Todd Mainprize

Reducing time-to-treatment decreases mortality of trauma patients with acute subdural hematoma.

Objectives:To determine if reducing prehospital time and time-to-craniotomy is associated with decreased mortality in trauma patients with acute subdural hematomas. Background:Time-to-treatment is an important performance filter for trauma systems, yet very little evidence exists to support its use. Despite the biological rationale supporting the notion of the “Golden Hour” for trauma patients, no evidence exists to support it. Likewise, it remains controversial whether or not time-to-craniotomy is associated with survival in patients with subdural hematomas. Previous studies may have been affected by selection bias. Methods:Retrospective cohort study of all trauma patients who arrived directly from the scene of injury. Study patients were all patients with acute subdural hematomas and without severe torso injuries, who required craniotomy at a Canadian level 1 trauma center from January 1 1996 to December 31 2007. The independent variables of interest were prehospital time and time-to-craniotomy. The primary outcome measure was in-hospital mortality. Results:Of 12,105 trauma patients assessed, 149 patients met inclusion criteria. Overall, 40% (n = 60) patients died. On univariate analysis, there was a strong trend suggesting that patients arriving within the “Golden Hour after trauma” had decreased mortality (37% vs. 53%, P = 0.09). However, there was no difference in mortality for patients undergoing craniotomy within 4 hours and after 4 hours (42% vs. 36%, P = 0.4). On multivariate logistic regression, increased prehospital time was found to be associated with increased mortality (odds ratio 1.03 per minute, 95% CI 1.004–1.05, P = 0.024). Surprisingly, there was a trend showing that increased trauma room to craniotomy times were associated with lower mortality (odds ratio 0.995 per minute, 95% CI 0.99–1.0, P = 0.056). However, patients who quickly had their craniotomy seemed to have more severe neurological injury. Conclusion:Rapid transport of patients with traumatic subdural hematomas hospital is associated with decreased mortality.

Hypofractionated Stereotactic Radiotherapy in Five Daily Fractions for Post-Operative Surgical Cavities in Brain Metastases Patients with and without Prior Whole Brain Radiation

Our purpose was to report efficacy of hypofractionated cavity stereotactic radiotherapy (HCSRT) in patients with and without prior whole brain radiotherapy (WBRT). 32 surgical cavities in 30 patients (20 patients/21 cavities had no prior WBRT and 10 patients/11 cavities had prior WBRT) were treated with image-guided linac stereotactic radiotherapy. 7 of the 10 prior WBRT patients had “resistant” local disease given prior surgery, post-operative WBRT and a re-operation, followed by salvage HCSRT. The clinical target volume was the post-surgical cavity, and a 2-mm margin applied as planning target volume. The median total dose was 30 Gy (range: 25–37.5 Gy) in 5 fractions. In the no prior and prior WBRT cohorts, the median follow-up was 9.7 months (range: 3.0–23.6) and 15.3 months (range: 2.9–39.7), the median survival was 23.6 months and 39.7 months, and the 1-year cavity local recurrence progression-free survival (LRFS) was 79 and 100%, respectively. At 18 months the LRFS dropped to 29% in the prior WBRT cohort. Grade 3 radiation necrosis occurred in 3 prior WBRT patients. We report favorable outcomes with HCSRT, and well selected patients with prior WBRT and “resistant” disease may have an extended survival favoring aggressive salvage HCSRT at a moderate risk of radiation necrosis.

Survival outcomes in elderly patients with glioblastoma.

AIMS Many elderly glioblastoma patients are excluded from randomised trials due to age, comorbidity or poor functional status. The purpose of this study was to describe the survival outcomes in all elderly patients with glioblastoma managed at a tertiary cancer centre. MATERIALS AND METHODS A retrospective chart review identified 235 elderly patients (age 65 years or over) with a histological diagnosis of glioblastoma between 1 December 2006 and 31 December 2013. The primary outcome of this study was overall survival by treatment type. Univariate and multivariate Cox proportional hazard models were used to explore significant prognostic variables associated with overall survival. RESULTS The median survival for all patients was 6.5 months (95% confidence interval 5.3-7.7), with 1 year overall survival of 23.7% (95% confidence interval 18.8-30.0). The median survival for patients treated with radiation and chemotherapy was 11.1 months (95% confidence interval 8.1-13.7). Patients treated with radiation alone had a median survival of 6.8 months (95% confidence interval 5.6-7.9). For patients managed with comfort measures only, the median survival was 1.9 months (95% confidence interval 1.6-2.6). Univariate analysis revealed age, performance status, surgery type (biopsy, subtotal resection, gross total resection) and type of treatment received (comfort measures only, radiotherapy alone, radiotherapy and chemotherapy) to be statistically associated with overall survival. In the multivariate analysis, only two predictive factors (treatment received and surgery type) were significant. CONCLUSIONS Elderly patients with glioblastoma selected for treatment (surgery followed by radiation alone or radiation and chemotherapy) survive longer than patients managed with comfort measures. Prospective randomised trials will help guide management for patients eligible for therapy. Elderly patients with glioblastoma who are deemed not eligible for active therapy have very short survival.

