Association of Radioactive Iodine Treatment with Cancer Mortality in Patients with Hyperthyroidism

Cari M. Kitahara, Amy Berrington De Gonzalez, Andre Bouville, Aaron B. Brill, Michele M. Doody, Dunstana R. Melo, Steven L. Simon, Julie A. Sosa, Mark Tulchinsky, Daphnée Villoing, Dale L. Preston

Research output: Contribution to journalArticle

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Abstract

Importance: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism. Objective: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. Design, Setting, and Participants: This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. Exposures: Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). Main Outcomes and Measures: Site-specific and all solid-cancer mortality. Results: A total of 18805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14671 [78.0%]), and most had a Graves disease diagnosis (17615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P =.002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P =.04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P =.01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. Conclusions and Relevance: In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

Original languageEnglish (US)
Pages (from-to)1034-1042
Number of pages9
JournalJAMA Internal Medicine
Volume179
Issue number8
DOIs
StatePublished - Aug 1 2019

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Hyperthyroidism
Iodine
Mortality
Neoplasms
Stomach
Therapeutics
Graves Disease
Breast
Breast Neoplasms
United States Social Security Administration
Cohort Studies
Sodium Iodide
Nodular Goiter
Death Certificates
Thyrotoxicosis
Poisons
Mouth Mucosa
Rectum
Esophagus
Uterus

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Kitahara, C. M., Berrington De Gonzalez, A., Bouville, A., Brill, A. B., Doody, M. M., Melo, D. R., ... Preston, D. L. (2019). Association of Radioactive Iodine Treatment with Cancer Mortality in Patients with Hyperthyroidism. JAMA Internal Medicine, 179(8), 1034-1042. https://doi.org/10.1001/jamainternmed.2019.0981
Kitahara, Cari M. ; Berrington De Gonzalez, Amy ; Bouville, Andre ; Brill, Aaron B. ; Doody, Michele M. ; Melo, Dunstana R. ; Simon, Steven L. ; Sosa, Julie A. ; Tulchinsky, Mark ; Villoing, Daphnée ; Preston, Dale L. / Association of Radioactive Iodine Treatment with Cancer Mortality in Patients with Hyperthyroidism. In: JAMA Internal Medicine. 2019 ; Vol. 179, No. 8. pp. 1034-1042.
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abstract = "Importance: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism. Objective: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. Design, Setting, and Participants: This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. Exposures: Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). Main Outcomes and Measures: Site-specific and all solid-cancer mortality. Results: A total of 18805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14671 [78.0{\%}]), and most had a Graves disease diagnosis (17615 [93.7{\%}]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95{\%} CI, 1.02-1.10; P =.002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95{\%} CI, 1.003-1.32; P =.04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95{\%} CI, 1.01-1.10; P =.01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95{\%} CI, 3-40) to 32 (95{\%} CI, 5-66) solid cancer deaths could occur. Conclusions and Relevance: In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.",
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Kitahara, CM, Berrington De Gonzalez, A, Bouville, A, Brill, AB, Doody, MM, Melo, DR, Simon, SL, Sosa, JA, Tulchinsky, M, Villoing, D & Preston, DL 2019, 'Association of Radioactive Iodine Treatment with Cancer Mortality in Patients with Hyperthyroidism', JAMA Internal Medicine, vol. 179, no. 8, pp. 1034-1042. https://doi.org/10.1001/jamainternmed.2019.0981

Association of Radioactive Iodine Treatment with Cancer Mortality in Patients with Hyperthyroidism. / Kitahara, Cari M.; Berrington De Gonzalez, Amy; Bouville, Andre; Brill, Aaron B.; Doody, Michele M.; Melo, Dunstana R.; Simon, Steven L.; Sosa, Julie A.; Tulchinsky, Mark; Villoing, Daphnée; Preston, Dale L.

In: JAMA Internal Medicine, Vol. 179, No. 8, 01.08.2019, p. 1034-1042.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of Radioactive Iodine Treatment with Cancer Mortality in Patients with Hyperthyroidism

AU - Kitahara, Cari M.

AU - Berrington De Gonzalez, Amy

AU - Bouville, Andre

AU - Brill, Aaron B.

AU - Doody, Michele M.

AU - Melo, Dunstana R.

AU - Simon, Steven L.

AU - Sosa, Julie A.

AU - Tulchinsky, Mark

AU - Villoing, Daphnée

AU - Preston, Dale L.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Importance: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism. Objective: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. Design, Setting, and Participants: This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. Exposures: Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). Main Outcomes and Measures: Site-specific and all solid-cancer mortality. Results: A total of 18805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14671 [78.0%]), and most had a Graves disease diagnosis (17615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P =.002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P =.04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P =.01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. Conclusions and Relevance: In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

AB - Importance: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism. Objective: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. Design, Setting, and Participants: This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. Exposures: Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). Main Outcomes and Measures: Site-specific and all solid-cancer mortality. Results: A total of 18805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14671 [78.0%]), and most had a Graves disease diagnosis (17615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P =.002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P =.04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P =.01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. Conclusions and Relevance: In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

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Kitahara CM, Berrington De Gonzalez A, Bouville A, Brill AB, Doody MM, Melo DR et al. Association of Radioactive Iodine Treatment with Cancer Mortality in Patients with Hyperthyroidism. JAMA Internal Medicine. 2019 Aug 1;179(8):1034-1042. https://doi.org/10.1001/jamainternmed.2019.0981