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Case Report: Neoadjuvant Selpercatinib in RET‐Mutated Medullary Thyroid Cancer

By: Julia Fiederlein
Posted: Tuesday, December 15, 2020

A noteworthy case of RET‐mutated advanced medullary thyroid cancer, which ultimately responded to neoadjuvant selpercatinib and surgical resection, was described by Maria Cabanillas, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues. This patient profile was recently published in the journal Head & Neck.

“Highly potent next-generation selective RET inhibitors have been clinically validated,” the investigators remarked. “Selpercatinib was recently Food and Drug Administration (FDA)‐approved for advanced medullary thyroid cancer.”

A 20-year-old man presented with metastatic disease involving his pituitary, neck, mediastinum, lungs, liver, and spine. Resection of the pituitary mass and core biopsy of a mediastinal mass was compatible with medullary thyroid cancer; pathologic analysis confirmed this diagnosis. The patient experienced elevated levels of serum carcinoembryonic antigen (886 ng/mL; normal reference: < 3.8 ng/mL) and calcitonin (12,356 pg/mL; normal reference: < 14.3 pg/mL). Genomic molecular testing revealed a somatic RET deletion.

Initially, the patient was not surgically resectable. He was enrolled in a single‐patient study, in which 160 mg of oral selpercatinib was administered twice daily for almost six cycles. Based on the results of a restaging CT performed after four cycles, there seemed to be a marked interval improvement in multicompartmental nodal and visceral metastases in the neck, chest, and abdomen. The multifocal osseous metastases appeared to be stable. Grade 1 transaminitis was the sole adverse event reported. Total thyroidectomy, bilateral central compartment dissection, bilateral lateral neck dissection, and median sternotomy with bilateral superior mediastinal dissection were performed after holding selpercatinib for 3 days; R1 resection was achieved.

Treatment was resumed after surgery. Over the following 18 months, the patient remained without evidence of locoregional disease and exhibited distant metastatic sites' stability. At last follow-up, the investigators reported a continued decline in levels of carcinoembryonic antigen (106 ng/mL) and calcitonin (308 pg/mL).

Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.

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