The Legacy Program

The Legacy program is a unique collaboration between a team of neuro-oncologists at Washington University School of Medicine and our patients, to use post-mortem brains with tumors in situ to investigate mechanisms of therapy resistance. Taking a three-tiered approach, we first use experimental Diffusion Basis Spectral Imaging to better define the extent of disease at the time of death. Our preliminary results suggest that clinically available anatomical MRI underestimates the extent of brain tumor dissemination. As local control with surgery and radiation therapy are the bedrock of successful brain tumor treatment, underestimation of the extent of disease may be a significant contributor to treatment failure. Second, we are using next generation sequencing of multiple post-mortem imaging directed “biopsies” to reconstruct the subclonal heterogeneity of the recurrent tumors. Parallel evaluation of the diagnostic specimens allows us to examine the sufficiency of current biopsy approaches for generating specimens used in molecular diagnostics and to evaluate the extent of tumor evolution with treatment. Finally, we are using histology, sequencing, and imaging results to create an atlas of intratumoral heterogeneity as it relates to the surrounding brain. We expect that regional differences in brain structures, hypoxia, immune infiltration, and other local and regional heterogeneity might inform multi-component mapping to optimally deliver radiation therapy and other spatially focused interventions such as ultrasound. Together, we believe that these studies can be translated as new treatment designs that anticipate resistance mechanisms and prevent recurrence of brain tumors.

Since establishing this program as a collaboration between physicians, scientists, and families, the emotional impact of the program and its name has become evident. We are in contact with donor families regularly and have held one retreat to which all families were invited to listen to research updates and to engage in open discussion with the investigative team. Families report that The Legacy Program provides ongoing hope that some good can still come from the suffering of their child, their parent, or their sibling. The intensity of that hope is evident each time we talk with families, providing tremendous motivation to continue this research.