Brandon R Laing, Melissa A Prah, Benjamin J Best, Max O Krucoff, Wade M Mueller, Kathleen M Schmainda
{"title":"Application of Delta T1 maps for quantitative and objective assessment of extent of resection and survival prediction in glioblastoma.","authors":"Brandon R Laing, Melissa A Prah, Benjamin J Best, Max O Krucoff, Wade M Mueller, Kathleen M Schmainda","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background and objectives: </strong>Gross-total resection (GTR) and low residual tumor volume (RTV) have been associated with increased survival in glioblastoma. Largely due to the subjectivity involved, the determination of GTR and RTV remains difficult in the postoperative setting. In response, the objective of this study is to evaluate the clinical efficacy of an easy-to-use MRI metric, called delta T1 (dT1), to quantify extent of resection (EOR) and RTV, in comparison to radiologist impression, to predict overall survival (OS) in glioblastoma patients.</p><p><strong>Methods: </strong>59 patients who underwent resection of glioblastoma were retrospectively identified. Delta T1 (dT1) images, automatically created from the difference between calibrated post- and pre-contrast T1-weighted images, were used to quantify EOR and RTV. Kaplan-Meier survival estimates were determined for EOR categories, an RTV cutoff of 5cm<sup>3</sup> and radiologist interpretation of EOR. Multivariate Cox proportional hazard regression analysis was used to evaluate RTV and EOR along with effects related to sex, KPS, MGMT, and age on OS.</p><p><strong>Results: </strong>Kaplan-Meier analysis revealed a statistically significant difference in median OS for a dT1-determined RTV cutoff of 5 cm<sup>3</sup> (P=.0024, HR=2.18 (1.232-3.856)), but not for radiological impression (P=0.666) or dT1-determined EOR (P=0.0803), which was limited to a comparison between partial and subtotal resections. Furthermore, when covariates were accounted for in multivariate Cox regression, significant differences in OS were retained for dT1-determined RTV. Additionally, a significantly strong yet short-term effect of MGMT methylation status on OS was revealed for each RTV and EOR model.</p><p><strong>Conclusion: </strong>The utility of dT1 maps to quantify EOR and RTV in glioblastoma and predict survival, suggests an emerging role for dT1s with relevance for intraoperative MRI, neuro-navigation and postoperative disease surveillance.</p>","PeriodicalId":74298,"journal":{"name":"Neurosurgery practice","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11198967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andres Ramos-Fresnedo, Rawan Al-Kharboosh, Erin L Twohy, Aleeshba N Basil, Ewa C Szymkiewicz, Abba C Zubair, Daniel M Trifiletti, Nisha Durand, Dennis W Dickson, Erik H Middlebrooks, David N Abarbanel, Stephany Y Tzeng, Joao Paulo Almeida, Kaisorn L Chaichana, Jordan J Green, Wendy J Sherman, Alfredo Quiñones-Hinojosa
{"title":"Phase 1, Dose Escalation, Nonrandomized, Open-Label, Clinical Trial Evaluating the Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells for Recurrent Glioblastoma: A Clinical Trial Protocol.","authors":"Andres Ramos-Fresnedo, Rawan Al-Kharboosh, Erin L Twohy, Aleeshba N Basil, Ewa C Szymkiewicz, Abba C Zubair, Daniel M Trifiletti, Nisha Durand, Dennis W Dickson, Erik H Middlebrooks, David N Abarbanel, Stephany Y Tzeng, Joao Paulo Almeida, Kaisorn L Chaichana, Jordan J Green, Wendy J Sherman, Alfredo Quiñones-Hinojosa","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background and objectives: </strong>Despite standard of care with maximal safe resection and chemoradiation, glioblastoma is the most common and aggressive type of primary brain cancer. Surgical resection provides a window of opportunity to locally treat gliomas while the patient is recovering, and before initiating concomitant chemoradiation. To assess the safety and establish the maximum tolerated dose of adipose-derived mesenchymal stem cells (AMSCs) for the treatment of recurrent glioblastoma (GBM). Secondary objectives are to assess the toxicity profile and long-term survival outcomes of patients enrolled in the trial. Additionally, biospecimens will be collected to explore the local and systemic responses to this therapy.</p><p><strong>Methods: </strong>We will conduct a phase 1, dose escalated, non-randomized, open label, clinical trial of GBM patients who are undergoing surgical resection for recurrence. Up to 18 patients will receive intra-cavitary application of AMSCs encapsulated in fibrin glue during surgical resection. All patients will be followed for up to 5 years for safety and survival data. Adverse events will be recorded using the CTCAE V5.0.</p><p><strong>Expected outcomes: </strong>This study will explore the maximum tolerated dose (MTD) of AMSCs along with the toxicity profile of this therapy in patients with recurrent GBM. Additionally, preliminary long-term survival and progression-free survival outcome analysis will be used to power further randomized studies. Lastly, CSF and blood will be obtained throughout the treatment period to investigate circulating molecular and inflammatory tumoral/stem cell markers and explore the mechanism of action of the therapeutic intervention.</p><p><strong>Discussion: </strong>This prospective translational study will determine the initial safety and toxicity profile of local delivery of AMSCs for recurrent GBM. It will also provide additional survival metrics for future randomized trials.</p>","PeriodicalId":74298,"journal":{"name":"Neurosurgery practice","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10923529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Theresa C Gammel, Leor N Alkadaa, Jordan R Saadon, Sabir Saluja, John Servider, Nathaniel A Cleri, Michael Egnor, Raphael P Davis, Chuan Huang, Yuri B Saalmann, Sima Mofakham, Charles B Mikell
{"title":"Brain Circuitry of Consciousness: A Review of Current Models and a Novel Synergistic Model With Clinical Application.","authors":"Theresa C Gammel, Leor N Alkadaa, Jordan R Saadon, Sabir Saluja, John Servider, Nathaniel A Cleri, Michael Egnor, Raphael P Davis, Chuan Huang, Yuri B Saalmann, Sima Mofakham, Charles B Mikell","doi":"10.1227/neuprac.0000000000000031","DOIUrl":"https://doi.org/10.1227/neuprac.0000000000000031","url":null,"abstract":"<p><p>How consciousness arises in the brain has important implications for clinical decision-making. We summarize recent findings in consciousness studies to provide a toolkit for clinicians to assess deficits in consciousness and predict outcomes after brain injury. Commonly encountered disorders of consciousness are highlighted, followed by the clinical scales currently used to diagnose them. We review recent evidence describing the roles of the thalamocortical system and brainstem arousal nuclei in supporting awareness and arousal and discuss the utility of various neuroimaging studies in evaluating disorders of consciousness. We explore recent theoretical progress in mechanistic models of consciousness, focusing on 2 major models, the global neuronal workspace and integrated information theory, and review areas of controversy. Finally, we consider the potential implications of recent research for the day-to-day decision-making of clinical neurosurgeons and propose a simple \"three-strikes\" model to infer the integrity of the thalamocortical system, which can guide prognosticating return to consciousness.</p>","PeriodicalId":74298,"journal":{"name":"Neurosurgery practice","volume":"4 2","pages":"e00031"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/75/neuopen-4-e00031a.PMC10193831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9502772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}