Radiation-Induced Hypothyroidism in Patients with Oropharyngeal Cancer Treated with IMRT: Independent and External Validation of Five Normal Tissue Complication Probability Models

Cancers (Basel). 2020 Sep 22;12(9):2716. doi: 10.3390/cancers12092716.


We aimed to externally validate five normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RIHT) in a prospectively recruited cohort of 108 patients with oropharyngeal cancer (OPC). NTCP scores were calculated using original published formulas. Plasma thyrotropin (TSH) level was additionally assessed in the short-term after RT. After a median of 28 months of follow-up, thirty one (28.7%) patients developed RIHT. Thyroid mean dose and thyroid volume were significant predictors of RIHT: odds ratio equal to 1.11 (95% CI 1.03-1.19) for mean thyroid dose and 0.87 (95%CI 0.81-0.93) for thyroid volume in univariate analyses. Two of the evaluated NTCP models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance with accuracies of 0.87 (95%CI 0.79-0.93) and 0.84 (95%CI: 0.76-0.91), respectively. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse, overestimating the risk of RIHT in this patient cohort. A short-term TSH level change relative to baseline was not indicative of RIHT development in the follow-up (OR 0.96, 95%CI: 0.65-1.42, p = 0.825). In conclusion, the models by Rønjom et al. and by Boomsma et al. demonstrated external validity and feasibility for long-term prediction of RIHT in survivors of OPC treated with Intensity-Modulated Radiation Therapy (IMRT).

Keywords: NTCP; dose–response relationship; head and neck neoplasms; hypothyroidism; oropharyngeal cancer; patient reported outcome measures; probability; radiation; radiation injuries.