-dose radioiodine ablation of remnant thyroid in high-risk differentiated thyroid carcinoma

Low

dose radioiodine ablation of remnant thyroid in high

risk differentiated thyroid carcinoma

Kunihito SUZUKI, Mana YOSHIMURA and Koichi TOKUUYE

Department of Radiology, Tokyo Medical University

Abstract

Recently, the potential of remnant thyroid ablation using 1,110 MBq ¹³¹I has been established, albeit under certain limitations, and guidelines have been issued on its use as an outpatient procedure in Japan. The aims of this study were to calculate the success rate of remnant thyroid ablation with 1,110 MBq as an outpatient proce- dure in high^-risk differentiated thyroid carcinoma (DTC) patients and explore the relationship between successful outcome and patient^-/disease^-related factors. Fifty high^-risk patients with DTC underwent remnant thyroid abla- tion with 1,110 MBq ¹³¹I on an outpatient basis between January 2009 and March 2011 at Tokyo Medical Univer- sity Hospital. The ablation success rate was evaluated using a whole body scan (WBS) performed at 4^-33 months (mean, 7 months) post^-

successful outcome was obtained in 41 patients, with a success rate of 82.0%, which was in agreement with that any patient^-/disease^-related factor. We believe that remnant ablation with 1,110 MBq ¹³¹I in high^-risk DTC ablation with low^-dose (1,110 MBq) ¹³¹I in high^-risk DTC patients.

Received October 15, 2013, Accepted January 6, 2014

Key words: radioiodine therapy, thyroid ablation, differentiated thyroid carcinoma, thyroid carcinoma

Corresponding author: Kunihito Suzuki, Department of Radiology, Tokyo Medical University, 6^-7^-1 Nishi^-Shinjuku, Shinjuku^-ku, Tokyo 160^-0023, Japan

TEL : +81^-(0)3^-3342^-6111 ext.5818 FAX : +81^-(0)3^-3348^-6314 E^-mail : [email protected] Educator name : Mana YOSHIMURA

Introduction

Patients with high

risk differentiated thyroid carci- noma (DTC) are typically treated with total thyroidec- tomy (TT) followed by

I ablation of the post

surgical thyroid remnant in accordance with the Japanese clinical guidelines

. Ablation of remnant thyroid tissue is also recommended by international consensus in high

risk patients

. The purpose of this procedure is to remove completely any remaining thyroid tissue following TT.

This has been reported to improve disease

free survival and local control rate in high

risk patients

. The level of iodine in the Japanese diet differs from that found in Europe or the United States, resulting in a higher rate of occurrence of papillary carcinoma. Therefore, surgery involves neck lymph node dissection due to the greater

number of lymph node metastases. However, fewer

distant metastases occur with this disease than usually

found with follicular carcinoma. Some studies have

noted that there is a lack of hospital wards and beds

available for non

sealed radioiodine therapy

. Based

on these two points, remnant thyroid ablation has often

been avoided in some DTC patients in Japan for a long

time. Recently, guidelines have been established on

remnant thyroid ablation as an outpatient procedure, with

ablation using 1,110 MBq

I becoming possible, albeit

under certain limitations

. The aims of this study were

to calculate the success rate of remnant thyroid ablation

with 1,110 MBq as an outpatient procedure in high

risk

DTC patients and explore the relationship between suc-

cessful outcome and patient

/disease

related factors (age,

sex, pT stage, presence of lymph node metastasis, dura-

tion from TT to ablation). To our knowledge, this is the

Materials and Methods 1. Patients

Fifty high

risk patients with DTC underwent remnant thyroid ablation with 1,110 MBq

I on an outpatient basis between January 2009 and March 2011 at Tokyo Medical University Hospital. Patient characteristics are shown in Table 1. All patients underwent TT as radical surgery and comprised 36 female and 14 male, with a mean age at ablation of 53.9 years. The diagnosis was - cation of pT2 in 1 patient, pT3 in 33, and pT4 in 16.

