RFA for AFTN(Autonomously Functioning Thyroid Nodule)

Radiofrequency Ablation for Autonomously Functioning Thyroid Nodules (AFTN): Multicenter Study of Korean Society of Thyroid Radiology (KSThR)

Jin Yong Sung1, Jung Hwan Baek1,3, So Lyung Jung5, Ji-hoon Kim6, Kyu Sun Kim1, Ducky Lee2, Jeong Hyun Lee3, Young Kee Shong4, Dong Kyu Na71Department of Radiology, Thyroid Center, Daerim St. Mary's Hospital, 2Department of Internal Medicine, Thyroid Center, Daerim St. Mary's Hospital, 3Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 4Department of Endocrinology and Metabolism, University of Ulsan College of Medicine, Asan Medical Center, 5Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 6Department of Radiology, Seoul National University College of Medicine, 7Department of Radiology, Human Medical Imaging & Intervention Center Thank you, Chairperson. Im Dr. Jin Yong Sung from Daerim St. Marys Hospital.

1Definition of AFTN Scintigraphy : increased uptake in the nodule compared with surrounding normal thyroid parenchyma Hormone TSH: low or undetectedScintigraphically, the AFTN shows increased uptake in the nodule compared with surrounding normal thyroid parenchyma and the TSH level is low or undetected.

2Problems of AFTN Malignancy : Papillary, follicular, medullary, poorly differentiated

Large nodule volume 1) symptomatic 2) cosmetic

Functional problem: Thyrotoxicosis 1) decreased bone density -- osteoporosis 2) atrial fibrillationBaek et al. Thyroid 2008;18(6):675-676 Baek et al. World J Surg 2009; 33(9):1971-7Hegedus L. N Engl J Med 2004; 351:17641771Toft AD. N Engl J Med 2001; 345:512516Problems of AFTN that needs treatment are malignancy, compressive symptom and cosmetic problem due to large volume, and thyrotoxic symptom. 3Treatment optionsRadioactive iodine therapy

SurgeryGharib H. J Clin Endocrinol Metab 2005; 90:581587Hegedus L. N Engl J Med 2004; 351:17641771Toft AD. N Engl J Med 2001; 345:512516Conventional treatment options are iodine therapy and surgery. 4Effect/Side effect is dose dependant10mCi: mild symptom, less than 3cm nodule TSH normalize in 6 months20mCi: 38/42 (normal), 1/42 (repeat) 3/42 (hypothyroidism)Radioactive iodine treatment Gharib H. J Clin Endocrinol Metab 2005; 90:581587Hegedus L. N Engl J Med 2004; 351:17641771Toft AD. N Engl J Med 2001; 345:512516In iodine therapy, the therapeutic effect and side effect are dose dependent. With increment of the dose, hypothyroidism can be occurred.5Scar formationHypothyroidismAnesthetic riskLong recovery timeVoice changeHypoparathyroidismSurgery, drawbacksAs you know, surgery has been used to treat AFTN, but there are several drawbacks.6Radiofrequency Ablation for AFTNAuthor (Year) CasesNormalized TSH (%)Volume Reduction at last follow-up (%) Follow up periods (Mo)Baek et al. (2008 and 2009)106072.212Deandrea et al. (2008)2321.752.66Small number of enrolled nodules, short F/U periods, different RFA technique (moving vs fixed)Baek et al. Thyroid 2008;18(6):675-676 Baek et al. World J Surg 2009; 33(9):1971-7Deandrea et al. Ultrasound Med Biol 34:784791Some alternative therapies have been introduced like ethanol and laser ablation. Dr. Baek and Dr. Deandrea reported RFA results to treat AFTN. In two studies, different RFA techniques were used, moving shot and fixed needle techniques. So, we planned multicenter RFA study for AFTN with same RF technique using moving shot technique and larger number of cases.

7Objectives To evaluate the efficacy and safety of RFA for the treatment of AFTN The objective of this study is to evaluate the efficacy and safety of RFA for the treatment of AFTN.

8

Materials and Methods

Patients Multicenter study, Korean Society of Thyroid Radiology 5 institutions, from August 2007 to July 2011

Selection Criteria Hot nodule with / without suppression of normal thyroid Low TSH Benign lesion: FNAB or CNB Refused or not suitable for Op. or iodine therapy 44 patients [M:F=2:42, 43 14.7 (range, 17-70) years] 25 (56.8%) toxic nodules, 19 (43.2%) pre-toxic nodulesKSThR planned this study and 5 institutions participated. Enrolled patients had hot nodules, low TSH level and benign cytologic or histologic results. They refused or were not suitable for operation or iodine therapy. Overall 44 patients were enrolled and there were 25 toxic nodules and 19 pre-toxic nodules.

