Safety of radiofrequency ablation of benign thyroid nodules and recurrent thyroid cancers: a systematic review and meta-analysis

Figures & data

Figure 1. Study flow diagram.

Figure 2. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria for the included studies.

Table 1. Characteristics of the included studies.

First author (year of publication) (ref.)	Affiliation institute	Year	No. of patients	No. of nodules	No. of RFA sessions	Mean age, years (range)	Pathology	Mean tumour diameter, cm (volume, ml)	Major complications	Minor complications	Side effects	Follow-up period, months
Deandrea (2008) [51]	Umberto I Hospital, Turin, Italy	2004–2005	31	33	232	66.8 (31–84)	Benign	4.1 (median) (27.7)	0	0	All (heat sensation), most (oedema)	6
Spiezia (2009) [8]	ASLNA1 Hospital, Naples, Italy	2005–2007	94	94	133	72.5 (66–89)	Benign	N/A (24.5)	0	0	All (all heat sensation, 14 mild pain, 5 fever)	24
Baek (2011) [17]	Daerim St. Mary’s Hospital, Seoul, South Korea	2004–2008	10	12	15	44.8 (23–71)	Well-differentiated thyroid cancer	1.38 (0.06)	1 (vocal cord palsy)	0	Some (pain, heat sensation)	23.0
Faggiano (2012) [13]	Federico II University of Naples, Rome, Italy	2010–2011	20	20	20	58.3 (31–86)	Benign	N/A (13.3)	0	0	Some (heat sensation)	12
Park (2011) [52]	Samsung Medical Center, Seoul, South Korea	2008–2009	11	16	30	69 (40–86)	Well-differentiated thyroid cancer	2.9 (9)	0	6 (1 2nd degree skin burn, 5 intolerable pain → incomplete ablation)	11 (swelling and regional discomfort)	6
Baek (2012) [24]	13 South Korean hospitals^a	2002–2009	1459	1543	2197	41.2 (N/A)	Benign	3.8 (N/A)	20 (15 transient voice change, 2 nodule rupture, 1 nodule rupture with abscess formation, 1 hypothyroidism, 1 brachial plexus injury)	28 (15 haematoma, 9 vomiting, 4 skin burn)	46 (38 pain, 5 vasovagal reaction, 3 cough)	N/A
Bernardi (2013) [5]	Cattinara Hospital, Trieste, Italy	2012–2013	37	37	38	58.3 (N/A)	Benign	3.57 (12.4)	1 (transient voice change)	3 (1 transient thyrotoxicosis, 2 pain)	N/A	12
Guenette (2013) [18]	Rhode Island Hospital, Providence, RI, USA	1998–2013	14	21	N/A	57.6 (27–89)	Well-differentiated thyroid cancer	1.5 (N/A)	1 (vocal cord palsy)	0	0	61.3
Sung (2013) [53]	Daerim St. Mary’s Hospital, Seoul, South Korea	2010–2011	25	25	27	44.9 (26–69)	Benign	3.0 (9.3)	0	0	25 (pain)	6
