ATA Highlights New Thyroid Cancer Research

Robert C. Smallridge, MD

The impact of radioactive iodine (RAI) on long-term outcomes, potential combination strategies, molecular profiling, and novel therapeutics for patients with thyroid cancer were among some of the topics highlighted at the 2014 American Thyroid Association (ATA) Annual Meeting.

The five-day conference, held in Coronado California from October 29 to November 2, 2014, is geared toward endocrinologists, internists, surgeons, nuclear medicine scientists, pathologists, and other healthcare professionals. Presentations at the meeting encompass a wide array of topics in thyroidology, including the treatment of various neoplasms.

One of the more exciting studies presented at the meeting, from researchers at the Massachusetts General Hospital, demonstrated the feasibility of BRAFV600E mutation detection using a blood-based assay in patients with papillary thyroid cancer (PTC). In general, BRAF mutations are associated with a worse overall prognosis, resistance to RAI therapy, and an increased risk of metastases and mortality. Results from the analysis suggest that a blood-based assay could be used for diagnosis, postoperative surveillance, and to monitor treatment response to BRAF inhibitors.

Adding to the importance of BRAF in PTC, researchers from the Beth Israel Deaconess Medical Center found lower levels of large non-coding RNA (LincRNA) neighboring the thyroid peroxidase gene in patients with BRAFV600E-positive PTC. These findings suggest that LincRNA could be involved in the regulation of iodine metabolism associated gene expression, suggesting LincRNA could be used for monitoring patients undergoing treatment.

Differentiated Thyroid Cancer

"The identification of new circulating markers, if validated, should improve both the diagnosis and longitudinal follow-up of patients with papillary thyroid cancer," Robert C. Smallridge, MD, president elect of the ATA, said in a statement.For patients with differentiated thyroid cancer (DTC), RAI therapy has been utilized as a standard therapy for more than half a decade. An examination of nearly 5000 patients from 1987 to 2012 revealed that thyroidectomy followed by RAI therapy correlated with a survival benefit in patients with high risk DTC. However, this analysis did not find the same benefit in patients with low risk disease, suggesting an optimal setting for RAI use.

Further insight was added through an examination of thyroid hormone suppression therapy (THST) administration over the same timeframe. Overall, moderate but not aggressive THST was associated with improved survival in all DTC stages. Furthermore, the use moderate THSH was predictive of improved disease-free survival following surgery.

"Their findings are important—that these patients don't need to be aggressively suppressed to an undetectable level of TSH, but rather somewhere in what they defined as a moderate hormone level," Naifa L. Busaidy, MD, associate professor at MD Anderson Cancer Center, said in an interview with OncLive. "It’s an interesting study with important findings that a lot of us had a gut feeling about but didn't have the data to back it up. Now we have several thousand patients' data showing that this might be important."

To build on treatment with RAI, researchers looked at the therapy in combination with lithium for patients with metastatic DTC who did not respond to initial RAI therapy. In this study, patients received oral lithium for 7 days, which started 5 days before RAI therapy. With the combination approach, 45% of patients had stable disease at 6 months, resulting in a significant improvement in progression-free survival.

Medullary Thyroid Cancer

After 10 years of follow up, patients in the combination arm showed slightly higher survival rates than with RAI alone (67.9% vs 66.8%). The median survival with the combination was 126.2 versus 105.4 months, after propensity score matching.Medullary thyroid cancer (MTC) is generally treated with surgery followed by adjuvant therapy. In the past few years, two novel therapies have gained approval as treatments for patients with this rare cancer.

“The biggest challenge we're having now in the field of medullary thyroid cancer, certainly as researchers, is that we don't have a third line, and there are patients now who are getting to that third line. And, unfortunately, now that is a big question mark," Ezra Cohen, MD, professor of medicine, UC San Diego Moores Cancer Center, said in an interview with OncLive.

To attempt to address this, a study explored a unimolecular micelles conjugated with the somatostatin analog KE108 as a delivery mechanism for the HDAC inhibitor AB3. In a culture, the targeted delivery of the nanocarrier was associated with increased uptake by MTC cells. These early findings suggest the possibility for better therapeutic outcomes with less systemic toxicity.

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