Economic Evaluations in the Diagnosis and Management of Traumatic Brain Injury: A Systematic Review and Analysis of Quality

BACKGROUND Economic evaluations provide a unique opportunity to identify the optimal strategies for the diagnosis and management of traumatic brain injury (TBI), for which uncertainty is common and the economic burden is substantial. OBJECTIVE The objective of this study was to systematically review and examine the quality of contemporary economic evaluations in the diagnosis and management of TBI. METHODS Two reviewers independently searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment Database, EconLit, and the Tufts CEA Registry for comparative economic evaluations published from 2000 onward (last updated on August 30, 2013). Data on methods, results, and quality were abstracted in duplicate. The results were summarized quantitatively and qualitatively. RESULTS Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were cost-utility, five were cost-effectiveness, three were cost-minimization, and seven were cost-consequences analyses. Only six studies were of high quality. Current evidence from high-quality studies suggests the economic attractiveness of the following strategies: a low medical threshold for computed tomography (CT) scanning of asymptomatic infants with possible inflicted TBI, selective CT scanning of adults with mild TBI as per the Canadian CT Head Rule, management of severe TBI according to the Brain Trauma Foundation guidelines, management of TBI in dedicated neurocritical care units, and early transfer of patients with TBI with nonsurgical lesions to neuroscience centers. CONCLUSIONS Threshold-guided CT scanning, adherence to Brain Trauma Foundation guidelines, and care for patients with TBI, including those with nonsurgical lesions, in specialized settings appear to be economically attractive strategies.

NIH workshop report on the trans-agency blood–brain interface workshop 2016: exploring key challenges and opportunities associated with the blood, brain and their interface

A trans-agency workshop on the blood–brain interface (BBI), sponsored by the National Heart, Lung and Blood Institute, the National Cancer Institute and the Combat Casualty Care Research Program at the Department of Defense, was conducted in Bethesda MD on June 7–8, 2016. The workshop was structured into four sessions: (1) blood sciences; (2) exosome therapeutics; (3) next generation in vitro blood–brain barrier (BBB) models; and (4) BBB delivery and targeting. The first day of the workshop focused on the physiology of the blood and neuro-vascular unit, blood or biofluid-based molecular markers, extracellular vesicles associated with brain injury, and how these entities can be employed to better evaluate injury states and/or deliver therapeutics. The second day of the workshop focused on technical advances in in vitro models, BBB manipulations and nanoparticle-based drug carrier designs, with the goal of improving drug delivery to the central nervous system. The presentations and discussions underscored the role of the BBI in brain injury, as well as the role of the BBB as both a limiting factor and a potential conduit for drug delivery to the brain. At the conclusion of the meeting, the participants discussed challenges and opportunities confronting BBI translational researchers. In particular, the participants recommended using BBI translational research to stimulate advances in diagnostics, as well as targeted delivery approaches for detection and therapy of both brain injury and disease.

Understanding Hospital Volume–Outcome Relationship in Severe Traumatic Brain Injury

BACKGROUND The hospital volume-outcome relationship in severe traumatic brain injury (TBI) population remains unclear. OBJECTIVE To examine the relationship between volume of patients with severe TBI per hospital and in-hospital mortality, major complications, and mortality following a major complication (ie, failure to rescue). METHODS In a multicenter cohort study, data on 9255 adults with severe TBI were derived from 111 hospitals participating in the American College of Surgeons Trauma Quality Improvement Program over 2009-2011. Hospitals were ranked into quartiles based on their volume of severe TBI during the study period. Random-intercept multilevel models were used to examine the association between hospital quartile of severe TBI volume and in-hospital mortality, major complications, and mortality following a major complication after adjusting for patient and hospital characteristics. In sensitivity analyses, we examined these associations after excluding transferred cases. RESULTS Overall mortality was 37.2% (n = 3447). Two thousand ninety-eight patients (22.7%) suffered from 1 or more major complication. Among patients with major complications, 27.8% (n = 583) died. Higher-volume hospitals were associated with lower mortality; the adjusted odds ratio of death was 0.50 (95% confidence interval: 0.29-0.85) in the highest volume quartile compared to the lowest. There was no significant association between hospital-volume quartile and the odds of a major complication or the odds of death following a major complication. After excluding transferred cases, similar results were found. CONCLUSION High-volume hospitals might be associated with lower in-hospital mortality following severe TBI. However, this mortality reduction was not associated with lower risk of major complications or death following a major complication.

