.

Radiotherapy for recurrent intracranial epidermoid cysts without malignant transformation: a single-institution case series.

INTRODUCTION: Recurrent intracranial epidermoid cysts may be difficult to address surgically given their proximity to critical neurovascular structures of the skull base. There are emerging reports of using radiotherapy (RT) for the treatment of recurrent epidermoid cysts. Here, we report a case series of adjuvant fractionated external beam RT for recurrent intracranial epidermoid cysts. METHODS: A single-institution review of all recurrent epidermoid cysts treated with adjuvant therapy between 2000 and 2017 was performed. RESULTS: Eight patients with recurrent epidermoid cysts who underwent adjuvant external beam RT were identified. Average age at initial diagnosis was 42.2 years, and median clinical follow-up after initial diagnosis and RT was 16.4 and 2.9 years, respectively. The median number of surgical resections prior to RT was 3 (range 2-5). Rationale for RT included multiple recurrent disease, rapid recurrence following prior resection, increased risk of further surgical morbidity, and patient preference. Median dose was 50.4 delivered in 1.8 Gy fractions (median 28 fractions). By the date of last follow-up, no patient has demonstrated progression, and there have been no cases of malignant degeneration. CONCLUSION: Adjuvant RT should be considered in the context of recurrent epidermoid cysts to decrease the likelihood of further recurrences.

Fertility treatment is associated with multiple meningiomas and younger age at diagnosis.

PURPOSE: Meningiomas are more common in females and 70-80% express the progesterone receptor, raising the possibility that high-dose exogenous estrogen/progesterone exposure, such as occurs during fertility treatments, may increase the risk of developing a meningioma. The goal of this study was to report the incidence of prior fertility treatment in a consecutive series of female meningioma patients. METHODS: A retrospective review (2015-2018) was performed of female patients with meningioma, and those with prior fertility treatment were compared to those without fertility treatment using standard statistical methods. RESULTS: Of 206 female patients with meningioma, 26 (12.6%) had a history of fertility treatments. Patients underwent various forms of assisted reproductive technology including: in vitro fertilization (50.0%), clomiphene with or without intrauterine insemination (34.6%), and unspecified (19.2%). Median follow up was 1.8 years. Tumors were WHO grade I (78.6%) or grade II (21.4%). Patients who underwent fertility treatments presented at significantly younger mean age compared to those who had not (51.8 vs. 57.3 years, p = 0.0135, 2-tailed T-test), and on multivariate analysis were more likely to have multiple meningiomas (OR 4.97, 95% CI 1.4-18.1, p = 0.0154) and convexity/falx meningiomas (OR 4.45, 95% CI 1.7-11.5, p = 0.0021). CONCLUSIONS: Patients in this cohort with a history of fertility treatment were more likely to present at a younger age and have multiple and convexity/falx meningiomas, emphasizing the importance of taking estrogen/progesterone exposure history when evaluating patients with meningioma. Future clinical studies at other centers in larger populations and laboratory investigations are needed to determine the role of fertility treatment in meningioma development.

Clinical, radiological, and histopathological predictors for long-term prognosis after surgery for atypical meningiomas.

BACKGROUND: Despite considerable rates of recurrence and mortality in atypical meningiomas, reliable predictors for estimating postoperative long-term prognosis remain elusive. METHODS: Clinical, histopathological, and radiological variables from 138 patients, including 64 females and 74 males (46% and 54%, median age 62 years), who underwent surgery for intracranial atypical meningioma were retrospectively analyzed. Associations between variables and recurrence and mortality were investigated using uni- and multivariate analyses. RESULTS: Gross total (GTR) and subtotal resection (STR) was achieved in 81% and 19% of cases, respectively. Within a median follow-up of 62 months, recurrence occurred in 52 (38%) and mortality in 22 (16%) cases. In patients who did not receive adjuvant irradiation, recurrence rates were higher after STR than after GTR (32% vs 63%, p = 0.025). In univariate analyses, only intratumoral calcifications on preoperative MRI (p = 0.012) and the presence of brain invasion in the absence of other histological grading criteria (p = 0.010) were correlated with longer progression-free intervals (PFI). In multivariate analyses, patient age was positively (HR 1.03, 95%CI 1.04-1.05; p = 0.018) and the presence of brain invasion as the only grading criterion (HR 0.37, 95%CI 0.19-0.74; p = 0.005) was negatively related with progression, while rising age at the time of surgery (HR 1.07, 95%CI 1.03-1.12; p = 0.001) was prognostic for mortality. CONCLUSIONS: PFI was longer in brain invasive but otherwise histological benign meningiomas and in tumors displaying calcifications on preoperative MRI. Advancing patient age and lower Karnofsky Performance Score were associated with higher overall mortality.

