CADD-30. A TREATMENT SIMULATOR FOR BRAIN CHEMOTHERAPY. (5th November 2018)

• Record Type: Journal Article
• Authors: Broaddus, William; Raghavan, Raghu
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi281
• Page End: vi281
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.1170
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Dosing of systemically administered chemotherapies for brain tumors is generally designed without the benefit of quantitative estimates of spatial drug distribution in the brain, even though the integrity of the BBB varies spatially, and over time. METHODS: We have designed a "Drug Entry Simulator" which displays a patient's contrast enhanced MRI, a display of serum concentrations of drug over time, and an overlay of drug concentrations over time superimposed on the MRI. In addition, the area under the concentration time curve can be assessed for any region of interest. The mathematical modeling utilizes pharmacokinetic models with patient specific information on brain anatomy, BBB permeability incorporated via DCE studies and scaling hypotheses for different therapeutic agents. RESULTS: We have made and reported[1] preliminary assessments using results from clinical trials employing microdialysis or biopsies to determine the concentrations of agents within brain tumors. Simulations on data obtained from the individual patients shows 1) significant variability in spatial distribution, 2) poor penetration of the margins and 3) poor residence time of the agent in tissue. Studies of efflux of both small and large molecule agents infused directly into the brain have shown excellent agreement with direct measurements of their concentrations. CONCLUSIONS: Pretreatment estimates of drug entry, maximal concentration, time over effective concentration, and area under the concentration curve can help in planning systemic administration of therapeutic agents in patients with brain tumors. Future studies will address calibration issues with DCE, improvement of MR image acquisition, improved incorporation of characteristics of the drugs used, and continuing validation of the modeling approach. [1] Modeling the Entry of Systemically Administered Antineoplastic Agents into Brain Tumors, Brain Adjacent to Tumor, and Normal Brain. Stuart A. Grossman, Arati Desai, Marshall Pitz, Jaishri Blakeley, Jana Portnow, Martin Brady, Raghu Raghavan. Journal of Clinical Oncology, SNO Proceedings, 2008.