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Background: The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM)., Objective: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012., Methods: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived., Results: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided., Conclusion: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis.https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Since its approval for use, reverse shoulder arthroplasty (RSA) has become the primary treatment for cuff tear arthropathy, with indications expanding more recently to include revision fracture, osteoarthritis with significant glenoid bone loss, tumor, and chronic instability. Instability is a well-described postoperative complication, occurring in 1to 31% of relatively small cohorts and case series. Given the relative infrequency of instability, there remains a need for a comprehensive review of instability with a focus on risk factors and management. Our goal of this systematic review is to describe the prevalence, risk factors, and management strategies for instability following RSA., Methods: A systematic review of the PubMed, EMBASE, MEDLINE, Scopus, and Cochrane Library databases was performed according to PRISMA guidelines. Inclusion criteria included primary RSA cohorts ≥ 100 patients, revision RSA cohorts of any size, and minimum 1-year follow-up. The primary outcome of interest was postoperative instability. MINORS criteria were used to assess study bias. Descriptive statistical analysis was performed with data reported as ranges., Results: Seventeen studies that included 7885 cases of RSA were reviewed. The mean follow-up ranged from 12 to 84 months. Mean age ranged from 64 to 77 years old, and males represented 19 to 39% of cohorts. There were 204 (2.5%) dislocations in 7885 cases, accounting for a rate of instability from 0.4 to 49% across all studies. By intervention, instability rates ranged from 1 to 5% (primary RSA cases), 1 to 49% (revision RSA cases only), and 0.4 to 10% (mixed cohorts). Subscapularis insufficiency and proximal humerus fractures, and fracture sequelae (malunion and nonunion) were identified as risk factors for instability. Closed reduction and casting and revision RSA were reported as successful treatment strategies with acceptable rates of stable prostheses (28-100% and 55-100%, respectively, across studies). Hemiarthroplasty or resection arthroplasty due to recurrent instability was not uncommon after 2 or more episodes of instability., Conclusion: Instability following RSA occurs infrequently (1-5%) following primary RSA and more commonly following revision RSA (1-49%). RSA for acute proximal humerus fracture and fracture sequelae carries a higher risk of instability. Subscapularis repair appears to be a protective factor. While instability may be successfully treated with closed management or revision RSA, recurrent instability may ultimately require hemiarthroplasty or resection arthroplasty., (© 2022 The Author(s).)

Glioblastoma (GBM) is highly aggressive and has a poor prognosis. Belinostat is a histone deacetylase inhibitor with blood-brain barrier permeability, anti-GBM activity, and the potential to enhance chemoradiation. The purpose of this clinical trial was to assess the efficacy of combining belinostat with standard-of-care therapy. Thirteen patients were enrolled in each of control and belinostat cohorts. The belinostat cohort was given a belinostat regimen (500-750 mg/m 2 1×/day × 5 days) every three weeks (weeks 0, 3, and 6 of RT). All patients received temozolomide and radiation therapy (RT). RT margins of 5-10 mm were added to generate clinical tumor volumes and 3 mm added to create planning target volumes. Median overall survival (OS) was 15.8 months for the control cohort and 18.5 months for the belinostat cohort ( p = 0.53). The recurrence volumes (rGTVs) for the control cohort occurred in areas that received higher radiation doses than that in the belinostat cohort. For those belinostat patients who experienced out-of-field recurrence, tumors were detectable by spectroscopic MRI before RT. Recurrence analysis suggests better in-field control with belinostat. This study highlights the potential of belinostat as a synergistic therapeutic agent for GBM. It may be particularly beneficial to combine this radio-sensitizing effect with spectroscopic MRI-guided RT.

Background: Accurate identification and discrimination of post treatment changes from recurrent disease remains a challenge for patients with intracranial malignancies despite advances in molecular and magnetic resonance imaging. We have explored the ability of readily available Rubidium-82 chloride ( 82 RbCl) positron emission tomography (PET) to identify and distinguish progressive intracranial disease from radiation necrosis in patients previously treated with radiation therapy., Methods: Six patients with a total of 9 lesions of either primary (N.=3) or metastatic (N.=6) intracranial malignancies previously treated with stereotactic radiation surgery (SRS) and persistent contrast enhancement on MRI underwent brain 82 RbCl PET imaging. Two patients with arteriovenous malformations previously treated with SRS, also had brain 82 RbCl PET imaging for a total of 11 lesions studied. Histological confirmation via stereotactic biopsy/excisional resection was obtained for 9 lesions with the remaining 2 classified as either recurrent tumor or radiation necrosis based on subsequent MRI examinations. 82 RbCl PET time activity curve analysis was performed which comprised lesion SUVmax, contralateral normal brain SUVmax, and tumor to background ratios (TBmax)., Results: 82 RbCl demonstrates uptake greater than normal brain parenchyma in all lesions studied. Time activity curves demonstrated progressive uptake of 82 RbCl in all lesions without evidence of washout. While recurrent disease demonstrated a greater mean SUVmax compared to radiation necrosis, no statistically significant difference between lesion SUVmax nor TBmax was found (P>0.05)., Conclusions: 82 RbCl PET produces high-contrast uptake of both recurrent disease and radiation necrosis compared to normal brain. However, no statistically significant difference was found between recurrent tumor and radiation necrosis.

