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This study aimed to evaluate the utility of the 11-variable modified Frailty Index (mFI) in prognosticating elderly patients with traumatic acute subdural hematomas (aSDHs). A state-service level 1 trauma center registry was interrogated to investigate consecutive patients ≥65 years of age presenting with traumatic aSDH, with or without major extracranial injury, between January 2013 and December 2017. mFI on admission, demographics, and admission details, including Glasgow Coma Scale (GCS) and pupillary status and radiological findings, were retrospectively retrieved from institutional records. Clinical outcome data were retrieved from medical records and the Victorian State Trauma Registry (VSTR). Outcome measures were 1) 30-day mortality and 2) 6-month unfavorable outcome, defined by the Extended Glasgow Outcome Scale (GOS-E). Five hundred twenty-nine consecutive cases were identified from the registry. Demographic data included: 1) age (median; interquartile range) = 80.46; 74.17-85.89; 2) mFI (mean ± standard deviation) = 1.96 ± 1.42 of 11 variables. Four hundred sixteen cases (79%) had complete outcome data. As mFI increased from 0/11 variables to ≥5/11 variables (≥0.45), 30-day mortality risk increased from 17.72% to 39.29% (

BackgroundDiffusion magnetic resonance (MR) characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-vascular endothelial growth factor (VEGF) therapy; however, its use in large volume recurrence has not been evaluated.ObjectiveTo determine if diffusion MR characteristics can predict survival outcomes in patients with large volume recurrent glioblastoma treated with bevacizumab or repeat resection.MethodsA total of 32 patients with large volume (>20 cc or > 3.4 cm diameter) recurrent glioblastoma treated with bevacizumab and 35 patients treated with repeat surgery were included. Pretreatment tumor volume and apparent diffusion coefficient (ADC) histogram analysis were used to phenotype patients as having high (>1.24 μm2/ms) or low (

PurposeThe objective of the current study was to explore the efficacy of using pH-weighted amine CEST-EPI as a potential non-invasive imaging biomarker for treatment response and/or failure in recurrent GBM patients treated with bevacizumab.MethodA total of 11 patients with recurrent GBM treated with bevacizumab were included in this prospective study. CEST-EPI, perfusion MRI, and standardized anatomic MRI were obtained in patients before and after bevacizumab administration. CEST-EPI measures of magnetization transfer ratio asymmetry (MTRasym) at 3ppm were used for pH-weighted imaging contrast. Multiple measures were examined for their association with progression-free survival (PFS).ResultTumor acidity, measured with MTRasym at 3ppm, was significantly reduced in both contrast enhancing and non-enhancing tumor after bevacizumab (p = 0.0002 and p

2018 Background: VB-111 is a non-replicating adenovirus carrying a pro-apoptotic transgene for TNFR1/Fas under the control of a modified murine promoter to pre-proendothelin 1. The transgene is expressed only in angiogenic endothelial cells, and therefore VB-111 results in targeted apoptosis of neovascular vessels. The current study characterizes the quantitative radiographic results and impact on OS in phase 2 and 3 trials of recurrent glioblastoma (GBM) patients treated with VB-111 with or without bevacizumab (BV) or BV monotherapy. Methods: MRI data from a phase 2 (NCT01260506) and randomized, double arm, controlled phase 3 (GLOBE; NCT02511405) trial of VB-111 in recurrent GBM were used in current study: Arm A) VB-111 monotherapy until progression followed by combination VB-111 and bevacizumab (BV) (“Primed Combination”; Phase 2; N = 24); Arm B) VB-111 in combination with BV (“Unprimed Combination”; Phase 3; N = 124) and Arm C) BV monotherapy (“Control”; Phase 3; N = 120). Contrast enhanced T1-weighted digital subtraction was used to quantify tumor volume at all time points. Results: Baseline tumor volume was not significantly different between patient cohorts (Kruskal-Wallis; P = 0.1482; median~20mL). Continuous measures of baseline tumor volume were prognostic for OS in all treatment groups when controlling for therapy and age (Cox, P < 0.001, HR = 1.02). In patients with small tumors ( < 25mL), the “primed combination” cohort (Arm A) from the phase 2 trial had a significant OS advantage compared to both upfront combination of VB-111 and BV (Arm B; P = 0.0094, HR = 0.5328; median OS = 7mo vs. 15mo) as well as BV alone (Arm C; P = 0.0248, HR = 0.5776; median OS = 8.5mo vs. 15mo). Patients with a radiographic response ( > 65% reduction) had a significant survival difference from non-responders when controlling for age, baseline tumor volume, and treatment arm ( P = 0.0014, HR = 0.5822). Notably, in responders to VB-111 monotherapy or combination therapy after priming with VB-111 exhibited characteristic, expansive areas of necrosis in areas of initial disease. Conclusions: Small recurrent tumors have a significant OS advantage when “priming” with VB-111 monotherapy prior to combination VB-111 and BV at recurrence. Patients responding to VB-111 exhibit specific imaging characteristics related to the drug mechanism of action. Clinical trial information: NCT02511405; NCT01260506.