Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Two-year prognosis of multinodular goiter following radiofrequency ablation based on all nodule burdens

Two-year prognosis of multinodular goiter following radiofrequency ablation based on all nodule... Objective: Few studies use all nodule burdens to specify the prognosis of multinodular goiter (MNG) following radiofrequency ablation (RFA), so this study addresses this question for MNG after completely ablating dominant nodules. Methods: The RFA indications for MNG include 2–5 benign nodules with over 50% normal tissue on ultrasound, 1–3 well-defined benign dominant nodules on cytology, largest diameter ≥20 mm and/or with clinical complaints, and patient refusal or unable to undergo surgery. A retrospective study of 185 MNG patients with completely ablated dominant nodules in a single-session RFA was conducted. The efficacy and complications were evaluated at 1, 6, 12 months, and yearly thereafter. Based on retreatment risks, progressive disease (PD), stable disease (SD), and complete relief (CR) were introduced to assess all nodule load changes. PD was clarified as having new/non-target nodules that newly appeared to ACR TI-RADS≥4, or new/enlarged non-target nodules ≥1 cm. Results: The initial ablation ratios of target nodules were 100% at one month. During a mean 22.38 ± 13.75 months (range, 12–60 months), the volume reduction rate of ablated nodules was 98.25% at 24 months without regrowth. Cosmetic and symptomatic scores decreased to 1 and 0, respectively, after 48 months. Of the patients, 9.7% (18/185) had PD and the retreatment rate was 2.2% (4/185). The complication rate was 2.7% (5/185). Conclusion: RFA provides cosmetic and symptomatic relief for an average of two years. RFA is a useful minimally invasive treatment modality for selected MNG patients. Keywords: radiofrequency ablation; nodular goiter; efficacy; retreatment Published by Bioscientifica Ltd. This work is licensed under a Creative Commons https://etj.bioscientifica.com Attribution 4.0 International License. © 2024 the author(s) R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 condition of non-target nodules may change and new Introduction nodules may appear, possible retreatment may be inevitable. However, to our knowledge, no systematic Thyroid nodules (TNs) are commonly detected via study has focused on the actual magnitude of this high-resolution ultrasonography (US) and affect problem, and little is known. Given our experience, we approximately 70% of the general population (1, 2). hypothesized that RFA might be clinically efficacious Although most are benign TNs (BTNs) and asymptomatic, for MNG patients whose dominant TNs were a noticeable but small percentage will progressively completely ablated. If this is proven to be the case, enlarge and cause cosmetic and/or symptomatic this may suggest the possibility of RFA for selected problems necessitating surgical resection (3, 4, 5). suitable MNG patients. However, surgical interventions for TNs are somewhat Therefore, in this retrospective study, we evaluated disadvantageous in that the risks of trauma, scar the prognosis of MNG based on all nodule burdens for formation, and mild to severe complications are high, patients whose dominant nodules were completely as is the prevalence of hypothyroidism. As a result, ablated in a single session of RFA. nonsurgical and minimally invasive interventions like radiofrequency ablation (RFA) have been widely used and recognized as highly effective and Materials and methods safe treatment options for BTNs in many authoritative guidelines (6, 7, 8, 9, 10). Institutional guidelines for RFA and However, it is well recognized that over half of the patient selection patients with BTNs are MNG, which presents as two or more nonpalpable or palpable nodules within This retrospective study was approved by the Ethics an enlarged thyroid (11). This condition poses some Committee of the Third Affiliated Hospital of Sun challenges for RFA (9, 10), because, unlike surgery, Yat-sen University (no. (2015)2-215), and all patients which allows the removal of the entire lobe or provided written informed consent for treatment. gland in MNG patients, RFA is only indicated for the In our institute, by combining many guidelines for treatment of well-defined