Conclusion. RAI was associated with improved survival in patients with stage IV DTC, while EBRT was associated with poorer survival outcomes.
Commentary
Radioiodine therapy has been used for treatment of DTC since the 1940s. Radioactive iodine (I-131) is largely taken up by thyroid follicular cells via their sodium-iodide transporter causing acute thyroid cell death by emission of short path length beta particles [1].
External beam radiation therapy (EBRT) is the most common radiation therapy approach to deliver radiation from a source outside of the patient. EBRT machines produce radiation by either radioactive decay of a nuclide or by acceleration of charged particles such as electrons or protons. Using a linear accelerator, charged particles are accelerated to a high enough energy to allow transmission of particles as an electron beam or x-ray, which is subsequently directed at the tumor [2].
This study by Yang and colleagues aimed to examine survival differences in patients with stage IV DTC who received one of these adjuvant radiation modalities post-thyroidectomy. All treatment groups showed improved survival, with RAI with decreases in death hazard in both univariate and multivariate analysis. Patients with stage IV DTC prolonged their survival by a factor of 1.53–4.66 in multivariate models and 1.63–4.92 in univariate models. This clearly supports the effectiveness of RAI as an adjuvant treatment to DTC following surgical resection.
However, this study has several limitations. As this was a retrospective cohort study, the lack of randomization introduces a potential source of bias. In addition, since data was collected via the National Cancer Database, there was limited information that could be obtained on the subjects studied. Disease-specific survival and recurrence rates were not reported and even histological grades were missing more than 50% of the time. Finally, older age and more advanced stage in the EBRT cohorts were likely confounders in the results of increased death hazard and mortality that were observed. It should be noted, however, that attempts to adjust for these covariates were made by the authors by analyzing the data using multivariate analysis.
There are a number of potential reasons as to why the RAI-treated patients did significantly better than the EBRT-treated patients. Based on the current literature and guidelines, EBRT is mainly recommended as a palliative treatment of locally advanced, unresectable, or metastatic disease in primarily noniodine-avid tumors. Therefore, it is certainly feasible that patients in this study who underwent treatment with EBRT had more aggressive disease and were thus at higher risk to begin with. Perhaps the indications to treat with EBRT inherently confer a poorer prognosis in advanced DTC patients. In addition, RAI is a systemic treatment modality whereas EBRT is only directed locally to the neck and thus may miss micro-metastatic lesions elsewhere in the body.
Applications for Clinical Practice
Current standard practice in thyroid cancer management involve the use of radioiodine therapy in treatment of selected intermediate-risk and all high-risk DTC patients after total thyroidectomy. These patients are treated with 131-I to destroy both remnant normal thyroid tissue and microscopic or subclinical disease remaining after surgery. The decision to administer radioactive iodine post-thyroidectomy in patients with DTC is based on risk stratification of clinicopathologic features of the tumor. The efficacy of RAI is dependent on many factors including sites of disease, patient preparation, tumor characteristics, and dose of radiation administered.
EBRT is currently used much less frequently than RAI in the management of differentiated thyroid cancer. Its main use has been for palliative treatment of locally advanced, unresectable, or metastatic disease in primarily noniodine-avid tumors. It has also been suggested for use in older patients (age 55 years or older) with gross extrathyroidal extension at the time of surgery (T4 disease), or in younger patients with T4b or extensive T4a disease and poor histologic features, with tumors that are strongly suspected to not concentrate iodine. The use of EBRT in other settings is not well established [3,4].
Treatment benefits of RAI in DTC have been extensively studied; however, this is the largest study that has examined long-term survival in a cohort of just under 12,000 patients with stage IV DTC. The results from this large cohort with advanced disease further demonstrates improved overall survival in stage IV DTC patients treated with RAI at 5 and 10 years. It is clear that RAI is the first-line adjuvant radiation therapy of DTC and should remain the standard of care in thyroid cancer management.
—Kayur Bhavsar, MD, University of Maryland School of Medicine
Baltimore, MD