A review on the radiobiological modeling of radiation-induced hypothyroidism after radiation therapy of head-and-neck cancers, breast cancer, and Hodgkin’s lymphoma is presented. The current review is based on data relating to dose-volume constrains and normal tissue complication probability (NTCP) as a function of either radiobiological or (pre)treatment-clinical parameters. Also, these data were explored in order to provide more helpful criteria for radiobiological optimization of treatment plans involving thyroid gland as a critical normal organ.
 Mirinezhad SK, Somi MH, Jangjoo AG, et al. Survival rate and prognostic factors of esophageal cancer in East Azerbaijan province, North-west of Iran. Asian Pac J Cancer Prev. 2012;13(7):3451-3454.
 Mirinezhad SK, Somi MH, Seyednezhad F, et al: Influence of chemoradio therapeutic strategies and factors on the five yearssurvival of patients with esophageal cancer. Journal of Isfahan Medical School 2014;32(291):982-990.
 Mohammadzadeh M, Faramarzi E, Mahdavi R, et al. Effect of conjugated linoleic acid supplementation on inflammatory factors and matrix metalloproteinase enzymes in rectal cancer patients undergoing chemoradiotherapy. Integr Cancer Ther. 2013;12(6):496-502.
 Mesbahi A, Dadgar H, Ghareh-Aghaji N, Mohammadzadeh M. A Monte Carlo approach to lung dose calculation in small fields used in intensity modulated radiation therapy and stereotactic body radiation therapy. J Cancer Res Ther. 2014;10(4):896-902.
 Mesbahi A, Dadgar H. Dose calculations accuracy of TiGRT treatment planning system for small IMRT beamlets in heterogeneous lung phantom. Int J Radiat Res. 2015;13(4):345-354.
 Mesbahi A, Akcay D, Tekcan IV, Alikus ZA. The impact of residual geometric inaccuracies on normal organ doses in image guided-radiation therapy of prostate cancer using on-board kilovoltage Cone-Beam computed tomography. Iran J Med Phys. 2017;14(2):104-113.
 Mohammadzadeh M, Mesbahi A. MC estimation of out-of-field organ doses from scattered photons, photoneutrons, and capture gamma rays in prostate radiation therapy. Nuclear Technology and Radiation Protection. 2010;25:78-84.
 Boyle P, Levin B: World Cancer Report 2008. International Agency for Research on Cancer.
 Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43-66.
 Wang SA, Rahemtullah A, Faquin WC, et al. Hodgkin’s lymphoma of the thyroid: a clinicopathologic study of five cases and review of the literature. Mod Pathol. 2005;18(12):1577-1584.
 Alterio D, Jereczek-Fossa BA, Franchi B, et al. Thyroid disorders in patients treated with radiotherapy for head-and-neck cancer: a retrospective analysis of seventy-three patients. Int J Radiat Oncol Biol Phys. 2007;67(1):144-150.
 Bethge W, Guggenberger D, Bamberg M, et al. Thyroid toxicity of treatment for Hodgkin’s disease. Ann Hematol. 2000;79(3):114-118.
 Reinertsen KV, Cvancarova M, Wist E, et al. Thyroid function in women after multimodal treatment for breast cancer stage II/III: comparison with controls from a population sample. Int J Radiat Oncol Biol Phys. 2009;75(3):764-770.
 Hancock SL, McDougall IR, Constine LS. Thyroid abnormalities after therapeutic external radiation. Int J Radiat Oncol Biol Phys. 1995;31(5):1165-1170.
 Jereczek-Fossa BA, Alterio D, Jassem J, et al. Radiotherapy-induced thyroid disorders. Cancer Treat Rev. 2004;30(4):369-384.
 Bhandare N, Kennedy L, Malyapa RS, et al. Primary and central hypothyroidism after radiotherapy for head-and-neck tumors. Int J Radiat Oncol Biol Phys. 2007;68(4):1131-1139.
