Point/Counter

Should pediatric cancer survivors previously exposed to neck irradiation undergo ultrasound screening for thyroid cancer?

POINT

Yes.

Radiation is one of the few identifiable risks for developing papillary thyroid cancer, and younger age at exposure increases that risk.

We have limited data on whether active surveillance of patients treated with radiation therapy of a nonthyroid head and neck cancer is associated with benefit. 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 recommended that pediatric oncology survivors treated with radiation be counseled about the options for surveillance by either palpation or ultrasound. Active surveillance is likely to detect papillary thyroid cancer (PTC) at an earlier state of metastasis, with the potential to reduce future therapy. 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. These recommendations were mostly extrapolated from children with sporadic differentiated thyroid cancer, not from studies of radiation-induced PTC. Thus, to avoid overdiagnosis, the recommendations left us without a clear direction of how to counsel patients who are at an increased risk for cancer that has a higher risk for regional and distant metastasis than in adults.

Andrew J. Bauer

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 and an increased disease burden.

Two important points arose from the Fukushima nuclear accident: (1) The high prevalence of detected thyroid cancer does not appear to be secondary to radiation exposure, and (2) 70% of the patients diagnosed with PTC had lymph node metastasis. Thus, we really do not know if surveillance was associated with overdiagnosis of subclinical disease or early diagnosis of more aggressive disease.

So, what is the burden and what is the benefit? 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, but not disease-specific mortality. The burden of performing an ultrasound should be minimal.

The burden to the patient and family knowing that they are at increased risk for a secondary malignancy should not be minimized. In experienced hands, the rate of permanent complications from thyroid surgery should be less than 3% to 5%, and with early diagnosis, patients may achieve surgical remission, obviating the need for radioactive iodine.

  • 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.
  • 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.

COUNTER

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.

Denise Rokitka

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 significant 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 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 has not 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.

POINT

Yes.

Radiation is one of the few identifiable risks for developing papillary thyroid cancer, and younger age at exposure increases that risk.

We have limited data on whether active surveillance of patients treated with radiation therapy of a nonthyroid head and neck cancer is associated with benefit. 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 recommended that pediatric oncology survivors treated with radiation be counseled about the options for surveillance by either palpation or ultrasound. Active surveillance is likely to detect papillary thyroid cancer (PTC) at an earlier state of metastasis, with the potential to reduce future therapy. 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. These recommendations were mostly extrapolated from children with sporadic differentiated thyroid cancer, not from studies of radiation-induced PTC. Thus, to avoid overdiagnosis, the recommendations left us without a clear direction of how to counsel patients who are at an increased risk for cancer that has a higher risk for regional and distant metastasis than in adults.

Andrew J. Bauer

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 and an increased disease burden.

Two important points arose from the Fukushima nuclear accident: (1) The high prevalence of detected thyroid cancer does not appear to be secondary to radiation exposure, and (2) 70% of the patients diagnosed with PTC had lymph node metastasis. Thus, we really do not know if surveillance was associated with overdiagnosis of subclinical disease or early diagnosis of more aggressive disease.

So, what is the burden and what is the benefit? 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, but not disease-specific mortality. The burden of performing an ultrasound should be minimal.

The burden to the patient and family knowing that they are at increased risk for a secondary malignancy should not be minimized. In experienced hands, the rate of permanent complications from thyroid surgery should be less than 3% to 5%, and with early diagnosis, patients may achieve surgical remission, obviating the need for radioactive iodine.

  • 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.
  • 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.

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COUNTER

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.

Denise Rokitka

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 significant 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 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 has not 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.