Quantitative Imaging and Biofluid Biomarkers Predictive of Neurocognitive Toxicity from Brain Irradiation (PI: Chung/Wefel)
This project, funded by NASA, will provide comprehensive data on structural, physiological and functional imaging changes related to clinical neurocognitive changes in patients exposed to photon and proton brain. The findings from this proposal will accelerate identification of potential non-invasive biomarkers of later neurocognitive decline that can be translated to prospective investigations of astronauts. These biomarkers may also serve as promising surrogates for future trials of countermeasures aimed at neurocognitive preservation following radiation exposure to the brain. Using longitudinal multidimensional assessments of cognition, multimodal neuroimaging, and blood-based biomarkers, we will investigate the temporal onset of imaging and biofluid biomarker changes following brain radiation exposure relative to neurocognitive changes. We will also explore spatial correlations between radiation dose, brain volume and anatomical brain subregions with spatial and temporal patterns of imaging and the associated neurocognitive changes.
Predicting Neurocognitive Decline in Patients with Breast Cancer (PI: Wefel)
Women with breast cancer who receive chemotherapy are at significantly increased risk for neurocognitive decline, frequently called “chemobrain”, which reduces quality of life and extends disease-related disability. This project will identify neuroimaging biomarkers of chemotherapy-related neurocognitive decline and develop methods to help predict which women are most vulnerable. Using longitudinal multidimensional assessments of neurocognitive function, a multimodal neuroimaging approach and patient genotyping we will determine the incidence, nature and course of neurocognitive changes associated with chemotherapy, and identify genetic and neuroimaging biomarkers predictive of chemotherapy-related neurocognitive decline.
Brain and neurocognitive effects of immune checkpoint inhibitor therapy in patients with melanoma (PI: Wefel/McQuade)
Immune checkpoint inhibitor (ICI) therapies have been approved in melanoma and many other malignancies based on significant improvements in patient survival. Using longitudinal multidimensional assessments of neurocognitive function, multimodal neuroimaging, immune system surveillance, neuronal auto-antibody monitoring and patient genotyping, we will determine the effects of ICI therapy on neurocognitive function, impact on brain structure and function and potential biological correlates of these effects. We will link neurocognitive outcomes to multimodal brain imaging signatures using advanced brain connectomic analyses and immune biomarkers associated with and potentially predictive of neurocognitive toxicity.
Promoting Brain Health and Maximizing Neurocognitive Function Through Precision Medicine
Clinical and translational work in the Wefel Laboratory seeks to increase our understanding of risk and protective factors associated with the development of neurotoxicity, brain resilience and personalization of cancer care with the goal of optimizing brain health, neurocognitive function and quality of life.
Neurocognitive Outcomes in Multi-site Clinical Trials
The Wefel Laboratory develops and leads neurocognitive outcomes on numerous multinational cooperative group, multi-site investigator initiated and industry sponsored clinical trials to help improve the standard of care for cancer patients.