Risk Of Subsequent Thyroid Cancer Research Articles

6893 The Interaction Effect Between BMI, Diabetes, and Age at Diabetes Onset on the Risk of Thyroid Cancer: A Population-Based Cohort Study

Abstract Disclosure: T. Hou: None. Y. Li: None. J. Tian: None. Z. Bloomgarden: None. Y. Shi: None. ObjectiveThe relationship between type 2 diabetes mellitus (T2DM) and thyroid cancer was confounded by some characteristics of diabetes. We aimed to determine the association of the presence of diabetes and, among persons with diabetes, the age at T2DM onset, BMI, and the interactive effect with the subsequent thyroid cancer risk. MethodsWe conducted a population-based longitudinal cohort study including 428,568 persons with new-onset T2DM matched with the general population (100,649,346 person-years). Risk of thyroid cancer by subgroups were calculated based on standardized incidence ratio (SIR), hazard ratio (HR), and Cox proportional hazards models. ResultsIn T2DM patients, 1142 thyroid cancer cases were identified during eight years of follow-up, with an incidence rate of 59.01/100,000 person-years and a higher SIR: 1.21 (95% CI: 1.14-1.28) compared to the general population. New-onset T2DM had an overall 21% higher risk of thyroid cancer. Both the earlier age at T2DM onset and higher BMI were associated with a significant increasing risk of thyroid cancer independently (T2DM onset age <50: SIR 1.46 (1.27-1.69); BMI ≥30.0 Kg/m2 SIR: 1.93 (1.57-2.38)). The highest risk of cancer appeared in the patients with both BMI ≥30.0 Kg/m2 and T2DM onset age <50 years (SIR=3.91, HR=3.04). Among patients with T2DM onset age <60 years, SIR shows an increasing trend of cancer risk with higher BMI levels, while no significant increasing trends with higher BMI in T2DM onset age ≥60 years. For patients with BMI ≥25.0 Kg/m2, SIR of cancer risk decreases with an later T2DM onset age, whereas no significant decreasing trends of cancer risk in BMI <24.9 Kg/m2 group. Obese (BMI ≥30.0 Kg/m2) patients had a significant higher HR of thyroid cancer only when T2DM onset age <60 years. ConclusionsBoth earlier age of T2DM onset (<50 years) and higher BMI (≥30 Kg/m2) contributed to higher risk of thyroid cancer. These results suggest that earlier screening of thyroid cancer might be appropriate in patients diagnosed with T2DM, especially in individuals with young-onset T2DM and obesity. Presentation: 6/3/2024

The interaction effect between BMI, diabetes and age at diabetes onset on the risk of thyroid cancer: A population-based cohort study in Shanghai, China.

To determine the association of the presence of diabetes and, among persons with diabetes, the age at type 2 diabetes mellitus (T2DM) onset, BMI and the interactive effect with the subsequent thyroid cancer risk. We conducted a population register-based longitudinal cohort study in Shanghai, including 428 568 persons with new-onset T2DM matched with the general population. The risk of thyroid cancer among subgroups was calculated based on standardized incidence ratio (SIR), hazard ratio (HR) and Cox proportional hazards models. In total, 1142 thyroid cancer cases were identified during 8 years of follow-up, with an incidence rate of 59.01/100 000 person-years and a higher risk (SIR = 1.21) compared with the general population. The earlier age at T2DM onset and higher BMI were associated with an increasing risk of thyroid cancer independently (onset age <50, SIR: 1.46; BMI ≥30.0 kg/m2, SIR: 1.93), with the highest risk in patients with both BMI ≥30.0 kg/m2 and onset age <50 years (SIR = 3.91, HR = 3.04). Among patients with T2DM onset age <60 years, SIR increased with higher BMI, while there were no trends when onset age ≥60 years. Among patients with BMI ≥25.0 kg/m2, SIR increased with an earlier onset age, whereas no trends were shown in the BMI <24.9 kg/m2 groups. Obese (BMI ≥30.0 kg/m2) patients had a significantly higher HR of thyroid cancer only when T2DM onset age <60 years. Both earlier age of T2DM onset (<50 years) and higher BMI (≥30 kg/m2) contributed to the higher risk of thyroid cancer. Patients with young-onset T2DM and obesity are considered more vulnerable to thyroid cancer development.

