Consensus and controversy of radioiodine and PET (or PET/CT) in the management of well- differentiated thyroid cancer 彰濱秀傳醫院 核子醫學科 洪光威

American Thyroid Association Guidelines Thyroid Feb;16(2):

1.Complete ablation is the first goal 2.Tg is the main tool for follow-up (Tg-Ab) I-DxWBS usually unnecessary 4.rhTSH in substitution of T4 withdrawal for Dx or remnant ablation 5.Complementary roles for RxWBS and FDG- PET Consensus

1. High or low dose for ablation? Clinical Medicine & Research; Volume 5, Number 2: 87-90, 2007 Successful ablation rate:

Eur J Nucl Med (1987) 12: We therefore recommend a 30 mCi ablation dose for all patients with differentiated thyroid cancer after surgical thyroidectomy, followed by a 300 mCi treatment dose in pT2- 3N1M x or pT2-3N x M1 patients, while in pT2-3NoMo low dose ablation will be a sufficient treatment. 7/10 8/10 7/10Effect nd Rx 3010 pT2-3NxM pT2-3NoMo 1 st Rx No.

Side effect: Incidence of radiation thyroiditis and thyroid remnant ablation success rates following 1110 MBq (30 mCi) and 3700 MBq (100 mCi) post surgical I-131 ablation therapy for differentiated thyroid carcinoma. Clin Endocrinol (Oxf) Apr Incidence and severity of radiation thyroiditis following I-131 remnant ablation therapy is directly related to thyroid remnant I-131 uptake. (p=<0.0001) 2.Severe thyoriditis was only seen with remnant I-131 uptake >2 mCi. 3.As 30 mCi I-131 is associated with a significantly lower frequency of thyroiditis (12% and 27%, p=0.02), but similar remnant ablation rate to 100 mCi (76% and 84%, p=NS). 4.It warrants consideration for thyroid remnant ablation particularly in patients with low risk disease.

Radioiodine lobar ablation as an alternative to completion thyroidectomy in patients with differentiated thyroid cancer C.S. BAL,* A. KUMAR and G.S. PANT The mean 24 h radioiodine neck uptake at the first visit was 17.2 ± 7.3% (4.4~34%). Low doses of radioiodine (15~60 mCi, 31.8 ± 11.7) were administered to the patients; The thyroid lobe was completely ablated in 53 patients (56.9%) after one dose; and cumulative ablation rate was 92.1% after two doses. 15 patients (16.1%) complained of throat discomfort and neck pain. All of them were managed with mild analgesics except three patients who needed additional oral prednisolone Nuclear Medicine Communications 2003, 24, 203±208

Successful ablation rate: high  low Long-term benefit: ? Side effect: low Radiation burden: low Cost: low Convenience: low

Considerations High dose: –Low or high risk disease –Be careful for large remnant Low dose: –Low risk disease –Large remnant –1st ablation for high risk

2. Fractionated dose or not ? Clin Nucl Med Oct;15(10):676-7 Arad E, Flannery K, Wilson GA, O'Mara RE. Fractionated doses of radioiodine for ablation of postsurgical thyroid tissue remnants. 1.Ablation was achieved in 9 out of 12 patients treated in a fractionated manner (a 75% success rate), whereas in 16 out of 20 patients given a single dose the thyroid remnants were completely eradicated (an 80% success rate). 2.That the use of split, smaller doses administered at weekly intervals on an ambulatory basis presents a reasonable alternative for ablation of postsurgical, residual-functioning thyroid tissue.

Comparison of the Effectiveness Between a Single Low Dose and Fractionated Doses of Radioiodine in Ablation of Post-operative Thyroid Remnants Guang-Uei Hung, Shih-Te Tu, Iuan-Sheng Wu, and Kwang-Tao Yang 1.Successful ablation was obtained in 20 of 38 patients (52.6%) treated with a single low dose compared with 14 of 21 patients (66.7%) treated in a fractionated manner. (P = 0.296). 2.As the fractionated-dose protocol has the drawbacks of a much longer hypothyroid state and a higher total expense, we suggest that a single low dose is more feasible than fractionated doses for outpatient ablation therapy. Jpn J Clin Oncol 2004;34(8)469–471

Decreased uptake after fractionated ablative doses of iodine-131 Hurng-Sheng Wu, Huey-Herng Hseu, Wan-Yu Lin, Shyh-Jen Wang, Yao-Chi Liu Eur J Nucl Med Mol Imaging (2005) 32:167–173 1.The mean uptake of 131I was 2.73% 7 days after the first administration, and decreased significantly to 0.26% 7 days after the second administration. The mean decrease was as high as 80.7%. 2.In the two patients with lung metastases, no definite evidence of decreased uptake was noted. 3.The use of fractionated ablative doses of 131I is not to be recommended in patients without lung metastases.

There was a 92.8% decrease in 131 I uptake between these two applications (from 0.732% to 0.053%). There was a 70.8% increase in 131 I uptake between these two applications (from 0.024% to 0.041%). Park et al., visual reduction in uptake was seen in 15 of 24 thyroid remnants or cervical lymph node metastases after 111–370 MBq 131I but in only one of 11 distant metastases. Eur J Nucl Med Mol Imaging (2005) 32:167–173 Thyroid 1994;4:49–54.

