Impact of time of day on outcomes after stereotactic radiosurgery for non-small cell lung cancer brain metastases.

BACKGROUND: This study tested the hypothesis that time of day of treatment with stereotactic radiosurgery (SRS) has an effect on local control (LC) and overall survival (OS) in a large cohort of patients with non-small cell lung cancer (NSCLC) brain metastases. METHODS: At Washington University in St. Louis, 437 patients with NSCLC were treated with SRS for NSCLC brain metastases. Receiver operating characteristics analysis was used to identify an optimal cut-point for OS relative to time of day. Kaplan-Meier log-rank statistics, and Cox regression univariate and multivariate analysis were employed to isolate any independent effect of treatment time on OS and LC. Matched-pair analysis was performed to isolate any independent effect of time on OS and LC of day while controlling for confounding variables. RESULTS: Receiver operating characteristics analysis identified a cut-point of 11:41 AM as providing the highest predictive value for OS. On univariate analysis, late SRS was associated with decreased OS, as was age, Karnofsky performance status, risk-stratification schemes, extracranial disease status, and overall burden of brain metastases. On univariate analysis for LC, late SRS was associated with decreased LC, as was burden of brain metastases. On multivariate analysis, only Graded Prognostic Assessment remained predictive of OS, and total number of targets and total tumor volume remained predictive of LC. Matched-pair analysis demonstrated no significant effect of time of day on LC or OS. CONCLUSIONS: Although earlier treatment appears to be associated with improved LC and OS, treatment time fails to remain significant when accounting for confounding variables.

Extreme Risk Protection Orders: Legislative Intent and Clinician Guidance.

In this second column of a 2-part series exploring extreme risk protections orders, we utilize recent events in Colorado, including legislative efforts to expand the list of eligible petitioners to include clinicians, as an opportunity to explore questions and challenges faced by mental health and medical professionals serving in this capacity. Clinicians are in need of more clear guidance, given an emerging role that comes without clear evidence or practice standards to inform individualized clinical decision-making, and which potentially pits public safety interests against patient care needs, especially those pertaining to therapeutic relationships. In the interim, clinicians will best serve their patients by continuing to practice in a fashion that is analogous to decision-making around other interventions with serious implications for patient autonomy such as involuntary hospitalization. Ongoing collaboration with legislators is needed to arrive at laws that are informed by the limitations inherent in clinical risk assessment and that can be translated into clinical practices that simultaneously support patient needs and community safety.

Oligodendrogliomas in children.

Oligodendrogliomas are rare central nervous system (CNS) tumors in children. The purpose of this study was to identify prognostic factors for progression free survival (PFS) and overall survival (OS) in pediatric patients with oligodendrogliomas. We retrospectively analyzed clinical data on 37 pediatric patients with oligodendroglial tumors treated at Washington University. Kaplan-Meier method was used to calculate survival rates. Log-rank was used to detect the difference between survival curves. The median age was 11.1 years (range 10 months-18 years), and median follow-up was 4.5 years (range 2 months-30.5 years). The 5-year PFS and OS were 66.4 and 93.4%, respectively. Mixed histology was associated with worse OS compared to patients with pure oligodendroglioma, 5-year OS 77.6 versus 100% (P < 0.01). Patients who underwent gross total resection (GTR) experienced an improved 5-year PFS of 100% compared to 28.8% (P = 0.03) in patients treated with subtotal resection (STR) or biopsy alone. Age >3 years at diagnosis correlated with improved 5-year PFS, 33.3 versus 69.8% (P = 0.01). Neither post-operative chemotherapy nor radiation therapy correlated with improved outcome. GTR and age >3 years at diagnosis remained significant for improved PFS on multivariate analysis. There were no factors correlated with improved overall survival on multivariate analysis. Pediatric oligodendroglial tumors are associated with excellent OS; however, a third of patients developed progressive disease. Our data demonstrate that patients with less than GTR and <3 years at diagnosis are at increased risk for progression and may benefit from more aggressive therapy.

Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases.