Exposure to radiotherapy for first primary cancer as a risk factor for second primary thyroid cancer: A case-control study

BackgroundSecond primary neoplasms are associated with high mortality and morbidity rates in cancer survivors successfully treated for the first malignancy. Studies suggested an association between the type of first neoplasm and risk of subsequent thyroid cancer, with part of this risk attributable to exposure to radiotherapy during treatment of the first primary tumor. This study aimed to determine whether radiotherapy is a risk factor for thyroid cancer in patients previously treated for another neoplasm. MethodsThis retrospective case-control study included patients diagnosed with their first cancer between 2007 and 2017. Patients who subsequently developed thyroid cancer as a second primary neoplasm were defined as “cases”, and patients who did not develop a second cancer were defined as “controls”. Exposure to radiotherapy was the primary risk factor of interest; other risk factors were the site to which radiotherapy was delivered and the first neoplasm type. ResultsExposure to radiotherapy was associated with an increased risk of thyroid cancer (odds ratio [OR]=2.410, 95% confidence interval [CI]: 1.219–4.764), in particular, in women (OR=3.121, 95% CI: 1.232–7.907) and in patients receiving radiotherapy to the thorax (OR=6.298, 95% CI: 2.581–15.370). The median survival time from first cancer recovery to thyroid cancer occurrence was 63.80 months; there was no difference in survival between patients who did and did not receive radiotherapy (P=0.899). ConclusionRadiation to the thorax can increase the risk of thyroid cancer as a second neoplasm among patients with cancer successfully treated for their first cancer.

Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Thyroid Cancer in Women

Background: Both polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) have been associated with thyroid hormone disruption, but their relationship to thyroid cancer is not known. Methods: We investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010-2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, and body mass index. Sub-analyses included stratification by tumor size (&lt;=1 cm and &gt;1 cm) and birth cohort (born before or in 1960 and born after 1960). We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with exposures to multiple PCB/OCPs. Results: No PCB/OCPs were positively associated with PTC risk in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the younger birth cohort based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. Conclusions: Our results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC risk, but some associations in the younger birth cohort suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

Exposure to polychlorinated biphenyls and organochlorine pesticides and thyroid cancer in connecticut women

BackgroundThyroid cancer incidence has increased substantially over the past decades, and environmental risk factors have been suggested to play a role. Polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) are established thyroid hormone disruptors, but their relationship to thyroid cancer is not known. MethodsWe investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010 to 2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, age, and body mass index. Sub-analyses included stratification by tumor size (≤ and >1 cm) and birth before or during peak PCB production (born in 1960 or earlier and born after 1960), as exposures during early life may be important. We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with co-exposures to multiple PCB/OCPs. ResultsNo PCB/OCPs were positively associated with PTC in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the those born during peak production based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. ConclusionsOur results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC, but some associations in those born during peak production suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

Thyroid cancer after hysterectomy and oophorectomy: a nationwide cohort study.

Little is known about the role of estrogen in thyroid cancer development. We aimed to evaluate the association between hysterectomy or bilateral salpingo-oophorectomy (BSO) and the risk of subsequent thyroid cancer. A nationwide cohort study. Data from the Korea National Health Insurance Service between 2002 and 2017 were used. A total of 78 961 and 592 330 women were included in the surgery group and no surgery group, respectively. The surgery group was categorized into two groups according to the extent of surgery: hysterectomy with ovarian conservation (hysterectomy-only) and BSO with or without hysterectomy (BSO). During 8 086 396.4 person-years of follow-up, 12 959 women developed thyroid cancer. Women in the hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) and BSO (adjusted hazard ratio = 1.4, P < 0.001) groups had increased risk of thyroid cancer compared to those in the no surgery group. In premenopausal women, hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) or BSO (adjusted hazard ratio = 1.4, P < 0.001) increased the risk of subsequent thyroid cancer, irrespective of hormone therapy, whereas, there was no significant association between hysterectomy-only (P = 0.204) or BSO (P = 0.857) and thyroid cancer development in postmenopausal women who had undergone hormone therapy. Our findings do not support the hypotheses that sudden or early gradual decline in estrogen levels is a protective factor in the development of thyroid cancer, or that exogenous estrogen is a risk factor for thyroid cancer.

Uterine Fibroids Increase the Risk of Thyroid Cancer.

