Background: The objective of this study was to evaluate the overall survival (OS) of radioiodine (¹³¹I) treatments alone or combined with non-¹³¹I treatments in patients with bone metastases (BM) of differentiated thyroid cancer (DTC). Methods: This was a retrospective study of patients who were evaluated between 2001 and 2018 at MedStar Washington Hospital Center and who had DTC, BM, and at least one ¹³¹I treatment after the diagnosis of BM. The OS was analyzed by Kaplan-Meier survival curves and was compared by log-rank test between two groups: patients who received ¹³¹I treatments alone and those who received treatments combining ¹³¹I with non-¹³¹I treatments (CombTx). Non-¹³¹I treatments include surgery, radiofrequency ablation, cryotherapy, arterial embolization, external beam radiation, Cyberknife, systemic targeted therapy, and anti-resorptive medication. Results: A total of 77 patients met the above criteria and were followed up to 41 years. Thirty percent (23/77) of patients received ¹³¹I treatment alone, and 70% (54/77) received CombTx. For ¹³¹I treatment alone, the median survival was 3.9 years, and the 1-, 2-, 3-, 5-, and 10-year OS rates were 86%, 81%, 61%, 35%, and 23%, respectively. For CombTx, the median survival was 7.7 years, and the 1-, 2-, 3-, 5-, and 10-year OS rates were 96%, 92%, 86%, 69%, and 30%, respectively. Patients who had undergone initial ¹³¹I therapy within six months post thyroidectomy demonstrated a better median survival after BM diagnosis than those whose initial ¹³¹I therapy was six months or more after thyroidectomy (6.5 vs. 0.5 years; p < 0.001). Patients who received external beam radiation therapy demonstrated a better median survival than those who did not (7.8 vs. 4.4 years; p = 0.016). Patients who received denosumab demonstrated a better median survival than those who did not (7.7 vs. 5.2 years; p = 0.03). Patients who were <55 years of age at the initial diagnosis of DTC or at the initial diagnosis of BM had a better median OS than those diagnosed at ≥55 years of age (both p = 0.01). In the multivariate analysis, only age at initial diagnosis of DTC and initial ¹³¹I therapy within six months post thyroidectomy, and multiple ¹³¹I treatments were independent prognostic factors. Conclusions: In patients with DTC with BM, ¹³¹I treatment in combination with one or more non-¹³¹I direct and systemic treatments was associated with a significant increase in OS compared with those patients who were treated by ¹³¹I treatment alone.

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