Among 40 cases of lymph node metastasis, 38 were pN1b and 2 were pN1a. The mean duration from TT to ablation was 245.5 days (range 53

1327 days). High risk was defined according to the following criteria : tumor size larger than 5 cm ; lymph node metastasis larger than 3 cm ; lymph node metastasis extending to the internal jugular vein, carotid artery, or major nerves such as the recurrent laryngeal nerve or pre

vertebral fascia ; multiple and intensely swollen lymph node metastases ; or extra

thyroid extension to the trachea or esophageal mucosa

. Exclusion criteria were the pres- ence of distant metastases (e.g., lung or bone) or a treat- ment history of

I thyroid ablation.

2. Radioiodine ablation of remnant thyroid All patients underwent remnant thyroid ablation with 1,110 MBq

I. Administration of levothyroxine was withdrawn for 4 weeks and replaced with triiodothyro- preparation for the procedure. The patients were instructed to follow a low

iodine diet for 2 weeks prior to surgery until the 4

5th day after ablation. No recom- binant human TSH (rhTSH) was used for the ablation.

The TSH and serum Tg values were measured in all patients at ablation. Four days after oral administration

-

camera equipped with high

resolution parallel

hole collimator (E.CAM, Siemens, Erlangen, Germany). Whole body planar images and spot views of the neck were acquired in ante- rior and posterior projections on a photo peak of 365 keV with a 15% window.

3. Evaluation

Post

ablation WBS was performed at 4

33 (mean, 7 months) months after the ablation. WBS and serum Tg value measurement were performed either thyroid hor- mone withdrawal (THW) or rhTSH

aided

. WBS by THW was obtained on the fourth day with 481

1,110 MBq of

I with measurement of Tg value on the first day. On the other hand, by rhTSH

aided protocol, rhTSH was given at a dose of 0.9 mg intramuscularly on

day 1, and day 2. On the day 3, 185

1,110 MBq of

I was administered. On day 5 or 6, WBS was performed of ablation was negative of WBS.

4. Statistical analysis (multiple logistec-regression analysis)

For statistical analysis, we used SPSS version 17.0 for Windows (SPSS Inc, Chicago, Illinois, USA). The quantitative data (continuous parameters) were analyzed using the forward selection method of likelihood ratio test. We selected as variable factors of age, gender, pT stage, presence of lymph node metastasis, duration from difference was considered when

considered to indicate a statistically significant differ- ence.

Results

The success rate of remnant thyroid ablation was 82%

in 41 of 50 patients (Fig. 1). The procedure was deemed to have failed in the remaining 9 patients based on their post

ablation WBS results (Fig. 2). The presence of thyroid tissue in the thyroid bed was indicated in these patients and additional ablation therapy administered.

There were no cases of local recurrence or cancer death during the study period. On the other hand, a high Tg value (ranging from 20 to 210 ng/ml) was observed in 7 patients during the post

ablation follow

up and cervical lymph node and/or pulmonary metastases confirmed, indicating the need for additional treatment.

In the multiple logistic

-

cant correlation was observed between the success of remnant thyroid ablation and age, sex, pT stage, lymph node metastases, or duration from TT to ablation (Table 2). The goodness

of

fit in this model was verified by the Hosmer

Lemeshow test (p=0.671).

Discussion

Differentiated thyroid carcinoma is the most common endocrine malignancy. The 10

year survival rate is reported to be 93% in papillary carcinoma and 85% in follicular carcinoma according to a large cohort study in the USA

. The diagnosis in patients with DTC is also good. For high

risk DTC, TT is recommended under the Japanese guidelines

. A multivariate analysis of over 50,000 patients with papillary thyroid carcinoma revealed that TT significantly improved recurrence and survival rates for tumors >1.0 cm

. Remnant thyroid ablation increases the rates of local control and cause

specific survival rates, especially in high

risk patients undergoing TT

.