10Pre-Ablation Assessment Clinical sign / symptom : Symptom (Visual Analogue Scale, 0-10cm) and cosmetic grading score (grade 1-4) T3, fT4, TSH, TSH-R-Ab US gray scale and color doppler : Diameter, volume and vascular grade FNAB and/or CNB Thyroid scan with 99mTc pertechnetate Clinical signs and symptoms, laboratory, US findings, FNA or CNB results and thyroid scan were assessed prior to RFA.

11RFA Procedure Internally cooled electrode: 18 G 0.5-1.5 cm active tip

Trans-Isthmic Approach and Moving-Shot Technique

Termination of ablation: Whole nodule changed to transient hyperechoic Methimazole was prescibed to control thyrotoxicosis for 1 month before RFA. Internallly cooled electrode was used with trans-isthmic approach and moving shot technique. When whole nodule was changed to hyperechoic, the ablation was terminated.

12Patient Care and Follow up Post-treatment care : Evaluation of complications and observation for 1-2 hours Following at 1, 3, 6 months and every 6-12 months : Symptom (self-check list) and cosmetic grading score Complication T3, fT4 and TSH US : diameter, volume and vascularity Thyroid scan : nodule and surrounding thyroid gland

We evaluated complications and observed patients for 1-2 hours after RFA procedure. At each follow up periods, we evaluated findings as shown.

13Treatment EffectsComplete Cure (CC) : Normal hormone level & Hot nodule converted to cold or invisible nodulePartial Cure (PC) Hormonal Remission (HR) Failure (F) SymptomScanHormoneNoduleExtranodularT3 / fT4TSHCC-NNNPC-/NNNHR-/NF+Treatment effects can be classified as complete cure, partial cure, hormonal remission and failure. In complete cure, hot nodule was changed to cold nodule and symptom and hormone level were normalized.

In partial cure, nodule was still hot or show similar uptake to extranodular area. In hormonal remission, merely thyroid hormone level was declined to normal level but TSH level was still subnormal.

14Statistical Analysis Wilkoxon signed rank test : At each follow up periods The nodule volume change and % volume reduction Changes of T3, fT4 and TSH Changes in thyroid scan (nodule and extranodular area) Changes of cosmetic and symptom grading scores

Significance : P < 0.05The statistical significance was assigned for p value less than 0.05.

15

Results

RFA Characteristics Treatment Sessions: 1-6 (mean, 1.8 0.9)

Ablation Time: 2.5-30 minutes (range, 12 5.9) Ablation Power: 20-120 W (range, 63.3 26.3)

Total Energy: 4500-539460 J (mean, 76939.6 87264.2) Mean Energy/mL: 1589-19014 J/mL (mean, 6417.3 4318.4) The mean number of RFA sessions was 1.8. The mean ablation time and power were 12 minutes and 63 W.

17US and Clinical FindingsPre-RFA1 M3 M6 MLast F/UDiameter (cm)3.8 1.4 3.1 1.4*2.8 1.6* 2.5 1.4* 2.1 1.2*Volume (ml)18.5 30.111.8 26.9*12.2 28.2*7.0 14.7*4.7 10.1*Volume Reduction (%) 028.6 109.664.1 18.4 61.5 77.270.8 69.9Vascularity Grade3.1 0.70.9 1.0*Symptom Grade Score3.3 2.10.9 1.0*Cosmetic Grade Score3.8 0.51.8 0.9** P < 0.001 vs pre-RFA.The mean volume reduction at last follow up was 70.8 %. Mean largest diameters and volumes at each follow up were significantly lower than pre-RFA data. All P value was below 0.001.

Vascular grade, symptom score and cosmetic score were significantly decreased at last follow up.

18Changes in T3, fT4 and TSHHormonePre-RFA1 M3 M6 MLast F/UT3 (ng/dL)179.3 102.5* 124.4 44.5*121.4 43.6*143.8 69.1* 132.4 63.3*fT4 (ng/dL)1.94 1.29*1.20 0.37*1.24 0.27*1.32 0.68*1.34 0.44*TSH (uIU/ml)0.12 0.12*0.72 0.81*0.94 0.80*1.69 2.84*1.50 2.15* Normal range (T3 : 61-173, fT4 : 0.89-1.76, TSH : 0.4-4). * P < 0.001 vs pre-RFA.

Hormonal levels were also changed with statistical significance.

19Changes in ScintigraphyPre-RFA1 M3 M6 MLast F/UNodule*1.0 0.21.9 1.02.0 1.02.1 0.82.3 0.8Extranodular area**1.4 0.52.0 0.82.3 0.82.2 0.62.4 0.5 * 1 : Hot nodule, 2 : Similar uptake to extranodular area, 3 : Cold nodule. ** 1 : non-visualized, 2 : weak uptake, 3 : normal uptake.

P < 0.001 vs pre-RFA.

Nodular uptake were decreased and extranodular uptake were restored with statistical significance, too.

20Treatment Effects: Nodule VolumePre-RFA Vol. (ml) Nodule number (n=44)CC*(n=21)PC* (n=16)HR* (n=5)F* (n=2)< 10241374010