A reanalysis of thyroid neoplasms in the Israeli tinea capitis study accounting for dose uncertainties

In the 1940s and 1950s, children in Israel were treated for tinea capitis by irradiation to the scalp to induce epilation. Follow-up studies of these patients and of other radiation- exposed populations show an increased risk of malignant and benign thyroid tumors. Those analyses, however, assume that thyroid dose for individuals is estimated precisely without error. Failure to account for uncertainties in dosimetry may affect standard errors and bias dose-response estimates. For the Israeli tinea capitis study, we discuss sources of uncertainties and adjust dosimetry for uncertainties in the prediction of true dose from X-ray treatment parameters. We also account for missing ages at exposure for patients with multiple X-ray treatments, since only ages at first treatment are known, and for missing data on treatment center, which investigators use to define exposure. Our reanalysis of the dose response for thyroid cancer and benign thyroid tumors indicates that uncertainties in dosimetry have minimal effects on dose-response estimation and for inference on the modifying effects of age at first exposure, time since exposure, and other factors. Since the components of the dose uncertainties we describe are likely to be present in other epidemiological studies of patients treated with radiation, our analysis may provide a model for considering the potential role of these uncertainties.