Endocrine Abstracts

JOINT998

Introduction: The medullary thyroid carcinoma (MTC) is one of the most aggressive forms of thyroid malignancy, accounting for up to 10% of all types of this disease. The molecular profile of MTC is well-known. A germline activating mutation of the RET proto-oncogene occurs in nearly all patients with hereditary MTC, while a somatic RET mutation is found in about 50% of sporadic tumors. In this group of patients, selective tyrosine kinase inhibitors (IKT)are successfully used, particularly in cases of metastatic disease. Management of metastatic disease in patients without RET mutations presents a clinical challenge. The aim of this study is to present the case of a patient with MTC, who 18 years after thyroid surgery, developed liver metastases despite an excellent initial response to treatment. Molecular profile of the primary tumor was not conducted. At the time of liver metastases diagnosis, circulating tumor DNA analysis was performed, allowing determination the molecular profile of the cancer. The driver mutation for MTC was identified as a mutation in the PIK3CA gene, which encodes the catalytic subunit of the PI3K protein, playing a key role in the phosphatidylinositol-3 kinase/AKT pathways (PI3K/Akt) signaling pathway. This mutation is known from other cancers, such as colorectal, ovarian, breast, brain, liver, stomach and lung cancers. The PIK3CA mutation is very rare in MTC. Our patient did not have a dynamic progression of MTC (stable disease according to RECIST 1.1 after 12 months of observation). Currently, no decision has been made to initiate systemic therapy, but knowledge of the molecular profile of the disease may help guide targeted molecular therapy in the future. The alpelisib an α-specific inhibitor of PI3K that targets p110α is currently available. The use of this drug, which has been shown to effectively inhibit tumor progression in patients with the PIK3CA mutation, including those with breast cancer, may be a promising therapeutic option for our patient.

Conclusions: Patients with MTC, even though an excellent response to treatment, require lifelong oncological follow up. Liquid biopsy is a new and valuable tool for molecular diagnostics of cancer, particularly in cases where tumor cells cannot be obtained for analysis.