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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 8  |  Page : 244-247

Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma


1 Department of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province 310022, People's Republic of, China
2 Department of Ultrasonography, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province 310022, People's Republic of, China
3 Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province 310022, People's Republic of, China

Date of Web Publication26-Nov-2015

Correspondence Address:
Linfa Li
Department of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province 310022
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.170530

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 > Abstract 

Purpose: To determine whether postoperative radioiodine (RAI) combined with radiofrequency ablation (RFA) is an effective, safe, and feasible method for elimination of excessive postsurgical thyroid remnant for differentiated thyroid carcinoma (DTC).
Materials and Methods: We took a prospective study and treated 12 DTC patients (4 males, 8 females, age 20–78 years) who underwent thyroidectomy for RFA followed by 131 I ablation. The pretreatment requires iodine-free diet and thyroid hormone withdrawal for 3–4 week. All the patients showed the level of serum thyroid-stimulating hormone (TSH) <30 mU/L, and obvious thyroid remnant in 99m Technetium (99m Tc) imaging. Serum TSH level was determined 1 day before RFA and on days 1, 7, 14 after RFA, and 99m Tc imaging was performed on day 14 after RFA. Subsequently, the patients were given an oral dosage of 3700 MBq 131 I for remnant ablation, and posttreatment whole body scan was performed on day 5 after ablation. Efficacy evaluation was done 4–6 months after treatment. The changes of variants before and after RFA were analyzed using Wilcoxon signed rank sum test.
Results: Serum TSH was <30 μIU/ml (mean value 10.27 ± 6.16 μIU/ml) before RFA, and increased to more than 30 μIU/ml (34.73 ± 3.93 μIU/ml) 2 weeks later (P = 0.002, Wilcoxon rank sum test). The 99m Tc uptake ratio on day 14 postRFA was (0.31 ± 0.12)%, which is significantly lower than before RFA (0.80 ± 0.16)% (P = 0.002, Wilcoxon rank sum test). The success rate of thyroid remnant ablation was 91.7% (11/12), which was assessed 4–6 months after treatment. All patients reported neck discomfort and some are self-limiting, with no hoarseness, choking, or radiation thyroiditis symptoms. Five patients had puncture area pain, among which one patient had neck edema, which was relieved after prednisone treatment.
Conclusion: Combined use of RAI therapy and radiofrequency ablation in treating excessive postsurgical thyroid remnant of DTC can be an effective approach and avoids re-operation. Long-term efficacy monitoring would further determine its feasibility.

Keywords: Radiofrequency ablation, radioiodine therapy, thyroid cancer, thyroid remnant ablation


How to cite this article:
Long B, Li L, Yao L, Chen S, Yi H, Ye X, Xu D, Wu P. Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma. J Can Res Ther 2015;11, Suppl S4:244-7

How to cite this URL:
Long B, Li L, Yao L, Chen S, Yi H, Ye X, Xu D, Wu P. Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma. J Can Res Ther [serial online] 2015 [cited 2019 Sep 16];11:244-7. Available from: http://www.cancerjournal.net/text.asp?2015/11/8/244/170530


 > Introduction Top


The standard therapy for differentiated thyroid carcinoma (DTC) is surgery followed by radioiodine (RAI) therapy and thyroid hormone suppression, and postoperative RAI remnant ablation is increasingly being used to eliminate the postsurgical thyroid remnant. When the thyroid remnant is excessive, most guidelines suggested re-operation to remove remnant before RAI therapy to completely eliminate the remnant and avoid the side effect from 131 I radiotherapy. However, re-operation is often technique-challenging and increases the risk of complications.[1],[2] Radiofrequency ablation (RFA) has been applied in the treatment of thyroid cancer with good efficacy, but the efficacy of combined use of RFA and 131 I treatment has not been reported. In this study, we designed a clinical trial to determine whether iodine radiotherapy combined with RFA is an effective, safe, and feasible method for elimination of excessive postsurgical thyroid remnant for DTC.


 > Materials and Methods Top


Clinical characteristics

We screened 978 DTC patients with postsurgical 131 I irradiation between October 2013 and December 2014 in our hospital, and 47 patients were considered excessive remnant based on clinical examinations, imaging, and laboratory data. Among these 47 patients, 12 patients were treated by combined therapy of 131 I radiotherapy and RFA. There were 4 males and 8 females with median age of 36.3 ± 14.8 years (20–78 years). Pathological data showed all patients are thyroid papilloma with the status of Stage I (10/12), Stage II (1/12), and Stage IV (1/12) by AJCC TNM staging guideline (2010 version). A blood test showed thyroid-stimulating hormone (TSH) level were lower than 30 μIU/ml for all the patients after 4 weeks of iodine-free diet and thyroid hormone withdrawal, and ultrasonography indicated obvious thyroid remnant. All the patients received and signed the informed consent form for the combination therapy of 131 I radiotherapy and RFA.