Thyroid tissue remains in approximately 90% of

patients undergoing TT, but is often impossible to detect

by various imaging modalities such as ultrasonography

Table 1 Patient characteristics and clinical data Number Age Sex pT stage pN status Total thyroidectomy

to ablation (day) Pre^-ablation Tg

(ng/ml) Post^-ablation Tg

(ng/ml) WBS

1 72 F T3 N1a 359 2 undetectable negative

2 35 M T3 N1b 120 4 2 negative

3 69 M T4 N1b 126 37 230 negative

4 48 F T4 N1b 102 2 undetectable negative

5 27 F T3 N1b 88 2 undetectable negative

6 77 F T4 N1b 217 3 undetectable negative

7 22 F T3 N1b 155 16 2 negative

8 51 F T3 N1b 231 4 undetectable negative

9 39 M T3 N1b 199 5 undetectable negative

10 63 F T3 N1b 197 2 undetectable negative

11 62 F T3 N1b 154 2 undetectable negative

12 66 M T4 N1b 239 5 2 negative

13 43 F T3 N0 973 2 undetectable negative

14 57 F T3 N0 61 undetectable undetectable negative

15 36 F T4 N0 151 undetectable undetectable negative

16 49 M T3 N1b 113 undetectable undetectable negative

17 71 F T4 N0 365 2 2 negative

18 39 F T3 N1b 245 81 60 negative

19 46 F T3 N1b 156 21 5 negative

20 71 F T4 N1b 204 66 42 negative

21 79 F T4 N× 1,327 74 37 negative

22 23 F T3 N1b 119 9 3 negative

23 40 M T3 N1b 100 202 99 negative

24 71 M T4 N0 690 undetectable undetectable negative

25 64 M T4 N1b 161 50 210 negative

26 78 F T3 N1b 219 40 21 negative

27 64 F T3 N1b 53 49 35 negative

28 62 M T4 N1b 203 11 6 negative

29 19 F T3 N1b 122 21 7 negative

30 76 F T3 N1b 260 undetectable undetectable negative

31 63 F T2 N1a 211 undetectable undetectable negative

32 52 M T3 N1b 166 369 152 negative

33 59 F T3 N1b 543 174 160 negative

34 61 F T3 N1b 263 30 20 negative

35 80 F T3 N0 393 2 undetectable negative

36 38 F T3 N1b 105 38 26 negative

37 71 F T4 N0 147 undetectable undetectable negative

38 55 F T3 N1b 870 undetectable undetectable negative

39 38 F T3 N1b 155 63 27 negative

40 37 F T4 N1b 102 134 162 negative

41 80 F T4 N0 274 undetectable 2 negative

42 41 F T3 N1b 216 3 undetectable positive

43 58 M T4 N1b 141 70 27 positive

44 43 F T3 N1b 147 57 11 positive

45 56 F T3 N0 204 undetectable undetectable positive

46 23 M T4 N1b 97 136 118 positive

47 76 M T3 N1b 161 17 10 positive

48 45 F T3 N1b 77 7 2 positive

49 62 M T3 N1b 106 34 29 positive

50 37 F T3 N1b 190 undetectable undetectable positive

*Tg undetectable mean <1 ng/ml

and CT scans. Ablation with

I offers an effective method of destroying remnant thyroid tissue, reducing the possibility of local recurrence. Moreover, this method is more suitable than other procedures as it is convenient for use during post

surgical follow

up. The

serum Tg value is a good marker of recurrence and dis- tant metastases during post

surgical follow

up in DTC patients as it does not require anti

thyroglobulin anti- body. However, the serum Tg value cannot be deter- mined if thyroid tissue remains. As ablation erases Tg

Succcess Failure P value

Sex 0.243

Male 10 4

Female 31 5

Age 0.364

Mean (range 55.0 (19.0^-80.0) 49.0 (23.0^-76.0)

p Tstage* 0.46

T3 26 7

T4 14 2

Presence of lymph node metastases** 0.444

N0 8 1

N1a^-b 32 8

Total thyroidectomy to ablation (day) 0.18

Mean (SD) 258.5±266.8 148.8±46.1

Range 53.0^-1,327.0 77.0^-216.0

Quantitative data (continuous parameters) were analyzed using forward selection method of likelihood ratio test. No lymph node metastases, or duration from TT to ablation.

