Ablation of Residual Normal Thyroid Tissue

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In the management of differentiated thyroid cancer (DTC) ablation of thyroid remnants with 131I aims to destroy all residual normal thyroid tissue. Total (or near-total) thyroidectomy will permit this to be achieved with a modest administered activity. Remnant ablation after lobectomy is more difficult and a repeat administration may be required. Ablation of a large remnant may cause radiation thyroiditis with neck pain and swelling. Furthermore thyroid-stimulating hormone (TSH) levels may fail to rise above 30mU/L following hormone withdrawal, resulting in suboptimal 131I uptake.

The advantages of remnant ablation are that it permits subsequent identification by iodine whole-body scan (WBS) of any residual or metastatic carcinoma and facilitates interpretation of serial serum thyroglobulin (Tg) monitoring [1] (Figure 15.l). A large remnant may show a star burst artifact on WBS, obscuring tumor uptake in abnormal cervical nodes. Measurement of stimulated Tg is also facilitated following remnant ablation, and represents the most sensitive method of detecting recurrence [2-4]. Remnant ablation also destroys microscopic metastases; several retrospective studies have documented decreases in both local recurrence and death from thyroid cancer [5,6]. The benefit of 131I ablation is seen mainly in patients who are at high risk of recurrence, including those with larger tumors, extrathyroidal extension, involved lymph nodes, and residual disease [7,8]. However, in low risk patients and especially in those with microcarcinoma, prognosis is so favorable after surgery alone that little further benefit is achieved [9].

Mazzaferri and Kloos retrospectively studied 1510 patients without distant metastases. Remnant ablation was found to be an independent variable that reduced cancer recurrence, distant recurrence, and cancer death rates [10,11]. Other studies have demonstrated similar results [12].

Total (or near-total) thyroidectomy followed by radioiodine ablation is considered to be the ideal treatment for high risk tumors. However, 131I ablation remains possible following hemithyroidectomy. Bal et al. studied 93 patients with DTC and evaluated the role of radioiodine ablation in patients following hemithyroidectomy [13]. They were evaluated with a diagnostic 131I WBS, 48-hour neck uptake, and Tg measurement following 4-6 weeks withdrawal of thyroxine. The thyroid lobe was successfully ablated in 57% of patients after one ablation dose of 131I (mean activity 1.18 ± 0.4GBq, 31.8 ± 11.7mCi) and 92% after two ablation doses (mean activity 1.5 ± 0.51 GBq, 40.5 ± 13.8mCi). Hoyes et al. have also demonstrated successful lobar ablation following 3.5 GBq 131I (95mCi): 98% of patients treated by total thyroidectomy were successfully ablated by one 131I treatment, compared with 90% after lobectomy (P < 0.05) [14]. Ablation of an intact

Figure 15.1 Postablation whole-body 131I scan (anterior image). Focal uptake is displayed in the left side of neck. Additional uptake is visible in the apices but more diffusely in both lung fields compatible with extensive pulmonary metastases.

lobe therefore remains possible and can be achieved with moderate activities of radioio-dine. It remains an alternative for patients refusing completion thyroidectomy or for those in whom a second operation is contraindicated.

The optimal activity of 131I required to achieve successful ablation is controversial, with doses ranging from 0.85 to 9.5 GBq (23 to 257mCi) having been advocated. Many centers in North America previously used 1.1 GBq (30mCi) to ablate small thyroid remnants in order to avoid hospital admission. Administration of a lesser activity has the advantage of lower whole-body radiation exposure, lower cost, and patient convenience. Beierwaltes' philosophy of high dose ablation was based on the premise that it not only ablates normal remnants but also treats possible micrometastatic deposits [15].He also stressed the importance of delivering a high radiation dose from the first iodine administration because the biological half-life of subsequent administrations falls, therefore reducing the radiation dose delivered. Samuel and Rajashekharrao also support high initial dose rates to achieve successful ablation [16] but there has been no prospective randomized trial to substantiate these proposals. Proponents of high activity ablation argue that lesser activities are less effective at treating micrometastases, leading to higher recurrence rates. However, Mazzaferri and Jhiang found no difference in long-term recurrence rates (7% versus 9% after median follow-up of 14.7 years) between low dose (29-50 mCi) and high dose (51-200mCi) 131I remnant ablation [10].

