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16.1 INTRODUCTION

The purpose of clinical radiotherapy for cancer is to control tumor growth, the likelihood of which depends on the dose of radiation delivered. However, this dose is limited by the damage caused to surrounding normal tissues and the consequent risk of complications. Whether a certain risk of developing complications is regarded as acceptable depends both on the function of the tissue(s) and the severity of the damage involved. This risk must be compared to the probability of benefit (ie, eradicating the tumor) to determine the overall gain from the treatment. This gain can be estimated for an average group of patients, but it may vary for individual patients, depending on the particular characteristics of their tumors and the normal tissues at risk. The balance between the probabilities for tumor control and normal tissue complications gives a measure of the therapeutic ratio of a treatment (see Sec. 16.5.8). The therapeutic ratio can be improved either by increasing the effective radiation dose delivered to the tumor relative to that given to surrounding normal tissues, or by increasing the biologic response of the tumor relative to that of the surrounding normal tissues.

External beam radiation therapy is usually delivered in relatively small daily doses over the course of several weeks. The empiric development of such multifractionated treatments, which involve giving fractions of approximately 1.8 to 3 Gy daily for 5-8 weeks, is an example of exploiting biologic factors to improve the therapeutic ratio. More recently, technical improvements in the physical aspects of radiation therapy have allowed an increase in the effective dose of radiation to deep-seated tumors without increasing the dose to normal tissues. Some of these sophisticated treatment planning methods include 3-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), and stereotactic radiosurgery (SRS) / stereotactic body radiation therapy (SBRT) (Fig. 16–1). These new methods limit the volume of normal tissues irradiated to high doses and allow escalated doses to the tumor. Alternatively, low-dose-rate and high-dose-rate brachytherapy can deliver a highly localized dose by placing radioactive sources directly within or adjacent to tumors (see Fig. 16–2). Although these newer treatment strategies improve the efficiency of radiation therapy delivery, biologic factors may also provide opportunities to improve the therapeutic ratio. Biologic factors that may influence the outcome of radiation therapy and their exploitation to improve therapy are discussed in this chapter.

FIGURE 16–1

The evolution of modern radiotherapy planning techniques from conventional radiotherapy (RT) to 3-dimensional conformal radiotherapy (3D-CRT), to IMRT, and, finally, to image-guided radiotherapy (IGRT). For many tumor sites, IMRT and IGRT improve the therapeutic ratio by allowing for increased radiotherapy dose to tumor and decreased dose to normal tissues. IMRT, intensity-modulated radiation therapy; IGRT, image-guided radiation therapy.

FIGURE 16–2

Images of a prostate gland treated with high-dose rate radiotherapy using catheters ...

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