Purpose: Genetic analyses of gliomas have identified key molecular features that impact treatment paradigms beyond conventional histomorphology. Despite at-times lower grade histopathologic appearances, IDH-wildtype infiltrating gliomas expressing certain molecular markers behave like higher-grade tumors. For IDH-wildtype infiltrating gliomas lacking traditional features of glioblastoma, these markers form the basis for the novel diagnosis of diffuse astrocytic glioma, IDH-wildtype (wt), with molecular features of glioblastoma (GBM), WHO grade-IV (DAG-G). However, given the novelty of this approach to diagnosis, literature detailing the exact clinical, radiographic, and histopathologic findings associated with these tumors remain in development., Methods: Data for 25 patients matching the DAG-G diagnosis were obtained from our institution's retrospective database. Information regarding patient demographics, treatment regimens, radiographic imaging, and genetic pathology were analyzed to determine association with clinical outcomes., Results: The initial radiographic findings, histopathology, and symptomatology of patients with DAG-G were similar to lower-grade astrocytomas (WHO grade 2/3). Overall survival (OS) and progression free survival (PFS) associated with our cohort, however, were similar to that of IDH-wt GBM, indicating a more severe clinical course than expected from other associated features (15.1 and 5.39 months respectively)., Conclusion: Despite multiple features similar to lower-grade gliomas, patients with DAG-G experience clinical courses similar to GBM. Such findings reinforce the need for biopsy and subsequent analysis of molecular features associated with any astrocytoma regardless of presenting characteristics., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Nerve palsy is common after humeral shaft fracture, with the radial nerve being the most commonly injured nerve. Isolated nerve injuries usually recover spontaneously, and operative intervention is rarely indicated. Our goal was to study the predictors of traumatic nerve injury and recovery in a large cohort of patients with humeral shaft fractures., Methods: A total of 376 patients with humeral shaft fracture, including 96 patients with documented traumatic nerve palsy and 280 with intact neurovascular examination on presentation, were retrospectively included in the study. The primary outcome was incidence of a traumatic nerve palsy, and the secondary outcome was nerve recovery., Results: Nerve palsy was present in 96 patients (25.5%) at the time of injury. Radial nerve was the most commonly injured nerve (93.6%), followed by the ulnar (5.1%) and axillary (1.2%) nerves. Seventeen patients (17.7%) had multiple nerves palsies. A multivariable regression analysis revealed that the concomitant vascular injury (odds ratio [OR] 52, 95% confidence interval [CI] 5.6-480.6), distal one-third fractures (OR 6.3, 95% CI 2.7-14.7), and middle one-third (OR 2.8, 95% CI 1.2-6.5) vs. proximal fractures, open fracture (OR 2.1, 95% CI 1.1-4.4), and high-energy trauma (OR 1.7, 95% CI 1.1-2.9) were independent predictors of nerve palsy. Iatrogenic nerve injury was detected in 7 patients (4.6%), all affecting the radial nerve. Spontaneous recovery of traumatic nerve injuries was detected in 87 patients (91%), with 19% partial and 72% complete recovery. The initial sign of recovery was observed at median times of 7 and 9 weeks for those managed conservatively or fracture fixation. Operative treatment of the fracture had no effect on the outcome of nerve recovery (88.5% vs. 100%, P = .14). Ten patients (14.1%) had transected nerves at the time of exploration and open fractures (22.7% vs. 6.8%, P = .04), and concomitant vascular injury (33.3% vs. 7.3%, P = .02) were associated with nerve transection, portending a worse prognosis for nerve recovery compared with nerves in continuity (40% vs. 95.3%, P = .004)., Discussion: The incidence of nerve injury after humeral shaft fracture was 25%, reflecting an abundance of high-energy and open injuries in this cohort. Ninety-one percent of patients experienced improvement in their nerve function with a median time to recovery of 7-9 weeks. Operative treatment of the fracture did not change the rate of nerve recovery. Patients with multiple nerve palsies and concurrent vascular insult had worse nerve recovery. We recommend nerve studies if no sign of recovery is observed by 9 weeks., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Posterior fossa tumors (PFTs) can cause hydrocephalus. Hydrocephalus can persist despite resection of PFTs in a subset of patients requiring permanent cerebrospinal fluid (CSF) diversion. Characteristics of this patient subset are not well defined., Objective: To define preoperative and postoperative variables that predict the need for postoperative CSF diversion in adult patients with PFTs., Methods: We surveyed the CNS (Central Nervous System) Tumor Outcomes Registry at Emory (CTORE) for patients who underwent PFT resection at 3 tertiary-care centers between 2006 and 2019. Demographic, radiographic, perioperative, and dispositional data were analyzed using univariate and multivariate models., Results: We included 617 patients undergoing PFT resection for intra-axial (57%) or extra-axial (43%) lesions. Gross total resection was achieved in 62% of resections. Approximately 13% of patients required permanent CSF diversion/shunting. Only 31.5% of patients who required pre- or intraop external ventricular drain (EVD) placement needed permanent CSF diversion. On logistic regression, size, transependymal flow, use of perioperative EVD, postoperative intraventricular hemorrhage (IVH), and surgical complications were predictors of permanent CSF diversion. Preoperative tumor size was only independent predictor of postoperative shunting in patients with subtotal resection. In patients with intra-axial tumors, transependymal flow (P = .014), postoperative IVH (P = .001), surgical complications (P = .013), and extent of resection (P = .03) predicted need for shunting. In extra-axial tumors, surgical complications were the major predictor (P = .022)., Conclusion: Our study demonstrates that presence of preoperative hydrocephalus in patients with PFT does not necessarily entail the need for permanent CSF diversion. We report the major predictive factors for needing permanent CSF diversion., (© Congress of Neurological Surgeons 2021.)

Objective: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity., Methods: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables., Results: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume., Conclusions: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

