ORCID Profile
0000-0002-4349-1618
Current Organisations
University of Texas Southwestern Medical Center
,
University of Nevada Las Vegas
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Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999756
Abstract: TOLD MRI of patient receiving 0.17 mL/kg DDFPe pretreatment ( b A /b ) and posttreatment ( b B /b ) shows reversal of tumor hypoxia. T1 of tumor (mean ± SD) was 1,454 ± 75 ms preadministration of DDFPe and decreased to 1,281 ± 77 ms after treatment. NMR relaxation measurements before and after infusion of DDFPe ( b C /b ). NMR T1 measurements represent mean ± SD for the 4 patients encompassing tumor or contralateral normal brain imaged at 1.5 T. Baseline measurements (blue) were performed before administration of DDFPe, and postmeasurements (red) were made following intravenous administration of DDFPe, while patients breathed oxygen or carbogen following irradiation. Normal brain tissue showed no significant response ( i P /i = 0.70), while tumor showed significant change following administration of DDFPe and irradiation ( i P /i = 0.0059). Considering all measurements, tumor tissues had significantly longer T1 relaxation times than normal brain ( i P /i 0.0001). At baseline brain T1 was significantly shorter than tumor ( i P /i 0.0001) and this remained so after administering DDFPe ( i P /i = 0.0045).
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.CRC-22-0433
Abstract: Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM. In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.05, 0.10, or 0.17 mL/kg) while breathing supplemental oxygen prior to each 2 Gy fraction of radiotherapy (30 fractions over 6 weeks). Patients also received standard-of-care chemotherapy [temozolomide (TMZ)]. Serial MRI scans were taken to monitor disease response. Adverse events were recorded and graded. TOLD (tissue oxygenation level–dependent) contrast MRI was obtained to validate modulation of tumor hypoxia. Eleven patients were enrolled. DDFPe combined with radiotherapy and TMZ was well tolerated in most patients. Two patients developed delayed grade 3 radiation necrosis during dose escalation, one each at 0.1 and 0.17 mL/kg of DDFPe. Subsequent patients were treated at the 0.1 mL/kg dose level. Kaplan–Meier analysis showed a median overall survival of 19.4 months and a median progression-free survival of 9.6 months, which compares favorably to historical controls. Among 6 patients evaluable for TOLD MRI, a statistically significant reduction in tumor T1 was observed after DDFPe treatment. This trial, although small, showed that the use of DDFPe as a radiosensitizer in patients with GBM was generally safe and may provide a survival benefit. This is also the first time than TOLD MRI has shown reversal of tumor hypoxia in a clinical trial in patients. The recommended dose for phase II evaluation is 0.1 mL/kg DDFPe. Trial Registration: NCT02189109 This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD MRI. This strategy is being used in a larger phase II/III trial which will hopefully show a survival benefit by adding DDFPe during the course of fractionated radiation and concurrent chemotherapy.
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999759
Abstract: Swimmer plot for patients with GBM treated with DDFPe, radiotherapy, and TMZ, showing PD and survival in relation to tumor MGMT promoter methylation status (methylated indicated by dark gray bars and unmethylated by light gray bars) and IDH1 mutation status. WT, wild type IDH1 Mut, R132H IDH1 mutation present PD, progressive disease.
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999756.V1
Abstract: TOLD MRI of patient receiving 0.17 mL/kg DDFPe pretreatment ( b A /b ) and posttreatment ( b B /b ) shows reversal of tumor hypoxia. T1 of tumor (mean ± SD) was 1,454 ± 75 ms preadministration of DDFPe and decreased to 1,281 ± 77 ms after treatment. NMR relaxation measurements before and after infusion of DDFPe ( b C /b ). NMR T1 measurements represent mean ± SD for the 4 patients encompassing tumor or contralateral normal brain imaged at 1.5 T. Baseline measurements (blue) were performed before administration of DDFPe, and postmeasurements (red) were made following intravenous administration of DDFPe, while patients breathed oxygen or carbogen following irradiation. Normal brain tissue showed no significant response ( i P /i = 0.70), while tumor showed significant change following administration of DDFPe and irradiation ( i P /i = 0.0059). Considering all measurements, tumor tissues had significantly longer T1 relaxation times than normal brain ( i P /i 0.0001). At baseline brain T1 was significantly shorter than tumor ( i P /i 0.0001) and this remained so after administering DDFPe ( i P /i = 0.0045).
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999750.V1
Abstract: All-cause AEs of grade 2 or greater severity
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999753.V1
Abstract: Baseline patient characteristics
Publisher: American Scientific Publishers
Date: 03-2008
DOI: 10.1166/JNN.2008.317
Abstract: Dye-sensitized solar cells (DSSCs) represent an exciting application of nanotechnology and offer an appealing alternative to conventional solar cells based on photovoltaic devices, with significantly reduced production and material costs. However, further improvements are required to enhance the commercial viability of these solar cells. These improvements may be achieved through the careful manipulation of the structure at the nanoscale and the application of novel processing techniques, which may help to increase the efficiency of these solar cells, improve the ease of manufacture and allow the production of flexible, solid-state solar cells. For ex le, the use of a nanometre-thick coating of an insulating oxide over the semiconducting film in these solar cells may reduce recombination losses. Also, selective heating techniques such as microwave heating may assist in the production of efficient solar cells on polymer, rather than glass, substrates, by allowing a rapid heat treatment to be applied to the titanium dioxide film at a higher temperature than would be possible with conventional heating. Some novel approaches to the production of semiconducting thin films for dye-sensitized solar cells, as well as the use of alternative materials and nanostructures, are reviewed.
