Abstract
Background:
Radiofrequency ablation (RFA) is currently the mainstay of treatment for thyroid nodules (TNs), with indications that extend from initially benign nodules and micropapillary thyroid carcinoma to current low-risk papillary thyroid carcinoma. Our study aims to evaluate the impact of malignant nodules on the efficacy of RFA.
Methods:
A total of 970 eligible patients were divided into benign and malignant group. We analyzed whether the efficacy of RFA differed between the two groups in terms of TNs volume, volume reduction ratio (VRR), technical effectiveness (TE), complete ablation (CR), and regrowth rate, and used multivariate logistic and linear regression to assess whether malignant nodules were a risk factor for its efficacy.
Results:
The TE value was higher in the benign group than in the malignant group (81.7% vs. 70.5%, p=0.002 < 0.052). However, after excluding patients with less than 1 year of follow-up, the adjusted TE values were not significantly different between the two groups. The malignant group had a higher CR than the benign group (43.6% vs. 9.7%, p < 0.001) and its CR time was shorter (14.09 ± 11.50 months vs. 21.75 ± 13.18 months, p < 0.001). The regrowth rate was higher in the benign group than in the malignant group. Multivariate logistic analysis showed that there was no difference between the two groups in TE and regrowth, however, the benign group had a lower CR than the malignant (adjusted OR = 0.100, 95%CI 0.055- 0.181, P<0.001). Multivariate linear regression analysis showed that the VRR in the malignant group was lower than that in the benign at years 1 and 2 after RFA, but there was no difference after 2 years.
Conclusion:
Malignant thyroid nodules do not affect the efficacy of radiofrequency ablation. Although their early target regression is slower after RFA, there is no difference in long-term outcomes, and they are more likely to achieve complete regression.
1 Introduction
Thyroid nodules (TNs) are extremely common diseases in the general population and their incidence is increasing. Surgery is currently the mainstay of treatment for TNs (), and radiofrequency ablation (RFA) is an alternative approach. Many studies have confirmed that the efficacy of RFA for TNs is not significantly different from that of surgery; however, its risk of intraoperative and postoperative adverse events is significantly lower than that of surgery (). RFA was first reported for the treatment of benign thyroid nodules in 2006 (), and its use now extends to large benign nodules, micropapillary thyroid cancer, and even recurrent and low-risk thyroid cancer. As its indications have expanded, factors affecting its efficacy have increased. Volume reduction ratio (VRR) and regrowth after RFA are two important metrics to assess their efficacy. Sim et al. found that initial nodule volume, vascularity, and technical factors were associated with its efficacy (). Yan L et al. also demonstrated that initial volume, vascularity, and nodule location affect the efficacy of RFA (). One study found that the initial ablation ratio (IAR) was significantly associated with the likelihood of VRR, but not with nodule regrowth (). Bernardi et al. found that the energy delivered during RFA is significantly correlated with regrowth (), while Aljammal Jules et al. found that it is negatively correlated with VRR ().
The popularity of the RFA application and the expansion of its indications have resulted in many new clinical concerns. Previous studies have showed that RFA does not affect subsequent re-RFA or surgical procedures for TNs (); however, whether it affects the efficacy of subsequent RFA for residual nodules remains unclear. Due to the trend towards younger patients and the increasing importance of aesthetic concerns, more and more patients with micropapillary thyroid cancer, or even low-risk thyroid cancer, are opting for RFA treatment. Previous studies have found that the VRR of malignant nodules after RFA is significantly lower than that of benign nodules (), but there are currently few studies on the effect of malignant nodules on the efficacy of RFA.
Therefore, the aim of our study was to explore whether malignant nodules affect the efficacy of RFA.
2 Materials and methods
2.1 Patients and groups
Our study was a single-center prospective cohort study, which was approved by our Institutional Ethics Committee (No. 2022ZSY-LLK-456), and all patients obtained informed consent prior to RFA. We enrolled patients with TNs who underwent RFA between January 2017 and December 2022 at our institution. All thyroid nodules were assessed for malignancy risk before RFA by experienced sonographers according to the ACR TI-RADS grading system (). All patients underwent fine needle aspiration biopsy (FNA) before RFA to clarify their pathology.
