Lung cancer is by far the most common thoracic malignancy worldwide. Radiation in combination with chemotherapy is currently the standard treatment for locally advanced stages, sometimes in combination with targeted agents or immunotherapy. Treatment however is often associated with high rates of radiation-induced adverse effects. Strategies to reduce the likelihood of radiation-induced tissue damage are through adherence to dose-volume constraints or the use of radioprotectors. Using a dedicated precision image-guided small animal irradiation device, we already have shown the feasibility of longitudinal CT-based monitoring of targeted upper right lung irradiation and the possibility to monitor the effects of anti-fibrotic drugs. The overall objective of this project is to understand the biology of radiosensitivity and how to exploit this for therapeutic gain by investigating what thoracic organ sub-regions are most radiosensitive using dose painting approaches, how polyphenols as caffeic acid phenethyl ester (CAPE) protect these sub-regions by elevating oxidative stress to promote anti-inflammatory and immunomodulatory effects.
This project will provide insights in the differential radiosensitivity of thoracic organ sub-regions in order to identify the areas to be spared as much as possible or the areas that can withstand a higher dose. This will enable future biology-guided radiotherapy as opposed to current clinical practice. Additionally, the protective effects of CAPE and the molecular mechanisms supporting these effects will be elucidated for the different organ sub-regions.