scholarly journals E-122 Yttrium-90 radioembolization as a possible new treatment for brain cancer: proof of concept and safety analysis in a canine model

2020 ◽  
Author(s):  
S Manupipatpong ◽  
A Pasciak ◽  
F Hui ◽  
R Krimins ◽  
L Gainsburg ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Safety Analysis ◽  
Canine Model ◽  
Proof Of Concept ◽  
New Treatment ◽  
Yttrium 90

scholarly journals Correction to: Yttrium-90 radioembolization as a possible new treatment for brain cancer: proof of concept and safety analysis in a canine model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander S. Pasciak ◽  
Sasicha Manupipatpong ◽  
Ferdinand K. Hui ◽  
Larry Gainsburg ◽  
Rebecca Krimins ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Safety Analysis ◽  
Canine Model ◽  
Proof Of Concept ◽  
New Treatment ◽  
Yttrium 90

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Yttrium-90 radioembolization as a possible new treatment for brain cancer: proof of concept and safety analysis in a canine model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander S. Pasciak ◽  
Sasicha Manupipatpong ◽  
Ferdinand K. Hui ◽  
Larry Gainsburg ◽  
Rebecca Krimins ◽  
...  
Keyword(s):  
Cerebral Artery ◽  
Brain Cancer ◽  
Canine Model ◽  
Post Treatment ◽  
Cortical Atrophy ◽  
Proof Of Concept ◽  
Invasive Treatment ◽  
Treatment Research ◽  
Post Therapy ◽  
Yttrium 90

Abstract Purpose To evaluate the safety, feasibility, and preliminary efficacy of yttrium-90 (90Y) radioembolization (RE) as a minimally invasive treatment in a canine model with presumed spontaneous brain cancers. Materials Three healthy research dogs (R1–R3) and five patient dogs with spontaneous intra-axial brain masses (P1–P5) underwent cerebral artery RE with 90Y glass microspheres (TheraSphere). 90Y-RE was performed on research dogs from the unilateral internal carotid artery (ICA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) while animals with brain masses were treated from the ICA. Post-treatment 90Y PET/CT was performed along with serial neurological exams by a veterinary neurologist. One month after treatment, research dogs were euthanized and the brains were extracted and sent for microdosimetric and histopathologic analyses. Patient dogs received post-treatment MRI at 1-, 3-, and 6-month intervals with long-term veterinary follow-up. Results The average absorbed dose to treated tissue in R1–R3 was 14.0, 30.9, and 73.2 Gy, respectively, with maximum doses exceeding 1000 Gy. One month after treatment, research dog pathologic analysis revealed no evidence of cortical atrophy and rare foci consistent with chronic infarcts, e.g., < 2-mm diameter. Absorbed doses to masses in P1–P5 were 45.5, 57.6, 58.1, 45.4, and 64.1 Gy while the dose to uninvolved brain tissue was 15.4, 27.6, 19.2, 16.7, and 33.3 G, respectively. Among both research and patient animals, 6 developed acute neurologic deficits following treatment. However, in all surviving dogs, the deficits were transient resolving between 7 and 33 days post-therapy. At 1 month post-therapy, patient animals showed a 24–94% reduction in mass volume with partial response in P1, P3, and P4 at 6 months post-treatment. While P2 initially showed a response, by 5 months, the mass had advanced beyond pre-treatment size, and the dog was euthanized. Conclusion This proof of concept demonstrates the technical feasibility and safety of 90Y-RE in dogs, while preliminary, initial data on the efficacy of 90Y-RE as a potential treatment for brain cancer is encouraging.

scholarly journals Hemophilia gene therapy: ushering in a new treatment paradigm?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 226-233
Author(s):  
Lindsey A. George
Keyword(s):  
Clinical Trial ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Hemophilia A ◽  
Full Potential ◽  
Proof Of Concept ◽  
Aav Vector ◽  
Treatment Paradigm ◽  
Clinical Trial Enrollment ◽  
New Treatment

Abstract After 3 decades of clinical trials, repeated proof-of-concept success has now been demonstrated in hemophilia A and B gene therapy. Current clinical hemophilia gene therapy efforts are largely focused on the use of systemically administered recombinant adeno-associated viral (rAAV) vectors for F8 or F9 gene addition. With multiple ongoing trials, including licensing studies in hemophilia A and B, many are cautiously optimistic that the first AAV vectors will obtain regulatory approval within approximately 1 year. While supported optimism suggests that the goal of gene therapy to alter the paradigm of hemophilia care may soon be realized, a number of outstanding questions have emerged from clinical trial that are in need of answers to harness the full potential of gene therapy for hemophilia patients. This article reviews the use of AAV vector gene addition approaches for hemophilia A and B, focusing specifically on information to review in the process of obtaining informed consent for hemophilia patients prior to clinical trial enrollment or administering a licensed AAV vector.

scholarly journals Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Paolo Cassano ◽  
Cristina Cusin ◽  
David Mischoulon ◽  
Michael R. Hamblin ◽  
Luis De Taboada ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Near Infrared ◽  
Randomized Study ◽  
Proof Of Concept ◽  
Major Depressive ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Sham Treatment ◽  
New Treatment

Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 ± 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm2and a fluence of 84 J/cm2for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17scores decreased from 19.8 ± 4.4 (SD) to 13 ± 5.35 (SD) after treatment (t=7.905;df=3;P=0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.govNCT01538199.

scholarly journals Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

2021 ◽  
Vol 11 ◽  
Author(s):  
Onno Kranenburg ◽  
Kurt van der Speeten ◽  
Ignace de Hingh
Keyword(s):  
Colorectal Cancer ◽  
Treatment Strategies ◽  
Clinical Trial Design ◽  
Peritoneal Metastases ◽  
Proof Of Concept ◽  
Diffusion Weighted Mri ◽  
True Incidence ◽  
Recent Developments ◽  
To Come ◽  
New Treatment

The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.

scholarly journals Bruton Tyrosine Kinase Inhibition and Its Role as an Emerging Treatment in Pemphigus

2021 ◽  
Vol 8 ◽  
Author(s):  
Aikaterini Patsatsi ◽  
Dedee F. Murrell
Keyword(s):  
Tyrosine Kinase ◽  
Pemphigus Vulgaris ◽  
Lymphocytic Leukemia ◽  
Proof Of Concept ◽  
Phase 2 Trial ◽  
Mantle Cell ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor ◽  
New Treatment ◽  
Btk Inhibitors

Bruton Tyrosine Kinase (BTK) has a key role in multiple pathways involved in inflammation and autoimmunity. Therefore, BTK has become a new therapeutic target for a group of hematologic and autoimmune disorders. The pharmaceutical industry has invested in the clinical development of BTK inhibitors during the last decade. Ibrutinib, for example, which was the first BTK inhibitor to be used in clinical trials, has two approved indications, mantle cell lymphoma and chronic lymphocytic leukemia, and remains under evaluation for additional indications. Rillzabrutinib (PRN1008) is a new, highly potent and selective inhibitor of BTK. Early studies performed in canine pemphigus demonstrated effectiveness. A proof-of-concept, multicenter, phase 2 trial has recently showed the efficacy and safety of oral rilzabrutinib in pemphigus vulgaris. In this mini review, we present evidence regarding the mechanisms affected by BTK inhibition and the concept of BTK inhibition as an emerging new treatment in pemphigus.

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