Considerations Stunning effect: –True for remnants –Not true for metastases ? Side effect: yes/not Convenience: yes/not Cost: not Alternative protocol

3. Thyrogen (rhTSH) for persistent or recurrent disease Rx ? Diagnostic use: –U.S. in 1998 –Europe in 2001 Remnant ablation –Europe in 2005 –U.S. in 2007/12

Treatment of cervical nodal or nonoperable distant metastases ? Recombinant human TSH-aided radioiodine treatment of advanced differentiated thyroid carcinoma: a single- centre study of 54 patients. 1.The response to rhTSH-aided and WTH-aided treatment was similar in 52% of 44 evaluated patients, superior with rhTSH in 27% and superior with WTH in 16% patients. 2.Comparison is limited due to a greater number of courses and cumulative activity of 131 I administered under WTH. Jarzab B, Handkiewicz-Junak D, Roskosz J, et al. Eur J Nucl Med Mol Imaging. 2003;30:1077–1086.

T4 withdrwal Thyrogen

rhTSH Stimulation Before Radioiodine Therapy in Thyroid Cancer Reduces the Effective Half-Life of 131I Menzel C, Kranert WT, Döbert N, et al: 1.The effective half-life of 131 I was significantly prolonged after endogenous stimulation (e.g., 0.43 d for group A vs d for group B, P 0.001) than rhTSH-stimulated manner. 2.This is mainly due to a reduced renal iodine clearance in the hypothyroid state. J Nucl Med 2003; 44:1065–1068

Comparison of iodine uptake in tumour and nontumour tissue under thyroid hormone deprivation and with recombinant human thyrotropin in thyroid cancer patients. Potzi C, Moameni A, Karanikas G, et al. 1.All patients had lesser uptake of 123 I under rhTSH stimulation than after hormone withdrawal. 2.The median half-life in tumour tissue was 39·8 h (mean 65·9, range 11·5–194·0) with HS and 21·9 h (mean 38·7, range. 8·7–113·9) 3.The cumulative activity in metastatic tissue was lower after rhTSH than during hypothyroidism Clinical Endocrinology (2006) 65, 519–523

Considerations ‘‘Compassionate’’ use:  patients with hypopituitarism who cannot achieve adequate serum TSH levels after WTH  patients with serious comorbidities, such as older patients suffering from heart disease, poorly controlled hypertension, and/or depression, in whom hypothyroidism would be potentially hazardous

4. Discontinuing T4 with Thyrogen? Iodine excretion during stimulation with rhTSH in differentiated thyroid carcinoma. Löffler M, Weckesser M, Frenzies C, et al. 1.L-thyroxine, which contains 65.4% of its molecular weight in iodine, is a substantial source of iodine intake is maintained during rhTSH stimulation. 2.Iodine excretion was higher in patients under rhTSH-stimulation (75 micro g/l) than after T4 withdrawal (50 micro g/, p <0.027). 3.This may indicate an increased iodine pool in rhTSH-stimulated patients, thus limiting the sensitivity of radioiodine scanning to the level of endogenous stimulation Nuklearmedizin Dec;42(6):240-3.

Radioiodine treatment with 30 mCi after recombinant human thyrotropin stimulation in thyroid cancer: effectiveness for postsurgical remnants ablation and possible role of iodine content in L-thyroxine in the outcome of ablation Barbaro D, Boni G, Meucci G, et al. 1.We have evaluated the effectiveness of stimulation by rhTSH for radioiodine ablation of postsurgical remnants, stopping L-T4 the day before the first injection of rhTSH and restarting L-T4 the day after (131)I. 2.The percentage of ablation was 81.2% in patients treated by rhTSH withdrawal, and 75.0% in patients treated by L-T4 withdrawal, respectively. 3.No patient experienced symptoms of hypothyroidism during the 4 d of L- T4 interruption, and serum T4 remained in the normal range. 4.Urinary iodine was /- 4.0, /- 4.0, and /- 9.3 microg/liter for rhTSH withdrawl, L-T4 withdrawal, and control groups (P = 0.21 vs. the second group, P = vs. control group). J Clin Endocrinol Metab 88: 4110–4115, 2003

5. TSH stimulation for FDG- PET(PET/CT) ? Eur J Nucl Med Mol Imaging 29: , 2002

Max SUV : 26.1 (PET/CT study was performed under TSH stimulation)

6. FDG stunning by I-131 Rx ? Metabolic stunning: FDG uptake may be transiently reduced or absent shortly after chemotherapy and/or radiotherapy. Semin Nucl Med. 2004;34: Head Neck 23:942–946, 2001.

The influence of I-131 therapy on FDG uptake in differentiated thyroid cancer Guang-Uei Hung, Kwo-Whei Lee, Pei-Yung Liao, Li-Heng Yang, Kwang-Tao Yang Ann Nucl Med (2008) 22:481–485

Considerations Overcome “stunning” from I-131 Rx: 1.Wait 3~4 months after I-131 Rx 2. Immediately after I-131 scan (TSH stimulation status) ?

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