Mechanisms of normal tissue response

Abstract

Radiation therapy (RT) has been used for decades to treat a wide spectrum of cancers and remains an important tool for both definitive and palliative cancer treatment. Since high doses of irradiation are often required to halt cancer growth and promote tumor cell death, the surrounding normal tissues and organs often impose dose-limiting constraints. Irreparable normal tissue damage can result, leading to persistent toxicity for patients. This chapter focuses on the mechanisms of normal tissue response from RT in four frequently irradiated organs: brain, spinal cord, lung and gastrointestinal tract. A common theme among radiation-induced toxicities is a heightened pro-inflammatory response and inability of these normal tissues to recover to their original states, as vascular changes, fibrosis, and necrosis cause irreparable damage. Understanding the mechanisms of normal tissue response associated with these major toxicities and dose-limiting organs may allow for opportunities to reduce toxicity and improve patients’ quality of life by combining more sophisticated treatment delivery technology, such as intensity modulated RT, and therapeutic mitigators that interrupt the altered biological responses.