The inclusion criteria for eligible patients were as follows: 1) RFA performed at our institution between January 2017 and December 2022; 2) TNs with TI-RADS grading; and 3) TNs with definitive FNA pathology results. The exclusion criteria were as follows: 1) those who refused to participate; 2) patients who were lost to follow-up; 3) incomplete data; and 4) those who received other thermal ablation treatments before RFA, including laser ablation (LA), microwave ablation (MA), and high-frequency focused ultrasound (HIFU). All the above eligible patients were divided into benign group and malignant group based on TNs pathology. The malignant group were all papillary thyroid carcinomas and there was no evidence of capsule rupture or invasion of surrounding tissues on neck ultrasound examination. In addition, there is no evidence of cervical lymph node enlargement on neck ultrasound or Computed Tomography (CT) scan.
2.2 RFA procedure
All RFAs were performed by experienced surgeons and sonographers in an outpatient setting. The patient was placed in the supine position with full neck extension, and local anesthesia with lidocaine was applied for pain control. The RFA was performed under real-time ultrasound guidance with hydrodissection, trans-isthmic approach, and the moving shot technique. Hydrodissection involves injecting a 5% glucose solution in the perithyroidal capsule prior to RFA to form a liquid isolation zone greater than 5 mm, thereby avoiding damage to the recurrent laryngeal nerve, superior laryngeal nerve, trachea, esophagus, and other structures. During the injection of the liquid isolation zone, 5–20 ml of liquid is injected at a time, and multiple injections can be administered as needed during the procedure. All RFAs were performed using bipolar radiofrequency ablation needles with an 18G diameter, 10 cm length, and 0.9 or 2 cm active tip, with an energy delivered of 4–8 W, based on the size and location of the thyroid nodule. To ensure complete ablation of TNs, we determined the ablation area using contrast-enhanced ultrasound (CEUS) prior to the procedure, performed radiofrequency ablation under real-time ultrasound guidance, and repeated CEUS after the procedure to confirm complete ablation. During the RFA procedure, we assessed the patients for changes in voice, dyspnea, and other discomforts, and discharged them after 12 hours of post-operation observation without significant discomfort.
2.3 Post-RFA follow-up and variables
After RFA, ultrasound (US) was performed at months 1, 3, 6, 12, and every 6 or 12 months thereafter. Thyroid function was assessed again 1 month after RFA. We followed up to assess whether serious adverse events such as permanent nerve damage (including the superior laryngeal nerve, the recurrent laryngeal nerve, and the vagus nerve), or events requiring emergency surgery or prolonged hospitalization occurred after RFA.
We collected data on general demographic characteristics, and clinical characteristics of TNs preoperatively and postoperatively. General demographic characteristics included age, sex, and history of thyroid surgery and radiofrequency ablation. Preoperative clinical characteristics of TNs included their volume and TI-RADS classification. The clinical characteristics evaluated after RFA consisted of volume reduction ratio (VRR), technical efficiency (TE), regrowth rate, and reintervention rate. The three-dimensional size of the TNs was measured in ultrasound and its volume was calculated: Volume equation=[length(sagittal, cm)×depth(anteroposterior, cm)×width(transverse, cm)]×0.524. VRR = [(Initial Volume - Final Volume)×100%]/Initial Volume. We understand that in treatment of operable cancer the goal is to completely remove tumor in its entirety but to facilitate comparison with benign thyroid nodule we choose the technical efficacy as defined by a >50% reduction in thyroid nodule volume within 12 months after to be a main parameter. TNs regrowth was defined as a 50% increase in total volume over the previous minimum volume ().
2.4 Statistical analysis
In our study, continuous variables were described by mean ± standard deviation (SD) and statistically analyzed by Students to test or Mann Whitney U test according to their distribution. Categorical variables are expressed in frequency (percentage), and statistical analysis is performed using Chi-square tests or Fisher exact tests when appropriate. We used multivariate logistic and linear regression analysis to find the factors that affected the RFA effect, expressed by the adjusted odds ratio (OR) and 95% confidence interval (CI). P < 0.05 was considered statistically significant. All data were analyzed using SPSS 25.0 version.
