Dr. Paula Foster, Scientist/Associate Professor, Medical Biophysics, University of Western Ontario/Robarts Research Institute

Project Title: “Investigating the impact of radiation-induced damage on promoting metastatic tumour growth in the brain”

Project Summary

Brain metastasis occurs in 25-50% of metastatic breast cancer patients. The prospect of being diagnosed with brain metastases is terrifying; the median time from diagnosis with brain metastases to death is between 1 and 6 months, depending on the extent of metastases and how they are managed. Whole brain radiotherapy (WBRT) is standard treatment for breast cancer patients with multiple brain metastases. In this scenario the healthy brain tissue receives significant doses of radiation. Radiotherapy is known to have multiple negative consequences in normal brain including tissue death, cognitive deficits and inflammation.

Inflammation caused by radiotherapy is now known to promote metastasis, cancer cell migration and invasiveness. In this project we will use two mouse models of triple negative breast cancer brain metastasis along with advanced MRI techniques to monitor the impact of WBRT-induced inflammation on the arrest and persistence of metastatic cancer cells in the brain and the development of brain metastases.

It is crucial to understand whether radiotherapy induced inflammation in the healthy brain enhances the development of brain metastases. Our results will provide an understanding of the influence that radiotherapy has on brain tumour development and whether radiotherapy could be improved by the addition of anti-inflammatory agents.

Final Report

Radiotherapy of the whole head is the standard of care for breast cancer patients with multiple brain lesions. While this treatment has been essential in the management of existing tumours, there are also many known negative effects associated with radiation of normal brain.  In this study MRI was used to examine how radiotherapy of normal brain can effect the likelihood of growth of new tumours in an animal model of breast cancer brain metastasis. Imaging results showed that irradiated but otherwise healthy brain had an increased ability to support the growth of cancer. Investigating the impact of radiotherapy on normal brain could have implications in clinical patient management, particularly in patients with brain cancer that is resistant to radiotherapy or pre-exisiting cancer elsewhere in the body.

Publications

Cranial irradiation increases tumor growth in experimental breast cancer brain metastasis
Amanda M. Hamilton, Suzanne M. Wong, Eugene Wong, Paula J. Foster
July 2019
Nature Machine Intelligence