Laser interstitial thermal therapy for newly diagnosed glioblastoma.

Gliomas are the most frequent primary brain tumor in adults. Patients with glioblastoma (GBM) tumors deemed inoperable with open surgical techniques and treated only with chemo/radiation have a median overall survival of less than 9 months. Laser interstitial thermal therapy (LITT) has emerged as a cytoreductive alternative to surgery for these patients. The present study describes the outcomes of twenty patients with newly diagnosed, IDH wild-type glioblastoma treated with LITT. We retrospectively reviewed patients with newly diagnosed, unresectable GBM who underwent LITT at our institution. Progression-free survival (PFS) was the primary endpoint measured in our study, defined as time from LITT to disease progression. Results Twenty patients were identified with newly diagnosed, inoperable GBM lesions who underwent LITT. The overall median PFS was 4 months (95% CI = 2 - N/A, upper limit not reached). The median progression-free survival (PFS) for patients with less than 1 cm 3 residual tumor (gross total ablation, GTA) was 7 months (95% CI = 6 - N/A, upper limit not reached), compared to 2 months (95% CI = 1 - upper limit not reached) for patients with a lower GTA (p = .0019). The median overall survival was 11 months (95% CI = 6 - upper limit not reached). Preoperative Karnofsky performance score (KPS) less than or equal to 80 and deep-seated tumor location were significantly associated with decreased PFS (HR, .18, p = .03; HR, .08, p = .03, respectively). At the end of 1 month, only 4 patients (20%) experienced persistent motor deficits. LITT is a safe and effective treatment for patients with unresectable, untreated GBM with rates of survival and local recurrence comparable to patients with surgically accessible lesions treated with conventional resection. Careful patient selection is needed to determine if GTA is attainable.

Outcomes of orbital exenteration for craniofacial lesions.

BACKGROUND: Orbital exenteration (OE) is an ablative procedure used in the management of malignancies of the orbit of either primary or secondary origin. Publications evaluating this procedure have suffered from small patient numbers, heterogeneity of pathologies, and poor patient follow-up. The purpose of this study was to assess patient outcomes in a large cohort of patients undergoing OE at a tertiary cancer center. METHODS: A retrospective review was conducted of 180 consecutive patients who underwent OE at the authors' institution. Overall survival (OS) was the primary end point measured in the study. Time to locoregional recurrence (progression-free survival [PFS]) and disease-free survival were secondary end points. RESULTS: Between the years 1993 and 2011, 180 consecutive patients received OE for craniofacial malignancy at the authors' institution. The median follow-up for the cohort was 9.7 years (116 months). The median OS was 73 months, and the median PFS was 96 months. The presence of perineural invasion was associated with shorter OS (P = .01) and PFS (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter PFS than negative margins (P < .01) but with no change in OS (P = .15). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5), and there was 1 death observed (0.6%). CONCLUSIONS: Used judiciously in the setting of a multidisciplinary management plan, OE for tumor control is a safe therapy. LAY SUMMARY: Between the years 1993 and 2011, 180 consecutive patients received orbital exenteration for craniofacial malignancy at the MD Anderson Cancer Center. The median follow-up for the cohort was 9.7 years. The presence of perineural invasion was associated with shorter overall survival (P = .01) and progression-free survival (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter progression-free survival than negative margins (P < .01). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5).

Fractionated stereotactic radiotherapy for local control of resected brain metastases.

PURPOSE: Postoperative stereotactic radiosurgery (SRS) has been shown to establish local control in patients with resected brain metastases, yet its efficacy may be limited, particularly for resected lesions with large post-operative resection cavities. We describe the efficacy of postoperative fractionated stereotactic radiotherapy (FSRT) for local control in patients who have undergone resection for brain metastases. METHODS: In this retrospective cohort study, we analyzed patients who received FSRT for resected brain metastases in 3 or 5 fractions. Time to local recurrence was the primary endpoint in this study. RESULTS: Sixty-seven patients (n = 29 female, n = 38 male) met study criteria for review. The median age of the cohort was 62 years (range 18-79 years). Median preoperative tumor volume was 11.1 cm3 (range 0.4-77.0 cm3). The rate of local control was 91.0% at 6 months, 85.1% at 12 months, and 85.1% at 18 months. Estimates of freedom from local recurrence at 6 and 12 months were 90.9% and 84.3%, respectively. Higher biologically equivalent doses (BED10) were found to be predictive of longer freedom from local recurrence on univariate and multivariable analysis. Larger cavity volumes were found to correspond to longer time to local recurrence on univariate and multivariable analysis. CONCLUSION: Our results suggest that postoperative FSRT may be an effective method for providing local control to the surgical bed in patients with resected brain metastases, particularly for larger tumors not amenable to conventional, single-fraction SRS. Additional prospective studies are needed to confirm these findings.

Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy.

Purpose: Despite significant advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant treatment challenge. The study of MBM is limited, in part, by shortcomings in existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples with minimal processing that recapitulate genotypic and phenotypic features of parent tumors and are grown without artificial extracellular scaffolding. We aimed to develop the first matched patient-derived SXO and cell line models of MBM to investigate responses to targeted therapy. Methods: MBM SXOs were created by a novel protocol incorporating techniques for establishing glioma and cutaneous melanoma organoids. A BRAFV600K-mutant and BRAF-wildtype MBM sample were collected directly from the operating room for downstream experiments. Organoids were cultured in an optimized culture medium without an artificial extracellular scaffold. Concurrently, matched patient-derived cell lines were created. Drug screens were conducted to assess treatment response in SXOs and cell lines. Results: Organoid growth was observed within 3-4 weeks, and MBM SXOs retained histological features of the parent tissue, including pleomorphic epithelioid cells with abundant cytoplasm, large nuclei, focal melanin accumulation, and strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated to increase the number of replicates. Matched SXOs and cell lines demonstrated sensitivity to BRAF and MEK inhibitors. Conclusion: Here, we describe the creation of a scaffold-free organoid model of MBM. Further study using SXOs may improve the translational relevance of preclinical studies and enable the study of the metastatic melanoma tumor microenvironment.

Evaluating risk of recurrence in patients with meningioma.

OBJECTIVE: Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology. In this study, the authors aimed to test conventional predictors of meningioma recurrence, histopathology variables for which there exists some controversy (brain invasion), as well as a novel molecular-based location paradigm. METHODS: This is a retrospective study of a consecutive series of patients with WHO grade I-III meningioma resected at The University of Texas Southwestern Medical Center between 1994 and 2015. Time to meningioma recurrence (i.e., recurrence-free survival [RFS]) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS. RESULTS: A total of 703 consecutive patients with meningioma underwent resection at The University of Texas Southwestern Medical Center between the years 1994 and 2015. A total of 158 patients were excluded for insufficient follow-up (< 3 months). The median age of the cohort was 55 years (range 16-88 years) and 69.5% (n = 379) were female. The median follow-up was 48 months (range 3-289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade I meningioma (Cox univariate HR 0.92, 95% CI 0.44-1.91, p = 0.82, power 4.4%). Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence (n = 52, Cox univariate HR 0.21, 95% CI 0.03-1.61, p = 0.13, power 71.6%). Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p < 0.01, log-rank test). In patients with high-grade meningiomas (WHO grade II or III), location was predictive of RFS (p = 0.03, log-rank test), with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis. CONCLUSIONS: The data suggest that brain invasion does not increase the risk of recurrence in otherwise WHO grade I meningioma. Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model. Larger studies are needed to confirm these findings.

Psoas Muscle Index as a Predictor of Perioperative Outcomes in Geriatric Patients Undergoing Spine Surgery.

STUDY DESIGN: Single-center retrospective study. OBJECTIVE: The objective of this study was to evaluate the association of psoas muscle mass defined sarcopenia with perioperative outcomes in geriatric patients undergoing elective spine surgery. METHODS: We included geriatric patients undergoing thoracolumbar spinal surgery. Total psoas surface area (TPA) was measured on preoperative axial computerized tomography or magnetic resonance imaging at the L3 vertebra and normalized to the L3 vertebral body area. Patients were divided into quartiles by normalized TPA, and the fourth quartile (Q4) was compared to quartiles 1-3 (Q1-3). Outcomes included perioperative transfusions, length of stay (LOS), delirium, pseudoarthrosis, readmission, discharge disposition, revision surgery, and mortality. RESULTS: Of the patients who met inclusion criteria (n = 196), the average age was 73.4 y, with 48 patients in Q4 and 148 patients in Q1-3. Q4 normalized TPA cut-off was <1.05. Differences in Q4 preoperative characteristics included significantly lower body mass index, baseline creatinine, and a greater proportion of females (Table 1). Q4 patients received significantly more postoperative red blood cell and platelet transfusions and had longer ICU LOS (P < .05; Table 2). There was no difference in intraoperative transfusion volumes, delirium, initiation of walking, discharge disposition, readmission, pseudoarthrosis, or revision surgery (Tables 2 and 3). Mortality during follow-up was higher in Q4 but was not statistically significant (P = .075). CONCLUSION: Preoperative TPA in geriatric patients undergoing elective spine surgery is associated with increased need for intensive care and postoperative blood transfusion. Preoperative normalized TPA is a convenient measurement and could be included in geriatric preoperative risk assessment algorithms.

