Veroorzaakt de RAI-behandeling bij de ziekte van Graves kanker?
Geplaatst: 21 aug 2020, 09:06
What's the Future Cancer Risk of RAI Treatment?
Re-examining the relationship between dose and response in radioactive iodine treatment
Lisa Jaffe | Endocrineweb
Association of Radioactive Iodine, Antithyroid Drug, and Surgical Treatments With Solid Cancer Mortality in Patients With Hyperthyroidism
Cari M. Kitahara, Dale L. Preston, Julie Ann Sosa, Amy Berrington de Gonzalez
JAMA Netw Open. 2020;3(7):e209660. doi:10.1001/jamanetworkopen.2020.9660
Does radioactive iodine therapy for Graves’ disease cause cancer?
Clinical Thyroidology for the Public
Key Points
Question Are radioactive iodine or antithyroid drug treatments for hyperthyroidism associated with greater risk of solid cancer mortality compared with surgical management?
Findings In this cohort study of 31 363 patients who were cancer free at baseline, no association was found between treatment group (radioactive iodine, medications, and/or surgery) and risk of solid cancer mortality. Among patients receiving radioactive iodine treatment, the association with solid cancer mortality increased with greater total administered activity.
Meaning The findings suggest that the association between radioactive iodine treatment and solid cancer mortality is dose dependent.
Abstract
Importance The long-term health effects of radioactive iodine (RAI) and antithyroid drug (ATD) treatments compared with surgery for hyperthyroidism remain uncertain.
Objective To compare solid cancer mortality rates associated with RAI and ATD treatments vs surgical management for hyperthyroidism.
Design, Setting, and Participants This multicenter cohort study assessed patients treated for hyperthyroidism from January 1, 1946, to December 31, 1964, with follow-up through December 31, 2014. Data analysis was performed from August 1, 2019, to April 23, 2020.
Exposures Management with RAI, ATDs, surgical intervention, or combinations of these treatments.
Main Outcomes and Measures Comparisons of solid cancer mortality rates in each treatment group with expected rates from the general population were assessed using standardized mortality ratios (SMRs), and internal comparisons were assessed using hazard ratios (HRs) adjusted for age, sex, and underlying diagnosis (Graves disease or toxic nodular goiter).
Results Of 31 363 patients (24 894 [79.4%] female; mean [SD] age, 46.9 [14.8] years) included in the study, 28 523 (90.9%) had Graves disease. The median follow-up time was 26.0 years (interquartile range, 12.3-41.9 years). Important differences in patient characteristics existed across treatment groups at study entry. Notably, the drug-only group (3.6% of the cohort) included a higher proportion of patients with prior cancers (7.3% vs 1.9%-4.0%), contributing to an elevated SMR for solid cancer mortality. After excluding prior cancers, solid cancer SMRs were not elevated in any of the treatment groups (SMR for surgery only, 0.82 [95% CI, 0.66-1.00]; SMR for drugs only, 0.90 [95% CI, 0.74-1.09]; SMR for drugs and surgery, 0.88 [95% CI, 0.84-0.94]; SMR for RAI only, 0.90 [95% CI, 0.84-0.96]; SMR for surgery and RAI, 0.66 [95% CI, 0.52-0.85]; SMR for drugs and RAI, 0.94 [95% CI, 0.89-1.00]; and SMR for drugs, surgery, and RAI, 0.85 [95% CI, 0.75-0.96]), and no significant HRs for solid cancer death were observed across treatment groups. Among RAI-treated patients, HRs for solid cancer mortality increased significantly across levels of total administered activity (1.08 per 370 MBq; 95% CI, 1.03-1.13 per 370 MBq); this association was stronger among patients treated with only RAI (HR, 1.19 per 370 MBq; 95% CI, 1.09-1.30 per 370 MBq).
Limitations
This study has limitations. Those not already mentioned include lack of information on some potential confounding factors, such as cigarette smoking, obesity, and reproductive factors21,26; however, we found no association between treatment type (or radiation-absorbed dose to the lung21) and lung cancer mortality, suggesting that a major smoking-related bias did not occur. We lacked laboratory measures of thyroid function to assess severity of the underlying disease. The reliance on cancer mortality, as opposed to incidence, follow-up was another limitation because we could not distinguish between factors associated with cancer development vs survival. In addition, mortality follow-up is not ideal for capturing cancers with high survival rates (eg, thyroid or breast) or for studying cancer subtypes. Findings related to RAI treatment may not be generalizable to patients with thyroid cancer, who typically receive higher administered activities (>3700 MBq) in the context of postsurgical remnant ablation or therapy for presumed or known advanced or metastatic disease, potentially yielding higher or lower doses to individual organs or tissues, depending on the size and location of the residual thyroid tissue.36
Conclusions
This study found positive associations between total administered activity of RAI and risks of death from total solid cancer, female breast cancer, and nonbreast solid cancers. These findings were consistent with earlier results from this cohort based on organ-absorbed doses.21 The low, narrow range of total administered activity and the potential for residual confounding by risk factors not captured in this study may have hindered our ability to detect differences in risk between RAI-treated and non–RAI-treated patients. No evidence supporting an association between ATD treatment and risk of solid cancer death was found in this cohort.
After controlling for known sources of confounding, the study found no significant differences in the risk of solid cancer mortality by treatment group. However, among RAI-treated patients, a modest positive association was observed between total administered activity and solid cancer mortality, providing further evidence in support of a dose-dependent association between RAI and solid cancer mortality.