3 Results
The flow of our study is shown in Figure 1. A total of 1,703 patients underwent RFA from January 2017 to December 2022, excluding refusers, loss to follow-up, incomplete data, and patients who underwent other ablations (LA, MA, HIFU) prior to RFA, for a total of 970 eligible patients divided into the benign group (n=821) and malignant group (n=149). The demographic and clinical characteristics of all patients were shown in Table 1. There were 803 (82.8%) females and 167 (17.2%) males with a mean age of 43.63 ± 12.36 years. Among these patients, 201 (20.7%) patients ablated multiple nodules during the same RFA, 18 (1.9%) patients underwent multiple RFAs and 15 (1.5%) patients were postoperative residual thyroid.
Figure 1
Table 1
| Characteristic | n (%) |
|---|---|
| Genders | |
| Female/male n (%) | 803/167 (82.8%/17.2%) |
| Age, years | |
| (mean ± SD) | (43.63±12.36) |
| Number of TNs | |
| 1/>1 n (%) | (316/654) (32.6%/67.4%) |
| The number of TNs for RFA | |
| 1/>1 n (%) | (769/201) (79.3%/20.7%) |
| History of prior RFA | |
| Yes/no n (%) | (18/952) (1.9%/98.1%) |
| Postoperative residual thyroid | |
| Yes/no n (%) | (15/955) (1.5%/98.5%) |
| Pathologic results of TNs | |
| Benign/Malignant n (%) | (821/149) (84.6%/15.4%) |
Clinical characteristics of the study.
SD, Standard deviation; TNs, Thyroid nodules; RFA, radiofrequency ablation.
The demographic and clinical characteristics of the benign and malignant groups are shown in Table 2. The follow-up time in the benign group and malignant group was 18.10 ± 13.80 months and 15.30 ± 12.61 months, respectively. There were significantly more males in the malignant group than in the benign group (24.2% vs 16.0%, p=0.015<0.05). There were no significant differences between the two groups in the number of TNs, the number of TNs with RFA, the proportion of multiple RFAs, and the proportion of postoperative residual thyroid.
Table 2
| Variable | Benign group | Malignant group | P value |
|---|---|---|---|
| N (%) | 821 (84.6) | 14 9(15.4) | – |
| Follow-up time, months | |||
| (mean ± SD) | 18.10 ± 13.80 | 15.30 ± 12.61 | 0.021 |
| Genders | |||
| Female n (%) | 690 (84.0) | 11 3(75.8) | 0.015 |
| Male n (%) | 131(16.0) | 36 (24.2) | |
| Age, years | |||
| (mean ± SD) | 43.82 ± 12.44 | 42.56 ± 11.90 | 0.252 |
| Number of TNs | |||
| 1 n (%) | 258 (31.4) | 58 (38.9) | 0.072 |
| >1 n (%) | 563 (68.6) | 91 (61.1) | |
| The number of TNs for RFA | |||
| 1 n (%) | 650 (79.2) | 11 9(79.9) | 0.848 |
| >1 n (%) | 171 (20.8) | 30(20.1) | |
| History of prior RFA | |||
| Yes n (%) | 804 (97.9) | 148 (99.3) | 0.244 |
| no n (%) | 17(2.1) | 1 (0.7) | |
| Postoperative residual thyroid | |||
| Yes n (%) | 809 (98.5) | 146 (98.0) | 0.616 |
| no n (%) | 12 (1.5) | 3 (2.0) | |
Demographic and clinical characteristics of the two groups.
SD, Standard deviation; TNs, Thyroid nodules; RFA, radiofrequency ablation.