 Kuten A, Lubochitski R, Fishman G, et al. Postradiotherapy hypothyroidism: radiation dose response and chemotherapeutic radiosensitization at less than 40 Gy. J Surg Oncol. 1996;61(4):281-283.
 Boomsma MJ, Bijl HP, Langendijk JA. Radiation-induced hypothyroidism in head and neck cancer patients: a systematic review. Radiother Oncol. 2011;99(1):1-5.
 Mercado G, Adelstein DJ, Saxton JP, et al. Hypothyroidism: a frequent event after radiotherapy and after radiotherapy with chemotherapy for patients with head and neck carcinoma. Cancer. 2001;92(11):2892-2897.
 Tell R, Lundell G, Nilsson B, et al. Long-term incidence of hypothyroidism after radiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004;60(2):395-400.
 Akyurek S, Babaoglu I, Kose K, Gokce SC. Thyroid Dysfunction Following Supraclavicular Irradiation in the Management of Carcinoma of the Breast. In J Hemat Oncol. 2014;24(2):139-144.
 Kikawa Y, Kosaka Y, Hashimoto K, et al. Prevalence of hypothyroidism among patients with breast cancer treated with radiation to the supraclavicular field: a single-centre survey. ESMO Open 2017;2:e000161.
 Smith GL, Smith BD, Giordano SH, et al. Risk of hypothyroidism in older breast cancer patients treated with radiation. Cancer. 2008;112(6):1371-1379.
 Fuks Z, Glatstein E, Marsa GW, et al. Long-term effects on external radiation on the pituitary and thyroid glands. Cancer. 1976;37(2Suppl):1152-1161.
 Bakhshandeh M, Hashemi B, Mahdavi SR, et al. Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy. Int J Radiat Oncol Biol Phys. 2013;85(2):514-521.
 V.D’Avino, Conson M, Palma G, et al. Normal Tissue Complication Probability Models for Radiation-Induced Hypothyroidism in Hodgkin Lymphoma Survivors. Int J Radiat Oncol Biol Phys. 2016;96(2):E638.
 Goldberg RC, Chaikoff IL,Lindsay S, Feller DD. Histopathological changes induced in the normal thyroid and other tissues of the rat by internal radiation with various doses of radioactive iodine. Endocrinology. 1950;46(1):72-90.
 Nishiyama K, Tanaka E, Tarui Y, et al. A prospective analysis of subacute thyroid dysfunction after neck irradiation. Int J Radiat Oncol Biol Phys. 1996;34(2):439-444.
 Bakhshandeh M, Hashemi B, Mahdavi SR, et al. Evaluation of thyroid disorders during head-and-neck radiotherapy by using functional analysis and ultrasonography. Int J Radiat Oncol Biol Phys. 2012;83(1):198-203.
 Carr RF, LiVolsi VA. Morphologic changes in the thyroid after irradiation for Hodgkin’s and non-Hodgkin’s lymphoma. Cancer. 1989;64(4):825-829.
 Lo Galbo AM, Kuik DJ, Lips P, et al. A prospective longitudinal study on endocrine dysfunction following treatment of laryngeal or hypopharyngeal carcinoma. Oral Oncol. 2013;49(9):950-955.
 Hancock SL, Cox RS, McDougall IR. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med. 1991;325(9):599-605.
 Norris AA, Amdur RJ, Morris CG, Mendenhall WM. Hypothyroidism when the thyroid is included only in the low neck field during head and neck radiotherapy. Am J Clin Oncol. 2006;29(5):442-445.
 Brix TH, Kyvik KO, Hegedus L. A population-based study of chronic autoimmune hypothyroidism in Danish twins. J Clin Endocrinol Metab. 2000;85(2):536-539.
 Brix TH, Hansen PS, Kyvik KO, Hegedus L. Cigarette smoking and risk of clinically overt thyroid disease: a population-based twin case-control study. Arch Intern Med. 2000;160(5):661-666.
 Brix TH, Hegedus L. Twin studies as a model for exploring the aetiology of autoimmune thyroid disease. Clin Endocrinol (Oxf). 2012;76(4):457-464.
