[Prospective evaluation of radiation-induced thyroid disorders after breast and supraclavicular irradiation].

Purpose: The thyroid is an endocrine gland playing a major role in metabolism and development by the secretion of T4 and T3 thyroid hormones. Due to its anatomical position, it is often included in the target volume for the irradiation of certain tumours and thus receives significant doses (10 to 80Gy). The treatment of breast cancer requires in most cases a breast irradiation associated or not with a lymph node irradiation. The aim of our study was to investigate prospectively the frequency of thyroid disorders in patients with breast cancer treated by radiation, with or without irradiation of the supra- and subclavicular lymph nodes.

Material And Methods: This prospective multicentre study (institut Godinot, institut de cancérologie Strasbourg Europe and institut de cancérologie de Lorraine) concerned adult patients with non-metastatic breast carcinoma treated by adjuvant irradiation. They were included in a non-randomized way between February 2013 and June 2015 and divided into two groups according to treatment: (i) breast radiotherapy associated with irradiation of the supra- and subclavicular lymph nodes (group 1), or (ii) breast irradiation alone (group 2). The dose - volume histogram of the thyroid was systematically edited by the physics department. Each patient had a consultation with an endocrinologist at the beginning of the treatment and was monitored by blood analyses including TSH, T4L, antithyroglobulin and antiperoxidase antibodies every 6 months until the 60th month after the end of radiotherapy. Data were described by numbers and percentages for qualitative variables; by means, medians, standard deviation and ranges for quantitative variables. Statistical associations were tested by Chi, Fisher's, Student's, or analysis of variance tests depending on the conditions of application. Survival analyses were performed by log rank tests and Cox models.

Results: This study initially included 500 patients, 245 in group 1 and 252 in group 2 (three patients were later excluded for false inclusion). Thyroid abnormalities occurred in 76 patients, representing an incidence of 15.3%. The mean time of the first occurrence of thyroid disorders was 24.3 months. It was more frequent in group 1 with a prevalence of 19.2% against 11.5% in group 2 (P=0.01745). A maximal radiation dose delivered to the thyroid gland greater than 20Gy (odds ratio [OR]: 1.82; P=0.018) or 30Gy (OR: 1.89; P=0.013) was significantly associated with a higher incidence of thyroid disorders, as was a mean dose greater than 30Gy (OR: 5.69; P=0.049). A percentage of thyroid volume receiving 30Gy (V30) greater than 50% (P=0.006) or greater than 62.5% (P=0.021) was significantly associated with an increased incidence of thyroid disorder and more precisely, hypothyroidism (P=0.0007). In multivariate analysis, no factor associated with the occurrence of thyroid disorder was identified. However, in the subgroup analysis concerning group 1 (receiving supraclavicular irradiation), a maximal radiation dose greater than 30Gy appeared to be a risk factor for the occurrence of thyroid disorders (P=0.040).

Conclusion: Thyroid disorder, and in particular hypothyroidism, may be a late side effect of locoregional breast radiotherapy. Patients receiving this treatment should have a biological monitoring of thyroid function.