Abstract
Background:Recent trends suggest that physicians will diagnose thousands of children in the United States with a brain or central nervous system tumor in 2020. Malignant brain tumors are difficult to treat, with low life expectancy rates in children and adults. Convection-enhanced delivery (CED) shows promise for the treatment of brain tumors, yet remains in clinical trials despite being developed more than 20 years ago. To advance CED to standard of care status and help improve survival rates, this study group developed a quantitative computer simulation model to determine and optimize therapy distribution in brain tumors based on the catheter infusion locations for CED.Methods:The simulations resulted in the identification of four infusion reference locations, which were used to conduct an optimization study to identify the optimal locations for CED. Patient-specific T1-weighted images and diffusion-weighted images provided information regarding tumor shape and size and the approximate rate at which therapy distributes at spatial locations within the tumor. Using the images, the researchers in this study developed a model which allowed the calculation of therapy distribution within the tumor while considering its permeability, porosity, and interstitial fluid pressure characteristics. We divided the tumor into regions and calculated distribution for four infusion locations per region. Using the location from each region with the highest volume distribution allowed our study group to conduct the response surface optimization.Results:Twelve optimal locations emerged from the optimization with volume percentage distributions ranging from 7.92% to 9.09%, compared to 2.87% to 6.32% coverage for non-optimal locations. This optimization method improved distribution from 27.80% to 45.95%, which may improve therapeutic value.Conclusions:Catheter placement appears to influence volume therapy distribution percentages. The selection of the highest percentages per region may provide optimal therapy for the entire tumor region.
Highlights
Surgery, radiation therapy, and chemotherapy are the standard of care for brain tumors[1]
Volume distribution percentages from region one design points ranged from 3.01 % to 9.02%, region two ranged from 4.19%
Response surfaces in region one suggest that maximum therapy distribution percentage is approximately 9% (Figure 1)
Summary
Radiation therapy, and chemotherapy are the standard of care for brain tumors[1]. Using results from DOE and response surface, optimization determines the ideal locations for the maximum therapy distribution. To advance CED to standard of care status and help improve survival rates, this study group developed a quantitative computer simulation model to determine and optimize therapy distribution in brain tumors based on the catheter infusion locations for CED. Using the location from each region with the highest volume distribution allowed our study group to conduct the response surface optimization. Results: Twelve optimal locations emerged from the optimization with volume percentage distributions ranging from 7.92% to 9.09%, compared to 2.87% to 6.32% coverage for non-optimal locations This optimization method improved distribution from 27.80% to 45.95%, which may improve therapeutic value
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