The efficacy indicators after RFA were shown in Tables 3, 4. The technical efficiency (TE) was higher in the benign group than in the malignant group (81.7% vs. 70.5%, p=0.002 < 0.05). TE was defined as a volume reduction of >50% at 1 year after RFA, the validity of which would be confounded by less than 1 year of follow-up. Excluding those patients who had less than 1 year of follow-up and did not achieve a volume reduction of at least 50%, we saw no statistically significant difference in adjusted TE between the two groups (89.5% vs. 84.7%, p=0.117 > 0.05). Complete ablation (CA) rates were significantly higher in the malignant group than in the benign group (43.6% vs. 9.7%, p < 0.001). The time to CA was longer in the benign group than in the malignant group (21.75 ± 13.18 months vs. 14.09 ± 11.50 months, p < 0.001). Regrowth occurred in 15 patients in the benign group and none in the malignant group, and its regrowth rate did not differ between the two groups (1.8% vs 0%, p=0.096 > 0.05). The initial volume of TNs was significantly greater in the benign group than in the malignant group (7.33 ± 8.36 ml vs. 0.19 ± 0.49 ml; p < 0.001). VRR at year 1 after RFA was significantly greater in the benign group than in the malignant group (58.78 ± 49.47% vs -8.41% ± 251.29%, p=0.003 < 0.05), however, it was not statistically different between the two groups after 1 year.
Table 3
| Variable | Benign group | Malignant group | P value |
|---|---|---|---|
| TE | |||
| Yes n (%) | 671 (81.7) | 105 (70.5) | 0.002 |
| No n (%) | 150 (18.3) | 44(29.5) | |
| TE* | |||
| Yes n (%) | 671 (89.5) | 105 (84.7) | 0.117 |
| No n (%) | 79 (10.5) | 19 (15.3) | |
| CA rate | |||
| Yes n (%) | 80 (9.7) | 65 (43.6) | <0.001 |
| No n (%) | 741 (90.3) | 84 (56.4) | |
| CA time, months | |||
| (mean ± SD) | 21.75±13.18 | 14.09±11.50 | <0.001 |
| Regrowth rate | |||
| Yes n (%) | 15 (1.8) | 0 (0.0) | 0.096 |
| No n (%) | 806(98.2) | 149 (100.0) | |
| Regrowth time,months | |||
| (mean ± SD) | 29.80±12.47 | – | – |
The efficacy of RFA in the two groups.
TE, technical efficiency; TE*, The adjusted technical effectiveness; CA, Complete ablation; SD, Standard deviation.
Table 4
| Variable | Volumes (ml) | P value | VRR (%) | P value | ||
|---|---|---|---|---|---|---|
| Benign group | Malignant group | Benign group | Malignant group | |||
| Before RFA procedure | 7.33 ± 8.36 | 0.19 ± 0.49 | <0.001 | – | – | – |
| After RFA procedure | ||||||
| 12months | 2.11 ± 2.81 | 0.14 ± 0.34 | <0.001 | 58.78 ± 49.47 | -8.41 ± 251.29 | 0.003 |
| 24months | 1.86 ± 7.10 | 0.09 ± 0.22 | 0.091 | 74.03 ± 55.96 | 61.46 ± 47.32 | 0.106 |
| 36months | 2.10 ± 8.61 | 0.06 ± 0.10 | 0.250 | 76.54 ± 30.88 | 70.30 ± 41.45 | 0.388 |
| 48months | 1.67 ± 2.44 | 0.01 ± 0.01 | <0.001 | 75.30 ± 32.31 | 59.60 ± 66.64 | 0.591 |
| >48months | 0.98 ± 1.49 | 0.01 ± 0.02 | <0.001 | 84.21 ± 19.62 | 94.01 ± 7.48 | 0.334 |
Post RFA volume and VRR in both groups.
RFA, Radiofrequency ablation; VRR, Volume reduction ratio; ml, Milliliter.