 Laurberg P, Cerqueira C, Ovesen L, et al. Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab. 2010;24(1):13-27.
 Kumpulainen EJ, Hirvikoski PP, Virtaniemi JA, et al. Hypothyroidism after radiotherapy for laryngeal cancer. Radiother Oncol. 2000;57(1):97-101.
 Bonato C, Severino RF, Elnecave RH. Reduced thyroid volume and hypothyroidism in survivors of childhood cancer treated with radiotherapy. J Pediatr Endocrinol Metab. 2008;21(10):943-949.
 Garcia-Serra A, Amdur RJ, Morris CG, et al. Thyroid function should be monitored following radiotherapy to the low neck. Am J Clin Oncol. 2005;28(3):255-258.
 Grande C. Hypothyroidism following radiotherapy for head and neck cancer: multivariate analysis of risk factors. Radiother Oncol. 1992;25(1):31-36.
 Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2000;85(9):3227-3232.
 Akgun Z, Atasoy BM, Ozen Z, et al. V30 as a predictor for radiation-induced hypothyroidism: a dosimetric analysis in patients who received radiotherapy to the neck. Radiat Oncol. 2014;9:104.
 Cella L, Conson M, Caterino M, et al. Thyroid V30 predicts radiation-induced hypothyroidism in patients treated with sequential chemo-radiotherapy for Hodgkin’s lymphoma. Int J Radiat Oncol Biol Phys. 2012;82(5):1802-1808.
 Chyan A, Chen J, Shugard E, et al. Dosimetric predictors of hypothyroidism in oropharyngeal cancer patients treated with intensity-modulated radiation therapy. Radiat Oncol. 2014;9:269.
 Fujiwara M, Kamikonya N, Odawara S, et al. The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases. J Radiat Res. 2015;56(3):577-582.
 Sachdev S, Refaat T, Bacchus ID, et al. Thyroid V50 Highly Predictive of Hypothyroidism in Head-and-Neck Cancer Patients Treated With Intensity-modulated Radiotherapy (IMRT). Am J Clin Oncol. 2017;40(4):413-417.
 Zhai RP, Kong FF, Du CR, et al. Radiation-induced hypothyroidism after IMRT for nasopharyngeal carcinoma: Clinical and dosimetric predictors in a prospective cohort study. Oral Oncol. 2017;68:44-49.
 Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76:S10-S19.
 Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21(1):109-122.
 Boomsma MJ, Bijl HP, Christianen ME, et al. A prospective cohort study on radiation-induced hypothyroidism: development of an NTCP model. Int J Radiat Oncol Biol Phys. 2012;84:e351-e356.
 Kim ES, Yeo SG. Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage glottic cancer: A dosimetrical analysis. Oncol Lett. 2014;7(6):1987-1991.
 Tsougos I, Mavroidis P, Rajala J, et al. Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy. Phys Med Biol. 2005;50(15):3535-3554.
 Burman C, Kutcher GJ, Emami B, Goitein M. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys. 1991;21(1):123-135.
 Emami B. Tolerance of Normal Tissue to Therapeutic Radiation. Rep Radiother Oncol. 2013;1(1):123-127.
 Cella L, Liuzzi R, Conson M, et al. Development of multivariate NTCP models for radiation-induced hypothyroidism: a comparative analysis. Radiation Oncology. 2012;7:224.
 Ronjom MF, Brink C, Bentzen SM, et al. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: normal tissue complication probability modeling with latent time correction. Radiother Oncol. 2013;109(2):317-322.
 Ronjom MF, Brink C, Lorenzen EL, et al. Variation of normal tissue complication probability (NTCP) estimates of radiation-induced hypothyroidism in relation to changes in delineation of the thyroid gland. Acta Oncol. 2015;54(8):1188-1194.
 Johansen S, Reinertsen KV, Knutstad K, et al. Dose distribution in the thyroid gland following radiation therapy of breast cancer-a retrospective study. Radiat Oncol. 2011;6:68.
