Birgitta Versluijs

26 Pulmonary complications of radiotherapy Pulmonary complications of radiotherapy Radiation exposure of the lungs occurs during chest radiation for mediastinal disease or lung metastasis, Total Body Irradiation (TBI) in HCT setting, or by scattering from abdominal irradiation or spinal cord irradiation. Radiation induced lung injury takes place in 3 phases over weeks to months. The im- mediate effect of irradiation is oxidative damage to DNA, resulting in cell injury and apoptosis of pneumocytes. This stimulates the recruitment of inflammatory cells, cy- tokine production and loss of normal barrier function, leading to a local inflammatory response. During the repair process there is an influx of cells, mainly activated macro- phages with proinflammatory activity, contributing to tissue remodelling and the deve- lopment of fibrosis. During inflammation and repair, local oedema and vascular changes lead to hypoxia, again inducing cell injury and inflammation. This ongoing non-healing tissue response leads to chronic radiation injury (see Figure 2). 8 FIGURE 2. Early responses to pulmonary radiation include an increase in Reactive Oxygen (ROS) and Nitrogen (RNS) Species, cytokine induction and an increase in hypoxia, edema and a drop in lung perfusion. A delayed response, consisting of a second wave of cytokine induction and hypoxia, along with macrophage infiltration in the lung occurs at 6-8 weeks. Late injury is often observed in the form of fibrosis at 24-32 weeks. (Reproduced with permis- sion from P. Graves 8 ). 2 Cytokines RT IL-1 α TNF α TGF- β 1 IL-6 Cytokines Radiation effects ROS/RNS DNA damage Apoptosis Hypoxia Lung Density Edema Physiological effects Physiological effects Perfusion Physiological effects Perfusion Hypoxia Lung Density Edema Physiological effects Fibrosis Breathing difficulty Lung injury Increase Decrease growth factors chemokines VEGF IL-1 α TNF α TGF- β 1 IL-6 Leukocytes Infiltrating cells 1d 3d 6-8w 24 weeks