MON-307 - From Unresectable to Radioiodine-Avid: Sequential Targeted Therapy in Locally Advanced Papillary Thyroid Cancer

Locally advanced thyroid cancers with extensive extrathyroidal extension may require neoadjuvant systemic therapy to facilitate surgery. In BRAF V600E–mutated disease, MAP kinase inhibition can also restore radioiodine (RAI) avidity through tumor redifferentiation. This case illustrates the dual benefit of systemic therapy in achieving tumor shrinkage and restoring RAI uptake.
A 66-year-old man with a 4.8 cm thyroid mass identified on lung cancer screening CT underwent fine-needle aspiration suspicious for papillary thyroid carcinoma (PTC). Initial surgical exploration revealed tumor fixation to the larynx with deep mediastinal extension, precluding safe resection. Follow-up imaging demonstrated interval growth to 10.2 cm with significant mass effect. A second operation confirmed PTC with tall cell features and BRAF V600E mutation, but resection remained incomplete (R2). Neoadjuvant lenvatinib was initiated, resulting in approximately 50% tumor reduction to 5.6 cm and improvement in tracheal deviation. Despite grade 3 toxicities (hypertension and diarrhea), the patient subsequently underwent total thyroidectomy with therapeutic neck dissection and strap muscle resection. Persistent disease was suggested by an elevated thyroglobulin level of 70.7 ng/mL six weeks postoperatively. Given the BRAF V600E mutation, dabrafenib plus trametinib was started for redifferentiation. After six weeks of therapy, the patient received 100 mCi of I-131. Post-therapy imaging demonstrated uptake in the retromanubrial region not seen on the diagnostic I-123 scan, indicating successful restoration of RAI avidity.
A systematic review has shown that 83.3% of patients initially deemed inoperable underwent surgery after neoadjuvant multikinase inhibitor therapy, with tumor reduction ranging from 25% to 87%. NCCN guidelines recommend lenvatinib as first-line therapy for progressive RAI-refractory differentiated thyroid cancer. Following surgical debulking, the MERAIODE trial demonstrated that dabrafenib plus trametinib restored RAI uptake in 65% of patients with BRAF V600E–mutated RAI-refractory disease, with a 6-month objective response rate of 38%. In this patient, sequential lenvatinib followed by dabrafenib and trametinib enabled definitive surgery and restoration of RAI avidity. This case highlights the importance of a multidisciplinary approach and early molecular profiling to optimize treatment sequencing in advanced thyroid cancer.

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