Tell. IJROBP 2004: 60:395

The first reports on hypothyroidism (HT) from our department after thyroid irradiation were reported in the 1960s.. In the following years there have been many studies reporting thyroid dysfunction after both internal and external irradiation of malignant and nonmalignant diseases. Adjuvant risk factors for developing HT after external radiation therapy (RT) to the neck that have been suggested are higher dose, young age , female sex, and pre-RT elevated thyroid-stimulating hormone (TSH) level.. The published incidence of radiation-induced overt HT varies substantially, depending, e.g., on the dose, the duration of patient follow-up , the addition of surgery, the addition of chemotherapy, or the definition of HT.

Tumors of the head-and-neck are one of the most complex sites for RT, because many critical organs and normal tissues that are sensitive to radiation are involved. Monitoring complications of the treatment is therefore essential. The majority of head-and-neck tumors are locoregionally advanced (Stages III and IV) at the time of diagnosis . Subsequent HT after RT of patients with head-and-neck cancer is a well known side effect  but the level of the incidence of long-term HT has not been well established. Tumors in the head-and-neck are primarily a locoregional disease at diagnosis and the incidence of distant metastases is relatively low. Surgery, external beam RT, and brachytherapy, or combinations of these modalities constitute the basis for radical treatment. Despite major efforts for early diagnosis and treatment, a substantial proportion of the tumors can not be controlled and the mortality of head-and-neck cancer has not significantly changed over the last decades.. We previously showed that RT for head-and-neck cancer carries an actuarial risk of 15% for developing overt HT 3 years after treatment.. In the present study, we investigated the long-term incidence of radiation-induced HT in this cohort.To determine the long-term incidence of postirradiation hypothyroidism (HT) in patients with head-and-neck cancer.

Methods and materials

The incidence of overt HT was assessed prospectively in 391 patients with nonthyroid head-and-neck cancer admitted for radiotherapy (RT) consecutively between 1990 and 1996. Eighty-three patients were excluded from the analysis because of known thyroid disease before treatment (n = 27), no RT was given (n = 15), or inadequate follow-up (n = 41). Overt HT was defined as increased thyroid-stimulating hormone (TSH) in combination with decreased fT4/T4 or in combination with initiation of thyroxine replacement therapy.

Results

With a median follow-up of 4.2 years for 308 evaluable patients, the 5- and 10-year Kaplan-Meier actuarial risks of HT were 20% and 27%, respectively. The median time until development of HT was 1.8 years (3 months to 8.1 years). Multivariate analysis showed that patients with bilateral RT to the neck had a higher risk of HT in comparison with unilateral neck RT.. The addition of surgery to RT increased the overall risk of HT; and if surgery involved the thyroid gland, the relative hazard was 4.74. For an elevated pre-RT TSH value, the relative hazard was 1.58.

Conclusion

The incidence of overt HT after locoregional RT for nonthyroid head-and-neck cancer continues to increase with time, even after long-term follow-up.   We recommend life-long TSH testing in these patients.