9 results on '"Dylan Bobrow"'
Search Results
2. Supplemental Fig.1-4;Supplemental Tables 1-3; Suipplemental Methods from Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
- Author
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Antonio Omuro, Viviane Tabar, Jeffrey G. Supko, Percy Ivy, Katherine Panageas, Naoko Takebe, Nian Wu, Justin R. Cross, Adilia Hormigo, Dylan Bobrow, Timothy Chan, Christian Grommes, Craig Nolan, Elena Pentsova, Lisa DeAngelis, Thomas Kaley, J. Bryan Iorgulescu, Philip Gutin, Kyung K. Peck, Leif Droms, Sasan Karimi, Kathryn Beal, Koos Hovinga, Fumiko Shimizu, and Ran Xu
- Abstract
Supp. Fig.1. CONSORT Flow Diagram Supp. Fig.2. MRI Perfusion Parameters Supp. Fig. 3. Immunohistochemistry Supp. Fig. 4. Gene Expression Profile Supp. Table 1. Adverse Events Supp. Table 2. Pharmacokinetic Data Supp. Table 3. Molar Drug Levels Supplemental Methods
- Published
- 2023
3. Data from Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
- Author
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Antonio Omuro, Viviane Tabar, Jeffrey G. Supko, Percy Ivy, Katherine Panageas, Naoko Takebe, Nian Wu, Justin R. Cross, Adilia Hormigo, Dylan Bobrow, Timothy Chan, Christian Grommes, Craig Nolan, Elena Pentsova, Lisa DeAngelis, Thomas Kaley, J. Bryan Iorgulescu, Philip Gutin, Kyung K. Peck, Leif Droms, Sasan Karimi, Kathryn Beal, Koos Hovinga, Fumiko Shimizu, and Ran Xu
- Abstract
Purpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role.Experimental Design: In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood–brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment.Results: Treatment was well tolerated and no dose-limiting toxicities were observed. IHC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133+ CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors.Conclusions: The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood–brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. Clin Cancer Res; 22(19); 4786–96. ©2016 AACR.
- Published
- 2023
4. Ability of the Khorana score to predict recurrent thromboembolism in cancer patients with ischemic stroke
- Author
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Hooman Kamel, Babak B. Navi, Lisa M. DeAngelis, Dylan Bobrow, Mary Cushman, Santosh B. Murthy, Mitchell S.V. Elkind, and Alexander E Merkler
- Subjects
Adult ,Male ,medicine.medical_specialty ,Population ,030204 cardiovascular system & hematology ,Malignancy ,Severity of Illness Index ,Article ,Brain Ischemia ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Risk Factors ,Neoplasms ,Physiology (medical) ,Internal medicine ,Recurrent thromboembolism ,medicine ,Humans ,Leukocytosis ,education ,Stroke ,Aged ,Retrospective Studies ,education.field_of_study ,Proportional hazards model ,business.industry ,Cancer ,Venous Thromboembolism ,General Medicine ,Middle Aged ,medicine.disease ,Neurology ,Ischemic stroke ,Female ,Surgery ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Cancer patients with acute ischemic stroke (AIS) are high-risk for recurrent thromboembolic events (RTE). Currently, no risk stratification model exists to predict RTE in this population. We tested the hypothesis that the Khorana score, a validated risk model for predicting venous thromboembolism in cancer patients, can effectively classify RTE risk in cancer patients with AIS. We retrospectively identified adults with active solid or hematological cancer diagnosed with AIS at a tertiary-care cancer center from 2005 to 2010. The Khorana score at the time of index stroke was calculated. The primary outcome was arterial or venous RTE. Cox regression was used to evaluate the association of the Khorana score and its individual components with RTE. Harrell’s c-statistic was used to calculate the score’s discriminatory ability. Among 263 AIS patients, median survival was 84 days (IQR 24–149 days) and 90 (34%) had RTE. The median Khorana score was 2 (IQR 1–2, range 0–5). Cumulative rate of RTE was 28% among patients who scored 0, 36% with scores of 1–2, and 32% with scores of 3–6. The overall Khorana score was marginally associated with RTE (HR, 1.14; 95% CI, 1.02–1.28). Of its individual components, only leukocytosis was associated with RTE (HR adjusted for other components, 1.45; 95% CI 1.11–1.90). The score’s c-statistic for predicting RTE was 0.57. In this study, the Khorana score had poor discriminatory ability for predicting RTE in cancer patients with AIS. Future research is needed to identify better methods for predicting RTE in this high-risk population.