Lee (2014) [20]	St. Mary’s Hospital, Seoul, South Korea	2008–2011	32	35	45	53 (22–85)	Well-differentiated thyroid cancer	0.8 (0.17)	6 (5 transient voice change, 1 vocal cord palsy)	0	Some (heat sensation, pain)	30
Turtulici (2014) [56]	Ospedale Evangelico Internazionale, Genoa, Italy	2012–2013	45	45	45	44 (29–68)	Benign	N/A (13.5)	0	1 (first-degree skin burn)	0	6
Wang (2014) [21]	Zhejiang Cancer Hospital, Hangzhou, China	2013–2014	8	20	20	43.6 (30–58)	Metastatic lymph nodes from thyroid cancer	1 (0.21)	0	0	Some (heat sensation, pain)	9.3
Baek (2015) [56]	Asan Medical Center and Daerim St. Mary’s Hospital, Seoul, South Korea	2013	24	24	22	49.8 (24–76)	Benign	3.0 (8.6)	0	0	13 (pain)	6
Cesareo (2015) [25]	SM Goretti Hospital, Rome, Italy	2011–2013	42	42	42	56 (24–80)	Benign	N/A (24.5)	3 (2 transient voice change, 1 vocal cord palsy)	1 (severe chest pain → incomplete ablation)	8 (pain)	6
Che (2015) [14]	Dalian Medical University, Dalian, China	2012–2013	200	375	N/A	43.8 (15–84)	Benign	3.4 (5.4)	2 (1 transient voice change, 1 nodule rupture)	0	0	N/A
Deandrea (2015) [15]	“Umberto I” Hospital, Turin, Italy, and Daerim St. Mary’s Hospital, Seoul, South Korea	2010–2012	40	40	40	46.9 (26–83)	Benign	4 (15.1)	0	0	40 (heat sensation)	6
Kim (2015) [19]	Seoul National University Hospital, Seoul, South Korea	2008–2011	27	36	41	51.6 (N/A)	Recurrent thyroid cancer	0.98 (0.19)	1 (transient voice change)	0	0	N/A
Lim (2015) [26]	Asan Medical Center, Seoul, Korea	2008–2012	39	61	67	52.8 (21–92)	Recurrent papillary thyroid cancer	0.79 (0.2)	3 (transient voice change)	4 (local pain)	0	26.4
Sung (2015) [11]	5 South Korean hospitals^b	2007–2011	44	44	N/A	43 (17–70)	Benign	3.8 (18.5)	0	0	44 (pain, heat sensation)	19.9
Ugurlu (2015) [12]	Marmara University, Istanbul, Turkey	2013–2014	33	65	65	N/A	Benign	2.6 (7.3)	0	4 (pain)	Most (pain)	6
Aysan (2016) [23]	Bezmialem Vakif University, Istanbul, Turkey	2013–2015	100	100	100	44.5 (18–71)	Benign	N/A (16.9)	1 (transient voice change)	1 (skin burn)	0	15.4
Kohlhase (2015) [57]	University Hospital, Frankfurt, Germany	2014–2015	18	20	20	50 (15–72)	Benign	N/A (8)	0	0	0	3
Li (2016) [58]	Shanghai Tenth People's Hospital, Shanghai, China	2013–2015	35	35	35	42.69 (17–67)	Benign	N/A (8.8)	0	0	Most (pain, heat sensation)	6
Xu (2016) [27]	Zhejiang Cancer Hospital, Hangzhou, China	2014–2015	35	45	N/A	43.49 (N/A)	Remnant thyroid tissue	2.5 (2.4)	2 (transient voice change)	0	10 (pain, heat sensation)	N/A