In 1976, McCowen et al. first reported that doses of 3-3.7GBq were no more effective than 1.1 GBq and this has been confirmed by other retrospective analyses [17]. Despite numerous studies evaluating low dose ablation, one meta-analysis found that a single administered activity of 1074-1110MBq (29-30 mCi ) was more likely to be unsuccessful in fully ablating thyroid remnants compared to higher activities of 2775-3700MBq [18]. Of 13 studies evaluated, 518 patients were low dose and 449 were high dose. The average failure of a single low dose was 46% versus 27% for high dose ablation (P < 0.01).

Bal et al. performed the first prospective randomized clinical trial to evaluate the optimal 131I ablation dose in 149 patients and demonstrated that increasing the administered activity beyond 1.85 GBq (50 mCi) resulted in plateauing of the dose-response curve; a radiation absorbed dose greater than 300 Gy to the thyroid remnant did not appear to yield a higher ablation rate [19]. Successful ablation was defined as the absence of any detectable radioiodine-concentrating tissue in a diagnostic 5mCi 131I scan at 6 to 12 months (following discontinuation of thyroxine 4-6 weeks before), neck uptake of less than 0.2%, and a Tg level of less than 10 |mg/L. Overall successful ablation was achieved in 78% of thyroid remnants. Their more recent study assessed the smallest possible effective dose for remnant ablation [20] in a randomized prospective trial with different ablation activities between 15mCi up to 50mCi. In 509 eligible patients the overall ablation rate was 77.6%. The successful ablation rate was sta tistically different in patients receiving less than 25mCi 131I compared with those receiving at least 25mCi (63 of 102,61.8%,versus 332 of 407, 81.6%, P = 0.006). There was no significant inter-group difference in outcome among patients receiving 25-50mCi of 131I. However, patients receiving at least 25 mCi 131I had a three times better chance of remnant ablation than patients receiving lesser activities.

Maxon et al. individualized administered activity to deliver a radiation dose of 300 Gy to the thyroid remnants and reported an 81% ablation rate, with no apparent gain from using a dose greater than 300 Gy. Further evaluation of different administered activities with a large randomized prospective trial is required with ablation success rates and recurrence as the main outcome measures (Table 15.1) [21,22].

Sodium iodide 131I is available in the form of a capsule, liquid preparation, or intravenous injection. The capsule is most commonly used due to safety and ease of handling. Four weeks after total thyroidectomy, by which time the TSH level will be above 30mU/L, we recommend an ablation dose of 3 to 3.7GBq (111 to 137mCi) 131I to all patients after total thyroidectomy except for children over 10 years of age with small node-negative tumors and young patients with unifocal microcarcinoma [6,23] (Figure 15.2). This delivers a mean absorbed dose of 410 Gy and ablates 75% of remnants [24]. An 131I WBS is obtained after 3 days, when the patient is usually allowed to return home, subject to the total body radioactivity having fallen below the permitted level. In the USA, patients treated with 131I are usually permitted to go home, providing certain conditions are met. Replacement thyroid hormone is then commenced in the form of triiodothyronine (liothyronine, T3) 20mcg three times a day. A blood sample is taken on the day of iodine administration to confirm TSH elevation and also on day 6 to measure the protein bound (PBI) 131I level [25].

Regulations for use of radioiodine remain extremely variable throughout the world, although there is general acceptance of the basic protection measures. Treatment must be carried out in a protected environment (single-bedded shielded room with ensuite bathroom and toilet) approved for this purpose by the local radiation protection advisor. Written and oral information should be given to patients before treatment. Prior to therapy, pregnancy must be excluded in women of childbearing age. Because the concentration of 131I in maternal milk is significant, breastfeeding is strictly contraindi-cated for 4 months after administration.

