BACKGROUND
Thyroid cancer is common and there are effective treatments that result in an excellent prognosis for patients. Surgery is usually the initial treatment. If the cancer has spread outside the thyroid, then radioactive iodine is usually used. Radioactive iodine acts as a “magic bullet” to destroy any thyroid cancer that has spread outside the thyroid to other parts of the body, like the neck, lungs, or bones. Patients swallow a capsule containing a radioactive isotope of iodine, I-131. Once absorbed, the radioactive iodine will concentrate in the thyroid cancer cells. Over time, the radiation from radioactive iodine will destroy the cancer.

However, thyroid cancer cells must absorb the radioactive iodine for this treatment to work. The term radioiodine avidity refers to how well cancer cells can absorb the radioactive iodine. Cancer cells with high radioiodine avidity are better at taking in iodine, so the treatment will likely be effective. Studies have shown that the ability of thyroid cancer cells to absorb radioactive iodine depends on specific genetic mutations in the cancer cells, known as the cancer’s molecular signature.

This study explores how a cancer’s molecular signature affects its ability to absorb radioactive iodine.

THE FULL ARTICLE TITLE
Mu Z, Zhang X, Sun D, et al. Characterizing genetic alterations related to radioiodine avidity in metastatic thyroid Cancer. J Clin Endocrinol Metab 2024;109(5):1231-1240.

SUMMARY OF THE STUDY
The authors conducted genetic testing on 281 thyroid cancer samples from 214 patients with metastatic thyroid cancer (including papillary thyroid cancer, follicular thyroid cancer, or poorly differentiated thyroid cancer). Patients had undergone a thyroidectomy and received one or more doses of radioactive iodine at a single hospital in China between 2020 and 2022.

The genetic tests focused on four types of mutations found in thyroid cancer cells: a) BRAF V600E, b) RAS, c) fusions (RET or NTRK), and d) other mutations. The researchers then analyzed the pattern of radioactive iodine uptake, categorizing each cancer as either radioactive iodine avid (I-RAIA) or radioactive iodine resistant (I-RAIR), in relation to each type of mutation.

A total of 80 patients had cancers classified as radioactive iodine resistant (I-RAIR), while 134 had cancers classified as radioactive iodine avid (I-RAIA). Compared to patients with I-RAIA disease, those with I-RAIR were older at the time of diagnosis (average age of 45.7 years vs. 36.8 years), had a higher number of genetic mutations, and were more likely to have poorly differentiated thyroid cancer. Notably, the BRAF V600E mutation was linked to a higher incidence of non-RAI-avid patterns (I-RAIR) compared to thyroid cancer with RAS variants, fusions, and other mutations (64.4% vs. 4.5% vs. 20.7% vs. 20.9%). Furthermore, cancers with BRAF V600E mutations and other related mutations such as TP53 and TERT that were initially radioiodine avid tended to lose there ability to absorb I-131 with subsequent treatments.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that thyroid cancers with BRAF V600E, TERT promoter, and TP53 mutations predominantly showed resistance to radioactoive iodine therapy. In contrast, cancers with RAS mutations and RET or NTRK fusions were likely to respond to radioactive iodine therapy. These findings suggest that cancer treatment can be individualized based on the molecular signature of each cancer. Perhaps patients with cancers that have a molecular profile predicting radioiodine avidity should receive radioactive iodine therapy, while those with a profile predicting radioiodine resistance should not.

— Phillip Segal, MD

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