Radiation therapy to treat cancer is highly effective, but the doses that we can safely deliver are limited by the risk of toxicity to nearby organs. Despite using uniform clinical guidelines to deliver similar radiation doses to patients, there is a high degree of individual patient variability regarding radiation toxicity. Some of the observed variation in toxicity is likely secondary to the underlying health of the normal organs prior to radiation. We know that patients with lung disease, like emphysema, or cardiovascular disease, like atherosclerosis, have a higher risk of experiencing radiation toxicity to those respective organs. Patients with sub-clinical disease, or damage to organs ...

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Radiation therapy to treat cancer is highly effective, but the doses that we can safely deliver are limited by the risk of toxicity to nearby organs. Despite using uniform clinical guidelines to deliver similar radiation doses to patients, there is a high degree of individual patient variability regarding radiation toxicity. Some of the observed variation in toxicity is likely secondary to the underlying health of the normal organs prior to radiation. We know that patients with lung disease, like emphysema, or cardiovascular disease, like atherosclerosis, have a higher risk of experiencing radiation toxicity to those respective organs. Patients with sub-clinical disease, or damage to organs that has not yet reached a level that results in a medical diagnosis, are also at increased risk of radiation toxicity. Critically, we lack adequate markers of sub-clinical disease that could be used to identify individuals at higher risk of radiation toxicity. In this proposal, we aim to investigate a novel sub-clinical disease biomarker of radiation toxicity, known as clonal hematopoiesis (CH) mutations. CH mutations represent abnormal populations of cells in the blood that travel throughout the organs of the body and promote tissue damage through inflammation, including to the heart and lungs. We will test the hypothesis that CH mutations detected before radiation therapy are associated with radiation toxicity, specifically heart and lung toxicity. Our proposal will primarily focus on patients with cancer impacting the thorax, such as lung cancer. Our project has important implications for patient care as approximately 50% of patients with cancer undergo radiation therapy and approximately 30% of patients with cancer have CH mutations. The overall goal of our proposal is to establish a novel biomarker that can be used to identify patients at risk of radiation toxicity so that we can personalize and improve cancer care.

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