Repeat laser interstitial thermal therapy for recurrent primary and metastatic intracranial tumors.

Background: Repeat craniotomy in patients with primary and metastatic brain tumors carries significant morbidity and can delay adjuvant treatments. Repeat laser interstitial thermal therapy (LITT) for recurrent disease has been described and could benefit patients with limited cytoreductive options. We aim to describe the indications, safety, and efficacy of repeat LITT for recurrent primary and metastatic intracranial tumors. Methods: Patients undergoing repeat ablations for the same lesion were included in the study. We retrospectively analyzed 13 patients treated with 29 total LITT ablations. Results: Eleven patients were treated for glioblastoma (GBM), while two had brain metastases. Eleven patients had LITT performed only 2 times, while three patients underwent three total iterations of LITT for disease recurrence. Median length of stay after the 1st ablation was 2 days, while the median length of stay after the 2nd ablation was 1 day. The median time to resuming adjuvant treatments after the 1st LITT was 11 days. The median time to resuming adjuvant treatments after the 2nd LITT was 28 days. Four patients after the 1st and 2nd LITT sustained deficits persisting through 30-day follow-up. The median progression-free survival among the GBM patients from the first ablation was 6.0 months, 3.2 months from the 2nd ablation, and 2.1 months from the 3rd ablation. Conclusion: Recurrent tumors, especially GBM, can be safely treated using repeat LITT when surgery cannot be effectively performed. Our results indicate that patients tolerate the procedure well and have a meaningful survival given the salvage nature of the procedure.

Transcranial magnetic stimulation tractography and the facilitation of gross total resection in a patient with a motor eloquent glioblastoma: illustrative case.

BACKGROUND: In patients with perieloquent tumors, neurosurgeons must use a variety of techniques to maximize survival while minimizing postoperative neurological morbidity. Recent publications have shown that conventional anatomical features may not always predict postoperative deficits. Additionally, scientific conceptualizations of complex brain function have shifted toward more dynamic, neuroplastic theories instead of traditional static, localizationist models. Functional imaging techniques have emerged as potential tools to incorporate these advances into modern neurosurgical care. In this case report, we describe our observations using preoperative transcranial magnetic stimulation data combined with tractography to guide a nontraditional surgical approach in a patient with a motor eloquent glioblastoma. OBSERVATIONS: The authors detail the use of preoperative functional and structural imaging to perform a gross total resection despite tumor infiltration of conventionally eloquent anatomical structures. The authors resected the precentral gyrus, specifically the paracentral lobule, localized using intraoperative mapping techniques. The patient demonstrated mild transient postoperative weakness and made a full neurological recovery by discharge 1 week later. LESSONS: Preoperative functional and structural imaging has potential to not only optimize patient selection and surgical planning, but also facilitate important intraoperative decisions. Innovative preoperative imaging techniques should be optimized and used to identify safely resectable structures.

Neurological outcomes following awake and asleep craniotomies with motor mapping for eloquent tumor resection.