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999750
Abstract: All-cause AEs of grade 2 or greater severity
Publisher: American Geophysical Union (AGU)
Date: 09-2015
DOI: 10.1002/2015GC005966
Publisher: Mary Ann Liebert Inc
Date: 02-2007
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999762
Abstract: Kaplan–Meier analysis of PFS (left) and OS (right) for all 11 patients and for the 9 patients with IDHwt.
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999753
Abstract: Baseline patient characteristics
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.C.6760500.V1
Abstract: Purpose: Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM. Experimental Design: In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.05, 0.10, or 0.17 mL/kg) while breathing supplemental oxygen prior to each 2 Gy fraction of radiotherapy (30 fractions over 6 weeks). Patients also received standard-of-care chemotherapy [temozolomide (TMZ)]. Serial MRI scans were taken to monitor disease response. Adverse events were recorded and graded. TOLD (tissue oxygenation level–dependent) contrast MRI was obtained to validate modulation of tumor hypoxia. Results: Eleven patients were enrolled. DDFPe combined with radiotherapy and TMZ was well tolerated in most patients. Two patients developed delayed grade 3 radiation necrosis during dose escalation, one each at 0.1 and 0.17 mL/kg of DDFPe. Subsequent patients were treated at the 0.1 mL/kg dose level. Kaplan–Meier analysis showed a median overall survival of 19.4 months and a median progression-free survival of 9.6 months, which compares favorably to historical controls. Among 6 patients evaluable for TOLD MRI, a statistically significant reduction in tumor T sub /sub was observed after DDFPe treatment. Conclusions: This trial, although small, showed that the use of DDFPe as a radiosensitizer in patients with GBM was generally safe and may provide a survival benefit. This is also the first time than TOLD MRI has shown reversal of tumor hypoxia in a clinical trial in patients. The recommended dose for phase II evaluation is 0.1 mL/kg DDFPe. Trial Registration: NCT02189109 Significance: This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD MRI. This strategy is being used in a larger phase II/III trial which will hopefully show a survival benefit by adding DDFPe during the course of fractionated radiation and concurrent chemotherapy. /
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.C.6760500
Abstract: Purpose: Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM. Experimental Design: In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.05, 0.10, or 0.17 mL/kg) while breathing supplemental oxygen prior to each 2 Gy fraction of radiotherapy (30 fractions over 6 weeks). Patients also received standard-of-care chemotherapy [temozolomide (TMZ)]. Serial MRI scans were taken to monitor disease response. Adverse events were recorded and graded. TOLD (tissue oxygenation level–dependent) contrast MRI was obtained to validate modulation of tumor hypoxia. Results: Eleven patients were enrolled. DDFPe combined with radiotherapy and TMZ was well tolerated in most patients. Two patients developed delayed grade 3 radiation necrosis during dose escalation, one each at 0.1 and 0.17 mL/kg of DDFPe. Subsequent patients were treated at the 0.1 mL/kg dose level. Kaplan–Meier analysis showed a median overall survival of 19.4 months and a median progression-free survival of 9.6 months, which compares favorably to historical controls. Among 6 patients evaluable for TOLD MRI, a statistically significant reduction in tumor T sub /sub was observed after DDFPe treatment. Conclusions: This trial, although small, showed that the use of DDFPe as a radiosensitizer in patients with GBM was generally safe and may provide a survival benefit. This is also the first time than TOLD MRI has shown reversal of tumor hypoxia in a clinical trial in patients. The recommended dose for phase II evaluation is 0.1 mL/kg DDFPe. Trial Registration: NCT02189109 Significance: This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD MRI. This strategy is being used in a larger phase II/III trial which will hopefully show a survival benefit by adding DDFPe during the course of fractionated radiation and concurrent chemotherapy. /
Publisher: Springer Science and Business Media LLC
Date: 25-05-2021
Publisher: Elsevier BV
Date: 2018
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999762.V1
Abstract: Kaplan–Meier analysis of PFS (left) and OS (right) for all 11 patients and for the 9 patients with IDHwt.
Publisher: Wiley
Date: 21-09-2022
DOI: 10.1002/MRM.29450
Abstract: Radiation therapy is a major component of cancer treatment pathways worldwide. The main aim of this treatment is to achieve tumor control through the delivery of ionizing radiation while preserving healthy tissues for minimal radiation toxicity. Because radiation therapy relies on accurate localization of the target and surrounding tissues, imaging plays a crucial role throughout the treatment chain. In the treatment planning phase, radiological images are essential for defining target volumes and organs‐at‐risk, as well as providing elemental composition (e.g., electron density) information for radiation dose calculations. At treatment, onboard imaging informs patient setup and could be used to guide radiation dose placement for sites affected by motion. Imaging is also an important tool for treatment response assessment and treatment plan adaptation. MRI, with its excellent soft tissue contrast and capacity to probe functional tissue properties, holds great untapped potential for transforming treatment paradigms in radiation therapy. The MR in Radiation Therapy ISMRM Study Group was established to provide a forum within the MR community to discuss the unmet needs and fuel opportunities for further advancement of MRI for radiation therapy applications. During the summer of 2021, the study group organized its first virtual workshop, attended by a erse international group of clinicians, scientists, and clinical physicists, to explore our predictions for the future of MRI in radiation therapy for the next 25 years. This article reviews the main findings from the event and considers the opportunities and challenges of reaching our vision for the future in this expanding field.
Publisher: American Association for Cancer Research (AACR)
Date: 21-08-2023
DOI: 10.1158/2767-9764.23999759.V1
Abstract: Swimmer plot for patients with GBM treated with DDFPe, radiotherapy, and TMZ, showing PD and survival in relation to tumor MGMT promoter methylation status (methylated indicated by dark gray bars and unmethylated by light gray bars) and IDH1 mutation status. WT, wild type IDH1 Mut, R132H IDH1 mutation present PD, progressive disease.
Location: No location found
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kevin Konrad.