Objectives: The formation of uterine fibroids (UF) is potentially linked to the development of thyroid cancer through a common factor: female sex hormones. Methods: We conducted a nationwide population-based cohort study to determine whether Taiwanese women with UF have an increased risk of thyroid cancer. The data of both the UF and control groups were derived from the National Health Insurance Research Database (NHIRD) of Taiwan. Groups were matched by the year of UF diagnosis, age, income, urbanization level, occupation, and comorbidities. A Cox proportional hazard regression model was used to compare the incidence of thyroid cancer between the UF and control groups. In addition, the model was used to determine the hazard ratio of thyroid cancer in the UF group in comparison with the control group. Results: Women with UF had a statistically significantly increased risk of thyroid cancer compared with controls (adjusted hazard ratio (aHR): 1.64, 95% confidence interval (CI): 1.26–2.13). Stratified analyses showed that women with UF who had a significantly increased risk of thyroid cancer were more likely to be middle aged, have middle and higher income levels, and a medium follow-up period (1–5 years) of UF. No other UF patient characteristics and comorbidities showed association with the risk of thyroid cancer. In addition, UF patients had a significantly increased risk of thyroid cancer regardless of whether or not they underwent myomectomy. Conclusions: The results suggest that women with UF have an increased risk of subsequent thyroid cancer. Further research is needed to explore whether surveillance strategies for the early detection of thyroid cancer using ultrasonography should be implemented among patients with UF.

Polygenic risk of subsequent thyroid cancer after childhood cancer: A report from St. Jude lifetime cohort (SJLIFE) and Childhood Cancer Survivor Study (CCSS).

10060 Background: Subsequent thyroid cancer (STC) is among the most common malignancies in childhood cancer survivors, especially those with thyroid exposure to radiotherapy (RT). Identification of genetic risk factors may inform screening practices. Methods: Twelve SNPs were previously identified as thyroid cancer risk loci in the general population of European ancestry. A polygenic risk score (PRS) was calculated as a sum of risk alleles carried by a survivor, weighted by the natural logarithm of the published per-allele odds ratios (range: 1.2-1.8). With piecewise exponential models, associations of STC rates with PRS were assessed, both overall and stratified by neck RT exposure. Models were adjusted for sex, age at primary diagnosis, attained age, neck RT dose, epipodophyllotoxin therapy, and eigenvectors within survivors of European ancestry from SJLIFE with whole-genome sequencing data and CCSS with SNP data imputed to Haplotype Reference Consortium. Results: Among 2,324 SJLIFE survivors, 61 (43 with, 18 without neck RT) developed STC. The rate of STC was increased by 5.3-fold (95% confidence interval (CI), 2.2-12.6) and 3.1-fold (CI, 1.3-7.7) for survivors in the third and second PRS tertiles, respectively, compared to those in the first tertile, with corresponding cumulative incidence at age of 40 years of 5.3% (CI, 3.3-7.3%), 2.5% (CI, 1.1-3.9%), and 1.0% (CI, 0.005-2.0%), respectively. Stratified by neck RT, the corresponding rate increases were 7.6 (CI, 2.3-25.3) and 3.8 (CI, 1.1-13.4), respectively, among survivors exposed to neck RT; however, no association was observed among survivors without neck RT (only 18 STC cases). Replication was performed among 4,302 CCSS survivors, 100 (61 with, 39 without neck RT) developed STC. The rates of STC were increased by 2.3-fold (CI, 1.4-3.9) and 1.7-fold (CI, 1.0-2.9) for survivors in the third and the second PRS tertiles, compared to those in the first tertile. The similar significant associations were observed in survivors with and without neck RT ( Ptrend = 0.04 and 0.02, respectively). Conclusions: High PRS conferring STC risk can inform screening practices and help personalize and improve survivorship care.

Radiotherapy for childhood cancer and subsequent thyroid cancer risk: a systematic review.

Most of the pooled analyses and reviews reported an association between radiotherapy for childhood cancer and an increased thyroid cancer risk. Up to now this article presents the first systematic literature review on this association combined with a critical assessment of the methodological quality of the included articles. PubMed and Web of Science databases were searched for relevant articles until May 2016. We included peer-reviewed cohort and case-control studies that investigated an association between radiotherapy for childhood cancer and the occurrence of subsequent thyroid cancer. A systematic overview is presented for the included studies. We identified 17 retrospective cohort studies, and four nested case-control studies, representing 100,818 subjects. The age range at first cancer diagnosis was 0-25.2years. Considerable variability was found regarding study sizes, study design, treatment strategies, dose information, and follow-up periods. 20 of the 21 identified studies showed increased thyroid cancer risks associated with childhood radiation exposure. The large majority showed an increased relative risk or odds ratio confirming the association between radiotherapy and thyroid cancer although the variation in results was large. Additionally to a pooled analysis that has been published recently, we systematically included 17 further studies, which allowed us to cover information from countries that were not covered by large-scale childhood cancer survivor studies. The methodological limitations of existing studies and inconsistencies in findings across studies yielded a large study heterogeneity, which made a detailed comparison of study results difficult. There is a need to strengthen standardisation for reporting.

Risk of second primary malignancies among patients with prostate cancer: A population-based cohort study.

