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Nataliya Smith, Debra Saunders, Randy L. Jensen, and Rheal A. Towner

, : Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT Trial . Stroke 38 : 2262 – 2269 , 2007 17 Nien HC , Hsu SJ , Su TH , Yang PJ , Sheu JC , Wang JT , : High serum lipopolysaccharide-binding protein level in chronic hepatitis C viral infection is reduced by anti-viral treatments . PLoS One 12 : e0170028 , 2017 18 Peckham JC : Experimental oncology , in Baker HJ , Lindsey JR , Weisbroth SH (eds): The Laboratory Rat . New York : Academic Press , 1979 , Vol II , p 119 19 Schröder NW , Schumann

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Nataliya Smith, Debra Saunders, Randy L. Jensen, and Rheal A. Towner

, : Safety and tolerability of NXY-059 for acute intracerebral hemorrhage: the CHANT Trial . Stroke 38 : 2262 – 2269 , 2007 17 Nien HC , Hsu SJ , Su TH , Yang PJ , Sheu JC , Wang JT , : High serum lipopolysaccharide-binding protein level in chronic hepatitis C viral infection is reduced by anti-viral treatments . PLoS One 12 : e0170028 , 2017 18 Peckham JC : Experimental oncology , in Baker HJ , Lindsey JR , Weisbroth SH (eds): The Laboratory Rat . New York : Academic Press , 1979 , Vol II , p 119 19 Schröder NW , Schumann

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Dennis C. Shrieve, Lisa Hazard, Kenneth Boucher, and Randy L. Jensen

: The treatment of meningiomas in childhood. Cancer 37: 2709–2712, 1976 16. Loeffler JS , Flickinger JC , Shrieve DC , et al : Radiosurgery for the treatment of intracranial lesions , in DeVita VT , Hellman S , Rosenberg SA (eds): Important Advances in Oncology. Philadelphia : JB Lippincott , 1995 , p 141 Loeffler JS, Flickinger JC, Shrieve DC, et al: Radiosurgery for the treatment of intracranial lesions, in DeVita VT, Hellman S, Rosenberg SA (eds): Important Advances in Oncology. Philadelphia

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Michael T. Bounajem, Michael Karsy, and Randy L. Jensen

biopsies in pediatric brain tumors are listed in Table 1 . CTCs = circulating tumor cells. Adapted with permission from Macmillan Publishers Limited: Springer Nature. Nature Reviews Clinical Oncology . 18 Integrating liquid biopsies into the management of cancer, by Siravegna G, Marsoni S, Siena S, Bardelli A. Copyright 2017. Methods A literature review was conducted to examine the extant studies on liquid biopsies, with particular attention paid to the options for indirectly isolating tumor samples, the success in doing so in vivo and in vitro, clinical applications

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Brian T. Ragel, William T. Couldwell, Robert D. Wurster, and Randy L. Jensen

. Calcium Channel Antagonists and Chemotherapeutic Combination Therapy Clinical trials for treatment of meningiomas using hydroxyurea and RU486 reported in the neurosurgical oncology literature have been generally disappointing. 6 , 10 , 11 , 21–25 , 28 Although the drugs are well tolerated in most patients, the results have not been consistent or durable. Given the earlier discussion, it is natural to propose that adding a CCA to the relatively weak activity of hydroxyurea or RU486 might result in increased meningioma cell growth inhibition compared with the use of

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Matthew Womeldorff, David Gillespie, and Randy L. Jensen

. 240 Pyruvate Dehydrogenase Kinase In metabolic oncology, decreased glucose oxidation in the mitochondria and increased glycolysis provides a proliferative advantage, increased angiogenesis, and resistance to apoptosis in cancer cells. This shift in metabolism is largely mediated by the mitochondrial enzyme PDK. When PDK is activated, it selectively inhibits pyruvate dehydrogenase, a group of enzymes that catalyzes the oxidative decarboxylation of cytosolic pyruvate to mitochondrial acetyl-CoA, the substrate for the Krebs cycle, promoting increased cytosolic

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Michael Karsy, Brian Burnett, Antonio Di Ieva, Michael D. Cusimano, and Randy L. Jensen

OBJECTIVE

Quantitative assessment of tumor microvascularity has the potential to improve prognostication, advance understanding of tumor biology, and help narrow potential molecular therapies. While the role of tumor microvascularity has been widely studied in meningiomas, this study examines both the role of automated measurements and the impact on surgical outcome.

