Thyroid Center Frontier Program Tackles Unknowns of Pediatric Thyroid Cancer

Frontier status expands the resources for the Thyroid Center to research pediatric thyroid cancer.

shafere1 [at] chop.edu (By Emily Shafer)

Very little research has been done on thyroid cancer, particularly pediatric thyroid cancer. The reason for this limited research is simple: The prognosis for these patients is actually pretty good. However, despite its outlook, there is still a lot that is unknown about the disease.

The research gap is unacceptable to Aime Franco, PhD, a thyroid cancer survivor herself, who will be directing the newly established Pediatric Thyroid Cancer Translational Research Laboratory at Children’s Hospital of Philadelphia.

“Thyroid cancer has lifelong consequences,” said Dr. Franco, who is also assistant professor of Pediatrics at Perelman School of Medicine at the University of Pennsylvania. “What we don’t understand is why do children get this disease to begin with? Why do children and adults develop the disease differently? Can we be better understand the biology of the disease? Do all patients need to undergo aggressive therapies? These are all questions we want to answer.”

The Thyroid Center at CHOP now has expanded resources to answer these questions, thanks to its newly acquired Frontier status. The CHOP Frontier Program directs funds to clinical and research efforts at CHOP that show promise in areas of need.

Since its establishment in 2009, the Thyroid Center has grown into a well-known center for the treatment of thyroid cancer, attracting patients from throughout the country and around the world. The creation of the Thyroid Center Frontier Program will allow Dr. Franco and colleagues to understand why pediatric thyroid cancer behaves the way it does, and hopefully improve treatment options.

Sometimes, knowledge about adult thyroid cancer guides treatment of pediatric thyroid cancer, because on a genomic level, they are similar. But the similarities stop there.

“The clinical behavior and the biology of pediatric and adult thyroid cancers are very different,” said Andrew Bauer, MD, medical director and co-leader of the Thyroid Center. “These differences underscore the need for specific research programs and tools to guide diagnostics, prognostics, and treatment for patients with pediatric thyroid cancer. The Thyroid Center Frontier Program will build on the extensive clinical and genomic research infrastructure that exists in the CHOP Cancer Center and the Center for Applied Genomics.

Sogol Mostoufi-Moab, MD, MSCE, the Richard and Sheila Sanford Endowed Chair of Pediatric Oncology at CHOP, is the other co-leader of the Thyroid Center. She brings expertise in both oncology and endocrinology, as the only dual-trained pediatric endocrinologist and oncologist in the United States. In addition, Theodore Laetsch, MD, director of the Very Rare Malignant Tumors Program and the Developmental Therapeutics Program at CHOP, will play a key role in the Frontier Program.

The multidisciplinary expertise is necessary for pediatric thyroid cancer treatment. It encompasses expertise in endocrinology, oncology, general surgery, otolaryngology, radiology, and many others. Because of this, in 2015, the American Thyroid Association wrote guidelines that encouraged the creation of thyroid centers to improve treatment for these patients.

“Five years into this national effort to improve care for pediatric patients with thyroid cancer, we’re starting the next phase of that process, because as medicine advances, you gain better tools, better information, and better data on how to stratify our approach to evaluating and treating kids with thyroid cancer,” said Dr. Bauer, who is also professor of Pediatrics at Perelman School of Medicine at the University of Pennsylvania. “Frontier status will allow us to leverage our clinical and research programs to improve the therapeutic options for pediatric thyroid cancer patients.”

One of the main aims of the Thyroid Center Frontier Program is translational research. The Thyroid Center boasts the world’s first pediatric thyroid cancer translational research laboratory, created in 2019 and led by Dr. Franco. One of the goals is to study the genetic and molecular landscape of pediatric thyroid cancer: validating driver mutations of thyroid cancer; identifying mRNA, micro-RNA, and protein signature of thyroid tumors; and correlating these signatures with diagnosis, prognosis, and predictors of response to therapy.

This research takes advantage of the extensive biorepository housed within the Center for Childhood Cancer Research (CCCR), which includes more than 300 pediatric thyroid cancer samples. Since 2016, all thyroid samples have undergone oncogene analysis.

“Thyroid cancer is not a very complex cancer, as far as the genes that are associated with its development, but there is almost no information on why there is such diversity between patients in how the cancer behaves,” Dr. Bauer said. “We know some of the driver mutations of cancer, but we don’t understand how they work.”

In addition to understanding the molecular and genetic landscape of the disease, another aim of the program is to build the diagnostic and developmental therapeutics program for thyroid cancer. Approximately 2 percent of pediatric thyroid cancer patients develop progressive disease, and a greater number of patients develop metastasis to the lungs and don’t respond to therapy.

“We are bringing the type of precision medicine that’s occurring in other pediatric cancers, and in adult cancers, and bringing it to pediatric thyroid cancer,” Dr. Bauer said.

The Frontier program also aims to expand the Child and Adolescent Thyroid Consortium, which has been in a work in progress for several years. The purpose of the international consortium is to collect clinical data, increase the tissue repository, and increase the number of clinical trials available to patients at CHOP. The consortium includes five centers currently, with plans to expand to over 20 more this coming year.

What makes pediatric thyroid cancer different from other cancers, is that despite its good prognosis, it still often requires lifelong treatment, Dr. Franco said. Almost all patients undergo thyroid removal, and they are on thyroid hormone replacement therapy for life.

“We don’t think about the fact that these patients have lifelong consequences,” Dr. Franco said. “We forget that these patients have to undergo therapy and deal with having had cancer for the rest of their life, even if they don’t die from the disease. That’s what is really foundationally and fundamentally different about the Thyroid Center Frontier Program. We are putting so much resource and investigation into understanding basic questions like, why did you even get this disease to begin with? That is really the crux of some of the questions we want to answer.”