Salvage therapy outcomes for atypical meningioma.

Atypical menginomas demonstrate increased clinical aggressiveness characterized by recurrence and diminished survival. The optimal management of atypical meningioma in the recurrent setting is especially not well defined. To characterize outcomes following salvage treatment of recurrent atypical meningioma and to identify risk factors for further recurrence. Retrospective chart review was performed on 65 patients who underwent salvage treatment of atypical meningioma at a single institution. Data were analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. Sixty-five patients with recurrent atypical meningioma and median imaging follow-up of 4.0 years (range 1.9-6.6 years) underwent 62 surgeries and 114 radiation treatments (RT) for salvage therapy. Salvage modality was surgery (21%), surgery/RT (25%), or RT alone (54%), associated with 2 year local freedom from recurrence (LFFR) of 36, 59, and 73%, respectively (P = 0.01). Twenty percent of patients experienced CTCAE grade ≥ 3 toxicity with salvage therapy. Thirty-nine percent of patients experienced ≥ 3 recurrences. The median disease-free survival intervals after first and second salvage treatments were 2.9 and 1.3 years, respectively. On univariate Cox analysis, prior subtotal resection, prior RT, tumor diameter > 2.5 cm, and multifocal local recurrence were associated with recurrence after salvage therapy. On multivariate logistic regression, only multifocal local recurrence was associated with further recurrence. Recurrent atypical meningioma is clinically and pathologically more aggressive than primary atypical meningioma, and the likelihood of durable local control with salvage therapy is lower. Future efforts should identify patients at risk of recurrence, and aggressive upfront treatment should be employed.

Relationship between tumor location, size, and WHO grade in meningioma.

OBJECTIVE Prior studies have investigated preoperative risk factors for meningioma; however, no association has been shown between meningioma tumor size and tumor grade. The objective of this study was to investigate the relationship between tumor size and grade in a large single-center study of patients undergoing meningioma resection. METHODS A retrospective chart review of patients undergoing meningioma resection at the University of California, San Francisco, between 1985 and 2015 was performed. Patients with incomplete information, spinal meningiomas, multiple meningiomas, or WHO grade III meningiomas were excluded. The largest tumor dimension was used as a surrogate for tumor size. Univariate and multivariate logistic regression models were used to investigate the relationship between tumor grade and tumor size. A recursive partitioning analysis was performed to identify groups at higher risk for atypical (WHO grade II) meningioma. RESULTS Of the 1113 patients identified, 905 (81%) had a WHO grade I tumor and in 208 (19%) the tumors were WHO grade II. The median largest tumor dimension was 3.6 cm (range 0.2-13 cm). Tumors were distributed as follows: skull base (n = 573, 51%), convexity/falx/parasagittal (n = 431, 39%), and other (n = 109, 10%). On univariate regression, larger tumor size (p < 0.001), convexity/falx/parasagittal location (p < 0.001), and male sex (p < 0.001) were significant predictors of WHO grade II pathology. After controlling for interactions, multivariate regression found male sex (OR 1.74, 95% CI 1.25-2.43), size 3-6 cm (OR 1.69, 95% CI 1.08-2.66), size > 6 cm (OR 3.01, 95% CI 1.53-5.94), and convexity/falx/parasagittal location (OR 1.83, 95% CI 1.19-2.82) to be significantly associated with WHO grade II. Recursive partitioning analysis identified male patients with tumors > 3 cm as a high-risk group (32%) for WHO grade II meningioma. CONCLUSIONS Larger tumor size is associated with a greater likelihood of a meningioma being WHO grade II, independent of tumor location and male sex, which are known risk factors.

Safety and outcomes of resection of butterfly glioblastoma.

