**1. Introduction**

Successive trials conducted by the National Wilms Tumor Study (NWTS) have led to major improvements in the overall survival of children afflicted with Wilms tumor (WT). These trials have also been successful in reducing the indications for and dosages of radiation therapy (RT) and doxorubicin in the majority of children with WT. However, late toxicity of treatment continues to be a concern with radiation therapy (RT) as a major contributor [1]. Organs in the abdomen such as the liver, pancreas, spleen and bowel may be included in the flank RT field. For whole abdominal RT (WART), in addition to these organs, the remaining kidney, uterus and the ovaries are included in the RT field, and the testicles and breast tissue receiving scatter radiation. The heart, lungs, thyroid gland and breast tissue are at risk for late effects when whole lung irradiation (WLI) is utilized.

The bone, muscles and soft tissues are also at risk for growth disturbances when the abdomen and/or chest are irradiated. Finally, there is a potential risk of secondary malignant neoplasms in all of these organs exposed to any dose of RT.

Long-term follow up of the NWTS cohort showed that the standardized mortality ratio (SMR) was 24.3 for the first 5 years, 12.6 for the next 5 years, and remained greater than 3.0 thereafter. Secondary malignant neoplasms and congestive heart failure (CHF) were the commonest causes of long-term mortality [2]. Likewise, in the Childhood Cancer Survival Study (CCSS), the overall survival rate at 25 years after diagnosis of WT was 93.9%. The overall SMR was 4.9, and SMR for survivors who received abdominal and chest RT without doxorubicin was 6.1, and with doxorubicin the SMR was 12.3. Also, the cumulative incidence of chronic health conditions at 25 years after diagnosis was 65.4% and that of severe conditions (grades 3 to 5) was 24.2%. WT survivors had twice the rate of grades 1 to 4 chronic health conditions (Hazard Ratio [HR] 2.0) and 4.7 times higher rates of severe chronic health conditions (grades 3 or 4) (HR 4.7) than the sibling comparison group [3].

Children with WT are typically young, as the median age at initial presentation is between 3 to 4 years; hence, any reduction in RT dose and volume may have an impact on lowering treatment complications. RT dose reduction from 40 to 10 Gy in Stage III FH and the omission of WLI in Stage IV FH WT patients with isolated pulmonary metastases, favorable biology and complete response to chemotherapy are some of the strategies that have been used in the NWTS and Children's Oncology Group (COG) to minimize RT late effects [4, 5]. The use of more modern techniques of RT delivery such as intensity modulated radiation therapy (IMRT) and proton therapy can likewise potentially reduce RT complications. This chapter will examine the acute and late RT toxicities observed in Wilms tumor patients as well as some of the strategies that have been employed to minimize long-term complications.
