Open Access

Johannes von Hinten, Oliver Viering, Ralph A. Bundschuh, Feyza Cagliyan, Hermann Wengenmair, Christian H. Pfob, James Nagarajah, Constantin Lapa, Malte Kircher

• Radioactive iodine-refractory thyroid cancer (TC) has a poor prognosis, and restoring iodine uptake is a major therapeutic goal. Recent studies have used tyrosine kinase inhibitors (TKIs) for 3-6 wk to achieve redifferentiation, but preclinical data suggest that maximal effects occur within 8-12 d. Methods: In this retrospective study, 8 patients with metastatic radioactive iodine-refractory TC received trametinib plus dabrafenib (for BRAF-mutated disease) or trametinib alone (for BRAF wild-type disease) for 10 d. Iodine uptake was assessed by 123I-scintigraphy; responders received high-dose radioactive iodine therapy, and nonresponders continued TKIs for another 10 d. Results: Two patients (both with BRAF wild-type disease) achieved successful iodine uptake restoration with significant thyroglobulin reduction after radioactive iodine therapy. Extending TKI treatment to 21 d did not yield further benefit. Conclusion: Our pilot study supports preclinical findings that maximalRadioactive iodine-refractory thyroid cancer (TC) has a poor prognosis, and restoring iodine uptake is a major therapeutic goal. Recent studies have used tyrosine kinase inhibitors (TKIs) for 3-6 wk to achieve redifferentiation, but preclinical data suggest that maximal effects occur within 8-12 d. Methods: In this retrospective study, 8 patients with metastatic radioactive iodine-refractory TC received trametinib plus dabrafenib (for BRAF-mutated disease) or trametinib alone (for BRAF wild-type disease) for 10 d. Iodine uptake was assessed by 123I-scintigraphy; responders received high-dose radioactive iodine therapy, and nonresponders continued TKIs for another 10 d. Results: Two patients (both with BRAF wild-type disease) achieved successful iodine uptake restoration with significant thyroglobulin reduction after radioactive iodine therapy. Extending TKI treatment to 21 d did not yield further benefit. Conclusion: Our pilot study supports preclinical findings that maximal restoration of iodine uptake is achieved after only 10 d of TKI therapy, reducing toxicity and treatment costs. Longer treatment did not provide any additional benefit. Larger prospective trials are needed to confirm these findings.…