OBJECTIVE Butterfly glioblastoma (bGBM) is a rare type of GBM, characterized by a butterfly pattern on MRI studies because of its bihemispheric involvement and invasion of the corpus callosum (CC). There is a profound gap in the knowledge regarding the optimal treatment approach as well as the safety and survival benefits of resection in treating this aggressive brain tumor. In this retrospective study, authors add to our understanding of these tumors by identifying the clinical characteristics and outcomes of patients with bGBM. METHODS An institutional database was reviewed for GBM cases treated in the period from 2004 to 2014. Records were reviewed to identify adult patients with bGBM. Cases of GBM with invasion of the CC without involvement of the contralateral hemisphere and bilateral GBMs without involvement of the CC were excluded from the study. Patient and tumor characteristics were gleaned from the medical records, and volumetric analysis was performed using T1-weighted MRI studies. RESULTS From among 1746 cases of GBM, 39 cases of bGBM were identified. Patients had a mean age of 57.8 years at diagnosis. Headache and confusion were the most common presenting symptoms (48.7% and 33.3%, respectively). The median overall survival was 3.2 months from diagnosis with an overall 6-month survival rate of 38.1%. Age, Karnofsky Performance Status at diagnosis, preoperative tumor volume, postoperative tumor volume, and extent of resection were found to significantly impact survival in the univariate analysis. On multivariate analysis, preoperative tumor volume and treatment approach of resection versus biopsy were identified as independent prognostic factors regardless of the patient-specific characteristics of age and KPS at diagnosis. Resection and biopsy were performed in 35.9% and 64.1% of patients, respectively. Resection was found to confer a better prognosis than biopsy (HR 0.37, p = 0.009) with a minimum extent of resection of 86% to observe survival benefits (HR 0.054, p = 0.03). The rate of persistent neurological deficits from resection was 7.14%. Patients younger than 70 years had a better prognosis (HR 0.32, p = 0.003). Patients undergoing resection and receiving adjuvant chemoradiation had a better prognosis than patients who lacked one of the three treatment modalities (HR = 0.34, p = 0.015). CONCLUSIONS Resection of bGBM is associated with low persistent neurological deficits, with improvement in survival compared to biopsy. A more aggressive treatment approach involving aggressive resection and adjuvant chemoradiation has significant survival benefits and improves outcome.

Cost-effectiveness development for the postoperative care of craniotomy patients: a safe transitions pathway in neurological surgery.

OBJECTIVE The authors' institution is in the top 5th percentile for hospital cost in the nation, and the neurointensive care unit (NICU) is one of the costliest units. The NICU is more expensive than other units because of lower staff/patient ratio and because of the equipment necessary to monitor patient care. The cost differential between the NICU and Neuro transitional care unit (NTCU) is $1504 per day. The goal of this study was to evaluate and to pilot a program to improve efficiency and lower cost by modifying the postoperative care of patients who have undergone a craniotomy, sending them to the NTCU as opposed to the NICU. Implementation of the pilot will expand and utilize neurosurgery beds available on the NTCU and reduce the burden on NICU beds for critically ill patient admissions. METHODS Ten patients who underwent craniotomy to treat supratentorial brain tumors were included. Prior to implementation of the pilot, inclusion criteria were designed for patient selection. Patients included were less than 65 years of age, had no comorbid conditions requiring postoperative intensive care unit (ICU) care, had a supratentorial meningioma less than 3 cm in size, had no intraoperative events, had routine extubation, and underwent surgery lasting fewer than 5 hours and had blood loss less than 500 ml. The Safe Transitions Pathway (STP) was started in August 2016. RESULTS Ten tumor patients have utilized the STP (5 convexity meningiomas, 2 metastatic tumors, 3 gliomas). Patients' ages ranged from 29 to 75 years (median 49 years; an exception to the age limit of 65 years was made for one 75-year-old patient). Discharge from the hospital averaged 2.2 days postoperative, with 1 discharged on postoperative day (POD) 1, 7 discharged on POD 2, 1 discharged on POD 3, and 1 discharged on POD 4. Preliminary data indicate that quality and safety for patients following the STP (moving from the operating room [OR] to the neuro transitional care unit [OR-NTCU]) are no different from those of patients following the traditional OR-NICU pathway. No patients required escalation in level of nursing care, and there were no readmissions. This group has been followed for greater than 1 month, and there were no morbidities. CONCLUSIONS The STP is a new and efficient pathway for the postoperative care of neurosurgery patients. The STP has reduced hospital cost by $22,560 for the first 10 patients, and there were no morbidities. Since this pilot, the authors have expanded the pathway to include other surgical cases and now routinely schedule craniotomy patients for the (OR-NTCU) pathway. The potential cost reduction in one year could reach $500,000 if we reach our potential of 20 patients per month.