Objectives: To evaluate the incidence of nonunion and wound complications after open, complete articular pilon fractures. Second, to study the effect that both timing of fixation and timing of flap coverage have on deep infection rates., Design: Retrospective case series., Setting: Three Academic Level 1 Trauma Centers., Patients: One hundred sixty-one patients with open OTA/AO type 43C distal tibia fractures treated with open reduction internal fixation (ORIF) between 2002 and 2018. The mean (SD) age was 46 (14) years, 70% male, with median (interquartile range) follow-up of 2.1 (1.3-5.0) years (minimum 1 year). There were 133 (83%) type 3A and 28 (17%) type 3B open fractures., Intervention: Fracture fixation: acute, primary (<24 hours) versus delayed, staged ORIF (>24 hours). Soft-tissue coverage: rotational or free flap., Main Outcome Measurement: Primary outcomes included deep infection and nonunion. Secondary outcomes included rates of soft-tissue coverage and reoperation., Results: Acute fixation (<24 hours) was performed in 36 (22%) patients; 125 (78%) underwent delayed, staged fixation. Deep infection occurred in 27% patients and was associated with men (33% vs. 16%, P = 0.029), smoking (38% vs. 23%, P = 0.047), and type 3B fractures (39% vs. 25%, P = 0.046). Acute fixation of type 3A fractures demonstrated a higher rate of infection (38% vs. 20% P = 0.036) than delayed, staged fixation. In type 3B fractures, early flap coverage (<1 week) demonstrated a lower rate of infection (18% vs. 53%, P = 0.066) and 20% (vs. 43%) with a single-staged "fix and flap" procedure (P = 0.408). Nonunion occurred in 36 (22%) and was associated with deep infection (43% vs. 15%, P < 0.001). Fifteen (42%) were septic nonunions. Twenty-nine of the 36 (81%) nonunions achieved radiographic union after median (interquartile range) 27 (20-41) weeks and median (range) 1 (1-3) revision ORIF procedures. There was no difference in the rate of secondary union between septic and aseptic nonunions (85% vs. 86%, P = 1.00). There was a high rate of secondary procedures (47%): revision ORIF (17%), irrigation and debridement (15%), and removal of implants (11%)., Conclusions: Complete articular, open pilon fractures are associated with a high rate of complications after ORIF. Early fixation carries a high risk of deep infection; however, early flap coverage for 3B fractures seems to play a protective role. We advocate for aggressive management including urgent surgical debridement and very early soft-tissue cover combined with definitive fixation during single procedure if possible., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction  Atypical meningiomas (AM) are meningiomas that are more aggressive than their grade-I counterparts and have a higher rate of recurrence. The effect of adjuvant radiotherapy (ART) on AM of the skull base is not defined. Methods  A retrospective review of all AM's of the skull base primarily resected at our institution from 1996 to 2018 was completed. ART was defined as radiotherapy (RT) that occurred within 6 months of initial resection, regardless of Simpson's grade. Minimum time length of follow-up after resection was 2 years. Statistical analysis was performed using SAS. Results  There were a total of 59 skull base-located (SBL) AMs resected at our institution from 1996 to 2018. The average age of our cohort was 53.2 years. Gross total resection, defined as Simpson's grades I to III resection, was achieved in 36 (61%) of cases. Thirty-five of 59 (59%) patients received ART. Recurrence was observed in 14 patients (24%), and mean time to recurrence was 63.8 months. Patients who received ART had a lower observed rate of recurrence (8 vs. 46%); however, time to recurrence was not significantly different between the two populations. Conclusion  We observe that AM in the skull base location have higher recurrence rates than we would expect from grade-I meningioma. These data suggest that ART may offer benefit to the overall observed frequency of recurrence of SBL AM; however, the time to recurrence between patients who received ART and those who did not was not statistically significant in survival analysis., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objectives: To compare the deep infection rates after immediate versus staged open reduction internal fixation (ORIF) for pilon fractures., Design: Retrospective cohort study., Setting: Three academic Level I trauma centers., Patients: Four hundred one patients with closed OTA/AO type 43C distal tibia fractures treated with ORIF. Sixty-six percent were men, and the mean age was 45.6 years. The median (interquartile range) follow-up was 1.7 (1.0-3.7) years., Intervention: Acute, primary (<24 hours) versus delayed, staged ORIF (>24 hours)., Main Outcome Measurement: Deep infection or wound complication as defined by return to operating room for surgical irrigation and debridement., Results: Patients were grouped by time from presentation to surgery: acute ORIF (n = 99) and delayed ORIF (n = 302). Acute ORIF was more frequent in patients with OTA/AO type 43C1 fractures, low-energy mechanisms (ie, fall from standing), younger and female patients. Patients who demonstrated severe swelling (242, 80%), swelling and fracture blisters (26, 9%), swelling and ecchymosis precluding planned surgical approach (4, 1%), polytrauma requiring resuscitation (20, 6%), who were transferred from an outside facility with external fixator in place (6, 2%), who had evolving compartment syndrome (2, 1%), and who required medical clearance (2, 1%) underwent staged, delayed fixation. There were significantly more 43C1 fractures in the acute fixation group (31% vs. 7%, P < 0.001) and significantly more 43C3 fractures in the delayed group (63% vs. 37%, P < 0.001). The overall deep infection rate was 17%. Early surgery was not associated with an increased risk of postoperative wound complication (early 12% vs. delayed 18%, P = 0.235). Multivariate analysis adjusted for timing of surgery found high-energy trauma [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.1-13.8], smoking (OR 2.4, CI 1.3-4.6), male sex (OR 2.1, CI 1.0-4.1), and increasing age (OR 1.02, CI 1.00-1.04, P = 0.040) to be independent predictors of deep infection. Diabetes demonstrated a nonstatistically significant increased risk (OR 2.6, 95% CI 0.9-7.3, P = 0.063)., Conclusions: This study confirms the high risk of infection after the fixation of tibial plafond fractures. If early definitive fixation is considered, extreme care should be taken to carefully evaluate the soft tissue envelope and assess for other risk factors (such as age, male sex, smokers, diabetics, and those with higher-energy fracture patterns) that may predispose the patient to a postoperative soft tissue infection. Our study has shown that the judicious use of early definitive fixation in closed pilon fractures, in the appropriate patient, and with careful evaluation of the soft tissue envelope, is likely safe and does not seem to increase the risk of wound complications and deep infection in the hands of experienced fracture surgeons., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Antiretroviral therapy has improved the life expectancy of HIV patients, leading to an increase in total joint replacement for age-related osteoarthritis. HIV patients are inherently hypercoagulable at baseline. The goal of our study was to compare the incidence of venous thromboembolism (VTE) in HIV patients with HIV-negative controls after total joint replacement., Methods: A multicenter, retrospective cohort study of 110 HIV patients (85 hips and 25 knees) and 240 HIV-negative controls (180 hips and 85 knees) between 2000 and 2018. Prophylactic anticoagulation was used in 98% of patients postoperatively-low-molecular weight heparin (73%), warfarin (19%), aspirin (6%), and clopidogrel (1%)., Results: The VTE rate was 3.6% in the HIV-positive group (2.5% total hip arthroplasty [THA] and 8.0% total knee arthroplasty [TKA]) and 0.4% in the control group (0% THA and 1.7% TKA). VTEs occurred at the median (interquartile range) time of 40 days (1 to 52) post-op in the HIV group and 3 days post-op in the one control. Multivariable logistic regression adjusting for sex, smoking, history of VTE, and joint replaced identified HIV as an independent predictor of VTE (odds ratio 10.9, 95% confidence interval 1.1 to 114.0, P = 0.046). All patients with VTE were treated with warfarin (5 to 9 months); two cases were complicated by hemarthrosis and excessive bleeding at the insulin injection site., Conclusion: We observed increased rates of symptomatic VTE in HIV patients after THA (2.5%) and TKA (8%) compared with HIV-negative control patients (0% and 1.7%, respectively). HIV positivity was identified as an independent predictor of perioperative VTE. Our data suggests that HIV patients may be at higher risk for post-op VTE than HIV-negative patients. Surgeons may want to consider the use of more potent anticoagulation (ie, warfarin or novel anticoagulants) for a longer duration in HIV-positive patients. However, further studies are necessary to form evidence-based guidelines regarding this practice., Level of Evidence: Level III, prognostic., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)

Background: Atypical meningiomas (AMs) are meningiomas that have a higher rate of recurrence than grade I meningioma. Due to the higher risk of recurrence, adjuvant radiotherapy (RT) after resection of AM has been employed. At our institution, some neurosurgeons employ adjuvant RT on all primarily resected AMs, while others employ watchful waiting with serial imaging., Objective: To study the effect of adjuvant RT on newly resected AMs., Methods: A retrospective review of all AMs primarily resected at our institution from 1996 to 2018 was completed. Data on patient demographics, radiographic findings, use of adjuvant RT, time of follow-up, and recurrences were collected. Adjuvant RT was defined as RT that occurred within 6 mo of initial resection., Results: A total of 162 patients met the inclusion criteria. Gross total resection was achieved in 73% of cases. Average time until recurrence in the cohort was 37 mo. A total of 108 patients had adjuvant RT, while 54 patients did not. On multivariate survival analysis, sex, Simpson grade resection, and use of adjuvant RT were independent predictors of recurrence. Mean time to recurrence in patients who received adjuvant RT was 43.7 mo versus 34.7 mo for those who did not receive adjuvant RT., Conclusion: This study includes the largest retrospective cohort of patients who have received adjuvant RT after primary resection of AM. Our results suggest that the use of adjuvant RT is independently associated with a lower chance of recurrence. These data suggest that practitioners can consider the use of adjuvant RT for newly resected AMs, regardless of Simpson grade resection., (© Congress of Neurological Surgeons 2021.)

The enantiomeric non-natural cyclic amino acids (3 R ,4 R )-1-amino-3-fluoro-4-(fluoro- 18 F)cyclopentane-1-carboxylic acid and (3 S ,4 S )-1-amino-3-fluoro-4-(fluoro- 18 F)cyclopentane-1-carboxylic acid ( [ 18 F]5 ) have been prepared as a racemic mixture in 1.3% decay corrected radiochemical yield and in greater than 99% radiochemical purity. [ 18 F]5 is transported primarily via system L with some transport occurring via system ASC, as assessed in rat 9L gliosarcoma, human U87 ΔEGFR glioblastoma, and human DU145 androgen-independent prostate carcinoma tumor cells. In rats bearing intracranial 9L gliosarcoma, [ 18 F]5 gave tumor to contralateral brain tissue ratios of up to 2.8. Biodistribution studies in healthy rats demonstrated that bladder accumulation is delayed until 10 min postinjection., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Glioblastoma (GBM) is composed of heterogeneous tumor cell populations, including those with stem cell properties, termed glioma stem cells (GSCs). GSCs are innately less radiation sensitive than the tumor bulk and are believed to drive GBM formation and recurrence after repeated irradiation. However, it is unclear how GSCs adapt to escape the toxicity of repeated irradiation used in clinical practice. To identify important mediators of adaptive radioresistance in GBM, we generated radioresistant human and mouse GSCs by exposing them to repeat cycles of irradiation. Surviving subpopulations acquired strong radioresistance in vivo, which was accompanied by a reduction in cell proliferation and an increase in cell-cell adhesion and N-cadherin expression. Increasing N-cadherin expression rendered parental GSCs radioresistant, reduced their proliferation, and increased their stemness and intercellular adhesive properties. Conversely, radioresistant GSCs lost their acquired phenotypes upon CRISPR/Cas9-mediated knockout of N-cadherin. Mechanistically, elevated N-cadherin expression resulted in the accumulation of β-catenin at the cell surface, which suppressed Wnt/β-catenin proliferative signaling, reduced neural differentiation, and protected against apoptosis through Clusterin secretion. N-cadherin upregulation was induced by radiation-induced IGF1 secretion, and the radiation resistance phenotype could be reverted with picropodophyllin, a clinically applicable blood-brain-barrier permeable IGF1 receptor inhibitor, supporting clinical translation.

