In this article, the principles regarding hypoxia as a therapeutic target, including the oxygen enhancement ratio, the relationship between the OER and linear energy transfer, and the role of reoxygenation, are discussed. When ionizing radiation interacts with tissue, it causes excitations and ionisations, causing molecules to fragment and produce free radicals. The most prevalent radiation-induced free radical is the hydroxyl radical because it is formed from the ionization of water, which makes up about 80% of cells. Free radicals are highly reactive, short-lived species. The oxygen effect refers to the increased sensitivity of cells to ionizing radiation-induced damage as oxygen concentration increases. Maximal radiosensitivity occurs around 40 mmHg, half maximum at around 3–7 mmHg. Hypoxia arises via different mechanisms and is often categorized as chronic/diffusion-limited or acute/transient/intermittent/perfusion-limited.

Cancer is characterized by uncontrolled proliferation, with tissues bypassing standard cellular homeostatic mechanisms and cell growth exceeding typical physiology requirements. As a result of these processes, cell proliferation exhausts the oxygen supply. There are many ways to assess tumor hypoxia; however, oxygen electrodes are the most direct method. There is evidence that is giving hypoxia-targeting treatment with radiotherapy improves cancer patient outcomes. A meta-analysis of 86 randomized trials involving 10,108 patients showed that giving a hypoxia-targeted treatment with radiotherapy increased locoregional control and overall survival. The UK BCON trial showed that giving carbogen and nicotinamide with radiotherapy improved overall survival by 13% in patients with muscle-invasive bladder cancer.