Second Primary Malignancy Risk After Radioactive Iodine Treatment for Thyroid Cancer: A Systematic Review and Meta-analysis
The risk of second primary malignancies (SPMs) associated with cancer therapies is an important concern of thyroid cancer survivors and physicians. Our objective was to determine if the risk of SPMs is increased in individuals with thyroid cancer treated with radioactive iodine (RAI), compared to those not treated with RAI.
We performed a systematic review of the literature and meta-analysis. Two independent reviewers screened citations and reviewed full-text papers. If not reported by the primary authors, the relative risk (RR) of SPMs was calculated by dividing the standardized incidence ratio of SPM in individuals with thyroid cancer treated with RAI compared to those not treated with RAI (with associated 95% confidence intervals [CI]). The natural logarithms of RRs of respective SPMs, weighted by the inverse of the variance, were pooled using fixed effects models and the exponential of the results was reported.
Two multi-center studies (one from Europe and the other from North America) were included in this review. The RR of SPMs in thyroid cancer survivors treated with RAI was significantly increased at 1.19 (95% confidence interval [CI] 1.04, 1.36, p = 0.010), relative to thyroid cancer survivors not treated with RAI (data from 16,502 individuals), using a minimum latency period of 2 to 3 years after thyroid cancer diagnosis. The RR of leukemia was also significantly increased in thyroid cancer survivors treated with RAI, with an RR of 2.5 (95% CI 1.13, 5.53, p = 0.024). We did not observe a significantly increased risk of the following cancers related to prior RAI treatment: bladder, breast, central nervous system, colon and rectum, digestive tract, stomach, pancreas, kidney (and renal pelvis), lung, or melanoma of skin.
The risk of SPMs in thyroid cancer survivors treated with RAI is slightly increased compared to thyroid cancer survivors not treated with RAI.
Available from: Brendan C Stack
- "In a review and meta-analysis of two multicenter studies (one from Europe and the other from North America), Sawka et al. (2009) concluded that the risk of SPMs in thyroid cancer survivors treated with RAI is slightly increased compared with thyroid cancer survivors not treated with RAI. Tuttle's group has recently published an analysis of the Surveillance, Epidemiology, and End Results (SEER) database and concluded that RAI therapy needed to be 'rationed' in low-risk DTC patients (Iyer et al. 2011). "
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ABSTRACT: Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the 5th most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post thyroidectomy patient has included radioactive iodine (RAI) ablation and/or therapy. Prior to 2000, a typical RAI post-operative dose recommendation was 100 mCi for remnant ablation, 150 mCi for locoregional nodal disease and 175-200 mCi for distant metastases (Thyroid 2013;23(6):683-694). Recent recommendations have been made to decrease the dose in order to limit the perceived adverse effects of RAI including salivary gland dysfunction and inducing secondary primary malignancies (SPM). Significant controversy has thus arisen surrounding the use of RAI, particularly in the management of the low risk DTC patient. This debate includes the definition of the low risk patient, RAI dose selection and whether or not RAI is needed in all patients. To allow the reader to form an opinion regarding post-operative RAI therapy in DTC, a literature review of the risks and benefits is presented.
Available from: Jakob Kist
- "Such patients will have received a total body irradiation of 450 millisievert (mSv) and may have suffered from side effects such as nausea, sialoadenitis, loss of taste, or reduced spermatogenesis. Furthermore, their risk of secondary malignancies has increased [31,32]. All induced by a treatment from which they derived no benefit. "
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After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.
In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.
This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.
Clinicaltrials.gov identifier: NCT01641679.
- "However, 131I is considered a very useful radionuclide in reducing thyroid activity, nevertheless, as a genotoxic agent that may produce secondary cancer incidence in patients. Incidence of leukemia was significantly increased in patients after iodine therapy. 131I emits gamma and beta rays. "
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131-radioiodine has been widely used as an effective radionuclide for treatment of patients with thyroid diseases. The purpose of the present study is to investigate the radioprotective effects of curcumin as a natural product that protects against the genotoxic effects of 131I in human cultured lymphocytes.
Materials and Methods:
Whole blood samples from human volunteers were incubated with curcumin at doses of 5, 10, and 50 μg/mL. After 1-hour incubation, the lymphocytes were incubated with 131I (100 μCi/1.5 ml) for 2 hours. The lymphocyte cultures were then mitogenically stimulated to allow for evaluation of the number of micronuclei in cytokinesis-blocked binucleated cells.
Incubation of lymphocytes with 131I at dose 100 μCi/1.5 mL induced genotoxicity shown by increase in micronuclei frequency in human lymphocytes. Curcumin at 5, 10, and 50 μg/mL doses significantly reduced the micronuclei frequency. Maximal protective effects and greatest decrease in micronuclei frequency were observed when whole blood was incubated with 50 μg/mL dose of curcumin with 52%.
This study has important implications for patients undergoing 131I therapy. Our results indicate a protective role for curcumin against the genetic damage and side effects induced by 131I administration.
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