The effect of malignant nodules on RFA efficacy is shown in Figures 2, 3 and 4 and Table 5. Risk factors for TE, CA, and regrowth after RFA are shown in Figures 2, 3 and 4. In terms of TE, it was associated with malignant nodules (OR = 1.875, 95%CI 1.264-2.780,P=0.002<0.05) and preoperative volume (OR = 1.105, 95%CI 1.061-1.150,P<0.001). However, we found no statistical correlation between malignant nodules and TE using multivariate logistic regression analysis to exclude confounders (adjusted OR = 1.125, 95%CI 0.726-1.743, P = 0.597>0.05). In terms of CR, it was significantly associated with malignant nodules (OR = 0.140, 95%CI 0.094-0.208, P<0.001), follow-up time (OR = 1.037, 95%CI 1.019-1.056,P<0.001), preoperative volume (OR = 0.916, 95%CI 0.867-0.968,P=0.002< 0.05), and 1-year VRR (OR = 1.029, 95%CI 1.018-1.040,P<0.001). We used multivariate logistic regression analysis excluding these factors above and found that malignant nodules remained statistically associated with CR (adjusted OR = 0.100, 95%CI 0.055-0.181, P<0.001). In terms of growth, it did not correlate with malignant nodules (OR = 1, P = 0.995 > 0.05).In our study, we used multiple linear regression analysis to find that malignant nodules affected volume after RFA at years 1 and 2 (p ≤ 0.001; p ≤ 0.001), but not after 2 years. Moreover, it was similar for VRR (p≤ 0.001; p=0.037<0.05). Our analysis indicated that the trend of malignant nodule volume reduction was less than that of benign nodules within two years after RFA, and there was no significant difference after two years.
Figure 2
Table 5
| Postoperative follow-up (p-value) | ||||||
|---|---|---|---|---|---|---|
| Variable | 1 year | 2 years | 3 years | 4 years | 5 years | >5 years |
| Volumes | ≤0.001 | ≤0.001 | 0.184 | 0.569 | 0.692 | 0.368 |
| VRR | ≤0.001 | 0.037 | 0.199 | 0.819 | 0.397 | 0.098 |
Impact of malignant nodules on volume and VRR after RFA.
VRR, Volume reduction ratio; RFA, Radiofrequency ablation.
Figure 3
Figure 4
4 Discussion
Radiofrequency ablation is currently an alternative treatment for thyroid nodules, and many studies have confirmed its favorable efficacy and safety (–). The indications for RFA are benign nodules ranging from initially small to giant nodules, and malignant nodules ranging from initially micropapillary thyroid cancer to low-risk thyroid cancer. Thyroid nodules undergo coagulative necrosis after RFA, which appears as high echogenicity similar to calcification on ultrasound examination. However, malignant nodules typically appear on ultrasound as poorly defined with peripheral calcification, which may affect the determination of the radiofrequency ablation range.
Koike E et al. found the incidence of calcification to be 8%-32% and 26%-54% in benign and malignant nodules, respectively (). Park KW et al. also indicated that large calcifications may lead to RFA treatment failure (). Most of the calcifications are concentrated in the periphery, which can diminish the thermal effect of RFA; these may limit complete ablation of the peripheral. Wu MH et al. showed that TNs after RFA were more likely to be characterized by calcification, heterogeneity, and ill-defined margin (). Many studies have found that the majority of recurrences after RFA are peripheral and have also confirmed that incomplete ablation of the periphery is an important risk factor for recurrence (, , ). Sim JS et al. found that re-expansion of the margins after RFA was an important cause of recurrence (). In our study, we saw that malignant nodules affected the technical efficiency of RFA (70.5% vs. 81.7%, p=0.002 < 0.05); however, after excluding other confounders, it was found that malignant nodules did not (84.7% vs. 89.5%, p=0.117 > 0.05). The CA rate was significantly more favorable in the malignant group than in the benign group (43.6% vs. 9.7%, p < 0.001 < 0.05), and the mean time to CA was significantly shorter in the malignant group than in the benign group (14.09 ± 11.50 months vs. 21.75 ± 13.18 months, p < 0.001 < 0.05). Our study showed that benign nodules were less likely to achieve CR than malignant nodules (OR = 0.140, 95%CI 0.094-0.208, P<0.001). These differences may be due to the proportions of their calcifications, as benign nodules usually show patchy, eggshell-like calcifications, whereas malignant nodules usually have diffuse loculated calcifications. These differences could also be due to the size of the nodules, as the volume of the benign group was significantly larger than that of the malignant group (7.33 ± 8.36 ml vs 0.19 ± 0.49 ml, p < 0.001). The regrowth rate was higher in the benign group than in the malignant group, but it was not statistically significant (1.8% vs 0%, p=0.096 > 0.05). Yan L et al. found that initial volume was an independent risk factor for regrowth of benign nodules after RFA (OR = 1.047, 95%CI 1.020-1.075) (), which is consistent with several studies (, ). One study also found that VRR at 12 months after RFA was associated with regrowth ().