Patients are reviewed 6 weeks after ablation with results of hematology, biochemistry, TSH, Tg, and ablation WBS. Provided the latter demonstrates uptake in only a small thyroid remnant, a stimulated Tg obtained either following withdrawal of T3 for 10-14 days or following use of recombinant TSH injections while continuing suppression therapy is measured 4 to 6 months postablation [26,27]. If this stimulated Tg level is <2 |mg/L, patients can be reviewed annually and the patient switched to thyroxine at an average daily dose of 200 mcg in order to suppress TSH secretion to a level of less than 0.1mU/L [2,28]. Follow-up assessment comprises clinical examination and monitoring of free T3, TSH, and Tg levels but we do not perform diagnostic iodine scans routinely except in patients with anti-Tg antibodies [29]. In the past, a diagnostic WBS with 150-185 MBq (4-5mCi) 131I was performed at 4-6 months to determine the success of remnant ablation but this is no longer standard practice. If the postablation scan demonstrates significant uptake in the thyroid bed or elsewhere (cervical node or

Table 15.1 Summary results of a systematic review of randomized trials of radioiodine ablation. Percentage of patients who had successful ablation according to administered activity (patient number in parentheses)

Study

30 mCi (1.1 GBq)

50mCi (1.8 GBq)

90 or 100 mCi (3.7GBq)

Creutzig 1987 [124]

50 (5/10)

60 (6/10)

Johansen 1991 [125]

58 (21/36)

52 (14/27)

Bal et al. 1996 [19]

63 (17/27)

78 (42/54)

74 (28/38)

Sirisalipoch 2004 [126]

65 (41/63)

89 (67/75)

Bal et al. 2004 [20]

83(61/73)

82 (63/77)

Combined

71 (104/146)

75 (146/194)

77 (115/150)

Test for difference between the percentages

P = 0.01

P = 0.06

P < 0.001

New patient referred with Differentiated Thyroid Cancer History and clinical examination I- Review histology -1

With total thyroidectomy

Without total thyroidectomy

Completion thyroidectomy + Level VI

± selective dissection of levels II, III, + IV

At 4 weeks - avoid sea food, added salt, iodine containing medicines and x ray contrast FBC, biochemistry, TSH, Tg, CXR

Ablation dose 3 GBq 131I

I whole body scan at 3 days, start T3

OPD appointment at 6 weeks

Abnormal scan or adverse feature Book 4 months after ablation 5.5 GBq 131I Stop T3 for 10 days FBC, biochemistry, TSH, Tg

Normal scan, no adverse feature 185 MBq 131I whole-body scan only if Tg-antibodies or clinical suspicion. Stop T3 for 10 days (or give rhTSH) TSH, Tg

Therapy dose 5.5 GBq 131IJ

131I whole body scan at 3 days, restart T3

OPD appointment at 6 weeks

Known tumour

Negative scan PBI < 0.01%

Reconsider surgery

Positive scan

Normal

OPD appointment at 6 months

TSH, T3, stimulated-Tg If tests negative, change to thyroxine < 200mcg target TSH < 0.1mU/l

External beam radiotherapy

Repeat 5.5 GBq 131I at 6 months

Annual follow-up

Figure 15.2 Royal Marsden Hospital policy for the management of differentiated thyroid cancer.T4, thyroxine;^, Liothyronine;TSH, thyroid-stimulating hormone; CXR, chest radiograph; FBC, full blood count; Tg, thyroglobulin; PBI, protein-bound radioactive iodine concentration; rhTSH, recombinant TSH (thyrogen).

distant metastasis) further investigation is required. A CT scan without contrast or preferably an enhanced MRI of the neck plus mediastinum ± CT of the lungs ± bone scintigraphy will clarify the extent and distribution of disease suitable for further neck surgery, metastasec-tomy, or radioiodine therapy.

Typical postablation scans demonstrate normal physiological uptake of iodine within the salivary glands, gastrointestinal tract, and bladder. Occasionally, false-positive 131I whole-body scans may occur [30]. These may be seen with esophageal retention of salivary secretions, gut motility disorders such as Meckel's diverticulum, malformations of the urinary tract, pathological transudates or exudates, inflammatory or infectious lesions, specific organ uptake such as in breast, liver or thymus, tumors containing thyroid tissue such as struma ovarii or teratoma, and lung or abdominal adenocarcinoma.