*Excluding one case of T2

**Excluding one case of Nx

Fig. 1. Successful case (Case 8 in Table 1)

a : WBS on 5^th day of ablation. Intense uptake of ¹³¹I in center of neck, indicating thyroid bed accumulation.

b : Post^-ablation WBS using 1,110 MBq ¹³¹I performed at 20 months after ablation. There was no accumulation in thyroid bed. Tg value decreased from 4 to undetectable level after ablation. This case was considered to be successful.

a b

from remnant thyroid tissue, its serum values can serve as a good marker of post

surgical recurrence or metasta- sis. Therefore, it is important for patients at high risk of post

surgical recurrence or metastasis to undergo abla- tion

.

Even allowing for differences in high

risk patients or dosage of

I, the success rate of ablation is approxi- mately 70%

95%

. Zidan et al. reported the ablation success rate as 94% in 238 patients receiving 1,110

3,145 MBq. Bal et al. reported the success rate as 72.8% in 149 patients receiving 1,110

5,735 MBq. In the present study, remnant thyroid ablation with 1,110 MBq in high

risk patients yielded an equivalent therapeutic result to as a negative WBS result, as the purpose of remnant thy- roid ablation is to destroy the remnant thyroid bed.

After TT and ablation, the serum Tg value is normally

-

presence of remnant thyroid tissue and investigate metastatic or recurrent lesions. A high Tg value with negative neck accumulation is thought to suggest microscopic metasta- ses in extra

thyroid lesions. During observation, cervi- cal lymph node and/or pulmonary metastases were found in 7 patients with high a Tg value by chest CT or neck ultrasonography. There is a real potential of local recur- rence or metastasis, so careful diagnostic imaging and observation are needed. If local recurrence or distant

metastases actually occur, then additional therapy is needed. There is no effective chemotherapy for local recurrent or distant metastases in DTC patients. It is difficult to control tangible local recurrences or lymph node metastases detected on imaging studies, so surgical treatment is the most appropriate response

.

Recently, few studies have reported any difference in the ablation success rate between low

dose (1,110 MBq) and high

dose (3,700 MBq)

I

. In this study, we administered 1,110 MBq on the basis of the established guidelines for outpatient treatment. We believe that the present results obtained with a low dose are of particular interest.

We analyzed the relationship between patient

/dis- ease

related factors and ablation success. No signifi- cant correlation was observed between the success of remnant thyroid ablation and age, sex, pT stage, or pres- ence of lymph node metastasis. No correlation was observed between ablation success and the duration from TT to ablation. To our knowledge, no studies to date have established the appropriate duration from TT to remnant thyroid ablation. However, the risk of death in patients undergoing initial radioiodine therapy at more than 180 days after TT is reported to be 4.22 times higher than that in those treated within 180 days in metastatic DTC

.

There was small number of failure cases in this study.

a b

Fig. 2. Failure case (Case 48 in Table 1)

a : WBS on 5^th of ablation. Intense uptake of ¹³¹I in center of neck, indicating thyroid bed accumulation.

b : Post^-ablation WBS using 1,110 MBq ¹³¹I performed at 6 months after ablation.

Neck accumulation remained. Presence of thyroid tissue in thyroid bed was suggested.

Further study is needed to elucidate the relationship between the success of ablation and such factors in larger samples of patients.

Conclusion

The success rate of remnant thyroid ablation was 82%

in 41 of 50 patients, which is in agreement with rates reported in earlier studies. The present results suggest that the success of remnant thyroid ablation is indepen- dent of age, sex, pT stage, presence of lymph node metastases, or duration from TT to ablation.

Acknowledgements

We are indebted to Professor Jeremy Williams, Chair- man of the Department of International Medical Commu- nications at Tokyo Medical University, for his review of the English of the manuscript.

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131I 1,110 MBq

2009 1 2011 3

1,110 MBq ¹³¹I 50

131I Whole body scan

41 82.0%

131I 1,110 MBq