N/A: not available.

^a Asan Medical Center, Daerim St. Mary’s Hospital, Ajou University School of Medicine, UNMEC Clinic, Mothers Clinic, BHS Hanseo Hospital, Samsung Medical Center, Hanyang University College of Medicine, Busan Paik Hospital, Seoul National University College of Medicine, Yonsei University College of Medicine, Seoul St. Mary’s Hospital, Human Medical Imaging & Intervention Center.

^b Daerim St. Mary’s Hospital, Asan Medical Center, Seoul St. Mary’s Hospital, Seoul National University College of Medicine, Human Medical Imaging & Intervention Center.

Figure 3. Forest plots to show the pooled proportions of (A) overall complications and (B) major complications of radiofrequency ablation.

Figure 4. Funnel plot to assess publication bias of (A) overall complications and (B) major complications of radiofrequency ablation.

Table 2. Summary of the meta-analytic pooled proportions of overall and major RFA complications.

			Summary estimate
Complications	No. of studies	No. of cases	Pooled proportion (95% CI)	p value for heterogeneity^a	I^2b	p value for reporting bias^c
Overall	24	2786	2.38% (1.42%–3.34%)	<0.001	21.79%	<0.001
Major	24	2786	1.35% (0.89%–1.81%)	0.5152	1.24%	0.0049

^a p value by the Cochran’s Q method to test the heterogeneity of the pooled data, with p < 0.05 indicating substantial heterogeneity.

^b Higgins’ index for heterogeneity (0–40%, may not be important; 30–60%, may represent moderate heterogeneity; 50–90%, may represent substantial heterogeneity; 75–100%, may represent considerable heterogeneity).

^c Test of publication/reporting bias by Egger’s test, with p < 0.10 indicating significant bias.

Table 3. Subgroup analysis according to nodule characteristics and origin of the study.

	Overall complications			Major complications
Variable	Pooled proportion (95% CI)	I^2a	p value^b	Pooled proportion (95% CI)	I^2a	p value^b
Nodule characteristics
Malignant	10.98% (4.82%–17.15%)	77.64%	0.0011	6.71% (3.05%–10.36%)	0%	0.0038
Benign	2.11% (1.15%–3.06%)	25.13%		1.27% (0.81%–1.73%)	0%
Origin of the study
Asia	2.51% (1.31%–3.72%)	24.26%	0.7286	1.43% (0.89%–1.97%)	0.38%	0.5856
Non-Asia	2.30% (0.62%–3.98%)	0.18%		1.11% (0.13%–2.09%)	0%

^a Higgins’ index for heterogeneity (0–40%, may not be important; 30–60%, may represent moderate heterogeneity; 50–90%, may represent substantial heterogeneity; 75–100%, may represent considerable heterogeneity).

^b Test of publication/reporting bias by Egger’s test, with p < 0.10 indicating significant bias.

Deandrea M, Limone P, Basso E, et al. (2008). US-guided percutaneous radiofrequency thermal ablation for the treatment of solid benign hyperfunctioning or compressive thyroid nodules. Ultrasound Med Biol 34:784–91.

 PubMed Web of Science ®Google Scholar

Spiezia S, Garberoglio R, Milone F, et al. (2009). Thyroid nodules and related symptoms are stably controlled two years after radiofrequency thermal ablation. Thyroid 19:219–25.

 PubMed Web of Science ®Google Scholar

Baek JH, Kim YS, Sung JY, et al. (2011). Locoregional control of metastatic well-differentiated thyroid cancer by ultrasound-guided radiofrequency ablation. Am J Roentgenol 197:W331–6.

 PubMed Web of Science ®Google Scholar

Faggiano A, Ramundo V, Assanti AP, et al. (2012). Thyroid nodules treated with percutaneous radiofrequency thermal ablation: a comparative study. J Clin Endocrinol Metab 97:4439–45.

 PubMed Web of Science ®Google Scholar

Park KW, Shin JH, Han BK, et al. (2011). Inoperable symptomatic recurrent thyroid cancers: preliminary result of radiofrequency ablation. Ann Surg Oncol 18:2564–8.

 PubMed Web of Science ®Google Scholar

Baek JH, Lee JH, Sung JY, et al. (2012). Complications encountered in the treatment of benign thyroid nodules with US-guided radiofrequency ablation: a multicenter study. Radiology 262:335–42.

 PubMed Web of Science ®Google Scholar

Bernardi S, Dobrinja C, Fabris B, et al. (2014). Radiofrequency ablation compared to surgery for the treatment of benign thyroid nodules. Int J Endocrinol 2014:934595.

 PubMed Web of Science ®Google Scholar

Guenette JP, Monchik JM, Dupuy DE. (2013). Image-guided ablation of postsurgical locoregional recurrence of biopsy-proven well-differentiated thyroid carcinoma. J Vasc Interv Radiol 24:672–9.

