Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts

Lubin, Jay H.; Adams, Michael; Shore, Roy E.; Holmberg, Erik; Schneider, Arthur B.; Hawkins, Michael M.; Robison, Leslie L.; Inskip, Peter D.; Lundell, Marie; Johansson, Robert; Kleinerman, Ruth A.; Vathaire, Florent de; Damber, Lena; Sadetzki, Siegal; Tucker, Margaret A.; Sakata, Ritsu; Veiga, Lene H.S.

doi:10.1210/jc.2016-3529

Cited by 131 publications

(104 citation statements)

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“…internal exposure. Both cohorts showed linear dose-response functions with little evidence of nonlinearity [45][46][47], though with an apparently lower risk per unit dose than seen in studies of children exposed to external radiation at fairly high dose rates [48]. The estimated thyroid doses are reasonably accurate though still uncertain [49], which lends support to a LNT interpretation following childhood exposures.…”

Section: Environmental Exposure Studiesmentioning

confidence: 60%

“…Conducting pooled studies [13] and meta-analyses [6,72,73] Although several studies showed null/negative dose-response relations for solid cancer (Table 1) or provided only limited evidence of a positive association at doses under about 100 mGy [32,43], a variety of studies has shown elevated solid cancer occurrence in the low-dose range [6,10,13,25,48]. Eleven (38%) studies provided moderate or strong support for the LNT model for radiation protection (Table 1), and other LD/LDR reports indicate dose-related elevations in leukemia risk [14,26,44,[81][82][83].…”

Section: Discussionmentioning

confidence: 99%

“…Studies of irradiation in childhood or adolescence and subsequent development of breast cancer generally support a linear dose response [53]. A recent pooled analysis of nine studies of external thyroid irradiation in childhood (primarily under age 15 y) and subsequent thyroid cancer showed a strong dose response, even over the range of 0 to 100 mGy, and little evidence of nonlinearity [48]. An analysis of solid cancer incidence among the Japanese atomic bomb survivors exposed before birth or during childhood showed a dose response with marginally significant upward curvature (p = 0.09), suggesting that the dose-response slope may be shallower in the low-dose range [63].…”

Section: Childhood Irradiation Studiesmentioning

confidence: 99%

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Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection

et al. 2018

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The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

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Section: Environmental Exposure Studiesmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Childhood Irradiation Studiesmentioning

confidence: 99%

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Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection

et al. 2018

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“…The fifth study is the pooled analysis of thyroid cancer incidence after childhood radiation exposures (58). One issue with this study is that thyroid cancer incidence is subject to considerable overdiagnosis.…”

Section: Discussion Of Ncrp Commentary 27mentioning

confidence: 99%

Are We Approaching the End of the Linear No-Threshold Era?

Doss

2018

J Nucl Med

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The linear no-threshold (LNT) model for radiation-induced cancer was adopted by national and international advisory bodies in the 1950s and has guided radiation protection policies worldwide since then. The resulting strict regulations have increased the compliance costs for the various uses of radiation, including nuclear medicine. The concerns about low levels of radiation due to the absence of a threshold have also resulted in adverse consequences. Justification of the LNT model was based on the concept that low levels of radiation increase mutations and that increased mutations imply increased cancers. This concept may not be valid. Low-dose radiation boosts defenses such as antioxidants and DNA repair enzymes. The boosted defenses would reduce the endogenous DNA damage that would have occurred in the subsequent period, and so the result would be reduced DNA damage and mutations. Whereas mutations are necessary for causing cancer, they are not sufficient since the immune system eliminates cancer cells or keeps them under control. The immune system plays an extremely important role in preventing cancer, as indicated by the substantially increased cancer risk in immune-suppressed patients. Hence, since low-dose radiation enhances the immune system, it would reduce cancers, resulting in a phenomenon known as radiation hormesis. There is considerable evidence for radiation hormesis and against the LNT model, including studies of atomic bomb survivors, background radiation, environmental radiation, cancer patients, medical radiation, and occupational exposures. Though Commentary 27 published by the National Council on Radiation Protection and Measurements concluded that recent epidemiologic studies broadly support the LNT model, a critical examination of the studies has shown that they do not. Another deficiency of Commentary 27 is that it did not consider the vast available evidence for radiation hormesis. Other advisory body reports that have supported the LNT model have similar deficiencies. Advisory bodies are urged to critically evaluate the evidence supporting both sides and arrive at an objective conclusion on the validity of the LNT model. Considering the strength of the evidence against the LNT model and the weakness of the evidence for it, the present analysis indicates that advisory bodies would be compelled to reject the LNT model. Hence, we may be approaching the end of the LNT model era.

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“…Children who have been exposed to radiation therapy (13)(14)(15) or chemotherapy (15) have an increased risk of developing thyroid nodules and thyroid cancer, as do patients with certain tumor predisposition syndromes, such as phosphatase and tensin hamartoma tumor and familial adenomatous polyposis syndromes (1). Although the American Thyroid Association does not currently recommend screening US of the thyroid in children in high-risk categories, it does recommend annual physical examination of the gland in these children (1).…”

mentioning

confidence: 99%

Thyroid Nodules in Pediatric Patients: Sonographic Characteristics and Likelihood of Cancer

et al. 2018

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Purpose To determine the relationship between demographic and sonographic characteristics of thyroid nodules and malignancy in a pediatric population. Materials and Methods All thyroid nodules in patients younger than 19 years that underwent ultrasound (US)-guided fine-needle aspiration biopsy between January 2004 and July 2017 were retrospectively identified. Age, sex, and background appearance of the thyroid gland were recorded for each patient, and sonographic characteristics and pathologic diagnosis were recorded for each nodule. Demographic and sonographic characteristics were assessed to determine which were associated with malignancy. Categorical and continuous variables and interobserver variability were assessed. Results A total of 404 nodules in 314 patients (82.8% female) (age range, 2-18 years; mean age, 14.9 years) were analyzed. A total of 77 nodules (19.1%) were malignant, the majority of which were papillary thyroid carcinoma (n = 68 [88.3%]). The likelihood of malignancy did not differ between boys and girls (27.8% vs 22.7%, P = .64), nor did it differ between prepubertal and pubertal patients (18.8% vs 19.1%, P > .99). The cancer rate in patients with a solitary nodule was higher than that in patients with multiple nodules (29.4% vs 14.2%, P = .003). Sonographic characteristics associated with malignant nodules included larger size, solid parenchyma, taller-than-wide shape, presence of speckled calcifications, lack of a smooth margin, and presence of abnormal lymph nodes. Interobserver variability for assessment of sonographic characteristics ranged from moderate to very strong. Conclusion In children with thyroid nodules, solitary nodules, larger nodule size, solid parenchyma, taller-than-wide shape, speckled calcifications, irregular margins, and abnormal lymph nodes raise concern for malignancy.

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Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts

Cited by 131 publications

References 44 publications

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection

Are We Approaching the End of the Linear No-Threshold Era?

Thyroid Nodules in Pediatric Patients: Sonographic Characteristics and Likelihood of Cancer

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