Withholding RAI Therapy in Low-Risk Pediatric DTC Continues to Yield Comparable Remission Rates

Following new guidelines in 2015, a retrospective analysis showed that withholding radioactive iodine therapy (RAIT) in pediatric patients with low-risk differentiated thyroid carcinoma (DTC) induced similar remission rates as those treated with the therapy at 1 year post-initial therapy, according to a presentation from the 91st Annual Meeting of the American Thyroid Association (ATA).

“In 2015, when the ATA created these pediatric guidelines, they were taking a leap of faith that these patients would be able to achieve remission without RAIT,” explained Mya Bojarsky, undergraduate student, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, during a presentation at the meeting, held October 19-23.

“And this is the first of hopefully many studies to validate those guidelines and support the sentiment that for ATA low-risk pediatric thyroid cancer patients withholding RAIT is clinically beneficial as it reduces exposure to radiation while having no negative impact on remission.”

Study Results

The retrospective study showed that at 1-year post-treatment there was no evidence of disease in 84% of those treated with RAIT, compared with 80% in those treated with it (P = .257). “Even though 1 year is an early assessment, 80% to 84% of patients had already achieved remission. And remission rates continue to increase with continued surveillance,” Bojarsky said.

After a median follow-up of 4.9 months (range, 3.2-6.7) in patients treated with RAIT and 2.7 months (range, 1.4-5.2) in patients treated without RAIT, 90% and 87%, respectively, had no evidence of disease (P = .833). In the same time frame, 6% and 7%, respectively, were biochemically incomplete and 4% and 7% had disease status that was unable to be determined.

“We just further supported our findings that there was no difference in remission,” Bojarsky said.

When investigators further evaluated the clinicopathologic findings, there was a significant difference in the primary tumor size in patients treated with (median IQR, 19.5 mm; 12.0-30.0) and without (median IQR, 12.0 mm; 7.0-16.5) RAIT (P = .0005).

“This would eventually lead us to our next question, which was to explore what factors were actually influencing why certain patients were receiving it and why certain patients weren't,” Bojarsky added. Therefore, investigators evaluated disease status with and without RAIT following the ATA guidelines in 2015.

At 1 year, 84% of patients treated with and without RAIT had no evidence of disease, while 11% and 8%, respectively, were biochemically incomplete and 5% and 8% were unable to be determined (P = .894). At last clinical evaluation, after a median follow-up of 4.1 months (range, 2.9-4.7) in those treated with RAIT and 2.0 months (range, 1.4-4.0) in those treated without it, 90% and 84%, respectively, had no evidence of disease, 5% and 8% were biochemically incomplete, and 5% and 8% were unable to be determined (P = .865).

Lastly, investigators evaluated risk factors for receiving RAIT, which included primary tumor size (odds ratio [OR], 1.072; 95% CI, 1.029-1.128; P = .003), lymph node metastases (OR, 3.719; 95% CI, 1.136-13.461; P = .036), and surgery pre-2015 (OR, 9.834; 95% CI, 3.362-32.966; P < .0001). “This is important because we wanted to ensure that our main finding, that there was no difference in remission with and without RAIT. It was not actually due to these underlying confounding variables that were determining why someone is receiving RAIT. It was due to the RAIT itself,” Bojarsky said.

However, reducing RAIT was not a risk factor for persistent/recurrent disease as evaluated through RAIT administration (OR, 1.11; 95% CI, 0.052-0.346; 95% CI, P = .866), lymph node metastases (OR, 1.81; 95% CI, 0.545-5.677; P = .313), and surgery pre-2015 (OR, 1.48; 95% CI, .430-5.190; P = .532). “None of these variables were significant. And this importantly showed that withholding RAIT did not increase risk of persistent disease, independent of the other possible confounding variables that we have found,” Bojarsky said.

Lastly, she added, somatic driver alterations did not influence the rate of persistent/recurrent disease. “We need additional genomic data to more fully understand the molecular landscape that drives metastasis.”

Study Rationale

In 2015, the ATA Pediatric Guidelines recommended against RAIT for low-risk DTC, as it exposes children to radiation and can increase their risk for secondary hematologic and solid malignancies Bojarsky explained. However, the impact of limiting RAIT on rates of remission for this patient population has not been explored.

“These guidelines were made based on physician expertise and prior studies that we're seeing in adults,” Bojarsky said. “So therefore, this is the first study to explore the submission rate with and without RAIT in this ATA low-risk pediatric population. … This is important to show because we want to ensure that as we're reducing RAIT use in this pediatric population, we are not negatively impacting their ability to achieve remission.”

In the retrospective trial, investigators compared rates of remission (defined as an undetectable Tg level, TgAb below the upper limit of normal detection, and no evidence of disease by neck ultrasound) in 95 patients younger than 18 with DTC, categorized as ATA low-risk, who were treated with (n = 50) or without (n = 45) RAIT at 1 year after their initial treatment between 2010 and 2020. They assessed differences between medical history surgical pathology, oncogene-driver prevalence, and post-operative surveillance data.

Since the ATA guidelines were implemented, there was a 37% decline in RAIT use from 2016 to 2015 (75% to 38%).

“For these ATA low-risk patients, 1 year is a first reliable look, but continued surveillance is recommended to ensure stable and long-term remission,” Bojarsky concluded.

_Reference:

_{Bojarsky M, Baran J, Halada S, et al. Outcomes of ATA Low-Risk Pediatric Thyroid Cancer Patients Not Treated With Radioactive Iodine Therapy. Thyroid. 2022;32(1): A-136-A-174. doi:10.1089/thy.2022.29140.lb.abstracts}