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

Abstract

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).

Prediction of radiation-induced hypothyroidism using radiomic data analysis does not show superiority over standard normal tissue complication models

“…We included non-radiomic patient characteristics in the study, reported models' quality statistics and validated models. Patients were recruited prospectively in 3 clinics for the study by Nowicka et al with the same endpoint of RIHT [7], however radiomic analysis was included in the protocol at the later stage. In the place of validation against "golden standard", that is not established for prediction of RIHT, we compared our models with those by other authors.…”

“…To avoid bias, laboratory assessment, contouring, outcome assessments, statistical and radiomic analysis were performed by independent researchers. Details of treatment protocol were described previously [7].…”

“…The studied cohort was a subgroup of patients included in previous study on validation of NTCP models for radiation-induced hypothyroidism by Nowicka et al [7], recruited between 01.05.2016 and 31.12.2018 and followed up until 02.2020. In addition to already collected clinical data, for this study we retrieved CT images from radiotherapy planning with thyroid glands retrospectively contoured by two experienced radiation oncologists according to the guidelines for organs at risk (OARs), as described previously.…”

“…Radiation-induced hypothyroidism (RIHT) has been reported in 25-65% of patients and typically develops during the first 2 years from RT completion. Since the symptoms of RIHT are non-specific and insufficient levels of thyroid hormones not only negatively impact patients' quality of life [2], but also mortality [3,4], adequate identification of patients at risk of this effect is of paramount importance [5][6][7].…”

“…Clinical and dosimetric parameters are typically used in normal tissue complication probability (NTCP) models to predict RIHT [1]. Recently, we [7] and others [6] have applied published NTCP models in homogenous cohorts of patients with oropharyngeal cancer (OPC). We concluded that two models based on thyroid mean dose and volume, published by Rønjom et al [8] and by Boomsma et al [9], performed best in terms of accuracy (84 to 87%), highlighting the feasibility of dose-response models to predict RIHT and their potential utility in the clinical setting.…”