Volume and VRR after RFA are important indicators to assess its efficacy. In our study, the initial volume was significantly greater in the benign group than in the malignant group (7.33 ± 8.36 ml vs 0.19 ± 0.49 ml, p < 0.001 < 0.05). VRR at year 1 after RFA was significantly greater in the benign group than in the malignant group (58.78 ± 49.47% vs -8.41% ± 251.29%, p=0.003 < 0.05), however, it was not statistically different between the two groups after 1 year. We have seen an increase in the volume of malignant nodules rather than a decrease in volume in the 1st year after RFA, which may be caused by the fact that during RFA to ensure complete ablation of the nodule, we usually ablate beyond the nodule border and, moreover, the initial volume of the malignant nodule is smaller. Lin WC et al. found that VRR at 1 month after RFA was better in large nodules (volume >30 ml) than in small nodules (volume <10 ml) (47.13 ± 21.51% vs. 30.25 ± 70.10%, p <0.001 < 0.05), which is consistent with our study (). We saw that malignant nodules were smaller than benign nodules after year 4, but there was a significant difference in their initial volumes. However, its VRR after 1 year was not statistically different. Two studies revealed that VRR after RFA was superior in small nodules than in large ones (, ). Two studies showed that VRR after RFA was not correlated with the initial volume of TNs (, ). We used multivariate logistic and linear regression to exclude confounding factors, including gender, follow-up time, initial volume, number of TN, number of ablated nodules, history of RFA, history of thyroid surgery, and technical efficiency, to explore the effect of malignant nodules on volume and VRR after RFA. We saw that volume at years 1 and 2 after RFA in benign nodules was superior to malignant nodules, and its difference was statistically significant (p ≤ 0.001<0.05; p ≤ 0.001<0.05). Its VRR was also similar (p ≤ 0.001<0.05; p=0.037<0.05); moreover, its trend was consistent between the two. However, Yi L et al. found that the VRR after RFA for benign TNs was significantly lower in the hypercalcification group than in the microcalcification group at years 3, 4, and 5 after RFA (). This discrepancy may be due to the fact that the difference between malignant and benign nodules is not just calcification.
The limitations of our study are as follows: 1. Our study is a single-center clinical study and its conclusions need to be validated in multicenter, large-sample studies. 2, our study only examined the effect of malignant nodules on the efficacy of RFA. The current increase in the indications for RFA and, therefore, the factors influencing its efficacy may increase, like nodules in residual glands after surgery, nodules after multiple ablations, and recurrent nodules. We will discuss these issues in subsequent studies.
5 Conclusion
Malignant thyroid nodules do not affect the efficacy of radiofrequency ablation. Although their early target regression is slower after RFA, there is no difference in long-term outcomes, and they are more likely to achieve complete regression.
Statements
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
Our study was a single-center prospective study, which was approved by our Institutional Ethics Committee (No. 2022ZSY-LLK-456), and all subjects obtained informed consent prior to surgery.
Author contributions
HL: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Validation, Visualization, Writing – original draft, Writing – review & editing. CS: Conceptualization, Methodology, Project administration, Resources, Supervision, Visualization, Writing – original draft. ZY: Investigation, Methodology, Resources, Supervision, Validation, Visualization, Writing – original draft. ML: Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing.