OBJECTIVE: Cortical mapping has been used as a tool to ensure maximal safe resection of intracranial tumors for several decades. Post-surgical motor and language deficits, including seizures, weakness, aphasia, and dysarthria have been well-documented in patients undergoing these operations, particularly on eloquent cortical regions. However, it is not known whether awake versus asleep cortical mapping contributes to differences in postoperative neurological deficits. METHODS: A comprehensive review of the literature utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was completed for articles describing cortical mapping for tumor resection. We critically assessed all articles published in the last 20 years describing complications of patients who had undergone either awake or asleep motor mapping for eloquent brain tumor resection. Studies were analyzed for number of patients, follow-up duration, rates of transient and permanent motor and sensory deficits in the perioperative period, and outcomes at one-month follow-up. RESULTS: Thirty-one studies met inclusion criteria, 24 of which reported long-term post-operative follow-up data. Follow-up among selected studies ranged from one month to four years. Nine of the 31 studies directly compared the postoperative outcomes of awake versus asleep mapping. The rate of transient deficits among patients who underwent awake and asleep mapping was 31.6% and 32.7%, respectively. The rate of permanent deficits was 10.8% in awake mapping patients and 12.7% in asleep mapping patients. Qualitative analysis showed that motor and sensory complications occurred at similar rates. CONCLUSIONS: Review of the current evidence suggests that the rates of transient and permanent postoperative neurologic deficits among awake versus asleep cortical mapping groups are similar. Thus, use of both techniques is reasonable to minimize perioperative morbidity.

The natural history of non-functioning pituitary adenomas: A meta-analysis of conservatively managed tumors.

BACKGROUND: Non-functioning pituitary adenomas (NFPA) are often discovered incidentally. The natural history of NFPA is not well understood, obfuscating evidence-based management decisions. Meta-data of radiographically followed NFPA may help guide conservative versus operative treatment of these tumors. METHODS: We searched PubMed, Medline, Embase, and Ovid for studies with NFPA managed nonoperatively with radiographic follow-up. Studies on postoperative outcomes after NFPA resection and studies that did not delineate NFPA data from functional pituitary lesions were excluded. NFPA were divided into micro- and macroadenomas based on size at presentation. We performed a meta-analysis of aggregate data for length of follow-up, change in tumor size, rate of apoplexy, and need for resection during follow-up. RESULTS: Our database search yielded 1787 articles, of which 19 were included for final analysis. The studies included 1057 patients with NFPA followed radiographically. Macroadenomas were significantly more likely to undergo growth (34% vs. 12%; p < 0.01) or apoplexy (5% vs. < 1%; p = 0.01) compared to microadenomas. Resection was performed in 11% of all NFPA patients during follow-up regardless of size at presentation. Meta-regression showed that surgery during follow-up was associated with macroadenomas and negatively associated with microadenomas that decreased in size. CONCLUSION: Low-quality evidence suggests that NFPA classified as macroadenomas have an increased rate of growth and apoplexy during follow-up compared to microadenomas. A significant minority of all NFPA patients ultimately underwent surgery. In select patients, nonoperative management may be the appropriate strategy for NFPA. Macroadenomas may require closer follow-up.

Surgical Management of a Massive Frontal Bone Hemangioma: Case Report.

Intraosseous hemangiomas are rare, benign tumors that can arise from the calvarium. These lesions often invade the outer table of the skull, but typically spare the inner table and intracranial structures. En bloc surgical resection is the standard treatment for intraosseous hemangiomas. However, a piecemeal resection may be required to safely remove the tumor in cases involving the inner table to protect the underlying brain parenchyma and vascular structures. Proper reconstruction is critical to optimize the cosmetic outcome, and a staged procedure allowing implantation of a custom-made implant can be considered for large lesions involving the forehead. We present a case of a patient with a large frontal intraosseous hemangioma with intradural involvement to highlight the surgical nuances of resection and review the existing literature regarding optimal management of these patients.

TMS Seeded Diffusion Tensor Imaging Tractography Predicts Permanent Neurological Deficits.

Surgeons must optimize the onco-functional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Optimal patient selection and surgical planning requires preoperative identification of nonresectable structures. Transcranial magnetic stimulation is a method of noninvasively mapping the cortical representations of the speech and motor systems. Despite recent promising data, its clinical relevance and appropriate role in a comprehensive mapping approach remains unknown. In this study, we aim to provide direct evidence regarding the clinical utility of transcranial magnetic stimulation by interrogating the eloquence of TMS points. Forty-two glioma patients were included in this retrospective study. We collected motor function outcomes 3 months postoperatively. We overlayed the postoperative MRI onto the preoperative MRI to visualize preoperative TMS points in the context of the surgical cavity. We then generated diffusion tensor imaging tractography to identify meaningful subsets of TMS points. We correlated the resection of preoperative imaging features with clinical outcomes. The resection of TMS-positive points was significantly predictive of permanent deficits (p = 0.05). However, four out of eight patients had TMS-positive points resected without a permanent deficit. DTI tractography at a 75% FA threshold identified which TMS points are essential and which are amenable to surgical resection. TMS combined with DTI tractography shows a significant prediction of postoperative neurological deficits with both a high positive predictive value and negative predictive value.