BACKGROUND: Patients with limited intracranial metastatic disease traditionally have been treated with surgery followed by WBRT. However, there is growing concern for the debilitating cognitive effects after WBRT in long-term survivors. We present a series of patients treated with surgery followed by SRS, while reserving WBRT as a salvage therapy for disease progression. METHODS: Medical records from 15 patients with 1 to 2 cerebral metastases who underwent both resection and SRS were reviewed. Outcome measures included overall survival, survival by RPA class, EOR, local tumor control, progression of intracranial disease, need for WBRT salvage therapy, and COD. RESULTS: Fifteen patients with cerebral metastases were treated with the combined surgery-SRS paradigm. Eight of the 15 patients (53.3%) were designated RPA class 1, with 6 of 15 (40.0%) in class 2 and 1 of 15 (6.7%) in class 3. Gross total resection was achieved in 12 cases (80.0%). Overall median survival was 20.0 months, with values of 22.0 and 13.0 months for RPA classes 1 and 2, respectively. Local recurrence occurred in 16.7% of those patients with GTR. Six patients (40.0%) went on to receive WBRT at a median of 8.0 months from initial presentation. Twelve patients (80.0%) had died at the completion of the study, and the COD was CNS progression in 33.3%. CONCLUSIONS: Surgical resection combined with SRS is an effective treatment for selected patients with limited cerebral metastatic disease. Survival using this combined treatment was equivalent to or greater than that reported by other studies using surgery + WBRT or SRS + WBRT.

Functional MRI lie detection: too good to be true?

Neuroscientists are now applying a 21st-century tool to an age-old question: how can you tell when someone is lying? Relying on recently published research, two start-up companies have proposed to use a sophisticated brain-imaging technique, functional magnetic resonance imaging (fMRI), to detect deception. The new approach promises significantly greater accuracy than the conventional polygraph--at least under carefully controlled laboratory conditions. But would it work in the real world? Despite some significant concerns about validity and reliability, fMRI lie detection may in fact be appropriate for certain applications. This new ability to peer inside someone's head raises significant questions of ethics. Commentators have already begun to weigh in on many of these questions. A wider dialogue within the medical, neuroscientific, and legal communities would be optimal in promoting the responsible use of this technology and preventing abuses.

Bad risk? An overview of laws prohibiting possession of firearms by individuals with a history of treatment for mental illness.

For nearly 40 years, federal law has barred certain individuals with a history of mental health treatment from purchasing, receiving, or possessing firearms. State laws are a patchwork of different regulations, some much more inclusive than the federal statute, others that parallel it closely. In some states, such laws are nonexistent. For the past 20 years, it has been possible to petition for relief from the federal prohibition; however, this is not the case with all state laws. The mechanisms for relief under state laws, when present, vary significantly, and not all require the input of a mental health professional or even of any physician. This article provides an overview of federal and state laws, a discussion of implications of these laws for mental health clinicians and forensic practitioners, and suggestions of directions for future research.

When Restoration Fails: One State's Answer to the Dilemma of Permanent Incompetence.

The landmark 1972 U.S. Supreme Court decision in Jackson v. Indiana prohibited the indefinite commitment of criminal defendants on grounds of incompetence to stand trial if there was no substantial probability of restoration to competency in the foreseeable future. Such defendants are still subject to ordinary civil commitment; however, not all will meet civil commitment criteria, given that the criteria for a finding of incompetency to stand trial do not map directly onto the general criteria for involuntary psychiatric hospitalization. If a person charged with a serious crime, such as murder, has no substantial probability of being restored to competency, but does not meet standard civil commitment criteria, compliance with Jackson would seem to require release into the community. This article describes a legislative response to this possibility that became law in California four decades ago, as well as the outcome of its main legal challenge a few years later. Although the law has received harsh criticism from some quarters, it has survived, and provides a legally straightforward, if ethically controversial, means of answering the question of what to do with a permanently incompetent defendant who is charged with a serious violent offense and does not meet traditional civil commitment criteria.

Radiation Therapy for Residual or Recurrent Atypical Meningioma: The Effects of Modality, Timing, and Tumor Pathology on Long-Term Outcomes.