To optimize radioiodine uptake by both residual normal thyroid and cancer, TSH stimulation is mandatory and dietary iodine should be restricted for one month before and for several days after ablation. Dietary restriction of iodine intake to 50 |mg per day can increase the 131I uptake twofold after ablation [31]. Iodized salt, dairy products, eggs, and seafood should be avoided [32]. Iodine-rich contrast media must also be avoided and T3 tablets omitted for 2 weeks; any patient on thyroxine would need to discontinue these tablets 4 weeks prior to ablation. As an alternative to thyroid hormone withdrawal patients may be prepared for remnant ablation with recombinant TSH (rhTSH, Thyro-gen, Genzyme). Robbins et al. reported that successful remnant ablation can be achieved after two injections of 0.9mg of rhTSH [33]. Their retrospective study compared the rate of complete ablation in 42 patients prepared with thyroid hormone withdrawal and 45 patients with rhTSH. Successful ablation was comparable in both groups (81% versus 84%, no statistical difference). However, Pacini et al. demonstrated contrasting results [34] in a prospective study using 30mCi 131I during thyroid hormone therapy. Patients were treated while hypothyroid (n = 50), hypothyroid with rhTSH stimulation (n = 42), or euthyroid on thyroid hormone therapy with rhTSH stimulation (n = 70). Outcome was assessed by a 4mCi diagnostic 131I WBS following conventional thyroid hormone withdrawal. The rate of successful ablation was similar in the hypothyroid and hypothyroid plus rhTSH groups (84% and 78.5%, respectively) but significantly lower (54%) in the euthyroid plus rhTSH group.

Recombinant TSH remains unlicensed in the UK for ablation or therapy but is available for diagnostic iodine WBS and stimulated Tg. It remains expensive but markedly improves patient quality of life, which is otherwise severely impaired during the prolonged period of hypothyroidism [35]. We recommend its routine use for diagnostic purposes and for ablation or therapy in patients unable to produce TSH, and especially those in whom thyroid hormone withdrawal is medically con-traindicated. This includes patients with cardiac disease, psychiatric disorders, postpartum, hypopituitarism, and patients unable to tolerate prolonged hypothyroidism [36,37]. Patient groups are campaigning for its routine use in diagnosis and therapy but cost and licensing restriction currently make wider availability impracticable in the UK. Thyrogen is well tolerated but may occasionally cause nausea or transient headache. Contraindications to its use are brain or spinal metastases as cerebral edema or cord compression may occur.

Differentiated thyroid cancer is common in women of childbearing age. Population-based studies have suggested that up to 10% of thyroid cancers occurring in women during their reproductive years are diagnosed in pregnancy or in the first year after giving birth. Outcome remains favorable with prognosis of DTC discovered in pregnancy similar to that occurring in nonpregnant women of similar age [38]. A small retrospective study of nine patients from the Royal Marsden Hospital assessed outcome during pregnancy [39]. Four were discovered at antenatal assessment to have a thyroid nodule; the reminder had a thyroid lump in the neck. In all cases, the thyroid nodule was reported to double in size during pregnancy. One patient had a subtotal thyroidectomy during the second trimester; eight were operated on within 3-10 months from delivery (five total thyroidec-tomy, 4 subtotal thyroidectomy). Eight patients remained disease free but one patient who had radioiodine treatment delayed due to a further pregnancy died 7 years later from distant metastases. For tumors discovered early in pregnancy, total thyroidectomy can be performed safely during the mid-trimester, while those found later can be managed after delivery. Radioiodine ablation can be deferred until after the pregnancy and breastfeeding, although should not be delayed for more than a year.

Thyroid cancer is discovered in 1-4% of patients undergoing surgery for hyperthy-roidism due to Graves' disease or multinodular goiter [40]. In most patients the tumors are small or microscopic and no further treatment is required. For larger tumors, multiple foci, or involved lymph nodes, completion thyroidec-tomy plus ablation should be considered.

Carcinoma of the thyroid is rare in children, although the incidence in Europe has increased as a result of exposure to radioactive fallout from Chernobyl [41]. Tumors are usually papillary and often of advanced local stage. More have metastatic disease at presentation and a higher proportion of disease-related deaths occur on prolonged follow-up, compared with adults [42]. Children under the age of 10 years are at higher risk of recurrence and should be treated with total thyroidectomy, paratracheal node dissection ± selective neck dissection, and radioiodine.

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  • lia giordano
    Which food contain during 131iscan?
    4 years ago

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