Development of Upper Aerodigestive Tract Complications in Patients with Stage IV Thyroid Cancer Receiving Tyrosine Kinase Inhibitors

Abstract

Objective: Tyrosine kinase inhibitors (TKIs) are a class of systemic chemotherapy used in patients with radioactive iodine-refractory metastatic thyroid cancer. TKIs have been linked with impaired wound healing, but their association with upper aerodigestive tract complications is not well defined. The objective of this case series was to demonstrate that upper aerodigestive tract complications can occur in thyroid cancer patients receiving TKIs.Methods: A retrospective chart review was conducted on 3 cases involving patients with stage IV differentiated or medullary thyroid cancer treated between the years from 2000 to 2015. Each patient received surgical management, external beam radiation therapy, and subsequent TKI therapy and they also developed upper aerodigestive tract complications during their clinical course.Results: Patient 1 received TKIs for radioactive iodine-refractory pulmonary metastases and developed a tracheoesophageal fistula 1 year after initiation of chemotherapy. Patient 2 received TKIs for pulmonary metastases and developed a tracheoesophageal fistula several months after initiation of chemotherapy. Patient 3 was placed on TKIs for progressive metastatic disease 9 years after initial intervention and later developed laryngeal necrosis.Conclusion: Systemic TKIs can offer a clinical benefit in patients with metastatic thyroid cancer. However, clinicians should monitor patients for upper aerodigestive tract fistula formation and tissue necrosis during and after TKI therapy. Although a history of external beam radiation therapy may place patients at increased risk for fistula development, further investigation is needed to determine the relative risk associated with subsequent TKI exposure in these patients. (AACE Clinical Case Rep. 2018;4:e270-e274) Abbreviations: DTC = differentiated thyroid cancer; EBRT = external beam radiation therapy; MKI = multikinase inhibitor; MTC = medullary thyroid cancer; RAI = radioactive iodine; TEF = tracheoesophageal fistula; TKI = tyrosine kinase inhibitor; VEGFR = vascular endothelial growth factor receptor