 PubMed Web of Science ®Google Scholar

Sung JY, Baek JH, Kim KS, et al. (2013). Single-session treatment of benign cystic thyroid nodules with ethanol versus radiofrequency ablation: a prospective randomized study. Radiology 269:293–300.

 PubMed Web of Science ®Google Scholar

Lee SJ, Jung SL, Kim BS, et al. (2014). Radiofrequency ablation to treat loco-regional recurrence of well-differentiated thyroid carcinoma. Korean J Radiol 15:817–26.

 PubMed Web of Science ®Google Scholar

Baek JH, Ha EJ, Choi YJ, et al. (2015). Radiofrequency versus ethanol ablation for treating predominantly cystic thyroid nodules: a randomized clinical trial. Korean J Radiol 16:1332–40.

 PubMed Web of Science ®Google Scholar

Wang L, Ge M, Xu D, et al. (2014). Ultrasonography-guided percutaneous radiofrequency ablation for cervical lymph node metastasis from thyroid carcinoma. J Cancer Res Ther 10:C144–9.

 PubMed Web of Science ®Google Scholar

Cesareo R, Pasqualini V, Simeoni C, et al. (2015). Prospective study of effectiveness of ultrasound-guided radiofrequency ablation versus control group in patients affected by benign thyroid nodules. J Clin Endocrinol Metab 100:460–6.

 PubMed Web of Science ®Google Scholar

Che Y, Jin S, Shi C, et al. (2015). Treatment of benign thyroid nodules: comparison of surgery with radiofrequency ablation. Am J Neuroradiol 36:1321–5.

 PubMed Web of Science ®Google Scholar

Deandrea M, Sung JY, Limone P, et al. (2015). Efficacy and safety of radiofrequency ablation versus observation for nonfunctioning benign thyroid nodules: a randomized controlled international collaborative trial. Thyroid 25:890–6.

 PubMed Web of Science ®Google Scholar

Kim JH, Yoo WS, Park YJ, et al. (2015). Efficacy and safety of radiofrequency ablation for treatment of locally recurrent thyroid cancers smaller than 2 cm. Radiology 276:909–18.

 PubMed Web of Science ®Google Scholar

Lim HK, Baek JH, Lee JH, et al. (2015). Efficacy and safety of radiofrequency ablation for treating locoregional recurrence from papillary thyroid cancer. Eur Radiol 25:163–70.

 PubMed Web of Science ®Google Scholar

Sung JY, Baek JH, Jung SL, et al. (2015). Radiofrequency ablation for autonomously functioning thyroid nodules: a multicenter study. Thyroid 25:112–17.

 PubMed Web of Science ®Google Scholar

Ugurlu MU, Uprak K, Akpinar IN, et al. (2015). Radiofrequency ablation of benign symptomatic thyroid nodules: prospective safety and efficacy study. World J Surg 39:961–8.

 PubMed Web of Science ®Google Scholar

Aysan E, Idiz UO, Akbulut H, Elmas L. (2016). Single-session radiofrequency ablation on benign thyroid nodules: a prospective single center study: radiofrequency ablation on thyroid. Langenbecks Arch Surg 401:357–63.

 PubMed Web of Science ®Google Scholar

Kohlhase KD, Korkusuz Y, Groner D, et al. (2016). Bipolar radiofrequency ablation of benign thyroid nodules using a multiple overlapping shot technique in a 3-month follow-up. Int J Hyperthermia 32:511–16.

 PubMed Web of Science ®Google Scholar

Li XL, Xu HX, Lu F, et al. (2016). Treatment efficacy and safety of ultrasound-guided percutaneous bipolar radiofrequency ablation for benign thyroid nodules. Br J Radiol 89:20150858.

 PubMed Web of Science ®Google Scholar

Xu D, Wang L, Long B, et al. (2016). Radiofrequency ablation for postsurgical thyroid removal of differentiated thyroid carcinoma. Am J Transl Res 8:1876–85.

 PubMed Web of Science ®Google Scholar