Side Effects of Radiation

Side effects of radiation therapy depend on the site of treatment and radiation dose. Acute and long-term side effects as well as tumor response may also be enhanced by concurrent use of radiosensitizing chemotherapy. Prior exposure to highly sensitizing chemotherapy may increase radiation toxicity and radiation recall effects are well described with subsequent use of these agents. The most highly sensitizing agents are doxorubicin and dactinomycin; these are generally contraindicated during radiation therapy. Other mild sensitizers include cisplatin, topotecan, and irinotecan, which are usually safe to give during radiotherapy. Little work has been done to attempt to exploit these synergistic relationships in neuroblas-toma. Research in this area would be appropriate, especially for patients with unfavorable predictors of local control such as high-risk patients with gross residual disease or MYCN amplification.

Abdominal therapy is often associated with nausea and anti-emetics are recommended. Diarrhea and cramping are less common acute effects. When large amounts of bone marrow are treated, blood counts may drop and these should be monitored during therapy.

Long-term sequelae of radiation are important factors to consider when designing treatment for young children and counseling parents (see Chap. 18). The highest risk of growth abnormalities is in very young children (Paulino et al. 2002). Although the anticipated effect on growth for most patients treated with fractionated doses of 21 Gy and less is negligible, when multiple vertebral bodies or growth centers of long bones are treated, a percentage of patients may experience impaired growth

(Roebuck 1999). Radiation doses >25 Gy are expected to cause bone growth arrest, and in young children, may cause significant abnormalities in skeletal development (Roebuck 1999). Growth centers of bones should be shielded whenever possible. It is also important to irradiate vertebral bodies symmetrically in order to prevent radiation-induced scoliosis.

Organ dysfunction may result from radiation exposure if tolerance doses are exceeded (see Chap. 18). Standard whole-organ tolerance doses are as follows: heart 15 Gy; lungs 15 Gy; kidneys 18 Gy; liver 30 Gy; bowel 30 Gy; ovaries 10 Gy; and testes 2 Gy. These doses are only general guidelines. Young children who are heavily pretreated with chemotherapy or who have had surgery may experience organ dysfunction at lower doses. Neurocognitive dysfunction and endocrine abnormalities as a result of brain irradiation are dependent upon the child's age, radiation dose, and volume of brain exposed. These issues are important to consider when treating skull and orbital lesions. Cataracts are common side effects of radiotherapy and thus doses to the lens should be minimized when treating the orbit. Most children will not have permanent alopecia after doses of 21 Gy or less, but a small percentage may have permanent thinning. Doses exceeding 21 Gy do pose the risk of permanent epilation in the radiotherapy portal.

Reliable risk estimates of second malignancies following radiotherapy for neuroblastoma are not available. One may extrapolate from a large body of literature in pediatric Hodgkin's disease survivors and assume that children who are cured after receiving radiation for neuroblastoma will develop an excess number of cancers 10-20 years later (Wolden et al. 1998). Common radiation-related malignancies include breast cancer, sarcomas, lymphomas, and other solid tumors. Data from Hodgkin's disease survivors also indicate that patients receiving thoracic radiotherapy likely have a higher risk of cardiac disease as adults; thus, long-term survivors of neuroblastoma will require lifelong screening for late sequelae of radiation therapy.

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