Purpose: Glioblastomas (GBMs), neoplasms derived from glia and neuroglial progenitor cells, are the most common and lethal malignant primary brain tumors diagnosed in adults, with a median survival of 14 months. GBM tumorigenicity is often driven by genetic aberrations in receptor tyrosine kinases, such as amplification and mutation of EGFR., Experimental Design: Using a Drosophila glioma model and human patient-derived GBM stem cells and xenograft models, we genetically and pharmacologically tested whether the YAP and TAZ transcription coactivators, effectors of the Hippo pathway that promote gene expression via TEA domain (TEAD) cofactors, are key drivers of GBM tumorigenicity downstream of oncogenic EGFR signaling., Results: YAP and TAZ are highly expressed in EGFR-amplified/mutant human GBMs, and their knockdown in EGFR-amplified/mutant GBM cells inhibited proliferation and elicited apoptosis. Our results indicate that YAP/TAZ-TEAD directly regulates transcription of SOX2 , C-MYC , and EGFR itself to create a feedforward loop to drive survival and proliferation of human GBM cells. Moreover, the benzoporphyrin derivative verteporfin, a disruptor of YAP/TAZ-TEAD-mediated transcription, preferentially induced apoptosis of cultured patient-derived EGFR-amplified/mutant GBM cells, suppressed expression of YAP/TAZ transcriptional targets, including EGFR, and conferred significant survival benefit in an orthotopic xenograft GBM model. Our efforts led us to design and initiate a phase 0 clinical trial of Visudyne, an FDA-approved liposomal formulation of verteporfin, where we used intraoperative fluorescence to observe verteporfin uptake into tumor cells in GBM tumors in human patients., Conclusions: Together, our data suggest that verteporfin is a promising therapeutic agent for EGFR-amplified and -mutant GBM., (©2020 American Association for Cancer Research.)

Brain tumor surgery involves a delicate balance between maximizing the extent of tumor resection while minimizing damage to healthy brain tissue that is vital for neurological function. However, differentiating between tumor, particularly infiltrative disease, and healthy brain in-vivo remains a significant clinical challenge. Here we demonstrate that quantitative oblique back illumination microscopy (qOBM)-a novel label-free optical imaging technique that achieves tomographic quantitative phase imaging in thick scattering samples-clearly differentiates between healthy brain tissue and tumor, including infiltrative disease. Data from a bulk and infiltrative brain tumor animal model show that qOBM enables quantitative phase imaging of thick fresh brain tissues with remarkable cellular and subcellular detail that closely resembles histopathology using hematoxylin and eosin (H&E) stained fixed tissue sections, the gold standard for cancer detection. Quantitative biophysical features are also extracted from qOBM which yield robust surrogate biomarkers of disease that enable (1) automated tumor and margin detection with high sensitivity and specificity and (2) facile visualization of tumor regions. Finally, we develop a low-cost, flexible, fiber-based handheld qOBM device which brings this technology one step closer to in-vivo clinical use. This work has significant implications for guiding neurosurgery by paving the way for a tool that delivers real-time, label-free, in-vivo brain tumor margin detection., Competing Interests: The authors declare no conflicts of interest., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

The Surgical Training and Educational Platform (STEP) was developed by the American Society for Surgery of the Hand (ASSH) as a cost-effective set of surgical simulation modules designed to assess critical skills in hand surgery. Previous study demonstrated that STEP can differentiate between novice trainees and board-certified, certificate of added qualification hand surgeons. The purpose of this study was to assess construct validity of STEP by testing its ability to differentiate psychomotor skill level among intermediate trainees., Methods: We evaluated 30 residents from 2 orthopaedic residency programs on 8 modules: (1) lag screw fixation, (2) depth of plunge during bicortical drilling, (3) flexor tendon repair, (4) phalangeal fracture pinning, (5) central axis scaphoid fixation, (6) full-thickness skin graft harvest, (7) microsurgery, and (8) wrist arthroscopy. Spearman correlation was used to correlate total and task-specific scores to case log numbers, months in training, and number of hand surgery rotations., Results: Senior residents had significantly higher mean number of total cases in their total case log (mean difference 96.2, 95% confidence interval [CI] 67.5-124.8, p < 0.01) and number of task-specific cases. Moderate correlation was observed between case log numbers and scaphoid fixation score (rs = 0.423, 95% CI 0.07-0.69) and total score (rs = 0.584, 95% CI 0.25-0.79). Moderate correlation was observed between months in training with: scaphoid fixation (rs = 0.377, 95% CI 0.01-0.66) and microsurgery (rs = 0.483, 95% CI 0.13-0.73); strong correlation was seen with total score (rs = 0.656, 95% CI 0.35-0.83). Moderate correlation with number of hand surgery rotations was observed with tendon repair (rs = 0.362, 95% CI -0.01 to 0.65), skin graft (rs = 0.385, 95% CI 0.01-0.66), wrist arthroscopy (rs = 0.391, 95% CI 0.02-0.67), microsurgery (rs = 0.461, 95% CI 0.10-0.71), and scaphoid fixation (rs = 0.578, 95% CI 0.25-0.79); and strong correlation was seen with total score (rs = 0.670, 95% CI 0.37-0.84)., Discussion/conclusion: The STEP is a validated ASSH education tool that provides a cost-effective simulation for the assessment of fundamental psychomotor skills in hand surgery. Total STEP score correlated with total task-related case volumes as well as months in training and number of hand rotations. Scoring could be modified to improve the fidelity of assessing surgical performance. And, while both time and human resource consuming to perform, administer, and score, this study demonstrates construct validity of STEP in assessing the progression of surgical skill through residency., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A251)., (Copyright © 2021 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Introduction: Evidence-based, clinical practice guidelines in the management of central nervous system tumors (CNS) continue to be developed and updated through the work of the Joint Section on Tumors of the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS)., Methods: The guidelines are created using the most current and clinically relevant evidence using systematic methodologies, which classify available data and provide recommendations for clinical practice., Conclusion: This update summarizes the Tumor Section Guidelines developed over the last five years for non-functioning pituitary adenomas, low grade gliomas, vestibular schwannomas, and metastatic brain tumors.