PurposeThe rising incidence and life expectancy associated with prostate cancer (PCa) has led to increasing interest in predicting the risk of second primary malignancies (SPMs) among PCa survivors, although data regarding SPMs after PCa are controversial.MethodsWe identified 30,964 patients from the National Health Insurance Research Database in Taiwan who had newly diagnosed PCa between 2000 and 2010. Each patient was randomly frequency-matched with an individual without PCa, based on age, comorbidity, and index year. Competing-risks regression models were used to estimate subhazard ratios (SHRs) of SPMs development associated with PCa. The Bonferroni adjustment was used in multiple comparisons.ResultsMen with PCa had a trend of lower risk of developing overall SPMs compared to those without PCa (adjusted SHR = 0.94, 99.72% confidence interval [CI] = 0.89–1.00, p = 0.06). The risks of lung and liver cancer were significantly lower. In contrast, these patients had a significantly higher risk of thyroid cancer. There is a trend for a higher risk of developing SPMs in the urinary bladder and rectum/anus. Further analyses indicated that PCa patients who received radiation therapy (RT) had an increased risk of overall SPMs, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer compared with those who did not receive RT.ConclusionMen with PCa tended to have a lower risk of SPMs, but a significantly higher risk of subsequent thyroid cancer. Continued cancer surveillance is required among PCa survivors, especially in specific sites and in individuals who received RT.

The contribution of radiotherapy to subsequent thyroid cancer risk may be confined to a subgroup of breast cancer patients

Based on the “National Health Insurance Research Database (NHIRD)” of Taiwan, Sun Li-Min et al. found that the increased risk of thyroid cancer among breast cancer survivors of Taiwanese women was not related to radiotherapy (RT).1 However, this conclusion may be assertive considering the neglects of the following issues. First, thyroid cancer incidence of the whole population from the Cancer Registry data should be described and compared. Although the controls were randomly selected from NHIRD which covered approximately 99% of the residents, it seems not be proved that the control was a representative sample of the whole population. Moreover, we noticed that the thyroid cancer incidence of the control group (2.16 per 10,000 person-year) was different from those in other reports.2, 3 Second, the incubation period for induction of thyroid cancer by RT should be considered. The authors used the index date (the first treatment day of RT for the patients) as the beginning of the follow-up, then some incident thyroid cancer cases occurred immediately after the index date were probably not caused by RT. Therefore, thyroid cancer patients who were diagnosed in a period of time (e.g. half a year) after the index date may need to be excluded. Simultaneously, a sensitive test to compare the results before and after the exclusion would be helpful. This phenomenon has implications with regard to nondifferential misclassification, which usually leads underestimation of the incidence risk ratios.4 Third, the risk of thyroid cancer did increase in some sub groups. For example, Table 3 showed that the adjusted hazard ratios (HRs) of thyroid cancer risk for women receiving RT was 1.97 among those aged older than 55 years, almost twice as much as those receiving no RT (reference), although it did not reach a statistical level, which was probably due to a small sample size. Moreover, Table 5 showed that those receiving RT had a significant higher risk of thyroid cancer compared with patients without RT (aHR = 1.93, 95%, CI = 1.09–3.40) among breast cancer survivors without chemotherapy, which was not found in women with chemotherapy. This phenomenon suggests that RT may be involved in subsequent thyroid cancer development among breast cancer survivors, and this association may be modified by other treatment factors, like chemotherapy. In fact, for the whole study subjects, a nonsignificant 28% increase of thyroid cancer risk was observed (Table 2). Finally, for the several stratification analyses, a heterogeneity test or an interaction (multiplicative or additive models) test would be beneficial to verify whether the differences between strata were sampling errors or real differences.5, 6 Yours sincerely, Wei Lin, Fang-Mei Ren and Ze-Fang Ren

Radiotherapy and subsequent thyroid cancer in German childhood cancer survivors: a nested case-control study.

BackgroundRadiotherapy is associated with a risk of subsequent neoplasms (SN) in childhood cancer survivors. It has been shown that children’s thyroid glands are especially susceptible. The aim is to quantify the risk of a second neck neoplasm after primary cancer radiotherapy with emphasis on thyroid cancer.MethodsWe performed a nested case–control study: 29 individuals, diagnosed with a solid SN in the neck region, including 17 with thyroid cancer, in 1980–2002 and 57 matched controls with single neoplasms were selected from the database of the German Childhood Cancer Registry. We investigated the risk associated with radiotherapy exposure given per body region, adjusted for chemotherapy.Results16/17 (94.1 %) thyroid SN cases, 9/12 (75 %) other neck SN cases and 34/57 (59.6 %) controls received radiotherapy, with median doses of 27.8, 25 and 24 Gy, respectively. Radiotherapy exposure to the neck region increased the risk of the other neck SNs by 4.2 % (OR = 1.042/Gy (95 %-CI 0.980-1.109)) and of thyroid SN by 5.1 % (OR = 1.051/Gy (95 %-CI 0.984-1.123)), and radiotherapy to the neck or spine region increased the thyroid risk by 6.6 % (OR = 1.066/Gy (95 %-CI 1.010-1.125)). Chemotherapy was not a confounder. Exposure to other body regions was not associated with increased risk.ConclusionsRadiotherapy in the neck or spine region increases the risk of thyroid cancer, while neck exposure increases the risk of any other solid SN to a similar extent. Other studies showed a decreasing risk of subsequent thyroid cancer for very high doses; we cannot confirm this.