Applying 3-Dimensional Printing and Modeling for Preoperative Reconstruction and Instrumentation Placement Planning in Complex Deformity Surgery.

BACKGROUND: Advances in three-dimensional (3D) printing technology have enabled the development of customized instrumentation and surgical training platforms. However, no existing studies have assessed how patient-specific 3D-printed spine models can facilitate patient education and operative planning in complex spinal deformity correction. OBJECTIVE: To present a cost-effective technique for constructing personalized 3D-printed spine models for patients with severe spinal deformities and to outline how these models can promote informed consent, trainee education, and planning for instrumentation placement and alignment correction. METHODS: We present 2 patients who underwent surgical correction of progressive thoracolumbar deformities. Full-scale 3D-printed models of each patient's spine were produced preoperatively and used during clinic evaluations, surgical planning, and as intraoperative references. RESULTS: Each model took 9 days to build and required less than 60 US dollars of material costs. Both patients were treated with a posterior approach and contiguous multilevel osteotomies. Postoperatively, their alignment parameters and neurological deficits improved. CONCLUSION: Personalized 3D-printed spine models can aid in patient education, surgical training, visualization, and correction of complex spinal deformities.

Distance traveled to glioblastoma treatment: A measure of the impact of socioeconomic status on survival.

BACKGROUND: Previous studies have shown improved post-surgical outcomes in patients who travel farther for glioblastoma treatment. This study investigates socioeconomic and facility factors that may influence this relationship. METHODS: Overall survival was calculated and compared by distance to treatment facility using univariate and multivariate survival models. The analysis was stratified by facility type, income quartile and insurance status and the association re-evaluated. Kaplan-Meier survival curves were created to analyze the relationship between overall survival and distance group. RESULTS: Individuals who traveled less than 5 miles to treatment had the shortest overall survival (11.8 months), while those who traveled greater than 50 miles had the longest survival (12.9 months). Stratification by income quartile failed to demonstrate an association between distance traveled and survival for those making less than $63,000 (adjusted hazard ratio range: 0.94-1.01). There was no association between survival and distance traveled for patients treated at a community cancer center, comprehensive community cancer center or an integrated network cancer program (adjusted hazard ratio range: 0.86-1.04). CONCLUSION: Financial strain, rather than distance traveled to treatment, may be associated with glioblastoma survival.

Molecular and Metabolic Mechanisms Underlying Selective 5-Aminolevulinic Acid-Induced Fluorescence in Gliomas.

5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. A subset of gliomas, especially low-grade tumors, do not accumulate PpIX intracellularly or readily fluoresce upon 5-ALA administration, making gross total resection difficult to achieve in diffuse lesions. We review existing literature on 5-ALA metabolism and PpIX accumulation to explore potential mechanisms of 5-ALA-induced glioma tissue fluorescence. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment.

Immunotherapy for Chordoma and Chondrosarcoma: Current Evidence.

Chordomas and chondrosarcomas are rare but devastating neoplasms that are characterized by chemoradiation resistance. For both tumors, surgical resection is the cornerstone of management. Immunotherapy agents are increasingly improving outcomes in multiple cancer subtypes and are being explored in chordoma and chondrosarcoma alike. In chordoma, brachyury has been identified as a prominent biomarker and potential molecular immunotherapy target as well as PD-1 inhibition. While studies on immunotherapy in chondrosarcoma are sparse, there is emerging evidence and ongoing clinical trials for PD-1 as well as IDH inhibitors. This review highlights potential biomarkers and targets for immunotherapy in chordoma and chondrosarcoma, as well as current clinical evidence and ongoing trials.

Patient-Derived Cancer Organoids for Precision Oncology Treatment.

