Radiographic Response Assessment Strategies for Early-Phase Brain Trials in Complex Tumor Types and Drug
Benjamin M Ellingson1,2,3, Victor A Levin4,5, Timothy F Cloughesy6,7
1UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
Summary
New methods improve brain tumor response assessment for complex cases. A tiered strategy using digital tools and control systems theory offers better evaluation of subtle therapeutic effects in challenging gliomas.
Area of Science:
- Neuro-oncology
- Radiology
- Computational Biology
Background:
- Current brain tumor response assessment methods are insufficient for complex or mixed-grade gliomas.
- Existing methods fail to capture subtle or subclinical therapeutic responses.
- There is a critical need for advanced drug development strategies in neuro-oncology.
Purpose of the Study:
- To develop a novel, tiered strategy for assessing therapeutic response in challenging brain tumors.
- To enhance the evaluation of subtle treatment effects and subclinical responses.
- To provide a framework for analyzing complex treatment schemes, including combination and sequential therapies.
Main Methods:
- Utilized digital "flipbooks" for rapid identification of subtle changes in complex tumor imaging.
- Applied modified Levin criteria to quantify visual changes and correlate with tumor volume.
- Introduced a control systems theory approach, employing proportional, integral, and derivative (PID) controllers to model therapeutic response.
Main Results:
- Demonstrated the utility of digital flipbooks in detecting subtle tumor changes.
- Established a quantitative link between visual assessment and tumor volume using modified Levin criteria.
- Proposed a PID controller model for quantifying therapeutic response based on volume dynamics.
Conclusions:
- The proposed tiered strategy enhances confidence in identifying therapeutic effects in difficult brain tumors.
- Novel methods provide a more nuanced understanding of treatment efficacy beyond simple response categories.
- Control systems theory offers a powerful framework for evaluating complex treatment responses in neuro-oncology.
