Improved laryngeal function after neoadjuvant therapy for advanced thyroid cancer: A potential outcome of interest for future clinical trials.

e18030 Background: Advanced thyroid cancers can invade the recurrent Laryngeal Nerve (RLN) resulting in vocal cord paralysis (VCP). This can significantly impact the surgical strategy given the need to sacrifice the invaded RLN, the potential for bilateral VCP and tracheotomy. Methods: We retrospectively identified patients diagnosed with advanced thyroid carcinomas (of any histology) at 3 high-volume tertiary centers who met the following criteria: treated between 01/2017 and 12/2022, tested for driver/targetable somatic mutations, received targeted neoadjuvant therapy, underwent laryngoscopic exam to assess vocal cords (VC) functional status before, during and after neoadjuvant therapy, and underwent surgery. Results: We identified 6 patients who met the eligibility criteria. Mean age at diagnosis is 69. Five patients were diagnosed with anaplastic thyroid carcinoma, while 1 with papillary thyroid carcinoma. Somatic mutations were detected in BRAFV600E in 6 patients (100%), TERT promoter in 3 (50%) and in PIK3CA & TP53 in 2 patients each (33%). Five patients received dabrafenib/trametinib & 1 patient received lenvatinib. One patient received radiotherapy before neoadjuvant therapy. Baseline laryngoscopic exam detected 5 left-sided VCP and 1 right-sided VCP. After neoadjuvant therapy, 4 patients (67%) regained VC function after 3 months of therapy. By 13.5 months, all patients (100%) regained normal VC function, with a mean time-to-return of VC function of 5 months. The affected RLN could be surgically spared in 5 patients (83%). Conclusions: Use of neoadjuvant targeted therapy resulted in return of VC function in all patients after initially abnormal laryngeal exams, with 67% of patients showing return of function after 3 months. Additionally, neoadjuvant therapy resulted in tumor response sufficient to spare 5 RLNs from surgical resection (83%). Serial laryngoscopic exams during neoadjuvant therapy could guide surgical strategy, impact surgical timing, and provide an additional meaningful treatment outcome. VC function could be used as an endpoint in future neoadjuvant trials. Potential limitations include tertiary center referral bias and selection bias (patients who met eligibility criteria may have favorable trajectory, while patients with aggressive disease who didn’t respond to therapy were excluded). Clinical trials are undergoing to further validate our results. [Table: see text]