99mTechnetium-pertechnetate scans

Scintigraphy of the neck was performed prior to RFA, 30 min after intravenous administration of 185 MBq of 99m Technetium (99m Tc)-pertechnetate, the patients were lying down on a soft pillow to fully expose thyroid and anterior imaging of the neck was acquired using single-photon emission computed tomography (Forte, Philips, Netherlands) with high-resolution low-energy collimator with an acquisition time of 3 min, using a 20% window centered around the 140 KeV peak of 99m Tc and a 512 × 512 computer matrix. The radioactive counting inside the syringe before and after injection was recorded for 1 min each time to calculate99m Tc uptake ratio of thyroid remnant using the region-of-interest technique that was drawn by hand after the visible contour of any recognizable thyroid remnant and the neck background.

Radiofrequency ablation

Patients were laid down on the back to expose fully the neck area. After local anesthesia, separation liquid (about 20 ~ 30 ml normal saline solution) was injected into anterior side of thyroid gland, interior carotid sheath, posterior and dorsal part of thyroid gland near trach by a radiofrequency generator with a 18-gauge 7 cm shaft length 0.5 cm straight fixed active-tip electrode (VRS01, STARmed Co., Ltd., Korea). The RFA was done under the guide of ultrasonography guidance (model: LOGIQ E9, GE Health Care) with 10 MHz linear probe, and either by penetration into the center for thyroid remnant, or multiple spot RFA by "moving shot" injection.

Radioiodine therapy

All the patients were tested for thyroid function (including TSH, thyroglobulin [Tg] and thyroglobulin antibodies [TgAb], chemiluminescence method, Tg normal range of 1.4–78 ng/ml) on day 1, 7, and 14, and 99m Tc-pertechnetate scans was performed on 1 day before RFA and the 14th day after RFA, as followed by in hospital treatment of Na 131 I solution 3.7 GBq. Posttreatment whole body scan (RxWBS) was performed 5 days after 131 I treatment. After 4 ~ 6 months, thyroid function, neck ultrasonography,99m Tc thyroid imaging, and diagnostic whole body scan (DxWBS) were performed to evaluate the efficacy of thyroid remnant ablation.

Image reading and efficacy evaluation

99m Tc thyroid imaging, DxWBS, and RxWBS were read by two senior radiologists/doctors from Department of Nuclear Medicine independently. The standard for successful thyroid remnant ablation was: No thyroid uptake by thyroid imaging, no remnant by neck ultrasonography, no thyroid uptake by DxWBS, and Tg < 1 ng/ml (TgAb negative) with TSH stimulation (TSH > 30 μIU/ml).

Statistical analysis

All the statistical analysis was performed usingSPSS software (version 22.0, IBM, New York, USA). The quantitative data were shown as mean ± standard deviation, and changes of variants before and after RFA was analyzed using Wilcoxon rank sum test. P <0.05 was considered statistically significant.


 > Results Top


This study reported the combination therapy of 12 DTC patients for thyroid remnant ablation. The patients received RFA followed by 131 I radiotherapy 14 days later, and the efficacy was evaluated 4–6 months posttreatment.

Time interval between RFA and 131 I radiotherapy

All the patients showed TSH < 30 μIU/ml before RFA (mean value = 10.27 ± 6.16 μIU/ml on 1 day before RFA); TSH decreased on day 1 after RFA, and increased on day 14 after RFA [all patients showed TSH > 30 μIU/ml with mean value = 34.73 ± 3.93 μIU/ml, P = 0.002 compared to TSH value before RFA, [Figure 1].
Figure 1: Serum thyroid-stimulating hormone level changes before and after radiofrequency ablation treatment

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RFA effect on 99m Tc uptake ratio of thyroid remnant

One day before RFA thyroid 99m Tc imaging showed the tissue uptake of thyroid remnant was (0.80 ± 0.16)%, and on day 14 postRFA the value dropped to (0.31 ± 0.12)% [Figure 2], which is significantly lower than before RFA (P = 0.002).
Figure 2: The changes of 99mTc uptake ratio by thyroid remant tissues before and after radiofrequency ablation treatment