BACKGROUND: Optimal use of stereotactic radiosurgery (SRS) vs external beam radiation therapy (EBRT) for treatment of residual/recurrent atypical meningioma is unclear. OBJECTIVE: To analyze features associated with progression after radiation therapy. METHODS: Fifty radiation-naive patients who received SRS or EBRT for residual and/or recurrent atypical meningioma were examined for predictors of progression using Cox regression and Kaplan-Meier analyses. RESULTS: Thirty-two patients (64%) received adjuvant radiation after subtotal resection, 12 patients (24%) received salvage radiation after progression following subtotal resection, and 6 patients (12%) received salvage radiation after recurrence following gross total resection. Twenty-one patients (42%) received SRS (median 18 Gy), and 7 (33%) had tumor progression. Twenty-nine patients (58%) received EBRT (median 54 Gy), and 13 (45%) had tumor progression. Whereas tumor volume (P = .53), SRS vs EBRT (P = .45), and adjuvant vs salvage (P = .34) were not associated with progression after radiation therapy, spontaneous necrosis (hazard ratio [HR] = 82.3, P < .001), embolization necrosis (HR = 15.6, P = .03), and brain invasion (HR = 3.8, P = .008) predicted progression in univariate and multivariate analyses. Tumors treated with SRS/EBRT had 2- and 5-year actuarial locoregional control rates of 91%/88% and 71%/69%, respectively. Tumors with spontaneous necrosis, embolization necrosis, and no necrosis had 2- and 5-year locoregional control rates of 76%, 92%, and 100% and 36%, 73%, and 100%, respectively (P < .001). CONCLUSION: This study suggests that necrosis may be a negative predictor of radiation response regardless of radiation timing or modality. ABBREVIATIONS: AM, atypical meningiomaEBRT, external beam radiation therapyGTR, gross total resectionLC, locoregional controlOS, overall survivalPOE, preoperative embolizationRT, radiation therapySRS, stereotactic radiosurgerySTR, subtotal resection.

Dose distribution outside of a sphere of P-32 chromic phosphorous colloid.

PURPOSE: To evaluate the dose distribution outside of a cyst instilled with phosphorous-32 (P-32, an electron emitter with a short effective range of 2-8 mm and average energy of 0.69 MeV, used to treat cystic craniopharyngioma) as a function of cyst size with and without plating (migration and adhesion of P-32 to the cyst surface). METHODS AND MATERIALS: A cystic craniopharyngioma treated with instillation of P-32 was approximated by a sphere of uniformly distributed and plated chromic P-32 colloid. The percent depth dose was calculated along a radial position vector exterior to the sphere with a three-dimensional convolution integral and a dose point kernel. RESULTS: The percent depth dose variation of surface or volume source external to a family of spheres was plotted. Complex cyst geometry is amenable to evaluation by approximation with simple spheres. Error estimates are calculated for the dose outside of truncated sphere segments. Plating might occur and raise the dose outside the cyst by more than a factor of 5.0. This has the potential to cause damage to adjacent tissues, including the optic chiasm. CONCLUSION: Clinicians are faced with a number of treatment options for cystic craniopharyngioma, including intracystic instillation of colloid P-32. Unfortunately, plating might occur and potentially damage adjacent normal tissues. It is recommended that the propensity for a craniopharyngioma to plate be evaluated before full treatment, especially after previous treatment.

Postoperative radiation therapy for grade II and III intracranial ependymoma.

PURPOSE: To retrospectively determine the long-term outcome of intracranial ependymoma patients treated with surgery and postoperative radiation therapy. METHODS AND MATERIALS: Sixty patients were treated at our institution between 1964 and 2000. Forty patients had World Health Organization Grade II ependymoma, and 20 patients had Grade III ependymoma. The median patient age was 10.7 years. The majority of patients were male (55%), had infratentorial tumors (80%), and had subtotal resections (72%). Postoperative radiation therapy was delivered to all patients to a median total dose of 50.4 Gy. Craniospinal radiation therapy was used in the earlier era in only 12 patients (20%). RESULTS: The median follow-up of surviving patients was 12.5 years. The 5-year and 10-year disease-free survival rates for all patients were 58.4% and 49.5%, respectively. The 5-year and 10-year overall survival rates for all patients were 71.2% and 55.0%, respectively. Supratentorial tumor location was independently associated with a worse disease-free survival. Subtotal resection and supratentorial location predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumor grade, patient age, or radiation dose or volume. CONCLUSION: Our long-term follow-up indicates that half of ependymoma patients will have disease recurrences, indicating the need for more effective treatments.

Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma.

PURPOSE: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. METHODS AND MATERIALS: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/µL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL. RESULTS: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V25Gy) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V25Gy <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). CONCLUSIONS: Female sex, older age, lower baseline TLC, and higher brain V25Gy are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V25Gy of brain below 56% may reduce the risk of ASL.

Impact of 1p/19q codeletion and histology on outcomes of anaplastic gliomas treated with radiation therapy and temozolomide.

