Model-based calculation of thyroid gland normal tissue complication probability in head and neck cancer patients after radiation therapy.

AIM: Primary hypothyroidism is one of the late complications that can occur after radiation therapy for malignant tumors in the head and neck region. The aim of this retrospective study was to show the validity of the Lyman-Kutcher-Burman (LKB) normal tissue complication model for thyroid gland based on clinical results. METHODS: Thyroid function was evaluated by measuring thyroid-stimulating hormone and free thyroxine serum levels before radiation therapy, 3 months after the beginning of radiation therapy, and afterwards at each follow-up visit. Cumulative incidence was calculated using the Kaplan-Meier method. Dose-volume histogram, total dose, fractionation schedule, total duration of the treatment, and other parameters were used for normal tissue complication probability calculation based on the LKB model. The model was evaluated after fitting with the three sets of parameters for grade 2 hypothyroidism: 1) "Emami," where n = 0.22; m = 0.26, and D50 = 80 Gy; 2) "mean dose," where n = 1; m = 0.27, and D50 = 60 Gy; and 3) "Lyman EUD," where n = 0.49; m = 0.24, and D50 = 60 Gy. A value 3.0 Gy was used for α/ß ratio RESULTS: Eighty-three patients treated with volumetric modulated arc therapy for head and neck cancers at the University Hospital Martin, Slovakia, from January 2014 to July 2017, were included in the retrospective study. Median follow-up was 1.2 years. Cumulative incidence of hypothyroidism grade 2 or higher after 12 and 24 months was 9.6 and 22.0%, respectively. Normal tissue complication probability values calculated with mean dose and Lyman EUD parameters showed the best correlation with our clinical findings. CONCLUSION: Empirically based modelling of normal tissue complication probability was valid for our cohort of patients. With carefully chosen parameters, the LKB model can be used for predicting the normal tissue complication probability value.

Long-term alterations of cell population in the adult rat forebrain following the exposure to fractionated doses of ionizing radiation.

We investigated radiation-induced delayed alterations of proliferating population, cells undergoing apoptosis and glial cells housed rat brain neurogenic region. Adult male Wistar rats were investigated 30, 60 or 90 days after whole-body irradiation with fractionated doses of gamma rays (the total dose of 4 Gy). Using immunohistochemistry for detection of cell proliferation marker Ki-67, caspase3 as apoptotic marker and GFAP for mature astrocytes we have been performed quantitative analysis in different forebrain's areas along the SVZ-OB axis, i.e. in the anterior subvetricular zone (SVZa), vertical arm, elbow and horizontal arm. In animals that survived thirty days after radiation treatment initial decrease of the Ki-67-positive cells was seen in regions along the SVZ-OB axis. The highest increase was observed in vertical arm on the 60th day followed by the most striking decline on the 90th day after irradiation. Cells undergoing apoptosis didn't showed expressive increase during entire experiment except of horizontal arm. The most striking changes of GFAP-positive cells were seen 30 and 60 days after irradiation in vertical arm and elbow. Results suggested that radiation response of proliferating cells and astrocytes resides the SVZa may play contributory role in development of more adverse radiation-induced late effects.