THU535 Anti-angiogenic Multi-kinase Inhibitor In NUTM1 Rearranged Carcinoma Of Thyroid
Authors: Tella Sri Harsha , Morris John C , Rivera Michael , Gupta Sounak , Ryder Mabel M 
Published: October 2023

Abstract
Disclosure: S. Tella: None. J.C. Morris: None. M. Rivera: None. S. Gupta: None. M.M. Ryder: None.
Introduction: NUT carcinoma is a rare subtype of squamous cell carcinoma defined by NUTM1 rearrangements encoding NUT-fusion oncoproteins with a very dismal prognosis. Recent data showed that NUTM1 rearranged carcinoma of the thyroid can mimic other thyroid primaries but NSD3-NUTM1 fusions aid in the diagnosis. Other than systemic chemotherapy with ifosfamide-based therapies and bromodomain inhibitors, therapeutic options for metastatic NUTM1 rearranged carcinoma of thyroid are limited. Herein, we describe a case of NUTM1 carcinoma of thyroid that had an impressive response to lenvatinib. Clinical case: We describe a case of a 41-year-old Caucasian male who presented to urgent care with acute onset aphonia and was eventually diagnosed with poorly differentiated thyroid carcinoma of size 4 x 4 cms extending into the internal jugular vein. He was managed with partial resection of the mass, internal jugular vein ligation, and a right select neck dissection. He had R2 resection due to possible vascular or airway invasion. As such, he received external beam radiation 70 Gy with 35 fractions with concurrent cisplatin followed by 200 mci radio-iodine therapy. The radiation therapy was complicated by the formation of a tracheo-esophageal fistula. A follow-up FDG-avid PET scan demonstrated residual thyroid bed disease and oligometastatic disease in bones. He received a couple of Stereotactic Body Radiation Therapy twice for bone lesions. Unfortunately, he had rapid disease progression with large pleural-based nodules and histology showed poorly differentiated thyroid carcinoma. NUT1 IHC stain was negative. We simultaneously obtained next-generation sequencing (NGS) and started him on lenvatinib 20 mg. Interestingly, NGS showed NSD3-NUTM1 fusions favoring the diagnosis of NUTM1 rearranged carcinoma of thyroid. He had an impressive partial response to lenvatinib within 4 weeks of initiation of lenvatinib and the response is sustained on 8-month follow-up. He tolerated lenvatinib reasonably without any unexpected complications. In an event of progression, we intend to consider a clinical trial, chemotherapy in combination with bromodomain inhibitors, or another anti-angiogenic tyrosine kinase inhibitor therapy. Conclusions: We noticed an impressive and sustained partial response in NUTM1 rearranged carcinoma of thyroid with anti-angiogenic multi-kinase inhibitor, lenvatinib opening new avenues of targeted therapy in the therapeutic landscape of NUT1 carcinomas. Importantly, NUT1 stain could be negative and NGS is the gold standard for accurate diagnosis. Although our study is limited by one case report, we hope that by highlighting the spectrum of this disease that more cases will be recognized, facilitating risk stratification and improved treatment, and further enabling future studies to explore the clinical management and biology of NUTM1 rearranged carcinoma of thyroid.
Presentation: Thursday, June 15, 2023