We have investigated the dose-response relationships for the incidence of salivary gland tumors in a cohort of 2945 individuals who were irradiated as children between 1939-1962. Most of the patients were treated to reduce the size of their tonsils and adenoids. The mean dose to the salivary glands (+/-SD) was 4.2 +/- 1.7 Gy. Eighty-nine patients developed 91 salivary gland neoplasms; 22 had single malignancies, 64 had single benign neoplasms, 2 developed two separate benign neoplasms, and 1 developed a single neoplasm but did not have surgery. The majority (81 of 89) of the patients developed neoplasms in the parotid glands. Mucoepidermoid carcinomas were the most common malignancy and mixed (pleomorphic) adenomas were the most common benign neoplasm. For all salivary gland tumors, the excess relative risk per gray (ERR/Gy) was 0.82; however, the 95% confidence interval was wide (0.04, upper bound indeterminate). The trend was determined principally by benign tumors, as there was no dose-response relationship for salivary gland cancer, although there were too few cases to draw definitive conclusions. Overall, our study provides support for an association between salivary gland tumors and radiation exposure. Although most salivary gland tumors are benign and are usually readily detected, they may cause morbidity, and people who have been irradiated in the area should be monitored for their occurrence.

It has been hard to establish with certainty that radiation exposure is a risk factor for developing hyperparathyroidism. In part this is because many cases of hyperparathyroidism remain asymptomatic and escape clinical detection. We present results from a study of 2555 subjects who received external beam radiotherapy to the head and neck area for benign conditions before their 16th birthday between 1939 and 1962. The average length of follow-up was 36.6 yr. There were 36 confirmed cases of hyperparathyroidism. Based on a relative risk model, the excess relative risk increased significantly by 0.11/centigray; however, the confidence interval was wide (95% confidence interval, 0.0-17.2). The hyperparathyroidism rates and dose-response relationships were not affected by gender or age at first radiation treatment. The demonstration of a dose-response relationship within an irradiated cohort supports an association between radiation exposure and hyperparathyroidism and suggests that the calcium levels of individuals irradiated to the head and neck area should be monitored.

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To determine the incidence of benign thyroid nodules and the risk factors for their recurrence after surgical removal, we followed 511 patients for 1 to 40.6 years (median, 11.2) after surgery for benign thyroid nodules arising after local irradiation for unrelated benign diseases in childhood. Recurrent thyroid nodules developed in 100 patients (19.5 percent). The risk of recurrence correlated inversely with the amount of thyroid tissue removed. Women had a higher recurrence rate than men (28.4 percent vs. 10.3 percent; P less than 0.05). Among the 299 patients who had been treated with thyroid hormone at the discretion of their physicians to suppress thyroid-stimulating hormone, 25 had recurrences (8.4 percent), as compared with 72 of 201 patients who did not receive thyroid hormone (35.8 percent) (hazard ratio taking into account the extent of surgery and the patient's sex, 2.5; 95 percent confidence interval, 1.5 to 4.1). Histologic analysis of the 73 tissue samples from patients with recurrences showed that 14 samples (19.2 percent) were malignant. Thyroid hormone treatment had no effect on the rate of thyroid cancer. We conclude that radiation-associated benign thyroid nodules have a high recurrence rate, similar to that reported among nonirradiated patients with benign thyroid nodules. We also conclude that treatment with thyroid hormone decreases the risk of benign recurrences, particularly in women, but not the risk of cancer.

Childhood radiation exposure has been associated with an increased risk for developing several neoplasms, particularly benign and malignant thyroid tumors, but little is known about the risk of developing acoustic neuromas. The aim of this study was to confirm whether there is a risk for acoustic neuromas and, if so, to determine its magnitude and duration. We investigated the time trend and dose-response relationships for acoustic neuroma incidence in a cohort of 3,112 individuals who were irradiated as children between 1939 and 1962. Most of the patients were treated to reduce the size of their tonsils and adenoids and received substantial radiation exposure to the cerebellopontine angle, the site of acoustic neuromas. Forty-three patients developed benign acoustic neuromas, forty of them surgically resected, far in excess of what might be expected from data derived from brain tumor registries. The mean dose (+/-SD) to the cerebellopontine angle was 4.6 +/- 1.9 Gy. The relative risk per Gy was 1.14 (95% confidence interval 1.0-1.3). The earliest case occurred 20.4 years after exposure and the latest 55 years after exposure (mean 38.3 +/- 10.1 years). Our study provides support for an association between acoustic neuromas and childhood radiation exposure. Although acoustic neuromas are usually benign and often asymptomatic, many cause significant morbidity. Following childhood radiation exposure, they appear after a long latency and continue to occur many decades afterward. Any symptoms of an acoustic neuroma in a patient with a history of radiation to the head and neck area should be investigated carefully, and the threshold for employing imaging should be lowered.