- Published
- 2018
5. Abstract TP72: Pilot Trial of Enoxaparin versus Aspirin in Cancer Patients with Stroke: the TEACH Study
- Author
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Costantino Iadecola, Mitchell S.V. Elkind, Hooman Kamel, Lisa M. DeAngelis, Babak B. Navi, Maria T. DeSancho, Katherine S. Panageas, Dylan Bobrow, Randolph S. Marshall, Jacqueline B. Stone, and Samuel Singer
- Subjects
Advanced and Specialized Nursing ,medicine.medical_specialty ,Aspirin ,business.industry ,Pilot trial ,Cancer ,medicine.disease ,Internal medicine ,Ischemic stroke ,medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Acute ischemic stroke ,Stroke ,medicine.drug - Abstract
Introduction: Anticoagulants are often used in cancer patients with acute ischemic stroke (AIS) because of concerns for hypercoagulability. However, cancer patients are also prone to bleeding. No prospective study has compared different antithrombotic strategies in this population. We aimed to perform the first randomized trial comparing anticoagulation to antiplatelet therapy in cancer patients with AIS. Methods: We conducted a pilot multicenter randomized trial in adult patients with active systemic cancer and MRI-confirmed AIS. Patients were randomized to subcutaneous enoxaparin (1 mg/kg twice daily) or oral aspirin (81 mg daily) for 6 months. Antithrombotic therapy beyond 6 months was dictated by treating clinicians. Exclusion criteria included clear indications for anticoagulant (e.g., DVT) or antiplatelet (e.g., recent stents) therapy, high-risk conditions for bleeding, symptomatic carotid stenosis, and severe hematologic derangements. Patients were followed at clinical visits at 1, 3, and 6 months and by chart review from 6 months to 1 year. The primary outcome was feasibility, defined as an enrollment rate among eligible patients for which the lower bound of the 95% confidence interval (CI) exceeds 30%. Secondary feasibility outcomes included patient dropout and crossover rates. Results: In this interim analysis, 469 patients with cancer and stroke were screened from January 2013 to April 2016 and 49 (10.4%) were eligible. Frequent exclusionary reasons were clear indications for anticoagulation (n=128) and inactive cancer (n=83). We enrolled 20 of the 49 eligible patients, equating to an enrollment rate of 41% (95% CI 27-55%). Enrollment failures primarily occurred because of patient aversion to injections (n=11), patient or physician preference for anticoagulation (n=9), and patient aversion to trial participation (n=7). Thus far, there have been no dropouts but 6 patients crossed over from the enoxaparin arm to the aspirin arm. Major bleeding occurred in 3 patients in the aspirin arm and 1 in the enoxaparin arm; no patients had intracranial hemorrhage. Conclusion: A randomized trial comparing anticoagulation to antiplatelet therapy in cancer patients with AIS may be feasible and safe, particularly with an oral anticoagulant.
- Published
- 2017
6. Abstract TP192: Ability of the Khorana Score to Predict Recurrent Thromboembolism in Cancer Patients With Ischemic Stroke
- Author
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Dylan Bobrow, Mary Cushman, Hooman Kamel, Alexander E Merkler, Mitchell S Elkind, Lisa M DeAngelis, and Babak B Navi
- Subjects
Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Cancer patients who develop acute ischemic stroke (AIS) are at high risk for recurrent thromboembolism. No risk stratification model exists to predict recurrent events in this population. The Khorana score is a validated risk score for predicting venous thromboembolism in newly diagnosed cancer patients. Hypothesis: The Khorana score can effectively classify the risk of recurrent thromboembolism (RTE) in cancer patients with AIS. Methods: We retrospectively identified all adults with active systemic cancer diagnosed with AIS by MRI at a tertiary-care cancer center from 2005 through 2009. Two neurologists independently reviewed all available medical records through July 31, 2012. The Khorana score at the time of index stroke was calculated for each patient. Points were assigned for specific cancer sites (2 points for very high-risk sites: stomach or pancreas; 1 point for high-risk sites: lung, lymphoma, gynecologic, bladder, testicular, or renal), platelet count ≥350,000/mcL, hemoglobin Results: Among 263 study patients, 90 (34%) were diagnosed with RTE, including 36 (14%) with recurrent AIS. The median Khorana score was 2 (IQR 1-2, range 0-5). None of the individual components of the score were independently associated with RTE, although there was a nonsignificant trend for high-risk cancer sites (OR 1.56, 95% CI 0.88-2.77). The rate of RTE was 28% among patients with a score of 0, 36% among patients with a score of 1-2, and 32% among patients with a score of 3-6. The c-statistic was 0.52 (95% CI 0.45-0.58) for predicting RTE and 0.49 (95% CI 0.38-0.59) for predicting recurrent AIS. Discussion: The Khorana score has poor discriminatory ability for predicting RTE in cancer patients with AIS, probably because these patients represent an especially high-risk group. Future research is needed to identify better methods for predicting RTE in this high-risk population.
