Radiation Pneumonitis and Esophagitis in Thoracic Irradiation

Without regard to normal tissue complications, most tumors could likely be eradicated by irradiation through escalating the dose. However, normal tissue complications limit our ability to administer the dose necessary for tumor control. Tumor control probability (TCP) for a given tumor is represented by a sigmoid curve in which an increase in dose results in greater tumor cell kill. Likewise, the normal tissue complication probability (NTCP) is represented by a second sigmoid curve sitting to the right of the TCP curve (Figure 1). The relationship between these two sigmoid curves is called the therapeutic ratio (see Figure 1). Ideally, the TCP and NTCP curves are separated so that a tumoricidal dose can be delivered without concern for toxicity. A clinical example is irradiating the para-aortic lymphatics in patients with resected stage I seminomas, in which tumoricidal dose (25 Gy) is less than the TD_5/5 for adjacent normal tissues. On the other hand, epithelial malignancies, such as carcinomas, require doses between 45 and 50 Gy for subclinical disease, and 65 and 80 Gy or higher doses for gross disease, which are beyond tolerance for most organs. Potential means of modifying the therapeutic ratio include radiation sensitizers that can shift the TCP curve to the left, and protectors that can shift the NTCP curve to the right. Examples of sensitizers include chemotherapy, oxygen, and hypoxic cell sensitizers. Examples of radiation-sparing approaches include amifostine and conformai or intensity modulated radiation therapy (IMRT) (see Figure 1). This review describes treatment-related pneumonitis and esophagitis; parameters for predicting these complications, their prevention, and management.