Case report highlights promising approach for treating pediatric thyroid cancer

A case report led by UCLA Health investigators suggests children with advanced papillary thyroid cancer driven by RET gene mutations may benefit from incorporating targeted therapy before starting standard treatment.

The study highlights the use of selpercatinib, a type of tyrosine kinase inhibitor, prior to radioactive iodine therapy, the cornerstone treatment for thyroid cancer. Traditionally, agents like selpercatinib have been reserved as a last resort when other treatments fail.

The case focused on a 10-year-old girl with metastatic papillary thyroid cancer caused by a RET gene mutation. Her disease had spread extensively to her lymph nodes, neck muscles and lungs. After surgery to remove her thyroid and affected lymph nodes, the patient received selpercatinib prior to her first radioactive iodine treatment. After six months of therapy, her lung metastases resolved, and her tumors shrank significantly.

“By moving selpercatinib earlier in the treatment timeline, we amplified the effectiveness of radioactive iodine,” said Harvey Chiu, MD, professor of pediatric endocrinology at UCLA Mattel Children's Hospital. “This dual action approach has the potential to change the standard treatment for young patients with RET-driven thyroid cancers.”

The findings were published in the Journal of Pediatric Endocrinology and Metabolism.

Challenges of treating aggressive pediatric thyroid cancer

Thyroid cancer, while rare in children, can be particularly aggressive when it spreads beyond the thyroid and is driven by genetic mutations like those in the RET gene. The standard approach to treating metastatic disease is to surgically remove the entire thyroid gland, along with any affected lymph nodes if needed, followed by radioactive iodine therapy to target any remaining cancer cells. However, only a small percentage of children with metastatic disease achieve full remission.

This can result in additional surgeries and radioactive iodine therapy. These repeated interventions increase the risk of long-term side effects, such as damage to surrounding tissues or the development of secondary cancers like leukemia or breast cancer. 

“Each additional surgery increases the risk of damaging surrounding structures, while excessive radioactive iodine treatments raise the likelihood of long-term health problems,” said Dr. Chiu, who was the first author on the report. “We accept these additional risks if there is a need for such further therapies, but if we can avoid such further interventions, we can decrease the risk of correlate adverse events.”

A game-changing approach

One way to minimize some of the long-term-risks is by using tyrosine kinase inhibitors like selpercatinib. These targeted therapies work by blocking specific pathways that fuel cancer growth. In the case of RET-driven thyroid cancer, selpercatinib inhibits the RET mutation’s activity, shrinking tumors and enhancing the effectiveness of other treatments.

Traditionally, these inhibitors have been reserved for advanced cases after other treatments fail. However, UCLA researchers hypothesized that introducing selpercatinib earlier could improve outcomes by amplifying the effects of radioactive iodine therapy. 

“The idea was to use the drug to shrink the cancer by cutting off the blood supply feeding it,” explained Dr. Chiu. “With a smaller tumor, the amount of radiation per cancer cell would increase, improving the chances of eliminating the cancer. It’s like giving an army of good soldiers an advantage by reducing the size of the opposing force. On top of that, the drug also helps cancer cells absorb more radiation, further boosting the likelihood of success.”

Promising results with minimal side effects

After five months of selpercatinib, scans showed the young patient’s lung nodules had significantly improved, with only a few tiny nodules remaining in her left lung. By six months, the patient’s tumors showed significant shrinkage, and her thyroglobulin levels, which are a marker of cancer activity, dropped from 23 ng/mL to 8.6 ng/mL.

At the eleven-month mark, her thyroglobulin levels reached a low of 1.0ng/mL, demonstrating the combined success of selpercatinib and radioactive iodine in shrinking her tumors and controlling the disease.

The patient experienced minimal side effects, such as a mild rash, and tolerated the treatment well. 

“The rapid development of new tyrosine kinase inhibitors targeting various genetic drivers of pediatric thyroid cancer presents exciting new treatment possibilities,” said senior author Noah Federman, MD, the Glaser Family Endowed Chair and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Pediatric Bone and Soft Tissue Sarcoma Program. “Even for patients who aren't completely cured, this treatment could help eliminate much more of the cancer than previously possible, reducing the need for additional surgeries and radiation. Our goal is to give these children the best chance at a long, healthy life with fewer long-term risks.”

The researchers emphasize that larger studies will be needed to confirm the effectiveness of this approach across more patients. Additionally, as new tyrosine kinase inhibitors continue to be developed, future studies will explore how these therapies target different genetic drivers of pediatric thyroid cancer.

Other authors, all from UCLA, are Theodore Nowicki, MD, PhD, Masha Livhits, MD, and James Wu, MD.