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 hypothyroidism. 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, 18 805 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 18 805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14 671 [78.0%]), and most had a Graves disease diagnosis (17 615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984

PURPOSE Since the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation. METHODS Using nine US SEER cancer registries (1975-2017), we estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes v no or unknown) using Poisson regression among ≥ 5- and ≥ 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively. RESULTS Among 27,050 ≥ 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among ≥ 20-year DTC survivors (RRsolid = 1.47; 95% CI, 1.24 to 1.74; RRbreast = 1.46; 95% CI, 1.10 to 1.95). Among 32,171 ≥ 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI. CONCLUSION In addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

This study demonstrates how the choice of the absorbed dose calculation algorithm may introduce a bias when gamma radiations are of importance, as is the case in nuclear medicine diagnostics.

Purpose The ARRONAX cyclotron facility offers the possibility to deliver proton beams from low to ultra‐high dose rates (UHDR). As a good control of the dosimetry is a prerequisite of UHDR experimentations, we evaluated in different conditions the usability and the dose rate dependency of several radiochromic films commonly used for dosimetry in radiotherapy. Methods We compared the dose rate dependency of three types of radiochromic films: GAFchromic™ EBT3 and GAFchromic™ EBT‐XD (Ashland Inc., Wayne, NJ, USA), and OrthoChromic OC‐1 (OrthoChrome Inc., Hillsborough, NJ, USA), after proton irradiations at various mean dose rates (0.25, 40, 1500, and 7500 Gy/s) and for 10 doses (2–130 Gy). We also evaluated the dose rate dependency of each film considering beam structures, from single pulse to multiple pulses with various frequencies. Results EBT3 and EBT‐XD films showed differences of response between conventional (0.25 Gy/s) and UHDR (7500 Gy/s) conditions, above 10 Gy. On the contrary, OC‐1 films did not present overall difference of response for doses except below 3 Gy. We observed an increase of the netOD with the mean dose rate for EBT3 and EBT‐XD films. OC‐1 films did not show any impact of the mean dose rate up to 7500 Gy/s, above 3 Gy. No difference was found based on the beam structure, for all three types of films. Conclusions EBT3 and EBT‐XD radiochromic films should be used with caution for the dosimetry of UHDR proton beams over 10 Gy. Their overresponse, which increases with mean dose rate and dose, could lead to non‐negligible overestimations of the absolute dose. OC‐1 films are dose rate independent up to 7500 Gy/s in proton beams. Films response is not impacted by the beam structure. A broader investigation of the usability of OC‐1 films in UHDR conditions should be conducted at intermediate and higher mean dose rates and other beam energies.