The emergence of three-dimensional human organoids has opened the door for the development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. The mainstays of preclinical cancer modeling include in vitro cell lines and patient-derived xenografts, but these models lack the cellular heterogeneity seen in human tumors. Moreover, xenograft establishment is resource and time intensive, rendering these models difficult to use to inform clinical trials and decisions. PDOs, however, can be created efficiently and retain tumor-specific properties such as cellular heterogeneity, cell-cell and cell-stroma interactions, the tumor microenvironment, and therapeutic responsiveness. PDO models and drug-screening protocols have been described for several solid tumors and, more recently, for gliomas. Since PDOs can be developed in clinically relevant time frames and share many characteristics of parent tumors, they may enhance the ability to provide precision oncologic care for patients. This review explores the current literature on cancer organoids, highlighting the history of PDO development, organoid models of glioma, and potential clinical applications of PDOs.

Computational Drug Repositioning Identifies Potentially Active Therapies for Chordoma.

BACKGROUND: Chordomas are aggressive bone tumors that often recur despite maximal resection and adjuvant radiation. To date there are no Food and Drug Administration (FDA)-approved chemotherapies. Computational drug repositioning is an expanding approach to identify pharmacotherapies for clinical trials. OBJECTIVE: To identify FDA-approved compounds for repurposing in chordoma. METHODS: Previously identified highly differentially expressed genes from chordoma tissue samples at our institution were compared with pharmacogenomic interactions in the Comparative Toxicogenomics Database (CTD) using ksRepo, a drug-repositioning platform. Compounds selected by ksRepo were then validated in CH22 and UM-Chor1 human chordoma cells in Vitro. RESULTS: A total of 13 chemical compounds were identified in silico from the CTD, and 6 were selected for preclinical validation in human chordoma cell lines based on their clinical relevance. Of these, 3 identified drugs are FDA-approved chemotherapies for other malignancies (cisplatin, cytarabine, and lucanthone). Cytarabine, a deoxyribonucleic acid polymerase inhibitor approved for the treatment of various leukemias, exhibited a significant concentration-dependent effect against CH22 and UM-Chor1 cells when compared to positive (THZ1) and negative (venetoclax) controls. Tretinoin exhibited a significant concentration-dependent cytotoxic effect in CH22, sacral chordoma-derived cell lines but to a much lesser extent in UM-Chor1, a cell line derived from skull base chordoma. CONCLUSION: Cytarabine administration reduces the viability of human chordoma cells. The equally effective reduction in viability seen with tretinoin seems to be cell line dependent. Based on our findings, we recommend the evaluation of cytarabine and tretinoin in an expanded set of human chordoma cell lines and animal models.

Contemporary Mouse Models in Glioma Research.

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study glioma-genesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.

Anisocoria Correlates With Injury Severity and Outcomes After Blunt Traumatic Brain Injury.

ABSTRACT: BACKGROUND: Automated infrared pupillometry (AIP) has been shown to be helpful in the setting of aneurysmal subarachnoid hemorrhage and stroke as an indicator of imminent irreversible brain injury. We postulated that the early detection of pupillary dysfunction after light stimulation using AIP may be useful in patients with traumatic brain injury (TBI). METHODS: We performed a retrospective review of the Establishing Normative Data for Pupillometer Assessment in Neuroscience Intensive Care database, a prospectively populated multicenter registry of patients who had AIP measurements taken during their intensive care unit admission. The primary eligibility criterion was a diagnosis of blunt TBI. Ordinal logistic modeling was used to explore the association between anisocoria and daily Glasgow Coma Scale scores and discharge modified Rankin Scale scores from the intensive care unit and from the hospital. RESULTS: Among 118 subjects in the who met inclusion, there were 6187 pupillometer readings. Of these, anisocoria in ambient light was present in 12.8%, and that after light stimulation was present in 9.8%. Anisocoria after light stimulation was associated with worse injury severity (odds ratio [OR], 0.26 [95% confidence interval (CI), 0.14-0.46]), lower discharge Glasgow Coma Scale scores (OR, 0.28 [95% CI, 0.17-0.45]), and lower discharge modified Rankin Scale scores (OR, 0.28 [95% CI, 0.17-0.47]). Anisocoria in ambient light showed a similar but weaker association. CONCLUSION: Anisocoria correlates with injury severity and with patient outcomes after blunt TBI. Anisocoria after light stimulation seems to be a stronger predictor than does anisocoria in ambient light. These findings represent continued efforts to understand pupillary changes in the setting of TBI.