*1.1. The Epidemiology and Pathophysiology of Thyroid Cancer*

Thyroid cancer is the most common endocrine malignancy and the most commonly diagnosed cancer in people aged 15 to 29 years, and its incidence has continuously increased with 567,233 cases and approximately 41,000 deaths worldwide in 2018 [1,2]. The incidence rate of thyroid cancer is approximately three-fold higher in females than in males but the mortality rate is higher in males than in females [3–5]. In addition, a recent study confirmed that the recurrence rate of well-differentiated thyroid cancer (DTC) is higher in men compared with women. Due to the COVID-19 epidemic, delayed investigations and treatment may further lead to increased morbidity and mortality of thyroid cancer [6]. The various clinical outcomes of thyroid cancer are considered to be related to patient age, sex, tumor type, distant metastases, and invasion of adjacent tissue and lymph nodes [7].

**Citation:** Cao, Y.; Zhong, X.; Diao, W.; Mu, J.; Cheng, Y.; Jia, Z. Radiomics in Differentiated Thyroid Cancer and Nodules: Explorations, Application, and Limitations. *Cancers* **2021**, *13*, 2436. https://doi.org/ 10.3390/cancers13102436

Academic Editors: Fabio Medas, Pier Francesco Alesina and Dietmar Georg

Received: 27 April 2021 Accepted: 16 May 2021 Published: 18 May 2021

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Thyroid tumors are divided into follicular-derived and neuroendocrine C-cell-derived cancers. Greater than 95% of thyroid cancer is DTC, which is follicular-derived thyroid cancer and can be further divided into well-DTC and poorly-DTC (more progressive than well DTC) [8]. Well DTC is a composite of papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and Hurthle cell thyroid cancer. Of these, papillary thyroid cancer is the most common thyroid cancer with the best prognosis, whereas follicular, Hurthle cell, poorly-differentiated, and C-cell derived thyroid cancers are relatively uncommon but have a high metastatic risk to the lung and bone [7]. Moreover, the increasing diagnostic rate of papillary thyroid cancers is regarded as the leading reason for increasing thyroid cancer incidence, in contrast, the incidence rate of other subtypes has been stable in the past 30 years [9].

Despite the generally stable course, favorable prognosis, and low mortality of thyroid cancer, the rate of local recurrence and distant metastases of DTC approaches 10% to 30%, which depends on the length of follow-up [10,11]. A previous study found that DTC can recur even up to 20 years after the initial diagnosis [12], therefore, a long-term follow-up of patients with DTC is essential [13]. Notably, several studies have investigated the factors related to DTC relapse. However, heterogenicity exists among these studies, and the results indicated the associations between early-onset and recurrence [14]. More specifically, the earlier DTC occurred, the more likely it was to recur. Therefore, timely diagnosis of DTC recurrence is critical.