Radiotherapy did not increase thyroid cancer risk among women with breast cancer: A nationwide population-based cohort study.

The aim of this study was to evaluate whether an increased risk of thyroid cancer exists among women with breast cancer in Taiwan, particularly among those receiving RT. We used data from the National Health Insurance system of Taiwan for the investigation. The breast cancer cohort contained 55,318 women (including 28,187 who received RT and 27,131 who received no RT), each of whom was randomly frequency matched according to age and index year with three women without breast cancer from the general population. Cox's proportion hazards regression analysis was conducted to estimate the effects of breast cancer with or without RT treatment on subsequent thyroid cancer risk. We found that women with breast cancer exhibited a significantly higher risk of subsequent thyroid cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.60-2.44). The two groups (with or without RT) in the breast cancer cohort exhibited significantly increased risks. However, in the breast cancer cohort, the risk of thyroid cancer among women who received RT was not significantly higher than that of women who received no RT (aHR = 1.28, 95% CI = 0.90-1.83). Stratified analysis according to age revealed that only younger women with breast cancer (20-54 y) had a significantly higher risk of developing thyroid cancer. This study determined that Taiwanese women with breast cancer had a higher risk of developing thyroid cancer; however, RT seems to not play a crucial role in this possible relationship.

Thyroid doses for evacuees from the Fukushima nuclear accident

A primary health concern among residents and evacuees in affected areas immediately after a nuclear accident is the internal exposure of the thyroid to radioiodine, particularly I-131, and subsequent thyroid cancer risk. In Japan, the natural disasters of the earthquake and tsunami in March 2011 destroyed an important function of the Fukushima Daiichi Nuclear Power Plant (F1-NPP) and a large amount of radioactive material was released to the environment. Here we report for the first time extensive measurements of the exposure to I-131 revealing I-131 activity in the thyroid of 46 out of the 62 residents and evacuees measured. The median thyroid equivalent dose was estimated to be 4.2 mSv and 3.5 mSv for children and adults, respectively, much smaller than the mean thyroid dose in the Chernobyl accident (490 mSv in evacuees). Maximum thyroid doses for children and adults were 23 mSv and 33 mSv, respectively.

Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.

To determine the risk of thyroid dysfunction and subsequent thyroid cancer among childhood acute lymphoblastic leukemia (ALL) survivors. Rates of self-reported thyroid dysfunction and thyroid cancer were determined among 3,579 ALL survivors participating in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of pediatric cancers diagnosed from 1970 to 1986, and compared with 3,846 siblings and population rates, respectively. The cumulative incidence of hypo- and hyperthyroidism among survivors 15 years following leukemia diagnosis was 1.6% (95% CI 1.1, 2.1) and 0.6% (95% CI 0.3, 1.1), respectively, both significantly increased compared with siblings. In multivariate analysis, survivors who received >or=20 Gy cranial radiotherapy plus any spinal radiotherapy had the highest risk of subsequent hypothyroidism (HR 8.3, 95% CI 3.3, 20.5) compared with those treated with chemotherapy alone. Craniospinal radiotherapy also was associated with an increased risk of subsequent hyperthyroidism (HR 6.1, 95% CI 1.1, 34.2) compared with chemotherapy alone, as well as an increased risk of subsequent thyroid cancers (SIR 30.3, 95% CI 14.5, 55.7) compared with population rates. In radiation dosimetry analysis, pituitary doses >or=20 Gy combined with thyroid doses >or=10 Gy were associated with hypothyroidism, whereas pituitary doses >or=20 Gy combined with thyroid doses >or=15 Gy were associated with hyperthyroidism. The risk of thyroid dysfunction and thyroid cancer was increased among childhood ALL survivors treated with craniospinal radiotherapy. In these individuals, long-term surveillance is warranted as no obvious plateau in risk was seen, even after 25 years of follow-up.