PURPOSE: Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion. METHODS AND MATERIALS: A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA. RESULTS: From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, P=.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA. CONCLUSIONS: RT + TMZ may be a promising treatment for both codeleted and non-codeleted AO/AOA, but its role for AA remains unclear.

Carcinoma of paranasal sinuses: long-term outcomes with radiotherapy.

PURPOSE: To assess the clinical features, prognostic factors, results, and complications of treatment of carcinomas of the paranasal sinus. METHODS AND MATERIALS: The records of 106 patients (72 men and 34 women) with paranasal sinus carcinoma treated with curative intent at Washington University between January 1960 and August 1998 were analyzed. Patient age ranged from 29 to 91 years (median, 64 years). Most tumors originated in the maxillary (76%) or ethmoid (18%) sinus. Most tumors were locally advanced at presentation. All patients underwent radiotherapy (RT), combined with surgery in 65%; 2% received chemotherapy. RESULTS: Follow-up ranged from 1.7 months to 24 years (median 5 years). The 5-year local tumor control, locoregional tumor control, disease-free survival (DFS), and overall survival rate was 58%, 39%, 33%, and 27%, respectively. A statistically significant improvement in DFS was noted with the addition of surgical resection to RT (35% vs. 29%, p = 0.05). Nodal status at presentation emerged as a statistically significant predictor for locoregional tumor control and DFS in multivariate analysis. Distant metastases occurred in 29% of patients. CONCLUSION: This review of a large, single-institution experience of paranasal sinus carcinoma patients who underwent RT showed that locoregional tumor progression and recurrence remain predominant patterns of failure despite aggressive local treatment with combined surgery and RT. DFS improved slightly with combined modality treatment. The overall survival rates remained suboptimal, suggesting a need for more accurate determination of tumor extent, as well as more effective locoregional and systemic therapies.

Radiation medicine innovations for the new millenium.

PURPOSE OF THE STUDY: To review technological advances in the field of radiation oncology in the management of benign and malignant diseases. BASIC PROCEDURES: We reviewed major advances in the field of radiation oncology in the past decade with special emphasis on reduction of treatment related toxicities, and technological improvements in planning and delivery of radiation. Modalities reviewed include computerized three-dimensional conformal treatment planning, stereotactic radiosurgery, intensity-modulated radiation therapy, ultrasound-guided transperineal permanent brachytherapy of the prostate, and high-dose rate brachytherapy. MAIN FINDINGS: There have been major technological advances as evidenced by a decrease in treatment-related toxicities and better target definition resulting in higher local control rates. PRINCIPAL CONCLUSIONS: Significant improvements in technique and equipment have firmly positioned radiotherapy as major artillery in the fight against both benign and malignant diseases.

DSM-5 and neurocognitive disorders.

The newest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduces several changes in the diagnostic criteria for dementia and other cognitive disorders. Some of these changes may prove helpful for clinical and forensic practitioners, particularly when evaluating less severe cognitive impairments. The most substantial change is that the cognitive disorder-not otherwise specified category found in prior editions has been eliminated. Those disorders that do not cause sufficient impairment to qualify for a diagnosis of dementia are now defined as neurocognitive disorders and placed on a spectrum with the more severe conditions. The concept of social cognition is also introduced as one of the core functional domains that can be affected by a neurocognitive disorder. This concept may be particularly significant in the evaluation of patients with non-Alzheimer's dementias, such as frontotemporal dementia. With the aging of the population and the increasing recognition of the possibility of long-lasting cognitive deficits after traumatic brain injury, the need for assessment of cognitive disorders in medicolegal contexts is certain to increase. Forensic psychiatrists who perform these evaluations should understand the conceptualization of Neurocognitive Disorders as presented in DSM-5 and how it differs from prior diagnostic systems.

Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide.

PURPOSE: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). METHODS AND MATERIALS: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/ß ratio of 5.6 for GBM. RESULTS: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. CONCLUSION: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

Predictors of individual tumor local control after stereotactic radiosurgery for non-small cell lung cancer brain metastases.

PURPOSE: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. RESULTS: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥ 1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. CONCLUSIONS: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas.

BACKGROUND: While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution's Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. METHODS: Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. RESULTS: Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. CONCLUSION: Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly predictive of recurrence and survival on multivariate analysis in aggressive meningioma patients treated with radiosurgery. Larger tumor size predicts poor survival, while nuclear atypia, necrosis, and increased mitotic rate are risk factors for recurrence. Clinical and pathologic predictors may help identify patients that are at higher risk for recurrence.