*2.2. Kinase Inhibitors*

Kinase inhibitors (KIs) were recently applied in the treatment of progressive RAIrefractory DTC with distant metastases, and they offered a favorable outcome [23]. The latest guidelines recommend systemic treatment for patients with progressive RAI-refractory disease and greater tumor burden [1,16,24].

In contrast, in cases of BM, several studies have reported a worse response to treatment and a shorter progression-free survival (PFS) rate among patients treated with sorafenib and sunitinib [25–28]. In a retrospective study to evaluate KI therapies for DMs from DTC, bone and pleural lesions were the most refractory to therapies [28]. A prospective study showed that the absence of BM independently predicted superior PFS and OS in patients with RAI-refractory DTC who were treated with sorafenib [29]. The BMs that had received external beam radiotherapy (EBRT) before the onset of KI therapy were more susceptible, whereas non-irradiated BMs showed progression despite the response to KI that was shown in non-BM lesions [25]. The progression of BM while on KI may occur despite the sustained benefit of KI at other metastatic sites. These findings indicate that KI therapies alone play a limited role in the treatment of BMs from DTC. The findings also suggest that, for patients with DTC-BM, a multimodal approach should be combined with local and systemic therapies, including KI therapy, which should be used for reducing systemic tumor burden.