dominant nodules of MNG thermal ablation (6, 7, 8, 9, 10), the indications for according to current guidelines (9, 10). Although MNG patients to receive RFA were as follows: (i) with four clinical trials have shown favorable results on a total of two to five nodules and at least 50% normal the shrinkage of ablated dominant nodules in MNG tissue left (Fig. 1A); (ii) with benign-appearing of patients (12, 13, 14, 15), evidence supporting the all TNs on ultrasound (ACR TI-RADS ≤3); (iii) with no efficacy of RFA in improving cosmetic outcomes and intra-thoracic extension on CT or MR imaging; (iv) relieving symptoms associated with whole thyroid with one to three well-defined dominant nodules ( Fig. swelling or all nodule burdens in a large sample 1A, blue nodule), which were confirmed as Bethesda remains scarce. In addition, considering that the class II on cytology, with a largest diameter ≥20 mm Figure 1 Diagram of the indications of RFA for MNG and observed indicators during the follow-up. (A) In the thyroid, the total number of nodules was less than five and at least 50% of normal tissue was left. All thyroid nodules had a benign appearance on ultrasound (ACR TI-RADS ≤3). RFA was performed for the dominant target nodules (red arrows), which were confirmed as Bethesda class II on cytology, with a largest diameter ≥20 mm and/or complaints of symptomatic or cosmetic problems, and the remaining small benign nodules (ACR TI-RADS ≤3 and ≤20 mm) except for dominant target nodules were non-target nodules (red nodules). (B–C) At 1 month, the IAR of ablated dominant nodules was measured by CEUS (red arrows). During the follow-up, the development of all thyroid nodules, including the VRR (red arrows) of ablated dominant nodules and the development of non-target (red nodules) and new nodules (green nodule), was monitored. The schematic was drawn by Figdraw. ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; CEUS, contrast-enhanced ultrasonography; IAR, initial ablation ratio; RFA, radiofrequency ablation; US, ultrasound; VRR, volume reduction rate. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 and/or complaining of cosmetic or symptomatic problems; and (v) refusal or unable to undergo thyroidectomy due to underlying diseases. The following were contraindications for RFA: (i) severe cardiopulmonary insufficiency and coagulation disorders; (ii) nodules with massive calcifications. Between December 2017 and December 2021, all 214 consecutive patients with MNG who qualified for the above criteria underwent the single-session RFA at the Third Affiliated Hospital of Sun Yat-sen University, Figure 2 and their complete medical records were reviewed. Flowchart of the retrospective study. MNG, multinodular goiter; RFA, We included subjects who fulfilled the following radiofrequency ablation. criteria: (i) complete ablation of all the dominant nodules in one session (The initial ablation ratios classified in terms of the proportion of its solid component (IAR) were 100% confirmed by contrast-enhanced US (17): (i) >75%, solid; (ii) 25%–75%, mixed; and (iii) <25%, (CEUS) at 1 month after RFA); (ii) no high-risk factors cystic. The total volume of the thyroid gland included the of thyroid cancer, including a family history of thyroid left lobe, the right lobe, and the volume of target dominant cancer, a history of hereditary syndromes indicating nodules in the isthmus (18). Moreover, in the clinical a predisposition to thyroid cancer, or a history of assessment, the patients were asked to provide their radiation exposure to the head and neck in childhood cosmetic grading scores and symptomatic grading scores. (16); (iii) no previous history of thyroid surgery or The cosmetic score is assessed by radiologists using the radioactive iodine treatment; and (iv) underwent following scale (6): (i) no visible or palpable mass, (ii) more than 1 year of follow-up. Based on our selection no cosmetic problem but palpable mass, (iii) cosmetic criteria, 29 patients were excluded due to their problem on swallowing only, (iv) a readily detected previous history of thyroid surgery or radioactive iodine cosmetic problem. The symptom score was obtained by treatment. Ultimately, 185 patients were included (Fig. 2). a questionnaire concerning five clinical symptoms ( 