Endocrine Abstracts

JOINT2781

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with a dismal prognosis despite multimodal treatment approaches. Tyrosine kinase inhibitors (TKIs), such as lenvatinib, and immune checkpoint inhibitors (ICIs), including nivolumab, have emerged as promising therapeutic options for ATC. Carotid blowout syndrome (CBS) is a rare but life-threatening vascular complication in patients with head and neck cancer, typically associated with prior surgical intervention and radiotherapy. Here, we report a fatal case of CBS following combination therapy with lenvatinib and nivolumab in an ATC patient who initially demonstrated a dramatic response to treatment. A 69-year-old male presented with a rapidly enlarging 6 cm right thyroid lobe mass and hoarseness. Total thyroidectomy and imaging studies confirmed ATC with tracheal and right recurrent laryngeal nerve invasion, along with synchronous lung and brain metastases (T4bN0M1, Stage IVc). Genomic profiling revealed NRAS (c.182A>G), TP53 (c.430C>T), TERT promoter (c.-146C>T) mutations with a high tumor mutational burden (23.4 mutations/Mb) and wild-type BRAF. The patient underwent external beam radiotherapy (EBRT; 6600 cGy in 30 fractions) followed by systemic therapy with lenvatinib (20 mg/day) and nivolumab (200 mg every 3 weeks). Two months after initiating systemic therapy, follow-up imaging demonstrated a significant partial response in pulmonary metastases and complete resolution of brain metastases, correlating with clinical improvement and weight gain. However, three months into therapy, the patient developed sudden-onset odynophagia. Neck computed tomography (CT) revealed a right tracheal wall defect with an exposed and unsupported right common carotid artery, indicative of impending CBS. Despite immediate cessation of systemic therapy and a recommendation for surgical intervention, rapid progression of tracheal necrosis led to acute carotid blowout, resulting in a fatal outcome. This case highlights the potential for severe vascular complications, such as CBS, in ATC patients receiving TKI and ICI combination therapy, even in the presence of an initial robust therapeutic response. Tracheal invasion and prior EBRT likely contributed to the pathogenesis of CBS, emphasizing the complex interplay between tumor biology, treatment modalities, and vascular integrity. These findings suggest that the administration of EBRT should be carefully considered or potentially omitted in ATC patients undergoing TKI and ICI combination therapy. Alternative treatment strategies should be explored to mitigate the risk of catastrophic vascular events.