METHODS

Two hundred seven patients with Grade I meningiomas underwent surgery between 1996 and 2011. Tissue samples from each patient were retrospectively evaluated for histopathological measures of microvascularity, including staining for von Willebrand factor (vWF), CD31, CD105, hypoxia-inducible factor 1 (HIF-1), vascular endothelial growth factor, glucose transporter 1, and carbonic anhydrase IX. Manual methods of assessing microvascularity were supplemented by a computational analysis of the microvascular patterns by means of fractal analysis. MIB-1 proliferation staining was also performed on the same tumors. These measures were compared with various patient characteristics, tumor volume, estimated blood loss (EBL) during surgery, progression-free survival (PFS), and overall survival (OS).

RESULTS

The mean patient age was 55.4 ± 14.8 years, and 63 (30.4%) patients were male. Patients harboring tumors ≥ 3 cm were significantly older (56.9 ± 15.2 years vs 53.1 ± 13.6 years; p = 0.07), more frequently male (40.8% vs 14.6%; p = 0.0001), and had greater EBL (446.5 ± 532.2 ml vs 185.4 ± 197.2 ml; p = 0.0001), greater tumor volume (33.9 ± 38.1 ml vs 29.4 ± 23.5 ml; p = 0.0001), higher MIB-1 index values (3.0% ± 5.4% vs 1.7% ± 1.7%; p = 0.03), higher vWF levels (85.6% ± 76.9% vs 54.1% ± 52.4%; p = 0.001), lower HIF-1 expression (1.4 ± 1.3 vs 2.2 ± 1.4; p = 0.004), and worse OS (199.9 ± 7.6 months vs 180.8 ± 8.1 months; p = 0.05) than patients with tumors < 3 cm. In the multivariate logistic regression, MIB-1 (OR 1.14; p = 0.05), vWF (OR 1.01; p = 0.01), and HIF-1 (OR 1.54; p = 0.0001) significantly predicted tumor size. Although multiple factors were predictive of EBL in the univariate linear regression, only vWF remained significant in the multivariate analysis (β = 0.39; p = 0.004). Lastly, MIB-1 was useful via Kaplan-Meier survival analysis for predicting patients with disease progression, whereby an MIB-1 cutoff value of ≥ 3% conferred a 36% sensitivity and 82.5% specificity in predicting disease progression; an MIB-1 value ≥ 3% showed significantly shorter mean PFS (140.1 ± 11.7 months vs 179.5 ± 7.0 months; log-rank test, p = 0.05). The Cox proportional hazards model showed a trend for MIB-1 in predicting disease progression in a hazards model (OR 1.08; 95% CI 0.99–1.19; p = 0.08).

CONCLUSIONS

These results support the importance of various microvascularity measures in predicting preoperative (e.g., tumor size), intraoperative (e.g., EBL), and postoperative (e.g., PFS and OS) outcomes in patients with Grade I meningiomas. An MIB-1 cutoff value of 3% showed good specificity for predicting tumor progression. The predictive ability of various measures to detect aberrant tumor microvasculature differed, possibly reflecting the heterogeneous underlying biology of meningiomas. It may be necessary to combine assays to understand angiogenesis in meningiomas.

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Hilary P. Bagshaw, Lindsay M. Burt, Randy L. Jensen, Gita Suneja, Cheryl A. Palmer, William T. Couldwell, and Dennis C. Shrieve

American Society for Radiation Oncology, October 18–21, 2015, San Antonio, Texas, and it was presented at the “Best of ASTRO” meeting November 13–14, 2015, San Diego, California.

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Yair M. Gozal, Erinç Aktüre, Vijay M. Ravindra, Jonathan P. Scoville, Randy L. Jensen, William T. Couldwell, and Philipp Taussky

the classification scheme. Subgroup analyses were performed according to neurosurgical subspecialty, specifically cranial trauma, spine & peripheral nerve, vascular (including endovascular and open vascular), neuro-oncology (including skull base surgery), functional, and general neurosurgery. Pediatric neurosurgical complications reported at the Morbidity and Mortality conference were specifically omitted because they reflected adverse events that occurred at an associated pediatric facility and not at our primary site. Definitions of Neurosurgical Complication

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Ricky Chen, Vijay M. Ravindra, Adam L. Cohen, Randy L. Jensen, Karen L. Salzman, Andrew P. Prescot, and Howard Colman

and accessibility based on IDH1 status in planning and carrying out resection. Implications for Chemotherapy and Radiation There is evidence that the presence of 1p19q codeletion is not only a positive prognostic indicator but also a strong predictor of chemosensitivity. In the Radiation Therapy Oncology Group (RTOG) 9402 trial, a prospective study of 291 patients with anaplastic oligodendroglioma and mixed anaplastic oligoastrocytomas, patients with tumors in which 1p19q was codeleted had a 2-fold longer survival (14.7 vs 7.3 years median OS, p = 0