Funding
The author(s) declare financial support was received for the research and/or publication of this article. Our study was funded by the Zhongshan Science and Technology Bureau (2024B1071).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1
TrimboliPCastellanaMSconfienzaLMViriliCPescatoriLCCesareoRet al. Efficacy of thermal ablation in benign non-functioning solid thyroid nodule: A systematic review and meta-analysis. Endocrine. (2020) 67:35–43. doi: 10.1007/s12020-019-02019-3
2
CheYJinSShiCWangLZhangXLiYet al. Treatment of benign thyroid nodules: comparison of surgery with radiofrequency ablation. AJNR Am J Neuroradiol. (2015) 36:1321–5. doi: 10.3174/ajnr.A4276
3
KimYSRhimHTaeKParkDWKimST. Radiofrequency ablation of benign cold thyroid nodules: initial clinical experience. Thyroid. (2006) 16:361–7. doi: 10.1089/thy.2006.16.361
4
SimJSBaekJH. Long-term outcomes of thermal ablation for benign thyroid nodules: the issue of regrowth. Int J Endocrinol. (2021) 2021:9922509. doi: 10.1155/2021/9922509
5
YanLZhangMLiXLiYLuoY. A nomogram to predict regrowth after ultrasound-guided radiofrequency ablation for benign thyroid nodules. Front Endocrinol (Lausanne). (2022) 12:774228. doi: 10.3389/fendo.2021.774228
6
BernardiSCavallaroMColombinGGiudiciFZuoloGZdjelarAet al. Initial ablation ratio predicts volume reduction and retreatment after 5 years from radiofrequency ablation of benign thyroid nodules. Front Endocrinol (Lausanne). (2021) 11:582550. doi: 10.3389/fendo.2020.582550
7
BernardiSGiudiciFCesareoRAntonelliGCavallaroMDeandreaMet al. Five-year results of radiofrequency and laser ablation of benign thyroid nodules: A multicenter study from the italian minimally invasive treatments of the thyroid group. Thyroid. (2020) 30:1759–70. doi: 10.1089/thy.2020.0202
8
AljammalJJasimSAlahdabFRowleyAFerencziASchmeltzLet al. Predictors of initial response of thyroid nodules treated with RFA, a multi-endocrinology centers experience from the United States. J Endocr Soc. (2025) 9:bvaf077. doi: 10.1210/jendso/bvaf077
9
DobrinjaCBernardiSFabrisBEramoRMakovacPBazzocchiGet al. Surgical and pathological changes after radiofrequency ablation of thyroid nodules. Int J Endocrinol. (2015) 2015:576576. doi: 10.1155/2015/576576
10
KimMKShinJHHahnSYKimH. Delayed cancer diagnosis in thyroid nodules initially treated as benign with radiofrequency ablation: ultrasound characteristics and predictors for cancer. Korean J Radiol. (2023) 24:903–11. doi: 10.3348/kjr.2023.0386
11
TesslerFNMiddletonWDGrantEGHoangJKBerlandLLTeefeySAet al. ACR thyroid imaging, reporting and data system (TI-RADS): white paper of the ACR TI-RADS committee. J Am Coll Radiol. (2017) 14:587–95. doi: 10.1016/j.jacr.2017.01.046
12
MauriGPacellaCMPapiniESolbiatiLGoldbergSNAhmedMet al. Image-guided thyroid ablation: proposal for standardization of terminology and reporting criteria. Thyroid. (2019) 29:611–8. doi: 10.1089/thy.2018.0604
13
AhnHSKimSJParkSHet al. Radiofrequency ablation of benign thyroid nodules: evaluation of the treatment efficacy using ultrasonography. Ultrasonography. (2016) 35:244–52. doi: 10.14366/usg.15083
14
KandilEOmarMAboueishaMAttiaASAliKMAbu AlhudaRFet al. Efficacy and safety of radiofrequency ablation of thyroid nodules: A multi-institutional prospective cohort study. Ann Surg. (2022) 276:589–96. doi: 10.1097/SLA.0000000000005594
15
LimHKChoSJBaekJHLeeKDSonCWSonJMet al. US-guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma: efficacy and safety in a large population. Korean J Radiol. (2019) 20:1653–61. doi: 10.3348/kjr.2019.0192
16
KoikeENoguchiSYamashitaHLeeKDSonCWSonJMet al. Ultrasonographic characteristics of thyroid nodules: prediction of Malignancy. Arch Surg. (2001) 136:334–7. doi: 10.1001/archsurg.136.3.334
