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Postoperative Radioactive Iodine Ablation and Treatment of Differentiated Thyroid Cancer
Introduction to Chapter 48, Postoperative Radioactive Iodine Ablation and Treatment of Differentiated Thyroid Cancer.
Introduction
The role of radioactive iodine (RAI) therapy in the postoperative management of patients with newly diagnosed differentiated thyroid cancer (DTC) is a highly controversial topic. Endocrinologists and nuclear medicine physicians strongly differ in their opinions regarding the diagnostic and therapeutic uses of RAI therapy in the postoperative setting. This has resulted in vastly different guidelines and position statements from the groups’ respective societies.
RAI therapy aims to improve the disease-specific survival, decrease the disease-specific recurrence risk, facilitate the initial staging, and allow for highly sensitive follow-up of patients with DTC. The difference in opinion is in the selection of patients that would most benefit from RAI therapy. The first position advocates using RAI therapy on all patients except those presenting with intrathyroidal papillary thyroid microcarcinoma without aggressive features. The second position advocates selective use of RAI, thus reserving RAI therapy for those patients who are most likely to benefit from it. Selection of patients who are candidates to be treated with RAI therapy is based on the (1) assessment of disease-specific risks for recurrence and mortality, (2) assessment of postoperative disease status, (3) likelihood of clinical benefit with RAI therapy, (4) likelihood of adverse effects with RAI therapy, (5) need for postoperative staging, (6) need for highly sensitive follow-up, (7) treatment philosophy of the treating multidisciplinary team, and (8) patient wishes and values.
The main reason for the controversy is that most of the evidence regarding the use of RAI therapy in the postoperative setting is largely gathered from retrospective, observational studies that vary greatly in their enrollment criteria, risk assessment models, definition of the RAI therapy role, clinical response criteria, and results. Outside of the two multicenter prospective randomized prospective clinical trials studying the role of RAI ablation in low-risk DTC patients, there are no well-conducted multicenter randomized control trials (RCTs) that support one position over the other.
Why RAI Therapy For Thyroid Cancer Management?
RAI therapy has been used in the management of DTC since the 1940s. Its use is based on the unique ability of thyroid cells to concentrate RAI through the activity of membrane sodium iodide symporter. Compared with normal thyroid tissues, tumors of follicular cell origin are less likely to concentrate RAI due to their lower membrane expression of transporter. Also, different histologies of DTC vary in their ability to express the membrane transporter with some tumors unable to concentrate enough RAI for an effective treatment response.
The two most commonly used RAI isotopes in thyroid cancer are 123 I and 131 I. These isotopes have different emitted radiation particles released from their decay, with gamma rays mostly emitted with 123 I and beta mostly emitted from the decay of 131 I. If absorbed in thyroid tissues after thyroid-stimulating hormone (TSH) stimulation, both gamma and beta rays can be visible on a gamma camera. Although gamma rays are high-energy particles that provide a good image resolution, their tissue absorption/concentration is low, making them less effective in thyroid cancer therapy. Thus 123 I is mostly reserved for diagnostic imaging. On the other hand, beta rays (emitted by 131 I) are moderately high energy particles with short median path length in human tissues, allowing them to penetrate tumoral tissues about 2 to 5 mm on average. They also interact with the surrounding tissues. This results in DNA injury and damage. In general, DTC cells can repair minor DNA damage through the activation of p53 pathways; however, more extensive DNA damage results in cell death (apoptosis). Because tumor cells lack efficient ways to repair double stranded DNA damage, they are more susceptible to the ionizing radiation effects than normal tissues. Due to low tissue penetrance, it is not to be expected that RAI therapy would destroy persistent disease exceeding 1 cm in the longest diameter.
Role of RAI Therapy
Whereas past definitions of RAI therapy regarded the treatment of locally persistent thyroid cancer or distant metastasis, the current consensus is that RAI therapy encompasses all the intended roles of RAI administration in patients with DTC. These roles are divided into (1) ablation, (2) adjuvant therapy, or (3) treatment of persistent thyroid cancer in the neck and/or distant metastatic disease ( Table 48.1 ).
Table 48.1
Aims of RAI Therapy
| Goals | Assumption | Potential Benefits | |
|---|---|---|---|
| RAI ablation | Eliminate persistent normal thyroid tissue | Patient is cured without persistent thyroid cancer | Improve staging Facilitate follow-up |
| RAI adjuvant therapy | Destroy persistent microscopic thyroid cancer deposits | Some patients are cured, whereas others have persistent subclinical disease | Achieve cure Decrease recurrence Improve disease-specific survival |
| Treatment of persistent thyroid cancer | Eliminate locally persistent or distant metastatic thyroid cancer | All patients have persistent disease that can be detected clinically by imaging or elevated thyroglobulin level | Achieve cure or stable disease Improve progression-free survival Improve disease-specific survival. |
RAI, radioiodine.
RAI Ablation
RAI ablation’s role is to eliminate normal thyroid tissue that is left behind after a total thyroidectomy. When electing to administer RAI for ablation, it is implicitly recognized that the patient is already cured of thyroid cancer and is at low risk of future recurrence and mortality from his or her disease. In this setting, RAI therapy is administered with the aims to facilitate the initial staging and allow for easier long-term patient follow-up with the elimination of postoperative thyroglobulin (Tg) level and/or any interfering antibodies and the eradication of thyroid remnant tissues that otherwise could be detected on follow-up sonogram and/or diagnostic whole-body scans.
Adjuvant Therapy
RAI adjuvant therapy’s role is to eliminate subclinical microscopic tumor deposits that may be present. The patients selected for adjuvant therapy are generally at intermediate or high risk for thyroid cancer recurrence but do not have clear evidence of persistent thyroid cancer on postoperative disease assessment. It is implicitly recognized that (1) many of these patients are already cured by the initial surgery and may not benefit from further therapy, but (2) other patients may still have microscopic tumor deposits in the neck, lungs, or elsewhere, which, left untreated, would increase their risk for recurrent thyroid cancer. Therefore the perceived benefit from adjuvant therapy is to hopefully decrease the risk for disease-specific recurrence, improve the progression-free survival (PFS) and the disease-specific survival, and achieve a cure for thyroid cancer.
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