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Efficacy evaluation

There was no metastasis for 11 patients by routine examination before 131 I treatment. Four to Six months after RAI therapy, DxWBS was performed after 3 weeks of thyroid hormone withdrawal, and the results showed no abnormal uptake by the whole body including thyroid tissue. All Tg values were below 1 ng/ml (TgAb negative), and neck ultrasonography identified no thyroid remnant or metastasis, indicating successful remnant ablation (11/12, success rate 91.7%). One patient showed pulmonary metastasis by computed tomography before 131 I treatment, and DxWBS showed no obvious thyroid iodine uptake after treatment [Figure 3].
Figure 3: An example of 99mTc uptake change for a differentiated thyroid carcinoma patient before and after radiofrequency ablation. The patient (male, 44-year-old) received thyroidectomy and the 99mTc thyroid imaging showed obvious remnant on right thyroid after 4 weeks of thyroid hormone withdrawal, with 99mTc uptake ratio of 0.9% (a), on day 14 after radiofrequency ablation, 99mTc thyroid imaging showed no obvious change in thyroid remnant shape, but the radiation distribution was less intense with 99mTc uptake ratio of 0.3% (b), the patient was given oral administration of 131I 3700 Mbq for iodine therapy, and posttreatment whole body scan showed lumpy iodine imaging at thyroid area and diffused imaging at lung area (c), after 4 months the patient received another 131I therapy, and posttreatment whole body scan showed no obvious iodine uptake at thyroid region, while iodine uptake was still present at lung region (d)

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Side effects

All the 12 patients reported minor neck discomfort after RFA, and the symptom was relieved 24–48 h postRFA. Five patients reported swollen pain at injection site. No patients reported vocal hoarseness or choking. No patients showed radiothyroiditis after 131 I treatment. One patient showed swollen neck, and the symptom was resolved 3 days after oral prednisone administration (10 mg with 3 times/day).


 > Discussion Top


Thyroid cancer is the most common malignant cancer type in the endocrine system, and it consists of about 1.1% of all the systemic cancer types. The incidence of thyroid cancer was among the top 10 malignant cancer types.[3] The most typical thyroid cancer type is DTC, including papillary thyroid carcinoma, follicular thyroid carcinoma and the mixed type.131 I radiotherapy uses beta irradiation from radioactive 131 I to ablate thyroid remnant and was considered the only effective approach postsurgery. RFA uses radiofrequency waves to treat the patient and the heat generated from high-frequency alternating electric current agitate the ions and charged molecules in human tissues, and they will increase the temperature by frictional heat within the tissue. When the tissue temperature reaches 39.0°C–41.5°C, oxygen pressure will increase in tumor and change the permeability of cell membrane and increase radiotherapy sensitivity. When the temperature reaches 60°C, it will induce cell coagulative necrosis and tissue coagulation to tumor tissues. In this study, we determined whether combined treatment of 131 I and RFA for thyroid remnant elimination can enhance radio-sensitivity and achieve synergistic efficacy.

Sodium Iodide Symporter (NIS) is expressed on the cell membrane of normal thyroid follicular epithelial cells and DTC cells. NIS is a membrane transporter protein mediating iodine transport, and is also named "iodine pump." NIS can transport extracellular iodine into cells by Ca 2+ concentration gradient through Na-K exchange. TSH can stimulate 131 I cellular uptake. Thus, thyroid elimination is generally performed after serum TSH reach 30 μIU/ml and above.[4] The major factors affect TSH level increase before RAI treatment are the time interval between thyroid hormone withdrawal, excessive thyroid remnant from surgery, and the patient disease conditions. In this study, none of the patients reach TSH requirement after 4 weeks of thyroid hormone withdrawal, mainly because of excessive thyroid remnant. RFA can destroy part of thyroid tissue by heat effect, and may facilitate the following 131 I therapy. The monitoring of TSH level changes on day 1, 7, and 14 postRFA found that TSH decreased on day 1 after RFA. It is likely that thyroid damage induces a large amount of triiodothyronine release into blood and cause TSH decrease by a negative feedback loop. On day 14 after RFA, the TSH levels of all patients increased and reached the thyroid ablation requirement (all >30 μIU/ml). Therefore,131 I therapy may not be carried out immediately after RFA. The exact time interval would be determined by TSH level monitoring as we did not have a control group in this study.

DxWBS is routinely used for thyroid remnant and metastasis evaluation before 131 I treatment. As 131 I has relatively long decay time and high energy, it may induce "stunning effect" on the following treatment.[5],[6] Therefore,99m Tc thyroid imaging is often used to evaluate thyroid remnant. Thyroid tissue can take up and concentrate 99m Tc similarly as 131 I, and by 99m Tc imaging it can display the position, size, shape, and irradiation distribution of thyroid remnant so that the 99m Tc uptake ratio indirectly quantify the remnant amount. We compared the 99m Tc uptake ratio before and after RFA, and found no obvious change in thyroid tissue shape but weaker 99m Tc imaging after RFA, suggesting that RFA is effective.