Introduction: Intra-articular distal humerus fractures present a challenge to orthopedic surgeons. Stable fixation is difficult to achieve in fractures with articular and metaphyseal comminution and osteoporotic bone. Hence, these fractures are more commonly being managed with total elbow arthroplasty. We describe a novel surgical technique that confers stable fixation, allowing for early range of motion resulting in a high rate of union, a functional range of motion, and excellent patient reported outcome scores without the activity restrictions of total elbow arthroplasty., Methods: Retrospective case series of 30 patients with AO/OTA type B and C intra-articular distal humerus fractures who underwent ORIF from 2014-2019 utilizing a novel surgical technique that focuses on reconstructing a comminuted articular surface through meticulous, transverse fixation of the tiny articular fragments with long, thin Kirchner wires, which are then bent over and trapped under locking compression plates to create a fixed angle support to the metadiaphysis., Results: Patient mean age of 59 (19-90) years and 61% were female. Median follow up was 1.2 years. Twenty-seven (87%) were type C fractures and 3 (13%) were type B. Five patients (16%) suffered a concurrent ipsilateral upper extremity injury and four (13%) had an open fracture. Two were polytrauma patients. All fractures healed with an average time to union of 11 weeks. Over 80% patients reported no or mild pain at final follow up. Mean arc of elbow motion was 102 degrees, mean QuickDASH score 25.2. Post-operative complications included ulnar nerve paresthesias (38%), wound infection (3.2%), heterotopic ossification (3.2%), and olecranon nonunion (3.2%). Eight patients underwent secondary procedures: 7 (23%) removal hardware, 3(9.6%) capsular release, 2 (6.4%) ulnar nerve transpositions, and 1 (3.2%) total elbow arthroplasty., Conclusion: We describe a novel surgical technique that we believe results in strong, stable fixation of complex intra-articular distal humerus fractures irrespective of bone quality. In our series, all fractures healed and post-operatively patients reported low levels of pain, achieved excellent elbow range of motion, high patient reported outcome scores. Patients should be counseled about high rates of post-operative ulnar nerve paresthesias that can be expected to improve over time and high reoperation rates for symptomatic hardware., (© 2020 The Authors.)

Background: Stereotactic radiosurgery (SRS) is often the primary treatment modality for patients with intracranial metastatic disease. Despite advances in magnetic resonance imaging, including use of perfusion and diffusion sequences and molecular imaging, distinguishing radiation necrosis from progressive tumor remains a diagnostic and clinical challenge. We investigated the sensitivity and specificity of 18 F-fluciclovine PET to accurately distinguish radiation necrosis from recurrent intracranial metastatic disease in patients who had previously undergone SRS., Methods: Fluciclovine PET imaging was performed in 8 patients with a total of 15 lesions that had previously undergone SRS and had subsequent MRI and clinical features suspicious for recurrent disease. The SUVmax of each lesion and the contralateral normal brain parenchyma were summated and evaluated at four different time points (5 min, 10 min, 30 min, and 55 min). Lesions were characterized as either recurrent disease (11 of 15 lesions) or radiation necrosis (4 of 15 lesions) and confirmed with histopathological correlation (7 lesions) or through serial MRI studies (8 lesions)., Results: Time activity curve analysis found statistically greater radiotracer accumulation for all lesions, including radiation necrosis, when compared to contralateral normal brain. While the mean and median SUV max for recurrent disease were statistically greater than those of radiation necrosis at all time points, the difference was more significant at the earlier time points (p = 0.004 at 5 min-0.025 at 55 min). Using a SUV max threshold of ≥ 1.3, fluciclovine PET demonstrated a 100% accuracy in distinguishing recurrent disease from radiation necrosis up to 30 min after injection and an accuracy of 87% (sensitivity = 0.91, specificity = 0.75) at the last time point of 55 min. However, tumor-to-background ratios (TBR max ) were not significantly different between recurrent disease and radiation necrosis at any time point due to variable levels of fluciclovine uptake in the background brain parenchyma., Conclusions: Fluciclovine PET may play an important role in distinguishing active intracranial metastatic lesions from radiation necrosis in patients previously treated with SRS but needs to be validated in larger studies.

Background: Vestibular schwannomas are benign tumors of the cerebellopontine angle that are often treated with radiation therapy. Radiation therapy maintains good tumor control rates but involves a small risk of radiation-induced malignancies. We present a case of high-grade sarcoma arising within a previously irradiated vestibular schwannoma and a literature review of this rare but important clinical entity., Methods: A 66-year-old woman presented with rapid clinical and radiographic deterioration 17 years after receiving stereotactic radiosurgery for vestibular schwannoma. After resection, pathology revealed a high-grade sarcoma arising within a conventional schwannoma. After further decline and tumor growth, the patient died of her disease 7 months postoperatively. Literature review was performed using PubMed and EMBASE databases and key words "vestibular schwannoma," "acoustic," "triton," "malignant," "sarcoma," "malignant peripheral nerve sheath tumor," "radiation," and "radiosurgery." All previous cases and the clinical circumstances related to these radiation-induced malignancies were assessed and quantified., Results: The systematic review yielded 20 prior cases of radiation-induced malignant transformation of a vestibular schwannoma in patients without neurofibromatosis. Most tumors (60%) transformed into malignant nerve sheath tumors. At the time of presentation, 70% of patients had new cranial neuropathies, and all had evidence of tumor growth with brainstem compression. Prognosis was poor with mean time to death of 7.6 months., Conclusions: Radiation-induced malignant transformation of vestibular schwannomas is a rare but important clinical entity. Given its scarcity, the risk of malignancy should not sway initial management, but rapid clinical deterioration and radiographic growth during follow-up should prompt consideration of malignant transformation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Target Population: These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma (GBM) QUESTION : For adult patients with newly diagnosed GBM does testing for Isocitrate Dehydrogenase 1 or 2 (IDH 1/2) mutations afford benefit beyond standard histopathology in providing accurate classification and outcome prognostication? Level III IDH 1/2 mutational status by immunohistochemistry (IHC) and/or sequencing is suggested for classification and prognostic information. Level III Non-canonical IDH 1/2 mutations are very rare in patients aged 55 or older and universal testing of variant mutations by sequence analysis is not suggested for this age range., Question: For adult patients with lower grade infiltrating astrocytomas (WHO grades II and III) can the IDH-wildtype status designation supersede histopathology to predict prognosis and biologic relevance to eventual behavior as a GBM? Level III The designation of infiltrating astrocytomas (WHO grades II and III) as IDH-wildtype is not suggested as sufficient for a higher grade designation alone. Level III It is suggested that IDH-wildtype WHO grades II and III astrocytomas be tested for molecular-genetic alterations typical of IDH-wildtype GBM such as EGFR amplification, gain of chromosome 7/loss of chromosome 10 and TERT-p mutation to substantiate prediction of behavior similar to IDH-wildtype glioblastoma. Level III It is suggested that a diagnosis of diffuse astrocytic glioma, IDH-wildtype, with molecular features of GBM, WHO grade IV be rendered for infiltrating astrocytomas that lack histologic criteria of GBM but harbors molecular-genetic alterations of IDH-wildtype glioblastoma., Question: For adult patients with newly diagnosed infiltrating glioma arising in the midline does testing for H3-K27M mutations provide information beyond that gained by histopathology for accurate classification and outcome prognostication? Level III It is suggested that infiltrating gliomas arising in midline anatomic locations be tested for the H3-K27M mutation as they tend to exhibit WHO grade IV behavior even if they lack histologic criteria for glioblastoma.

