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Should pediatric cancer survivors previously exposed to neck irradiation undergo ultrasound screening for thyroid cancer?
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Yes.
We have very limited data on whether active surveillance of patients treated with radiation therapy for a nonthyroid head and neck cancer is associated with benefit. Current arguments against screening raise concern over the risk for additional procedures, as well as the lack of data showing improved survival. In 2018, an international group published recommendations that pediatric oncology survivors treated with radiation should be counseled about the options for surveillance by either physical exam (palpation) or ultrasound. The recommendations suggested that active surveillance is likely to detect papillary thyroid cancer (PTC), at an earlier state of metastasis, with the potential to reduce the extent of surgery and/or need for radioactive iodine. The disadvantage is detection of benign nodules that require continued surveillance, detection of occult PTC that may have remained subclinical, and the low likelihood of benefit secondary to PTC having low disease-specific mortality. Unfortunately, these recommendations were mostly extrapolated from children with sporadic differentiated thyroid cancer, not radiation-induced PTC.
The data from the Chernobyl nuclear accident helped define the latency for radiation-induced PTC and highlighted the importance of active surveillance, as many patients diagnosed prior to active screening presented with palpable disease as well as an increased disease burden, including 25% having pulmonary metastasis.
The most recent thyroid surveillance program conducted by the Fukushima Health Management Survey was implemented after a similar concern, a nuclear accident; however, the radiation exposure was no greater than background for the targeted cohort. Nonetheless, 187 pediatric patients were diagnosed with PTC and 70% had lymph node metastasis.
Thus, even in this low-risk population, it is unlikely that these findings represent “overdiagnosis” and more likely that they represent early diagnosis of disease that would have ultimately been associated with a need for more aggressive therapy.
So, what is the burden and what is the benefit of thyroid screening? Data show that radiation increases the risk for PTC and that a delay of more than 5 years after exposure may increase the risk for greater burden of disease, although not disease-specific mortality. The risk of performing an ultrasound is minimal when a clinician experienced in reading thyroid ultrasound images and managing pediatric thyroid nodular disease is involved in the process. Complications from thyroid nodule aspiration are extraordinarily low and the rate of permanent complications from thyroid surgery should be less than 3% to 5% if performed by a high-volume thyroid surgeon. And last, diagnosing PTC at an earlier state of metastasis may reduce the extent of surgery and obviate the benefit from radioiodine therapy.
Whose anxiety are we reducing when we inform patients and families that they are at significantly risk for developing a secondary, radiation-induced cancer but that we recommend pursuing the least-sensitive path for detection (palpation)? We let them know that if PTC is diagnosed that it is very responsive to treatment, but should we also inform them that waiting until the PTC is palpable may increase the risk for a greater burden of metastasis compared with monitoring with ultrasound? A lack of definitive data on the benefit of ultrasound monitoring of (or in) a high-risk population does not equal a lack of benefit, it just depends on how you, the patient and the family define benefit.
References:
Bogdanova TI, et al. Br J Cancer. 2015;doi:10.1038/bjc.2015.372.
Clement SC, et al. Cancer Treat Rev. 2018;doi:10.1016/j.ctrv.2017.11.005.
Clement SC, et al. Cancer Treat Rev. 2015;doi:10.1016/j.ctrv.2014.10.009.
Tronko ND, et al. Thyroid cancer in children and adolescents in Ukraine after the Chernobyl accident (1986–1995). The radiological consequences of the Chernobyl accent (1st International conference, Minsk, Belarus:18022.03.1996).
Yamashita S, et al. Thyroid. 2018;doi:10.1089/thy.2017.0283.
Andrew J. Bauer, MD, is director of the thyroid center in the division of endocrinology and diabetes at Children’s Hospital of Philadelphia. He can be reached at 3500 Civic Center Blvd., Buerger Center, Room 12-149, Philadelphia, PA 19104; email: bauera@chop.edu. Disclosure: Bauer reports a consultant role with Hexal AG.
No.
Radiation therapy with impact to the thyroid has known long-term complications, including hypothyroidism, hyperthyroidism and benign or malignant thyroid nodules. Typically, surveillance includes blood work to assess thyroid function and focused physical exam. Routine thyroid ultrasound remains controversial due to several factors.
There have been several studies looking at the value of thyroid ultrasound as a screening modality in patients who have had cancer therapy with an impact on the thyroid. However, there are several reasons why routine use has remained controversial. Namely, many survivors have benign thyroid nodules. Schneider and colleagues found that 87% of cancer survivors had thyroid nodules after irradiation to the thyroid. The majority of these nodules were not palpable on exam and were likely benign.
Second, there is a high false-positive rate of detection of thyroid nodules found on ultrasound with poor diagnostic value for detection of thyroid carcinoma. The next step in evaluating these nodules is a thyroid uptake scan and/or fine needle aspiration. Further testing and workup can cause a significant amount of anxiety and stress for the patient. The prevalence of thyroid carcinoma in cancer survivors is approximately 7%, with most cases being differentiated thyroid carcinoma, which has a favorable prognosis.
Thyroid nodules can occur any time after cancer therapy but most commonly occur more than 5 to 10 years from exposure. So, when is the right time to start screening with ultrasound? There is a prediction tool based on multiple risk factors, including dose of radiotherapy and years since radiotherapy, but it hasn’t been validated yet. This may be helpful in the future to guide clinicians.
However, lack of nodules on ultrasound does not indicate that they cannot form in the future. Ultimately, a good clinical exam of the thyroid that is repeated yearly is the most important way to find nodules of concern. Yearly ultrasounds of the thyroid increase health care costs and cause a significant amount of anxiety for the patient and may lead to overdiagnosis of nonclinically significant thyroid nodules.
References:
Brignardello E, et al. Eur J Cancer. 2016;doi:10.1016/j.ejca.2015.12.006.
Schneider AB, et al. J Clin Endocrinol Metab. 1997;doi:10.1210/jcem.82.12.4428.
Denise Rokitka, MD, MPH, is assistant professor and director of the pediatric and adolescent cancer survivorship and adolescent and young adult and oncofertility programs in the department of pediatric oncology at Roswell Park Comprehensive Cancer Center. She can be reached at Roswell Park Comprehensive Cancer Center, Elm and Carlton streets, Buffalo, NY 14263; email: denise.rokitka@roswellpark.org. Disclosure: Rokitka reports no relevant financial disclosures.