BACKGROUND
Thyroid cancer is almost always treated with surgery initially. If the cancer is high risk and the entire thyroid was removed, radioactive iodine can be used to destroy and remaining thyroid cancer cells. After the initial therapy, our current American Thyroid Association 2015 guidelines categorize patient’s thyroid cancer in terms of how likely it is to recur in a neck lymph node in the next ten years. We use ultrasound imaging to identify any cancer remaining in the thyroid bed or in the lymph nodes in the neck (structural response to therapy) and measurement of thyroglobulin levels as thyroid cancer markers (biochemical response to therapy). The best-case scenario (low to undetectable thyroglobulin levels) is called “biochemically excellent response to therapy,” while the worst-case scenario (spread of the cancer to lymph nodes or other organs found on ultrasound) is called “structurally incomplete response to therapy.” In between is when thyroglobulin levels are rising or remain elevated and no evidence of cancer is noted on imaging (biochemically incomplete or indeterminate response to therapy).

This study was done because it is unclear whether patients who received radioactive iodine therapy right after their initial surgery will further benefit from more radioactive iodine if they are in either the “biochemically incomplete or biochemically indeterminate response to therapy” categories. The goal of this study is to better understand if additional doses of radioactive iodine therapy is beneficial when the thyroid cancer is not responding to therapy in the “biochemically indeterminate or incomplete” category.

THE FULL ARTICLE TITLE
Gambale C et al 2023 Usefulness of second 131I treatment in biochemical persistent differentiated thyroid cancer patients. Eur Thyroid J. Epub 2023 Sep 1. PMID: 37768697.

SUMMARY OF THE STUDY
A total of 153 patients from the University of Pisa were studied from 2009 to 2012 who had surgery and a first dose of radioactive iodine for their thyroid cancer. Of these 153 patients, 37% had a thyroid cancer that was a low risk of recurrence based on their surgical pathology. About half had a “biochemical incomplete response to therapy” and half had a “biochemical indeterminate response to therapy” on average 7.5 months after their first radioactive iodine dose (range of 30-100 millicurie, mCi) based on the 2009 ATA guidelines. In other words, the ranges of the thyroid cancer marker, thyroglobulin, were 1.3 and 3.7 μg/L and between 2.6 and 8.6 μg/L for the stimulated thyroglobulin level. These patients then received a second radioactive iodine dose of 100 mCi about 20 months after the first radioactive iodine dose. Patient were reassessed for response of therapy 8 months after the second radioactive iodine dose then followed for another 7.7 years.

A majority 71% of the patients remained in the “biochemically indeterminate or incomplete” response to therapy even after the second dose of radioactive iodine was given. Only 12% of the patients were reclassified into the desirable “biochemically excellent response to therapy” after the second dose. In fact, 17% of the patients were found to have spread of the cancer outside of the neck. In the long term 7 year follow up, 9 more people were found to have spread of the cancer outside of the neck. Over the 7 year period, 10 more people qualified for the “excellent” response to therapy after a third dose of radioactive iodine and 9 more did so with no additional radioactive iodine treatment.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that most of the patients in the “biochemical incomplete or indeterminate response to therapy” category stayed in the same category despite receiving a 2nd dose of radioactive iodine therapy. Overall, about 23% will develop a spread of the cancer outside of the neck that was not identified after the 2nd dose, usually within the first three years. Thus, these data suggest that a 2nd dose of radioactive iodine in patients with increased thyroglobulin levels but no evidence of cancer on a neck ultrasound is not very effective and can be deferred.

— Pinar Smith, MD

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