Target Population: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. QUESTION 1 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the addition of radiation therapy (RT) more beneficial than management without RT in improving survival?, Recommendations: Level I: Radiation therapy (RT) is recommended for the treatment of newly diagnosed malignant glioblastoma in adults. QUESTION 2 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the RT regimen of 60 Gy given in 2 Gy daily fractions more beneficial than alternative regimens in providing survival benefit while minimizing toxicity?, Recommendations: Level I: Treatment schemes should include dosage of up to 60 Gy given in 2 Gy daily fractions that includes the enhancing area. QUESTION 3 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is a tailored target volume superior to regional RT for reduction of radiation-induced toxicity while maintaining efficacy?, Recommendation: Level II: It is recommended that radiation therapy planning include 1-2 cm margin around the radiographically T1 weighted contrast-enhancing tumor volume or the T2 weighted abnormality on MRI. Level III: Recalculation of the radiation volume during RT treatment may be necessary to reduce the radiated volume of normal brain since the volume of surgical defect will change during the long period of RT. QUESTION 4 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, does the addition of RT of the subventricular zone to standard tumor volume treatment improve tumor control and overall survival?, Recommendation: No recommendation can be formulated as there is contradictory evidence in favor of and against intentional radiation of the subventricular zone (SVZ) QUESTION 5 : In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does the addition of RT to surgical intervention improve disease control and overall survival?, Recommendation: Level I: Radiation therapy is recommended for treatment of elderly and frail patients with newly diagnosed glioblastoma to improve overall survival. QUESTION 6 : In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does modification of RT dose and fractionation scheme from standard regimens decrease toxicity and improve disease control and survival?, Recommendation: Level II: Short RT treatment schemes are recommended in frail and elderly patients as compared to conventional 60 Gy given in 2 daily fractions because overall survival is not different while RT risk profile is better for the short RT scheme. Level II: The 40.05 Gy dose given in 15 fractions or 25 Gy dose given in 5 fractions or 34 Gy dose given in 10 fractions should be considered as appropriate doses for Short RT treatments in elderly and/or frail patients. QUESTION 7 : In adult patients with newly diagnosed glioblastoma is there advantage to delaying the initiation of RT instead of starting it 2 weeks after surgical intervention in decreasing radiation-induced toxicity and improving disease control and survival?, Recommendation: Level III: It is suggested that RT for patients with newly diagnosed GBM starts within 6 weeks of surgical intervention as compared to later times. There is insufficient evidence to recommend the optimal specific post-operative day within the 6 weeks interval to start RT for adult patients with newly diagnosed glioblastoma that have undergone surgical resection. QUESTION 8 : In adult patients with newly diagnosed supratentorial glioblastoma is Image-Modulated RT (IMRT) or similar techniques as effective as standard regional RT in providing tumor control and improve survival?, Recommendation: Level III: There is no evidence that IMRT is a better RT delivering modality when compared to conventional RT in improving overall survival in adult patients with newly diagnosed glioblastoma. Hence, IMRT should not be preferred over the Conventional RT delivery modality. QUESTION 9 : In adult patients with newly diagnosed glioblastoma does the use of radiosensitizers with RT improve the efficacy of RT as determined by disease control and overall survival?, Recommendation: Level III: Iododeoxyuridine is not recommended to be used as radiosensitizer during RT treatment for patients with newly diagnosed GBM QUESTION 10 : In adult patients with newly diagnosed glioblastoma is the use of Ultrafractionated RT superior to standard fractionation regimens in improving disease control and survival?, Recommendation: There is insufficient evidence to formulate a recommendation regarding the use of ultrafractionated RT schemes and patient population that could benefit from it. QUESTION 11 : In patients with poor prognosis with newly diagnosed glioblastoma is hypofractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival?, Recommendation: Level I: Hypofractionated RT schemes may be used for patients with poor prognosis and limited survival without compromising response. There is insufficient evidence in the literature for us to be able to recommend the optimal hypofractionated RT scheme that will confer longest overall survival and/or confer the same overall survival with less toxicities and shorter treatment time. QUESTION 12 : In adult patients with newly diagnosed glioblastoma is the addition of brachytherapy to standard fractionated RT indicated to improve disease control and survival?, Recommendation: Level I: Brachytherapy as a boost to external beam RT has not been shown to be beneficial and is not recommended in the routine management of patients with newly diagnosed GBM. QUESTION 13 : In elderly patients (> 65 year old) with newly diagnosed glioblastoma under what circumstances is accelerated hyperfractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival?, Recommendation: Level III: Accelerated Hyperfractionated RT with a total RT dose of 45 Gy or 48 Gy has been shown to shorten the treatment time without detriment in survival when compared to conventional external beam RT and should be considered as an option for treatment of elderly patients with newly diagnosed GBM. QUESTION 14 : In adult patients with newly diagnosed glioblastoma is the addition of Stereotactic Radiosurgery (SRS) boost to conventional standard fractionated RT indicated to improve disease control and survival?, Recommendation: Level I: Stereotactic Radiosurgery boost to external beam RT has not been shown to be beneficial and is not recommended in patients undergoing routine management of newly diagnosed malignant glioma.

Target Population: These recommendations apply to adults with a newly diagnosed lesion with a suspected or histopathologically proven glioblastoma (GBM)., Question: What are the optimal imaging techniques to be used in the management of a suspected glioblastoma (GBM), specifically: which imaging sequences are critical for most accurately identifying or diagnosing a GBM and distinguishing this tumor from other tumor types?, Recommendations: Critical Imaging for the Identification and Diagnosis of Glioblastoma Level II: In patients with a suspected GBM, it is recommended that the minimum magnetic resonance imaging (MRI) exam should be an anatomic exam with both T2 weighted, FLAIR and pre- and post-gadolinium contrast enhanced T1 weighted imaging. The addition of diffusion and perfusion weighted MR imaging can assist in the assessment of suspected GBM for the purposes of distinguishing GBM from other tumor types. Computed tomography (CT) can provide additional information regarding calcification or hemorrhage and also can be useful for subjects who are unable to undergo MR imaging. At a minimum, these anatomic sequences can help identify a lesion as well as its location, and potential for surgical intervention. Improvement of diagnostic specificity with the addition of non-anatomic (physiologic imaging) to anatomic imaging Level II: One blinded prospective study and a significant number of case series support the addition of diffusion and perfusion weighted MR imaging in the assessment of suspected GBM, for the purposes of distinguishing GBM from other tumor types (e.g., primary CNS lymphoma or metastases). Level III: It is suggested that magnetic resonance spectroscopy (MRS) and nuclear medicine imaging (PET 18F-FDG and 11C-MET) be used to provide additional support for the diagnosis of GBM.