To frame or not to frame? Cone‐beam CT‐based analysis of head immobilization devices specific to linac‐based stereotactic radiosurgery and radiotherapy

Abstract Purpose Noninvasive frameless systems are increasingly being utilized for head immobilization in stereotactic radiosurgery (SRS). Knowing the head positioning reproducibility of frameless systems and their respective ability to limit intrafractional head motion is important in order to safely perform SRS. The purpose of this study was to evaluate and compare the intrafractional head motion of an invasive frame and a series of frameless systems for single fraction SRS and fractionated/hypofractionated stereotactic radiotherapy (FSRT/HF‐SRT). Methods The noninvasive PinPoint system was used on 15 HF‐SRT and 21 SRS patients. Intrafractional motion for these patients was compared to 15 SRS patients immobilized with Cosman‐Roberts‐Wells (CRW) frame, and a FSRT population that respectively included 23, 32, and 15 patients immobilized using Gill‐Thomas‐Cosman (GTC) frame, Uniframe, and Orfit. All HF‐SRT and FSRT patients were treated using intensity‐modulated radiation therapy on a linear accelerator equipped with cone‐beam CT (CBCT) and a robotic couch. SRS patients were treated using gantry‐mounted stereotactic cones. The CBCT image‐guidance protocol included initial setup, pretreatment and post‐treatment verification images. The residual error determined from the post‐treatment CBCT was used as a surrogate for intrafractional head motion during treatment. Results The mean intrafractional motion over all fractions with PinPoint was 0.62 ± 0.33 mm and 0.45 ± 0.33 mm, respectively, for the HF‐SRT and SRS cohort of patients (P‐value = 0.266). For CRW, GTC, Orfit, and Uniframe, the mean intrafractional motions were 0.30 ± 0.21 mm, 0.54 ± 0.76 mm, 0.73 ± 0.49 mm, and 0.76 ± 0.51 mm, respectively. For CRW, PinPoint, GTC, Orfit, and Uniframe, intrafractional motion exceeded 1.5 mm in 0%, 0%, 5%, 6%, and 8% of all fractions treated, respectively. Conclusions The noninvasive PinPoint system and the invasive CRW frame stringently limit cranial intrafractional motion, while the latter provides superior immobilization. Based on the results of this study, our clinical practice for malignant tumors has evolved to apply an invasive CRW frame only for metastases in eloquent locations to minimize normal tissue exposure.

High-Intensity Focused Ultrasound Ablation Therapy of Gliomas

Ultrasound in clinical medicine is most commonly associated with imaging, but can be harnessed to yield an array of biological effects, including thermal ablation of brain tumors. Therapeutic ultrasound has been studied for many years, but only within the last decade has the technology reached a point where it is safe and practical for clinical adoption. Using large, multi-element arrays, ultrasound can be focused through the skull, and combined with MRI for image guidance and real-time thermometry, to create lesions in the brain with millimeter accuracy. Using this technology, true non-invasive surgery can be accomplished with immediate tumor killing. Combining the ablative capabilities of focused ultrasound with its other unique effects, such as blood-brain barrier disruption and radiosensitization, may eventually result in change of the current glioma treatment paradigm.

Accuracy of neuro-navigated cranial screw placement using optical surface imaging (Conference Presentation)

Cranial neurosurgical procedures are especially delicate considering that the surgeon must localize the subsurface anatomy with limited exposure and without the ability to see beyond the surface of the surgical field. Surgical accuracy is imperative as even minor surgical errors can cause major neurological deficits. Traditionally surgical precision was highly dependent on surgical skill. However, the introduction of intraoperative surgical navigation has shifted the paradigm to become the current standard of care for cranial neurosurgery. Intra-operative image guided navigation systems are currently used to allow the surgeon to visualize the three-dimensional subsurface anatomy using pre-acquired computed tomography (CT) or magnetic resonance (MR) images. The patient anatomy is fused to the pre-acquired images using various registration techniques and surgical tools are typically localized using optical tracking methods. Although these techniques positively impact complication rates, surgical accuracy is limited by the accuracy of the navigation system and as such quantification of surgical error is required. While many different measures of registration accuracy have been presented true navigation accuracy can only be quantified post-operatively by comparing a ground truth landmark to the intra-operative visualization. In this study we quantified the accuracy of cranial neurosurgical procedures using a novel optical surface imaging navigation system to visualize the three-dimensional anatomy of the surface anatomy. A tracked probe was placed on the screws of cranial fixation plates during surgery and the reported position of the centre of the screw was compared to the co-ordinates of the post-operative CT or MR images, thus quantifying cranial neurosurgical error.

MRIgFUS in the treatment of spontaneous intracerebral hemorrhage

Spontaneous cerebral hemorrhage (ICH) is a major cause of mortality and morbidity worldwide. Although the mechanisms leading to ICH are relatively well known, little improvement in outcomes has occurred over the years, in spite of significant advances in surgical techniques and medical management options. Evidence is available to suggest that liquefying and/or removing the clot after ICH might be beneficial. The objective of this work is to test the feasibility of use of MRI guided focused ultrasound (MRgFUS) in the treatment of ICH. Our hypotheses are that MRgFUS can be used safely to effectively cause clot lysis and it will provide good radiological resolution of ICH.