17
ParkKWShinJHHanBKKoEYChungJH. Inoperable symptomatic recurrent thyroid cancers: preliminary result of radiofrequency ablation. Ann Surg Oncol. (2011) 18:2564–8. doi: 10.1245/s10434-011-1619-1
18
WuMHChenKYChenAChenCN. Differences in the ultrasonographic appearance of thyroid nodules after radiofrequency ablation. Clin Endocrinol (Oxf). (2021) 95:489–97. doi: 10.1111/cen.14480
19
BaekJHMoonWJKimYSLeeJHLeeD. Radiofrequency ablation for the treatment of autonomously functioning thyroid nodules. World J surgery. (2009) 33:1971–7. doi: 10.1007/s00268-009-0130-3
20
HuhJYBaekJHChoiHKimJKLeeJH. Symptomatic benign thyroid nodules: efficacy of additional radiofrequency ablation treatment session–prospective randomized study. Radiology. (2012) 263:909–16. doi: 10.1148/radiol.12111300
21
YanLZhangMLiXLiYLuoY. A nomogram to predict regrowth after ultrasound-guided radiofrequency ablation for benign thyroid nodules. Front Endocrinol (Lausanne). (2022) 12:774228. doi: 10.3389/fendo.2021.774228
22
SimJSBaekJHLeeJChoWJungSI. Radiofrequency ablation of benign thyroid nodules: depicting early sign of regrowth by calculating vital volume. Int J hyperthermia. (2017) 33:905–10. doi: 10.1080/02656736.2017.1309083
23
ZhangYZhangMBLuoYKLiJZhangYTangJ. Effect of chronic lymphocytic thyroiditis on the efficacy and safety of ultrasound-guided radiofrequency ablation for papillary thyroid microcarcinoma. Cancer Med. (2019) 8:5450–8. doi: 10.1002/cam4.2406
24
LimHKLeeJHHaEJSungJYKimJKBaekJH. Radiofrequency ablation of benign non-functioning thyroid nodules: 4-year follow-up results for 111 patients. Eur Radiol. (2013) 23:1044–9. doi: 10.1007/s00330-012-2671-3
25
NegroRGrecoGDeandreaMRuccoMTrimboliP. Twelve-month volume reduction ratio predicts regrowth and time to regrowth in thyroid nodules submitted to laser ablation: A 5-year follow-up retrospective study. Korean J Radiol. (2020) 21:764–72. doi: 10.3348/kjr.2019.0798
26
LinWCWangCKWangWHKuoCYChiangPLLinANet al. Multicenter study of benign thyroid nodules with radiofrequency ablation: results of 762 cases over 4 years in Taiwan. J Pers Med. (2022) 12:63. doi: 10.3390/jpm12010063
27
DeandreaMGarinoFAlbertoMGarberoglioRRossettoRBonelliNet al. Radiofrequency ablation for benign thyroid nodules according to different ultrasound features: an Italian multicentre prospective study. Eur J Endocrinol. (2019) 180:79–87. doi: 10.1530/EJE-18-0685
28
DeandreaMTrimboliPGarinoFMormileAMaglionaGRamunniMJet al. Long-term efficacy of a single session of RFA for benign thyroid nodules: A longitudinal 5-year observational study. J Clin Endocrinol Metab. (2019) 104:3751–6. doi: 10.1210/jc.2018-02808
29
LiYHeHLiWZhaoJGeNZhangYet al. Efficacy and safety of radiofrequency ablation for calcified benign thyroid nodules: results of over 5 years’ follow-up. BMC Med Imaging. (2022) 22:75. doi: 10.1186/s12880-022-00795-5
Summary
Keywords
radiofrequency ablation (RFA), efficacy, thyroid nodules (TNs), papillary thyroid carcinoma, risk factors
Citation
Liu H, Shi C, Yan Z and Luo M (2025) Assessing the impact of malignant thyroid nodules on the efficacy of radiofrequency ablation: a single-center prospective study. Front. Endocrinol. 16:1669194. doi: 10.3389/fendo.2025.1669194
Received
19 July 2025
Accepted
15 September 2025
Published
13 October 2025
Volume
16 - 2025
Edited by
Erivelto Martinho Volpi, Hospital Alemão Oswaldo Cruz, Brazil
Reviewed by
Wu Songsong, Fujian Provincial Hospital, China
Ali Özdemir, Recep Tayyip Erdoğan University, Türkiye
Jules Aljammal, The Thyroid Clinic Utah, United States
Updates
Copyright
© 2025 Liu, Shi, Yan and Luo.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ming Luo, luomingzsszyy@126.com
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.