Radioactive Iodine 131I Therapy Thyroid Remnant Ablation

This is defined as 131I therapy administered to destroy presumably normal residual thyroid tissue. Routine 131I remnant ablation, although questioned by some [116], is widely used and has appeal for several reasons. First, it may destroy occult microscopic cancer [18,62]. Second, it enables earlier detection of persistent tumor by post 131I treatment whole-body scans (RxWBS) [81]. Third, it greatly facilitates the use of serum Tg measurements during follow-up. Few metastases can be visualized by 131I scanning when appreciable amounts of normal thyroid tissue remain after surgery. Lastly, serum Tg concentration, which is the most sensitive marker of persistent disease, is unreliable when a large thyroid remnant is present [117]. Thus 131I is given postoperatively even to patients without known residual disease who have a good prognosis [38,118,119]. Still, this approach continues to engender debate and calls for randomized clinical trials [120], but they are so difficult to design that they are likely not to be done in the near future [121,122].

Remnant ablation was initially done with 2775 and 5550MBq 131I (75 to 150mCi),but later clinicians began using 925 to 1110mg (25 to 30mCi) to avoid hospitalization, which is no longer necessary in the USA because of a change in federal regulations that permits much larger activities of 131I in ambulatory patients. Smaller amounts of 131I <1110MBq (30mCi), which can ablate thyroid remnants if the mass of residual thyroid tissue is small, has appeal because of the lower cost and lower whole-body radiation dose. One randomized prospective study of this question found that the first dose ablated thyroid bed uptake in 81% of patients given 225 MBq (30mCi) and in 84% treated with 3700 MBq (100mCi) [123]. Another randomized study [124] found that any activity of 131I between 925 and 1850 MBq (25 to 50mCi) appears to be adequate for remnant ablation [124]. Both studies were performed with a thyroid hormone withdrawal (THW) protocol in which the patient receives triiodothyronine (liothyronine, Cytomel) for 4 weeks and no thyroid hormone and a low iodine diet during the last 2 weeks before 131I therapy.

More recently, 131I remnant ablation has been done after intramuscular administration of recombinant human thyrotropin-a (rhTSH, Thyrogen), which stimulates thyroidal 131I uptake and Tg release while the patient continues thyroid hormone (T4) therapy, thus avoiding symptomatic hypothyroidism [125]. Although now approved only for diagnostic use, rhTSH, 0.9 mg, has been given intramuscularly every day for 2 days followed by 1110 to 3700 MBq (30 to 100 mCi) 131I on the third day and RxWBS about 5 days later. This protocol has been shown to successfully prepare patients for 131I remnant ablation. At the present time, the drug is approved in Europe and is likely to be approved in late 2005 for this purpose in the USA. Complete ablation, defined as an absence of uptake on an 85 MBq (5 mCi) 131I diagnostic whole-body scan (DxWBS) image about one year later, was achieved in over 84% of patients prepared with T4 withdrawal and in over 86% of those given rhTSH, who were treated, respectively, with an average of 4662 and 4403 MBq (126 and 119mCi) of 131I [119]. Another study found that 1110 MBq (30mCi) 131I given 48 hours instead of 24 hours after the last rhTSH injection failed to ablate the thyroid remnant when rhTSH was given [126]. Still another study showed that 1110 MBq (30 mCi) of 131I was successful when T4 was stopped the day before the first injection of rhTSH and started again the day after the 131I was administered, which was associated with a fall in urine iodine levels attributed to the ~50 mg iodine content in a daily dose of T4 compared with the 5mg content of 131I [127]. Patients tolerate rhTSH well, with only occasional transient mild headache and nausea. This is extensively reviewed in Chapter 17 by Professors Pacini and Schlumberger.

Long-Term Effects of Remnant Ablation and Treatment of Persistent Tumor with 131I

Although some studies find that total thy-roidectomy and 131I therapy does not have a better effect upon outcome than does postoperative treatment with thyroxine alone [128], long-term studies generally find a beneficial effect of 131I therapy. A study of 1599 patients treated between 1948 and 1989 found that 131I therapy was the single most powerful prognostic indicator for increased disease-free survival [129]. Multivariate analyses show that 131I has an independent prognostic effect when administered either to ablate the thyroid remnant or to treat metastases [18,38,130]. We found tumor recurrences in 7% of patients treated with 1073 to 3750 MBq (29 to 50 mCi) and in 9% treated with 1887 to 7400 MBq (51 to 200mCi) of 131I given to ablate thyroid remnants. In our study, 131I given either to ablate the thyroid bed or to treat metastases each independently lowered the rates of all recurrences, distant recurrence, and cancer deaths. In studies with shorter follow-up than ours, multivariate analyses show that 131I therapy lowers death rates in patients with bone [75,131] and lung [132] metastases providing they concentrate 131I, and reduces locoregional recurrences, whether given to treat metastases or to ablate the thyroid remnant [130,133,134].

