Objective A relationship between reduced brain tissue oxygenation (PbtO2) and poor outcome following severe traumatic brain injury (TBI) has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve PbtO2 levels in patients with severe TBI and the feasibility of a Phase III efficacy study. Design Randomized prospective clinical trial Setting Ten ICUs in the United States Patients One hundred nineteen severe TBI patients Interventions Patients were randomized to treatment protocol based on intracranial pressure (ICP) plus PbtO2 monitoring versus ICP monitoring alone. PbtO2 data were recorded in the ICP-only group in blinded fashion. Tiered interventions in each arm were specified and impact on ICP and PbtO2 measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale–Extended. Measurements and Main Results A management protocol based on PbtO2 and ICP monitoring reduced the proportion of time with brain tissue hypoxia after severe TBI (0.45 in ICP-only group, 0.16 in ICP+PbtO2 group; p<0.0001). ICP control was similar in both groups. Safety and feasibility of the tiered treatment protocol was confirmed. There were no procedure related complications. Treatment of secondary injury after severe TBI based on PbtO2 and ICP values was consistent with reduced mortality and increased proportions of patients with good recovery compared to ICP-only management; however, the study was not powered for clinical efficacy. Conclusions Management of severe TBI informed by multimodal ICP and PbtO2 monitoring reduced brain tissue hypoxia with a trend towards lower mortality and more favorable outcomes than ICP-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of ICP plus PbtO2-directed treatment of severe TBI is warranted.
PURPOSE Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. PATIENTS AND METHODS This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age > or = 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Results The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age < 60 years and KPS > or = 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae. CONCLUSION This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.