Currently, the success rates of thyroid remnant elimination vary from different reports. For example, Verkooijen et al.[7] reported 57% success rate on 235 patients, Verburg et al.[8] reported 56.6% success rate on 449 patients, Fu et al.[9] reported 59.6% success rate on 183 patients, and Liu et al.[10] reported 43% success rate on 51 DTC patients. We evaluated the efficacy of combination treatment of 131 I with RFA for thyroid remnant ablation on 12 DTC patients, and the success rate is much higher than that from literature while the sample size of our study is much smaller. It should be noted that the combination therapy may induce some side effects. For example, short-term side effect of 131 I radiotherapy (day 1–15 posttherapy) include: Fatigue, swollen neck and throat discomfort, dry mouth and salivary gland pain, taste changes, nasolacrimal duct obstruction, abdomen discomfort and sickness, urinary tract damage, etc., therapeutic dosage of 131 I may induce radiation inflammation, especially when there is excessive thyroid remnant. We did not observe radiothyroiditis in this study, but there was one patient showing neck edema. In addition, RFA may induce some complications and side effects as well. As reported from KSThR data including 1459 patients from 13 medical centers, complication occurrence ratio is 3.3% (48/1459), and the major complication occurrence ratio is 1.4% (20/1459). The most common major complication is the hoarseness from recurrent laryngeal nerve injury.[11],[12] To protect the surrounding healthy tissue from heat damage, we injected normal saline solution as "separation solution" around thyroid remnant, especially around trachea-esophagus groove where the recurrent laryngeal nerve travels. Moreover, we used "moving shot" technology to perform RFA while moving, which increase the area of single injection and avoid local over-heat. We did not observe side effect such as hoarseness or choking. For DTC patients with excessive thyroid remnant, our prospective study suggests that combination therapy by RFA prior to 131 I therapy is more effective for remnant ablation than re-operation, and it is an effective, safe and feasible approach. Due to the limit of patient numbers, we did not have a control group, and the optimal time interval, side effect management, and long-term efficacy will be determined in the future study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214.  Back to cited text no. 1
    
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Gharib H, Papini E, Paschke R, Duick DS, Valcavi R, Hegedüs L, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. J Endocrinol Invest 2010;33 5 Suppl: 1-50.  Back to cited text no. 2
    
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Hao J, Chen W. Chinese Cancer Registry Annual Report 2012. Beijing: Military Medical Sciences Press; 2012. p. 27-9.  Back to cited text no. 3
    
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Chinese Medical Association. Guidelines for 131 I therapy on differentiated thyroid cancer (2014 edition). Chin J Nucl Med Mol Imaging 2014;34:264-78.  Back to cited text no. 4
    
5.
Muratet JP, Giraud P, Daver A, Minier JF, Gamelin E, Larra F. Predicting the efficacy of first iodine-131 treatment in differentiated thyroid carcinoma. J Nucl Med 1997;38:1362-8.  Back to cited text no. 5
    
6.
Leger AF, Pellan M, Dagousset F, Chevalier A, Keller I, Clerc J. A case of stunning of lung and bone metastases of papillary thyroid cancer after a therapeutic dose (3.7 GBq) of 131 I and review of the literature: Implications for sequential treatments. Br J Radiol 2005;78:428-32.  Back to cited text no. 6
    
7.
Verkooijen RB, Stokkel MP, Smit JW, Pauwels EK. Radioiodine-131 in differentiated thyroid cancer: A retrospective analysis of an uptake-related ablation strategy. Eur J Nucl Med Mol Imaging 2004;31:499-506.  Back to cited text no. 7
    
8.
Verburg FA, Lassmann M, Mäder U, Luster M, Reiners C, Hänscheid H. The absorbed dose to the blood is a better predictor of ablation success than the administered 131 I activity in thyroid cancer patients. Eur J Nucl Med Mol Imaging 2011;38:673-80.  Back to cited text no. 8
    
9.
Fu H, Du X, Gu Z, Zou R, Wu Z, Wang H, et al. Analysis of influential factors for efficacy of 131 I thyroid remnant ablation for differentiated thyroid cancer. J Shanghai Jiaotong Univ (Med Sci) 2010;30:249-52.  Back to cited text no. 9
    
10.
Liu Y, Jin J, Liu J, Li S, Wu Z, Lu K, et al. Efficacy and influencing factors of radioactive 131 I for elimination of thyroid remnants following differentiated thyroid carcinoma resection. Chin Remedies Clin 2013;13:556-8.  Back to cited text no. 10
    
11.
Na DG, Lee JH, Jung SL, Kim JH, Sung JY, Shin JH, et al. Radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: consensus statement and recommendations. Korean J Radiol 2012;13:117-25.  Back to cited text no. 11
    
12.
Baek JH, Lee JH, Sung JY, Bae JI, Kim KT, Sim J, et al. Complications encountered in the treatment of benign thyroid nodules with US-guided radiofrequency ablation: a multicenter study. Radiology 2012;262:335-42.  Back to cited text no. 12
    


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