Program Project Grant
Treatment of Malignant Brain Tumors
Principal Investigator: Mitchel S. Berger MD
Total Project Period: 07/1/07 - 06/30/12
Brain tumors affected more than 17,000 people in the United States during 1998, resulting in more than 13,000 deaths. Although brain tumors are a prominent cause of cancer death in young adults and children, they are most common among middle-aged and older adults, and the incidence in people older than 65 years of age is increasing. Glioblastoma multiforme (GM) and anaplastic astrocytoma (AA)-the most malignant brain tumors with the poorest prognosis-comprise a significant proportion of these tumors.
The overall goal of this program is to integrate advances in technological development of physiologic neuro-imaging and tissue biomarkers in the management of patients with brain tumors and to translate this knowledge to optimize delivery of novel agents into the brain parenchyma.
Project 1: Imaging and Tissue Biomarkers for Improved Management of Patients with Newly Diagnosed Glioblastoma Multiforme
Principal Investigator: Sarah Nelson PhD
With the advent of new metabolic and physiologic imaging techniques that can provide information on the biological behavior of tumors, the objective of this project is to study the potential for connecting imaging trial of CED in patients with newly diagnosed GBM.
Project 2: Integrated imaging and tissue biomarkers in glioblastoma multiforme post therapy
Principal Investigator: Susan Chang MD
Project Summary: Increase in contrast enhancement on standard MRI is almost universal in patients who have been treated for GBM. In the majority of cases this is due to tumor progression; however, treatment-related MR imaging changes can confound interpretation of the scans. This is especially true following focal therapy such as CED of agents into the brain parenchyma. Repeated tissue sampling when increased contrast enhancement develops is limited by risks to the patient and the histological effects of prior therapy. Therefore, non-invasive determinants of the biological behavior of these imaging changes are needed. Project 2 is evaluating the utility of non-invasive physiologic and metabolic parameters in predicting the biological behavior of GBM following therapy. Prospective imaging studies will be performed in conjunction with a Phase I clinical protocol of CED of a novel therapeutic compound —nanoliposomal irinotecan— to assess the imaging effects of this therapy.
Project 3: Imaging to optimize convection-enhanced delivery
Principal Investigator: Krystof Bankiewicz MD, PhD
Clinical trials evaluating the delivery of agents intraparenchymally by using CED has been studied in several phase I trials and phase II trials are ongoing. CED is a promising method of delivery of therapeutic concentrations of drug to the brain while limiting systemic exposure, thereby limiting general side effects. A major barrier to the implementation of CED in clinical practice has been the inability to visualize the tumor and the agent during the procedure to assess the directionality, volume, and distribution of the agent in the brain. Another challenge is the current limited understanding of the differences between the composition of tumor tissue and normal tissue and its effect on the distribution of agents delivered via CED. The aims of this study are to investigate MRI techniques to determine the infusion parameters athat are necessary to optimize the delivery of agent to the tumor. Image-based convection modeling and infusion parameters for the distribution of therapeutic liposomes such as nanoliposomal irinotecan will be assessed in canines with spontaneous brain tumors.