(21.15) Neoadjuvant Tyrosine Kinase Inhibitor Therapy Enables Surgery for Previously Unresectable 15cm Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) is a rapidly growing, lethal malignancy posing challenges for timely diagnosis and treatment, resulting in a median survival of 5 months. Currently, effective neoadjuvant therapy has not been established for ATC and other advanced thyroid cancers, although both targeted therapy and immunotherapy are being actively investigated for these cases. This case highlights the transformative impact of neoadjuvant therapy with tyrosine kinase inhibitors (TKI) on an ATC, suggesting of potential implications of this treatment approach.

Case(s) Description :

A 63-year-old man initially diagnosed with papillary thyroid cancer in 2020 presented three years later with a progressively enlarging neck mass associated with dyspnea. Physical exam revealed a 15 cm anterior neck mass protruding beyond the level of the chin and manubrium with cutaneous involvement. A core needle biopsy was performed and urgent chemotherapy with carboplatin/paclitaxel was initiated based on the suspicion of ATC, but with minimal effect. The biopsy revealed ATC harboring BRAF V600E mutation, thus the neoadjuvant therapy was switched to targeted therapy with dabrafenib/trametinib against BRAF mutation. CT imaging of the neck merely 1 month later demonstrated an impressive 30% size reduction. After 5 months of neoadjuvant therapy, the tumor was reduced to 5 cm and surgical resection was considered feasible. The patient successfully underwent an extensive operation, entailing a total thyroidectomy with lymphadenectomy and central neck mass resection with overlying skin and pectoralis muscle flap reconstruction. Voice function was preserved. TKI therapy was well-tolerated initially but could not continue adjuvantly due to suspected TKI-induced cardiomyopathy. Two months post-operatively, the patient developed stridor from mucus plugging, ultimately requiring tracheostomy. Adjuvant radiation without chemotherapy was completed and the patient clinically improved with less dyspnea. CT chest 6 months post-operatively revealed a few new nodules currently being investigated for potential metastases. At 12 months post-presentation, the patient is alive with moderate performance and quality of life.

Discussion :

ATC represents only 1.7% of all thyroid cancers yet nearly half of all cancer-related deaths. This case highlights the efficacy of personalized neoadjuvant TKI therapy as a successful induction to surgery in patients with ATC. As demonstrated in our patient, this approach averted imminent mortality and enabled resection of a giant ATC without significant morbidities. Dabrafenib/trametinib, a potent TKI combination against BRAF mutation, is currently being studied in phase 2 clinical trials for BRAF V600E-mutated cancers, with 56% overall response rate for ATC.  This represents the most promising results to date for ATC. The purpose of this case report is to raise awareness of such novel therapeutic options. The trajectory of these recent medical advances suggests a foreseeable future when neoadjuvant TKI therapy emerges as a pivotal choice in the multi-disciplinary treatment of thyroid cancers.