Question: What is the role of temozolomide in the management of adult patients (aged 65 and under) with newly diagnosed glioblastoma?, Target Population: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma., Recommendation: Level I: Concurrent and post-irradiation Temozolomide (TMZ) in combination with radiotherapy and post-radiotherapy as described by Stupp et al. is recommended to improve both PFS and OS in adult patients with newly diagnosed GBM. There is no evidence that alterations in the dosing regimen have additional beneficial effect., Question: Is there benefit to adjuvant temozolomide treatment in elderly patients (> 65 years old?)., Target Population: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma., Recommendation: Level III: Adjuvant TMZ treatment is suggested as a treatment option to improve PFS and OS in adult patients (over 70 years of age) with newly diagnosed GBM., Question: What is the role of local regional chemotherapy with BCNU biodegradable polymeric wafers in adult patients with newly diagnosed glioblastoma?, Target Population: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma., Recommendation: Level III: There is insufficient evidence for the use of BCNU wafers following resection in patients with newly diagnosed glioblastoma who undergo the Stupp protocol after surgery. Further studies of higher quality are suggested to understand the role of BCNU wafer and other locoregional therapy in the setting of Stupp Protocol., Question: What is the role of bevacizumab in the adult patient with newly diagnosed glioblastoma?, Target Population: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma., Recommendation: Level I: Bevacizumab in general is not recommended in the initial treatment of adult patients with newly diagnosed GBM. It continues to be strongly recommended that patients with newly diagnosed GBM be enrolled in properly designed clinical trials to assess the benefit of novel chemotherapeutic agents compared to standard therapy.

Target Population: These recommendations apply to adults with newly diagnosed or suspected glioblastoma., Question: What is the effect of extent of surgical resection on patient outcome in the initial management of adult patients with suspected newly diagnosed glioblastoma?, Recommendation: Level II: Maximal cytoreductive surgery is recommended in adult patients with suspected newly diagnosed supratentorial glioblastoma with gross total resection defined as removal of contrast enhancing tumor. Level III: Biopsy, subtotal resection, or gross total resection is suggested depending on medical comorbidities, functional status, and location of tumor if maximal resection may cause significant neurologic deficit., Question: What is the role of cytoreductive surgery in adults with newly diagnosed bi-frontal "butterfly" glioblastoma?, Recommendation: Level III: Resection of newly diagnosed bi-frontal "butterfly" glioblastoma is suggested to improve overall survival over biopsy alone., Question: What is the goal of cytoreductive surgery in elderly adult patients with newly diagnosed glioblastoma?, Recommendation: Level III: Elderly patients (> 65 years) show survival benefit with gross total resection and it is suggested they undergo cytoreductive surgery., Question: What is the role of advanced intraoperative guidance techniques in cytoreductive surgery in adults with newly diagnosed glioblastoma?, Recommendation: Level III: The use of intraoperative guidance adjuncts such as intraoperative MRI (iMRI) or 5-aminolevulinic acid (5-ALA) are suggested to maximize extent of resection in newly diagnosed glioblastoma. There is insufficient evidence to make a suggestion on the use of fluorescein, indocyanine green, or intraoperative ultrasound.

Target Population: These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma., Imaging: Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma?, Recommendation: Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma., Surgery: Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma?, Recommendations: Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery., Neuropathology: Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas?, Recommendations: Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma., Radiation: Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas?, Recommendations: Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques., Chemotherapy: Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?, Recommendation: Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy., Molecular and Targeted Therapy: Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?, Recommendation: Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies IMMUNOTHERAPY: Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?, Recommendation: Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies., Novel Therapies: Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?, Recommendations: Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.

The non-natural cyclic amino acids (1 S ,3 R ,4 S )-1-amino-3-fluoro-4-(fluoro- 18 F )cyclopentane-1-carboxylic acid ( [ 18 F]9 ) and (1 S ,3 S ,4 R )-1-amino-3-fluoro-4-(fluoro- 18 F )cyclopentane-1-carboxylic acid ( [ 18 F]28 ) have been prepared in 10 and 1.7% decay corrected radiochemical yield, respectively, and in greater than 99% radiochemical purity. Cell assays in rat 9L gliosarcoma, human U87 ΔEGFR glioblastoma, and human DU145 androgen-independent prostate carcinoma tumor cells indicated that both compounds are substrates for amino acid transport primarily by system L, with some transport taking place via system ASC. In rats with 9L gliosarcoma, [ 18 F]9 and [ 18 F]28 provided high tumor to normal brain tissue ratios, with maximal ratios of 3.5 and 4.1, respectively. Biodistribution studies in healthy rats confirmed that both compounds are BBB permeable and that bladder accumulation is low until at least 5 min post injection.

Introduction: Humeral shaft fractures account for 3% of adult fractures. Optimal management remains a topic of debate given variable union rates reported in the literature after surgery or functional bracing. The primary aim was to compare these 2 cohorts of patients and their primary fracture union rates. A secondary aim was to identify predictors of nonunion., Methods: A retrospective cohort study of 164 adult patients with traumatic humeral shaft fractures was performed. Fractures were classified according to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association classification. Primary outcomes included rate nonunion, including symptomatic fractures requiring conversion to open reduction and internal fixation (ORIF). Secondary outcomes included rates of complications and secondary procedures., Results: Ninety-four (57%) patients were treated initially with ORIF. Nonoperative patients were older (47.1 vs. 41.5 years, P  = .028) and had more medical comorbidity (62% vs. 43%, P  = .017), low-energy trauma (62% vs. 34%, P < .0001), and isolated injuries (74% vs. 32%, P < .0001). All patients with open fractures (23%) were treated with débridement and ORIF, and surgical patients had more nerve injuries on presentation (36% vs. 9%, P < .0001). The overall rate of primary fracture union was 88%, similar after ORIF and nonoperative management (92% vs. 83%, P  = .095). Multivariate analysis found alcohol abuse (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.0-11.0, P  = .046) and deep infection (OR: 19.9, 95% CI: 2.6-150.5, P  = .004) to be significant predictors of nonunion. Chronic liver disease demonstrated a trend toward increased risk of nonunion (OR: 4.1, 95% CI: 0.8-20.9, P  = .088). Seventeen operative patients (18%) developed 17 postoperative complications: iatrogenic nerve palsy (5%), deep infection (5%), and implant failure (3%), the most common. Reoperation rate was 10%, primarily for revision ORIF (4%)., Conclusion: Patients managed nonoperatively were more often older patients with isolated fractures and more medical comorbidity. Surgical candidates were younger, more often with higher energy injuries, and were frequently with concomitant injury. Primary union occurred in 88%, with a trend toward a higher rate after ORIF. Patients with chronic liver disease and/or alcohol abuse are at greater risk for nonunion, irrespective of treatment., (© 2020 The Author(s).)

Background: Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system., Methods: Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed., Results: In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P < .03). The detriment to early initiation was consistent across each RPA class subgroup., Conclusions: The current data provide insight into the optimal timing of CRT in patients with glioblastoma and describe RPA class-specific outcomes. In general, short delays beyond 5 weeks did not negatively affect outcomes, whereas early initiation before 3 weeks may be detrimental., (© 2020 American Cancer Society.)

Purpose: Exploitation of altered glycosylation in cancer is a major goal for the design of new cancer therapy. Here, we designed a novel secreted chimeric signal peptide-Galectin-3 conjugate (sGal-3) and investigated its ability to induce cancer-specific cell death by targeting aberrantly N- glycosylated cell surface receptors on cancer cells., Experimental Design: sGal-3 was genetically engineered from Gal-3 by extending its N-terminus with a noncleavable signal peptide from tissue plasminogen activator. sGal-3 killing ability was tested on normal and tumor cells in vitro and its antitumor activity was evaluated in subcutaneous lung cancer and orthotopic malignant glioma models. The mechanism of killing was investigated through assays detecting sGal-3 interaction with specific glycans on the surface of tumor cells and the elicited downstream proapoptotic signaling., Results: We found sGal-3 preferentially binds to β1 integrin on the surface of tumor cells due to aberrant N -glycosylation resulting from cancer-associated upregulation of several glycosyltransferases. This interaction induces potent cancer-specific death by triggering an oncoglycan-β1/calpain/caspase-9 proapoptotic signaling cascade. sGal-3 could reduce the growth of subcutaneous lung cancers and malignant gliomas in brain, leading to increased animal survival., Conclusions: We demonstrate that sGal-3 kills aberrantly glycosylated tumor cells and antagonizes tumor growth through a novel integrin β1-dependent cell-extrinsic apoptotic pathway. These findings provide proof-of-principle that aberrant N -oncoglycans represent valid cancer targets and support further translation of the chimeric sGal-3 peptide conjugate for cancer therapy., (©2020 American Association for Cancer Research.)