- Published
- 2016
7. Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
- Author
-
Naoko Takebe, Ran Xu, Jeffrey G. Supko, J. Bryan Iorgulescu, Fumiko Shimizu, Christian Grommes, Timothy A. Chan, Sasan Karimi, Philip H. Gutin, Elena Pentsova, Craig Nolan, Nian Wu, Leif A. Droms, Lisa M. DeAngelis, Kyung K. Peck, Antonio Omuro, Dylan Bobrow, Justin R. Cross, Katherine S. Panageas, Adilia Hormigo, S. Percy Ivy, Kathryn Beal, Viviane Tabar, Thomas Kaley, and Koos E. Hovinga
- Subjects
0301 basic medicine ,Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Maximum Tolerated Dose ,Angiogenesis ,Population ,Notch signaling pathway ,Biology ,Article ,Neovascularization ,03 medical and health sciences ,0302 clinical medicine ,Glioma ,medicine ,Humans ,education ,Aged ,education.field_of_study ,Temozolomide ,Neovascularization, Pathologic ,Receptors, Notch ,Brain Neoplasms ,Chemoradiotherapy ,Benzazepines ,Middle Aged ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Neoplastic Stem Cells ,Immunohistochemistry ,Female ,medicine.symptom ,Neoplasm Recurrence, Local ,Anaplastic astrocytoma ,medicine.drug - Abstract
Purpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role. Experimental Design: In this phase 0/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic astrocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood–brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment. Results: Treatment was well tolerated and no dose-limiting toxicities were observed. IHC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133+ CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors. Conclusions: The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood–brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. Clin Cancer Res; 22(19); 4786–96. ©2016 AACR.
- Published
- 2016
8. Enoxaparin vs Aspirin in Patients With Cancer and Ischemic Stroke
- Author
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Randolph S. Marshall, Samuel Singer, Jacqueline B. Stone, Maria T. DeSancho, Dylan Bobrow, Lisa M. DeAngelis, and Babak B. Navi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Pilot Projects ,030204 cardiovascular system & hematology ,Brain Ischemia ,law.invention ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Fibrinolytic Agents ,Randomized controlled trial ,law ,Neoplasms ,Internal medicine ,Research Letter ,medicine ,Humans ,In patient ,cardiovascular diseases ,Enoxaparin ,Aged ,Retrospective Studies ,Aged, 80 and over ,Aspirin ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Stroke ,Treatment Outcome ,Ischemic stroke ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Follow-Up Studies ,medicine.drug - Abstract
This randomized clinical trial compares anticoagulation vs antiplatelet therapy in patients with cancer and acute ischemic stroke.
- Published
- 2018
9. Abstract W P205: Potential Hematological Biomarkers of Stroke in Cancer Patients
- Author
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Dylan Bobrow, Kajal J Kothadia, Hooman Kamel, Costantino Iadecola, Mitchell S Elkind, Ellinor I Peerschke, Gerald A Soff, Lisa M DeAngelis, and Babak B Navi
- Subjects
Advanced and Specialized Nursing ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: Cancer patients can develop hypercoagulability, leading to stroke. The pathophysiology of cancer-mediated hypercoagulability, however, is poorly understood and biomarkers associated with stroke in cancer patients are uncertain. Methods: We performed a pilot cross-sectional study at a tertiary-care cancer center to evaluate potential hematological biomarkers of stroke in cancer patients. From October 2013 through May 2014, we prospectively identified 15 inpatients with active systemic cancer and acute ischemic stroke and 15 inpatients with active systemic cancer and no stroke. Using collected plasma, we compared six potential biomarkers of stroke, selected in advance based on expert opinion and prior data, which included markers of coagulation (thrombin-antithrombin complex and D-dimer), platelet function (P-selectin), and endothelial activation state (sICAM-1, vICAM-1, and thrombomodulin). We used the Wilcoxon rank-sum test to compare biomarker levels between groups. Results: Each group comprised 14 patients with solid cancer and one patient with hematological cancer. All patients in the cancer and stroke group had stage 4 disease, while only 60% of the cancer and no stroke group had stage 4 disease. Age and demographics were similar between groups. Median levels of thrombin-antithrombin complex, D-dimer, P-selectin, sICAM-1, and vICAM-1 were significantly increased in cancer patients with stroke, but thrombomodulin was not (Table). Our results were substantially unchanged in a sensitivity analysis limited to patients with only stage 4 cancer. Conclusion: These preliminary data suggest that thrombin-antithrombin complex, D-dimer, P-selectin, sICAM-1, and vICAM-1 could serve as the focus of future prospective studies to elucidate the potential predictive, diagnostic, or etiologic role of hematological biomarkers for stroke in the cancer population.
- Published
- 2015
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