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1.
Neurosurgery ; 87(2): 368-376, 2020 08 01.
Article in English | MEDLINE | ID: mdl-31942635

ABSTRACT

BACKGROUND: Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined. OBJECTIVE: To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naïve pediatric AVMs. METHODS: To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes. RESULTS: The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P = .007) and higher margin dose (P = .005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively. CONCLUSION: Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect.


Subject(s)
Arteriovenous Fistula/surgery , Intracranial Arteriovenous Malformations/surgery , Radiosurgery/methods , Treatment Outcome , Adolescent , Child , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Postoperative Complications/epidemiology , Radiosurgery/adverse effects , Retrospective Studies
2.
Neuroimage ; 196: 200-206, 2019 08 01.
Article in English | MEDLINE | ID: mdl-30981859

ABSTRACT

Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus.


Subject(s)
Cervical Cord/anatomy & histology , Cervical Cord/diagnostic imaging , Diffusion Tensor Imaging , Image Processing, Computer-Assisted/methods , White Matter/anatomy & histology , White Matter/diagnostic imaging , Afferent Pathways/anatomy & histology , Afferent Pathways/diagnostic imaging , Humans , Male , Neural Pathways/anatomy & histology , Neural Pathways/diagnostic imaging
3.
Expert Opin Drug Saf ; 16(3): 277-287, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27989218

ABSTRACT

INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM. Areas covered: Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies. Trials include children, adolescents, and adults with either primary or recurrent GBM. Expert opinion: Based on the reviewed clinical trials, the current immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities which should be noted. However, the gains in patient survival have been modest. A safe and well-tolerated combinatory immunotherapeutic approach may be essential for optimal efficacy towards GBM.


Subject(s)
Brain Neoplasms/therapy , Glioblastoma/therapy , Immunotherapy/methods , Adolescent , Adult , Animals , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Cancer Vaccines/administration & dosage , Cancer Vaccines/adverse effects , Child , Cytokines/adverse effects , Cytokines/therapeutic use , Glioblastoma/immunology , Glioblastoma/pathology , Humans , Immunotherapy/adverse effects
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