Objectives: Evaluate the correlation between aortic stenosis and perioperative mortality in patients following surgical fixation of proximal femur fractures., Design: Retrospectively reviewed case series., Setting: Two Academic, Level 1 Trauma Centers., Patients/participants: One hundred fifty-eight patients, definitively diagnosed with aortic stenosis by means of echocardiogram, who underwent surgical fixation for an isolated proximal femur fracture (OTA/AO 31-A, 31-B, 32-A, 32-B, and 32-C fractures) between January 2000 and June 2015. The severity of the aortic stenosis was based upon accepted echocardiographic hemodynamic parameters designated by the 2014 American Heart Association guidelines., Main Outcome Measures: Post Injury mortality, 30-day mortality, and 1-year mortality., Secondary Outcome Measures: Postoperative mortality stratified by severity of aortic stenosis based on aortic valve area (AVA) and ejection fracture (EF) as determined by preoperative echocardiography., Results: One hundred fifty-eight patients were available for final analysis. Kaplan-Meier survival analysis revealed a significantly longer time to mortality among Non-severe aortic stenosis patients compared to Severe aortic stenosis patients, P value .006. Twenty-three percent of patients with Severe aortic stenosis and 10% of patients with Non-severe aortic stenosis died within 30 days of surgery. No significant difference was observed in mean survival among AS patients who underwent surgery within 48 hours of injury (34.5 months) and those delayed more than 48 hours after injury (25.0 months), P value .116. Among the commonly measured hemodynamic parameters of aortic stenosis, only AVA and EF were significantly associated with mortality, P value .015, and P value < .001, respectively. There were no significant effects for Aortic Vmax, Peak Δ P , and Mean Δ P . An AVA of 0.8 cm 2 or less is associated with a significantly shorter (22 months) postinjury mortality than patients with an AVA > 0.8 cm 2. (37 months), P value .009., Conclusions: Severe aortic stenosis is associated with a shorter postoperative time to mortality after surgical fixation of hip fractures compared to patients with Non-severe stenosis. Aortic valve area and Ejection Fraction are the only hemodynamic parameters significantly associated with postoperative mortality. Level of Evidence: Prognostic Level III., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset. 25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.

Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR ≥0.4 ), and ≥15% NAA (AMR ≥0.15 ), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10 -4 ; 11p11.12, p = 7.0 × 10 -4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR ≥0.4 . In addition, we identified a peak at rs1620291 (p = 4.36 × 10 -6 ) in 7q21.3. Among AMR ≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10 -4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10 -4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies., (© 2019 UICC.)

Medulloblastoma (MB) is a malignant pediatric brain tumor for which new therapies are urgently needed. We demonstrate that treatment with EPZ-6438 (Tazemetostat), an enhancer of zeste homolog 2 (EZH2) inhibitor approved for clinical trials, blocks MB cell growth in vitro and in vivo, and prolongs survival in orthotopic xenograft models. We show that the therapeutic effect is dependent on epigenetic reactivation of adhesion G-protein-coupled receptor B1 (BAI1/ADGRB1), a tumor suppressor that controls p53 stability by blocking Mdm2. Histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation is present at the ADGRB1 promoter, and inhibition of EZH2, the catalytic component of the Polycomb Repressive complex 2 (PRC2) that methylates H3K27, switches the gene into an active chromatin status and reactivates BAI1 expression. Mechanistically, targeting EZH2 promotes transition from H3K27me3 to H3K27ac at the promoter, recruits the C/EBPβ (CREB-binding protein) and CBP transcription factors and activates ADGRB1 gene transcription. Taken together, our results identify key molecular players that regulate ADGRB1 gene expression in MB, demonstrate that reactivation of BAI1 expression underlies EPZ-6438 antitumorigenic action, and provide preclinical proof-of-principle evidence for targeting EZH2 in patients with MB.

Purpose: Stereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBMs., Methods and Materials: From 2008 to 2016, 55 rBMs at a single institution that were treated postoperatively with 5-fraction linear accelerator-based SRS (25-35 Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included radiation therapy dose to normal brain, location and magnitude of hotspots, clinical target volume (CTV), and margin size. Hotspot location was stratified as within the tumor bed alone (CTV) or within the planning target volume (PTV) expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence. Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic., Results: Median age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cm 3 , the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed that max hotspots with a hazard ratio of 3.28 (P = .045), hotspots within the PTV expansion margin with relative magnitudes of 105%, 110%, and 111%, and an absolute dose of 33.5 Gy predicted for RN (P = .029, P = .04, P = .038, and P = .0488, respectively), but hotspots within the CTV did not., Conclusions: To our knowledge, this is the first study that investigated dosimetric factors that predict for RN after 5-fraction hypofractionated SRS for rBM. Hotspot location and magnitude appear important for predicting RN risk, thus these parameters should be carefully considered during treatment planning., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Brain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection., Objective: To investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD., Methods: One hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method., Results: Median imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, P = .015), cystic features (HR 2.34, P = .013), breast histology (HR 3.23, P = .016), and number of brain metastases >1 (HR 2.09, P = .032) were independently associated with increased risk of LMD., Conclusion: Hemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 μg/g and 0.069 μg/g (interquartile range (IQR): 0.032-0.161 and 0.031-0.150 μg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.

Rationale and Objectives: Analyze the impact of implementing a structured reporting system for primary brain tumors, the Brain Tumor Reporting and Data System, on attitudes toward radiology reports at a single institution., Materials and Methods: Following Institutional Review Board approval, an initial 22 question, 5 point (1-worst to 5-best), survey was sent to faculty members, house staff members, and nonphysician providers at our institution who participate in the direct care of brain tumor patients. Results were used to develop a structured reporting strategy for brain tumors which was implemented across an entire neuroradiology section in a staged approach. Nine months following structured reporting implementation, a follow-up 27 question survey was sent to the same group of providers. Keyword search of radiology reports was used to assess usage of Brain Tumor Reporting and Data System over time., Results: Fifty-three brain tumor care providers responded to the initial survey and 38 to the follow-up survey. After implementing BT-RADS, respondents reported improved attitudes across multiple areas including: report consistency (4.3 vs. 3.4; p < 0.001), report ambiguity (4.2 vs. 3.2, p < 0.001), radiologist/physician communication (4.5 vs. 3.8; p < 0.001), facilitation of patient management (4.2 vs. 3.6; p = 0.003), and confidence in reports (4.3 vs. 3.5; p < 0.001). Providers were more satisfied with the BT-RADS structured reporting system (4.3 vs. 3.7; p = 0.04). Use of the reporting template progressively increased with 81% of brain tumor reports dictated using the new template by 9 months., Conclusion: Implementing a structured template for brain tumor imaging improves perception of radiology reports among radiologists and referring providers involved in the care of brain tumor patients., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)