Browsing by Subject "brain cancer"

Now showing 1 - 3 of 3

Open Access
A model for optimizing delivery of targeted radionuclide therapies into resection cavity margins for the treatment of primary brain cancers.
(Biomed Phys Eng Express, 2017-06) Raghavan, Raghu; Howell, Roger W; Zalutsky, Michael R
Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67Ga, 77Br, 111In, 125I, 123I, 193mPt, 195mPt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.
Open Access
Microfluidics-Generated Biodegradable Polymeric Microparticles for Controlled Drug Delivery
(2014) Roberts, Emily Remsen Hogan
While drug-loaded biodegradable polymer microparticles have found many therapeutic applications, bulk manufacturing methods produce heterogeneous populations of particles. A more highly controlled manufacturing method may provide the ability improve the microparticle characteristics such as the drug release profile. Microfluidic droplet-makers manipulate liquids on the scale of tens of microns and can produce highly regular and controlled emulsions. However, microfluidic droplet manufacturing is not typically designed for clinical translation and the chemicals used are often not biocompatible.
I developed a two-chip PDMS-based microfluidic device that can manufacture PLGA microparticle loaded with hydrophilic or hydrophobic drugs. I characterized protein-loaded microparticles made using this device and compared them with bulk-generated microparticles. The microfluidics-generated microparticles had similar release curves and encapsulation efficiencies as bulk-generated microparticles but a much narrower size distribution. I generated peanut protein-loaded microparticles with this device and tested them in a mouse model of peanut allergy, improving the particles as the project evolved to have a higher loading level and lower burst release. The microparticles improved the safety and efficacy of an immunotherapy protocol. I also encapsulated hydrophilic and hydrophobic chemotherapeutic drugs for a brain cancer model.
Open Access
Primary brain tumor patients admitted to a US intensive care unit: a descriptive analysis.
(CNS oncology, 2021-09-21) Kang, Jennifer H; Swisher, Christa B; Buckley, Evan D; Herndon, James E; Lipp, Eric S; Kirkpatrick, John P; Desjardins, Annick; Friedman, Henry S; Johnson, Margaret O; Randazzo, Dina M; Ashley, David M; Peters, Katherine B
Purpose: To describe our population of primary brain tumor (PBT) patients, a subgroup of cancer patients whose intensive care unit (ICU) outcomes are understudied. Methods: Retrospective analysis of PBT patients admitted to an ICU between 2013 to 2018 for an unplanned need. Using descriptive analyses, we characterized our population and their outcomes. Results: Fifty-nine PBT patients were analyzed. ICU mortality was 19% (11/59). The most common indication for admission was seizures (n = 16, 27%). Conclusion: Our ICU mortality of PBT patients was comparable to other solid tumor patients and the general ICU population and better than patients with hematological malignancies. Further study of a larger population would inform guidelines for triaging PBT patients who would most benefit from ICU-level care.