*2.1. Radioiodine Therapy*

Radioactive iodine (RAI) therapy is the first-line treatment in patients with DTC and RAI-avid metastases [1]. However, RAI is ineffective for larger metastases, although it can extirpate small lesions [15]. RAI refractoriness in DTC metastases has a negative effect on prognosis [7,16].

In treating DTC-BM, RAI therapy is effective for patients with RAI-avid lesions [17], and such patients have a better prognosis than patients with non-RAI-avid lesions [11]. A recent retrospective study reported that RAI therapy in combination with one or more local or systemic therapies was associated with a better prognosis compared with RAI therapy alone [18]. However, this therapy was less effective for BM than for metastases in other organs. It was reported that patients with lung metastases had higher remission rates (50% to 74%) than those with BM (10% to 17%) [4,19]. Moreover, more than 20% of BMs do not show any RAI uptake [4,20].

Patients with small BMs that are undetectable on ordinary image inspections but that are detected on 131I diagnostic scans have a better prognosis than patients with large and symptomatic BMs [21]. Generally, large BMs are refractory to 131I and cause the occurrence or impending occurrence of SREs. Therapy is insufficient for multiple BMs; other treatment approaches are required [2,21]. RAI therapy may be contraindicated in patients with large BMs in the cranium or spine. This is because the enlargement of the tumor lesions can be induced by increased thyroid-stimulating hormone (TSH) levels, following either the administration of recombinant human TSH or hormone withdrawal, which can lead to compressive symptoms [22]. Specifically, in patients with BMs of the spine, pathological fractures and spinal cord compression from spinal lesions severely compromise PS. A reduced PS in patients with metastatic disease affects mortality directly and indirectly by hindering the delivery of systemic therapies, including radioiodine therapy. For patients with oligometastases, long-term control of large and symptomatic BMs by other treatment options, including metastasectomy, is ideal for prolonged survival and the future application of RAI therapy for other, newly-developed organ lesions. For patients with coexisting vital organ metastases and a large BM, the efficacy of RAI therapy for vital organ metastases can significantly increase after metastasectomy for BM by decreasing the total volume of the tumors.
