Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk.

BACKGROUND: Many case reports in the literature associate cranial radiation therapy with the development of brain tumors. Quantitation of the risk of second brain tumors after irradiation in childhood is available, but it is seldom reported for those treated by radiation therapy as adults.
METHODS: A retrospective review was made of 367 patient records registered at the Princess Margaret Hospital with a diagnosis of pituitary adenoma from 1972 to 1986. Three hundred five patients treated with megavoltage radiation therapy form the basis of this report. Second brain tumors were identified and the patient case histories described. The risk of second brain tumor after irradiation was estimated by calculating the observed/expected (O/E) ratio, age- and sex-adjusted to the Ontario population.
RESULTS: Of the 305 patients in this study, 4 had glioma of the brain. All gliomas arose within the previous radiation field(s), with a latency of 8-15 years after radiation therapy. Additional treatment was compromised by the location of the glioma and the moderately high doses of radiation received previously; all four patients died of their gliomas. Our cohort of patients had a relative risk of malignant brain tumor 16 times greater than that of the general population in Ontario (P < 0.001; 95% confidence interval, 4.4-41). The cumulative actuarial risk of secondary glioma after radiation therapy was 1.7% at 10 years and 2.7% at 15 years.
CONCLUSIONS: There was a clinically significant increased risk of malignant brain tumor developing after radiation therapy for pituitary adenoma. Because there is no reported association between pituitary adenomas and gliomas of brain, this excess risk is attributed to irradiation. Before advising radiation therapy for pituitary adenoma, the risk:benefit ratio, including the risk of secondary brain tumors, should be carefully considered.