*2.1. Study Population*

We retrospectively evaluated 71 patients with locally advanced or metastatic thyroid carcinoma treated with at least one TKI at our institution between November 2004 and October 2020.

The data collected included age at diagnosis, gender, histological findings, stage at diagnosis, numbers of anatomical site involved, information on treatment with TKIs (type of TKI, time-lapse between diagnosis and treatment start, duration of treatment, reason for discontinuation), tumor response, and data on last follow-up/death.

Patients without available complete biochemical data and those receiving statin treatment for cholesterol control with a serum total cholesterol <180 mg/dl were excluded from our study.

The final population was made of 42 patients (54.8% female). The mean age at the time of TKI treatment was 67.5 ± 13.8 years (median 69 years, 30–96 years). All patients had metastatic disease. In detail, the number of anatomical sites involved by metastatic disease was one in five patients (11.9%), two in 10 patients (23.8%), three in 18 patients (42.8%), four in four patients (9.5%), and five in five patients (11.9%). Histological diagnosis was

differentiated thyroid cancer (DTC) in 28 patients (66.7%), poorly differentiated thyroid cancer (PDTC) in nine patients (21.4%), and medullary thyroid cancer (MTC) in five (11.9%).

Time-lapse between cancer diagnosis and TKI treatment start ranged from 0.06 to 15.4 years (mean 5.4 ± 4.4, median 5.4 years) and ranged from 0 to 14.2 years (mean 3.43 ± 3.5, median 2.8 years) between the appearance of metastases and TKI treatment beginning.

The TKI used as first-line therapy was: lenvatinib in 16 patients (38.1%), sorafenib in 18 patients (42.8%), vandetanib in four patients (9.5%), and motesanib in four patients (9.5%). Ten out of the 42 patients (23.8%) were treated with other TKI.

The median body mass index (BMI) at baseline was 26.5 kg/m2 (mean 27.2 ± 6.0 range 18.1–47.0 kg/m2). The performance status at baseline, according to the Eastern Cooperative Oncology Group (ECOG) scale, was 0 in 36 patients (85.7%), one in four patients (9.5%), and two in two patients (4.8%).

All data are summarized in Table 1.

**Table 1.** Baseline clinical-pathological features in the whole population and according to histological diagnosis.


<sup>1</sup> ECOG PS was evaluated in 36 patients.
