Tumors of the Brain and Nervous System after Radiotherapy in Childhood

Abstract

We investigated the relation between radiotherapy in childhood for tinea capitis and the later development of tumors of the brain and nervous system among 10,834 patients treated between 1948 and 1960 in Israel. Benign and malignant tumors were identified from the pathology records of all Israeli hospitals and from Israeli national cancer and death registries. Doses of radiation to the neural tissue were retrospectively estimated for each patient (mean, 1.5 Gy). Sixty neural tumors developed in the patients exposed as children, and the 30-year cumulative risk (+/- SE) was 0.8 +/- 0.2 percent. The incidence of tumors was 1.8 per 10,000 persons per year. The estimated relative risk as compared with that for 10,834 matched general-population controls and 5392 siblings who had not been irradiated was 6.9 (95 percent confidence interval, 4.1 to 11.6) for all tumors and 8.4 (confidence interval, 4.8 to 14.8) when the analysis was restricted to neural tumors of the head and neck. Increased risks were apparent for meningiomas (relative risk, 9.5; n = 19), gliomas (relative risk, 2.6; n = 7), nerve-sheath tumors (relative risk, 18.8; n = 25), and other neural tumors (relative risk, 3.4; n = 9). A strong dose--response relation was found, with the relative risk approaching 20 after estimated doses of approximately 2.5 Gy. Our study confirms that radiation doses on the order of 1 to 2 Gy can significantly increase the risk of neural tumors.

Radiation epidemiology and recent paediatric computed tomography studies

“…Radiation-induced brain cancer is an example of the substantial variance with other studies of high-quality dosimetry and epidemiological rigor. The effect of age at CT exposure for radiation-induced brain tumour was the opposite of what has been observed in studies of Japanese atomic bomb survivors, Israeli children treated with radiation for ringworm of the scalp, and survivors of childhood cancer (Ron et al, 1988;Neglia et al, 2006;UNSCEAR, 2008). The risk following CT exposure in the UK increased with age at exposure, which is the opposite pattern seen in all previous studies where children under 5 years of age at exposure have the highest risk, and teenagers and young adults have minimal risk, if any.…”

Malignant glioma: genetics and biology of a grave matter

“…The observation that gliomas are part of the tumor spectrum seen in patients with Li-Fraumeni syndrome (Malkin et al 1990) serves to solidify a causal role for p53 inactivation in gliomagenesis. Because brain radiation during childhood is the only definitive risk factor for the development of gliomas (Ron et al 1988;Neglia et al 1991), it is possible that this link could reflect deactivation of the p53-dependent DNA damage checkpoint response so as to permit cell survival following radiation exposure. Although p53 status has been examined in several high-grade gliomas following radiation (Brat et al 1999), an examination of p53 mutations has not been conducted in lowgrade astrocytomas.…”

Low Dose Radiation Epidemiology: What Can It Tell Us?

“…Studies of the atomic bomb survivors and Israeli tinea capitis cohort provide information suggesting that the risk of developing a glioma among these exposed adult populations compared to unexposed populations is approximately doubled (5). A recent analysis of the atomic bomb survivor cohort suggests that not only high but also moderate doses of radiation (,1 Sv) elevate the risk of nervous system tumors.…”