Therapeutic 131I Dosimetry

Of the three dosimetry methods available, the simplest and most widely used is to administer an empiric fixed amount of 131I. From 1110 to 3700 MBq (30 to 100mCi) 131I is given to ablate a thyroid remnant [135]. Patients with lymph node metastases removed by surgery are treated with 3700 to 6475MBq (100 to 175mCi), and microscopic tumor extending through the thyroid capsule is treated with 5550 to 7400 MBq (150 to 200mCi). Diffuse pulmonary metastases that concentrate 50% or more of the test dose of 131I, which is very uncommon [136], are treated with 150 mCi 131I (5550 MBq) or less to avoid lung injury that may occur when more than 80 mCi (2960 MBq) are retained in the whole body 48 hours after the dose. Distant metastases are usually treated with 200 mCi (7400 MBq)


A second approach is to use quantitative dosimetry to predict radiation doses to the target tissues, namely thyroid remnant or metastases, and to radiosensitive tissues to which the radiation dose must be limited, including the bone marrow and lungs in those with diffuse pulmonary metastases, and the whole-body radiation dose. This is favored by some because radiation exposure from arbitrarily fixed doses of 131I can vary considerably [137]. If the lesional dose is less than 35Gy (3500 rads), it is unlikely that the tumor will respond to 131I therapy [137;138]. Conversely, 131I activities that deliver 80 to 120Gy (8000 to 12 000 rads) to the thyroid remnant or deliver 300Gy (30000rads) to metastatic foci are likely to be effective. To make these calculations it is necessary to estimate tumor size, which in some situations is not possible.

A third approach is to calculate an upper 131I activity limit that delivers a maximum of 2 Gy (200rad) to the whole blood while keeping the whole-body 131I retention less than 4440 MBq (120 mCi) at 48 hours or less than 2960 MBq (80 mCi) when there is diffuse lung uptake. Dosimetry is complicated and is performed in a limited number of large medical centers. Moreover, comparison of outcomes between empiric fixed dose methods and dosimetric approaches is difficult and unreliable, and prospective trials to address the optimal therapeutic approach have not been done [139]. The complications of 131I therapy are reviewed in detail in Chapter 15

Figure 1.9 The therapeutic response to 131I is due to three things: the effective Typological retention of the isotope in a tumor), the half-life of the isotope (~8 days for 131I) and the activity (amount) of 131I administered. The most common reason for failure of 131I treatment is a short biological half-life (Ty2) of 131I in a tumor. The most common way that the therapeutic response is enhanced is by increasing the 131I activity (dose). However, lithium increases the biological Ti/2 by as much as threefold, permitting the use of the smallest effective amount of 1311, thus reducing the complications of 131I therapy.

by Drs Haq and Harmer and in Chapter 16 by Dr Vini.

Lithium Pretreatment

The therapeutic response to 131I is related to the amount of radiation that is delivered to the follicular cell, which is a function of: (1) the amount of 131I administered, (2) the biological half-time (T/2), which is the retention time of 131I within the cell, and (3) the isotope physical halflife (Figure 1.9). The effective Iy2 is the combination of the biological T1/2 and the physical T1/2 of 131I. Maxon et al. found that the main reason for failure of 131I therapy was a short effective T/2 of 131I [140]. The biological retention T/2 of iodine in the thyroid is 60 days, but is only about 10h in tumors [140].

Studies by Robbins and associates [141] from the USA National Institutes of Health show that lithium given at a dosage of 300-900 mg daily (10mg/kg) for 7 days prolongs the biological Ty2 and thus the effective Ty2 in PTC and FTC [141], The mean increase in the biological Ty2, which was 50% in tumors and 90% in remnants, was proportionately greater in lesions with poor 131I retention [141]. When the control Ty2 was less than 3 days, lithium prolonged the effective T1/2 by more than 50%. More 131I accumulated during lithium therapy, probably as a consequence of its effect on iodine release without increasing radiation to other organs. Serum lithium levels should be measured daily and maintained in the usual therapeutic range between 0.8 and 1.2nmol/L.

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