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Since the discovery of radium by the Curies, radiotherapy has offered incalculable benefits for cancer patients. Radiation is used in a wide variety of tumors for both curative and palliative indications. Advances in treatment delivery, diagnostic imaging, and treatment planning systems have improved tumor control and, in many cases, reduced toxicity.

Neoplasms of the central nervous system (CNS) are a pathologically diverse group of benign and malignant tumors for which a variety of management strategies, including observation, surgery, radiation therapy, and/or chemotherapy, are employed. Shown in Table 1 are the usual radiation doses used to treat primary and metastatic brain and spinal cord tumors, which span a broad range of total doses and doses per fraction. Regardless of the type of CNS tumor treated, what usually limits the dose of radiation that can be utilized, and therefore what typically determines the local control and cure rate of that tumor, are the tolerance doses of the adjacent or underlying normal tissues in and around the CNS. This chapter will outline the biologic and clinical principles of CNS radiation tolerance and the management of radiation-induced CNS injury.

During the treatment of neoplastic diseases, unavoidable toxicities to normal cells may be produced. The mucosal lining of the upper respiratory and gastrointestinal tracts is a prime target for radiotherapy-related toxicity due to its rapid cell turnover rate. The oral cavity is highly sensitive to direct and indirect toxic effects of radiation therapy (RT); this is attributable to multiple factors such as a diverse and complex microflora, trauma to oral tissues during normal oropharyngeal function, and the high mucosal cell turnover rates.

Radiation of the head and neck (H&N) can irreversibly injure oral mucosa, vasculature, muscle, and bone. This can result in xerostomia, dental caries, trismus, soft tissue necrosis, and osteoradionecrosis (ORN). Severe oral toxicities can compromise delivery of optimal radiation-therapy protocols. For example, dose reduction or treatment schedule modifications may be necessary to allow for resolution of oral lesions. In cases of severe oral morbidity, the patient may no longer be able to continue cancer therapy; treatment is then usually discontinued. These disruptions in dosing due to oral complications can thus directly affect patient survivorship.

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 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.

Breast cancer is probably among the most common diagnoses found on daily patient treatment lists in the majority of Radiation Oncology departments. This makes understanding what type of toxicity to expect from radiation for breast cancer and its management of prime importance, since it affects significant numbers of patients daily. Radiation for breast cancer is predominantly to the intact breast for early stage disease with post-mastectomy radiation comprising a smaller proportion of radiation delivered for this diagnosis. The acute toxicity that develops as well as the type of late sequelae that can occur in each of these treatment scenarios is similar. During intact breast or chest-wall radiation, the organs commonly at risk for radiation injuries that manifest as acute and late toxicity include skin, chest wall, lung, and heart. When regional nodal irradiation is added, the shoulder, brachial plexus, and axillary lymphatics are also at risk for potential injury.

In general, radiation for breast cancer post-lumpectomy and post-mastectomy is very well tolerated by most patients and does not significantly impair their daily activities. Acute side effects of treatment are generally common in occurrence, self-limiting, and resolve within 4–6 weeks after the treatment is completed. Skin reactions and the constitutional symptom of fatigue dominate the early toxicity profile. Late toxicity or permanent sequelae can be divided into two groups: the more common effects on the appearance of the breast such as persistent breast edema, hyperpigmentation, and fibrosis and those that are very uncommon but can have significant health consequences as a result of permanent injury to other organs such as brachial plexopathy, radiation pneumonitis, cardiac morbidity, or secondary malignancy.

The upper gastrointestinal tract lies within the radiation field for most thoracic and abdominal cancers. Toxicity to the upper gastrointestinal tract often limits the radiation doses that can be given. Radiation therapy causes both acute and late effects. The acute effects of radiation include mucosal denudation, while late effects consist of fibrotic changes leading to decreased mobility and ischemia. Multifield and conformal radiation therapy, as well as patient positioning techniques, reduce the volume of normal tissue exposed to radiation and can decrease the potential toxicity. However, the treatment of radiation toxicity is mainly supportive. The increasing use of concurrent chemotherapy and radiation therapy has required enhanced awareness of potential effects and better methods to decrease toxicity, as this combination of treatments is associated with a higher rate of gastrointestinal toxicity. The first part of this chapter will review the pathologic changes of acute and chronic radiation effects, and the second part will discuss clinical effects, including radiation dosing and management of toxicities.

Radiation is used with or without chemotherapy to treat malignancies in the pelvis that occur in gynecologic, genitourinary, and gastrointestinal organs. One of the most sensitive organs in the pelvis can be the small bowel which is discussed in a separate chapter (upper GI). Radiation can cause functional effects on other organs including the rectum, anus, bone and bone marrow, bladder, urethra, ureter, vulva, vagina, uterus, ovaries, testicles, and sexual organs. This chapter will discuss the pathologic and clinical effects that can result during treatment and shortly thereafter. Long-term sequelae can be seen at variable intervals following radiation. Prevention and management issues will be discussed.

Irradiation of bone kills the cells that are responsible for bone maintenance and remodeling that renders the irradiated bone brittle and prone to injury. Though the incidence of bony injury has become increasingly uncommon with the use of megavoltage radiation and improved planning and radiation delivery techniques, even when careful attention is paid to radiation tolerance, bony injury can occur. Post-irradiation bony injuries include mandibular osteoradionecrosis (MORN), pelvic insufficiency fracture, hip fracture, fracture of long bones, rib fracture, and pediatric growth abnormalities. In this chapter, we will review the incidence, risk factors, techniques for risk reduction, and management of each of these bony radiation injuries.

Radiation therapy has a direct effect on the skin. The effects of radiation can be dramatic. Providers are challenged to classify and minimize both acute and late effects and to manage the complications of treatment. Strategies to manage radiation skin reactions are ongoing topics of research and have led to a variety of clinical management models. Managing skin reactions can help alleviate distress caused by these symptoms and improve quality-of-life during and following radiation therapy. In this chapter, we will describe our institutional approach to skin management during radiation therapy.