Re-examining the relationship between dose and response in radioactive iodine treatment
Lisa Jaffe | Endocrineweb
Association of Radioactive Iodine, Antithyroid Drug, and Surgical Treatments With Solid Cancer Mortality in Patients With Hyperthyroidism
Cari M. Kitahara, Dale L. Preston, Julie Ann Sosa, Amy Berrington de Gonzalez
JAMA Netw Open. 2020;3(7):e209660. doi:10.1001/jamanetworkopen.2020.9660
Does radioactive iodine therapy for Graves’ disease cause cancer?
Clinical Thyroidology for the Public
Key Points
Question Are radioactive iodine or antithyroid drug treatments for hyperthyroidism associated with greater risk of solid cancer mortality compared with surgical management?
Findings In this cohort study of 31 363 patients who were cancer free at baseline, no association was found between treatment group (radioactive iodine, medications, and/or surgery) and risk of solid cancer mortality. Among patients receiving radioactive iodine treatment, the association with solid cancer mortality increased with greater total administered activity.
Meaning The findings suggest that the association between radioactive iodine treatment and solid cancer mortality is dose dependent.
Abstract
Importance The long-term health effects of radioactive iodine (RAI) and antithyroid drug (ATD) treatments compared with surgery for hyperthyroidism remain uncertain.
Objective To compare solid cancer mortality rates associated with RAI and ATD treatments vs surgical management for hyperthyroidism.
Design, Setting, and Participants This multicenter cohort study assessed patients treated for hyperthyroidism from January 1, 1946, to December 31, 1964, with follow-up through December 31, 2014. Data analysis was performed from August 1, 2019, to April 23, 2020.
Exposures Management with RAI, ATDs, surgical intervention, or combinations of these treatments.
Main Outcomes and Measures Comparisons of solid cancer mortality rates in each treatment group with expected rates from the general population were assessed using standardized mortality ratios (SMRs), and internal comparisons were assessed using hazard ratios (HRs) adjusted for age, sex, and underlying diagnosis (Graves disease or toxic nodular goiter).
Results Of 31 363 patients (24 894 [79.4%] female; mean [SD] age, 46.9 [14.8] years) included in the study, 28 523 (90.9%) had Graves disease. The median follow-up time was 26.0 years (interquartile range, 12.3-41.9 years). Important differences in patient characteristics existed across treatment groups at study entry. Notably, the drug-only group (3.6% of the cohort) included a higher proportion of patients with prior cancers (7.3% vs 1.9%-4.0%), contributing to an elevated SMR for solid cancer mortality. After excluding prior cancers, solid cancer SMRs were not elevated in any of the treatment groups (SMR for surgery only, 0.82 [95% CI, 0.66-1.00]; SMR for drugs only, 0.90 [95% CI, 0.74-1.09]; SMR for drugs and surgery, 0.88 [95% CI, 0.84-0.94]; SMR for RAI only, 0.90 [95% CI, 0.84-0.96]; SMR for surgery and RAI, 0.66 [95% CI, 0.52-0.85]; SMR for drugs and RAI, 0.94 [95% CI, 0.89-1.00]; and SMR for drugs, surgery, and RAI, 0.85 [95% CI, 0.75-0.96]), and no significant HRs for solid cancer death were observed across treatment groups. Among RAI-treated patients, HRs for solid cancer mortality increased significantly across levels of total administered activity (1.08 per 370 MBq; 95% CI, 1.03-1.13 per 370 MBq); this association was stronger among patients treated with only RAI (HR, 1.19 per 370 MBq; 95% CI, 1.09-1.30 per 370 MBq).
Limitations
This study has limitations. Those not already mentioned include lack of information on some potential confounding factors, such as cigarette smoking, obesity, and reproductive factors21,26; however, we found no association between treatment type (or radiation-absorbed dose to the lung21) and lung cancer mortality, suggesting that a major smoking-related bias did not occur. We lacked laboratory measures of thyroid function to assess severity of the underlying disease. The reliance on cancer mortality, as opposed to incidence, follow-up was another limitation because we could not distinguish between factors associated with cancer development vs survival. In addition, mortality follow-up is not ideal for capturing cancers with high survival rates (eg, thyroid or breast) or for studying cancer subtypes. Findings related to RAI treatment may not be generalizable to patients with thyroid cancer, who typically receive higher administered activities (>3700 MBq) in the context of postsurgical remnant ablation or therapy for presumed or known advanced or metastatic disease, potentially yielding higher or lower doses to individual organs or tissues, depending on the size and location of the residual thyroid tissue.36
Conclusions
This study found positive associations between total administered activity of RAI and risks of death from total solid cancer, female breast cancer, and nonbreast solid cancers. These findings were consistent with earlier results from this cohort based on organ-absorbed doses.21 The low, narrow range of total administered activity and the potential for residual confounding by risk factors not captured in this study may have hindered our ability to detect differences in risk between RAI-treated and non–RAI-treated patients. No evidence supporting an association between ATD treatment and risk of solid cancer death was found in this cohort.
After controlling for known sources of confounding, the study found no significant differences in the risk of solid cancer mortality by treatment group. However, among RAI-treated patients, a modest positive association was observed between total administered activity and solid cancer mortality, providing further evidence in support of a dose-dependent association between RAI and solid cancer mortality.