 Tunio MA, Al AM, Bayoumi Y, et al. Is thyroid gland an organ at risk in breast cancer patients treated with locoregional radiotherapy? Results of a pilot study. J Cancer Res Ther. 2015;11(4):684-689.
 Sommat K, Ong WS, Hussain A, et al. Thyroid V40 Predicts Primary Hypothyroidism After Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2017;98(3):574-580.
 Kim MY, Yu T, Wu HG. Dose-volumetric parameters for predicting hypothyroidism after radiotherapy for head and neck cancer. Jpn J Clin Oncol. 2014;44(3):331-337.
 Jackson A, Kutcher GJ, Yorke ED. Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation. Med Phys. 1993;20(3):613-625.
 Niemierko A, Goitein M. Modeling of normal tissue response to radiation: the critical volume model. Int J Radiat Oncol Biol Phys. 1993;25(1):135-145.
 Yorke ED, Kutcher GJ, Jackson A, Ling CC. Probability of radiation-induced complications in normal tissues with parallel architecture under conditions of uniform whole or partial organ irradiation. Radiother Oncol. 1993;26(3):226-237.
 Lo Galbo AM, de BR, Kuik DJ, et al. The prevalence of hypothyroidism after treatment for laryngeal and hypopharyngeal carcinomas: are autoantibodies of influence? Acta Otolaryngol. 2007;127(3):312-317.
 Vogelius IR, Bentzen SM, Maraldo MV, et al. Risk factors for radiation-induced hypothyroidism: a literature-based meta-analysis. Cancer. 2011;117(23):5250-5260.
 Diaz R, Jaboin JJ, Morales-Paliza M, et al. Hypothyroidism as a consequence of intensity-modulated radiotherapy with concurrent taxane-based chemotherapy for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010;77(2):468-476.
 Wu YH, Wang HM, Chen HH, et al. Hypothyroidism after radiotherapy for nasopharyngeal cancer patients. Int J Radiat Oncol Biol Phys. 2010;76(4):1133-1139.
 Lin Z, Wu VW, Lin J, et al. A longitudinal study on the radiation-induced thyroid gland changes after external beam radiotherapy of nasopharyngeal carcinoma. Thyroid. 2011;21(1):19-23.
 Srikantia N, Rishi KS, Janaki MG, et al. How common is hypothyroidism after external radiotherapy to neck in head and neck cancer patients? Indian J Med Paediatr Oncol. 2011;32(3):143-148.
 Siala W, Mnejja W, Abid M, et al. Thyroid toxicity after radiotherapy of nasopharyngeal carcinoma. Annales d’Endocrinologie. 2011;72(1):19-23.
 Lin Z, Wang X, Xie W, et al. Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients. J Med Imaging Radiat Oncol. 2013;57(6):713-718.
 Lin Z, Chen L, Fang Y, et al. Longitudinal study on the correlations of thyroid antibody and thyroid hormone levels after radiotherapy in patients with nasopha-ryngeal carcinoma with radiation-induced hypothyroidism. Head Neck. 2014;36(2):171-175.
 Murthy V, Narang K, Ghosh-Laskar S, at al. Hypothyroidism after 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for head and neck cancers: Prospective data from 2 randomized con-trolled trials. Head Neck. 2014;36(11):1573-1580.
 Lauro C, Macy ME, Zeitler P, et al. The relationship between thyroid dose and diagnosis of primary hypothyroidism in pediatric brain tumor patients receiving craniospinal irradiation. J Pediatr Endocrinol Metab. 2014;27(3-4):299-303.
 Bernat L, Hrusak D. Hypothyroidism after radiotherapy of head and neck cancer. J Craniomaxillofac Surg. 2014;42(4):356-361.
 Lee V, Chan SY, Choi CW, et al. Dosimetric Predictors of Hypothyroidism After Radical Intensity-modulated Radiation Therapy for Non-metastatic Nasopharyngeal Carcinoma. Clin Oncol. 2016;28(8):e52-e60.