Increased Risk of Second Primary Malignancy in Pediatric and Young Adult Patients Treated with Radioactive Iodine for Differentiated Thyroid Cancer

Abstract

Introduction: The long-term sequelae of radioactive iodine (RAI) for differentiated thyroid cancer (DTC) in pediatric and young adult patients are not well-defined. Epidemiologic analyses of second primary malignancy (SPM) risk have only been performed in the adult population. Existing data are limited to case series with limited follow-up. The objective of this study was to analyze the elevated risk of SPM attributable to RAI in young patients treated for DTC. Methods: Population-based analysis of 3850 pediatric and young adult patients ( < 25 years old) undergoing treatment with surgery with/without RAI for DTC, followed in the Surveillance, Epidemiology, and End Results cancer registry , equating to 54,727 person-years at risk (PYR). The excess risk of SPM was calculated relative to a reference population and expressed as standardized incidence ratio (SIR) and excess absolute risk (EAR) per 10,000 PYR. Excess risk was compared in RAI-treated and non-RAI-treated patients. Results: A total of 1571 patients (40%) received RAI. The percentage of patients treated with RAI increased over time, from 4% in 1973 to 62% in 2008 ( p < 0.001). Among patients who received RAI, 26 SPMs were observed, and 18.3 were expected. The relative risk of SPM at any site was significantly elevated (SIR = 1.42), corresponding to 4.4 excess cases per 10,000 PYR. SPM risk was not elevated in the non-RAI-treated cohort (SIR = 1.01, EAR = 0). Patients treated with RAI were at dramatically elevated risk for development of a salivary malignancy (SIR = 34.1), corresponding to 1.7 excess cases per 10,000 PYR. The risk of leukemia in RAI-treated patients was elevated (SIR = 4.0, EAR = 0.9) but did not reach statistical significance. There was no elevated risk of salivary cancer or leukemia in the non-RAI-treated cohort. Conclusions: Pediatric and young adult patients who receive RAI for DTC experience an elevated risk of SPM, mainly salivary gland cancer. These risks appear to be only slightly higher than in adult patients. Over a decade, approximately 1 in 227 RAI-treated patients will develop an SPM, and 1 in 588 RAI-treated patients will develop a salivary cancer, attributable to RAI. Because the expected survival time for young DTC patients is long, it is critical to weigh the benefits of RAI carefully against the small, but real, increase in SPM risk.

Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors

“…Because of the rarity of paediatric DTC, the optimal initial and long‐term treatment has been controversial and specific ATA guidelines were developed for the management of DTC in children only in 2015 . These recommendations suggest reconsidering the traditional approach of extensive surgery and routine 131 I therapy in order to reduce the risk of surgical complications and of second malignancy . In our series, a more aggressive approach was used according to previous indications (as paediatric DTC guidelines from ATA became available only in 2015): prophylactic central node dissection was extensively performed when the diagnosis of malignancy was preoperatively established and 131 I therapy was widely used (82.3% of cases).…”

Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma?

“…A more comprehensive surgical approach raises the risk of important clinical complications, mainly transient or permanent hypoparathyroidism and recurrent laryngeal nerve damage. The RAI therapy is associated with an increase in the risk of second primary malignancy, especially salivary cancer (Marti et al 2015).…”

Excessive risk of second primary cancers in young‐onset colorectal cancer survivors

“…According to Survivorship Statistics released by American Cancer Society, it is estimated that more than 15 million survivors are living in the United States with a previous colorectal cancer diagnosis in 2016 . A large body of literatures reported the increased risk of second primary malignancies among population with certain prior cancers, including CRC . Several population‐based studies had validated that a history of prior CRC was a known risk factor for developing second malignancies subsequently in relation to the general population .…”

“…Introduction malignancies among population with certain prior cancers, including CRC [6][7][8][9][10]. Several population-based studies had validated that a history of prior CRC was a known risk factor for developing second malignancies subsequently in relation to the general population [11][12][13][14].…”