13): compression, cough, difficulty swallowing, voice change, and pain. Each positive symptom was allocated 1 point, Pre-RFA evaluation so that the symptom scores ranged from 0 to 5. All patients were subjected to US examination, clinical assessment, and thyroid function tests before RFA. RFA procedure Once fine-needle aspiration biopsy was performed to confirm the benignity of all target dominant When we ablated multiple nodules, to avoid causing nodules. The number, location, composition, size, and serious damage to the recurrent laryngeal nerves, all ACR TI-RADS score of all TNes were determined the dominant nodules in the ipsilateral thyroid lobe were ablated first, starting with the largest nodule, via US examination. The composition of the nodule was Table 1 The definitions of the criteria about all nodule burdens for MNG after RFA. Definitions PD Complete necrosis of ablated nodules and either non-target nodules enlarged to ≥1 cm with ACR TI-RADS ≤3; or new nodules developed to ≥1 cm with ACR TI-RADS ≤3; or non-target nodules or new nodules developed to ACR TI-RADS ≥4 SD Complete necrosis of ablated nodules and either unenlarged non-target nodules with ACR TI-RADS ≤3 or non-target nodules or new nodules developed to <1 cm with ACR TI-RADS ≤3 CR Complete necrosis of ablated nodules without other nodules Enlargement of the non-target nodule was defined as a 20% increase in ≥2 diameters with a minimum increase of 2 mm or a 50% increase in volume; Qualifying criteria of PD may increase the risk of retreatment. ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; CR, complete relief; MNG, multinodular goiter; PD, progressive disease; RFA, radiofrequency ablation; SD, stable disease. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 2 Baseline characteristics of all 185 MNG patients and until all the suitable dominant nodules of the unilateral thyroid lobe were completely ablated sequentially. 487 nodules. Data are presented as mean ± S.D. or as median In subsequent observation, the radiologist providing (range) or n (%). treatment subjectively assessed the patients’ voices for 10 min to determine the functional integrity of the Baseline characteristics Values recurrent laryngeal nerve of the treated side. Ablation Patients’ characteristics of the dominant nodules in the contralateral lobe was  Age (years) 43.38 ± 13.78 performed in the same manner.  Sex (Female) 148 (80.0%)  BMI (kg/m ) 22.10 ± 2.78 One radiologist with 7 years of experience completed all  FT3 (pmol/L) 4.40 (3.01–8.21) RFA procedures using the VRS01 RFA system (STARmed,  FT4 (pmol/L) 13.11 (9.34–22.62) Korea) and initiated internal cooling of the 18G  TSH (uIU/mL) 1.12 (0.01–6.39) electrodes with 10 mm or 7 mm active tips under the  Follow-up time (months) 22.38 ± 13.75 (12–60) guidance of the same US equipment. Local anesthesia,  Underlying diseases a lateral approach, a moving-shot technique, and a   Hypertension 9 (4.9%) hydrodissection approach (5% glucose) were used   Diabetes 6 (3.2%) during the RFA treatment.   Coronary heart disease 3 (1.6%) In particular, CEUS was performed preoperatively,   Liver transplant 3 (1.6%) intraoperatively, and immediately postoperatively to   Renal transplant 6 (3.2%)  Cosmetic score 4 (1–4) identify the active tissue of the dominant nodules. If there  Symptomatic score 1 (0–4) were areas of enhancement in the ablated nodule during Nodule characteristics the RFA procedure, supplementary ablation guided by  Number of nodules per patient CEUS was performed until the whole target nodule was   2 100 (54.1%) completely ablated.   3 58 (31.3%)   4 22 (11.9%) Follow-up evaluation   5 5 (2.7%)  Ablated target nodule For follow-up, patients underwent periodic US   Number of nodules per patient examination, clinical assessment, and thyroid function    1 114 (61.6%) tests at 1, 6, 12 months after RFA and then yearly    2 63 (34.1%) thereafter. All US examinations were performed by    3 8 (4.3%) three or four experienced radiologists, and another   Maximum diameter (mm) 30 (20–66) radiologist subsequently analyzed both cross-sectional   Volume (mL) 6.30 (0.64–59.50) and longitudinal dynamic images of the whole thyroid   Left 114 (43.2%) gland at each visit and included nodules with a largest   Right 130 (49.2%) diameter ≥3 mm for analysis.   Isthmus 20 (7.6%)   Cystic 47 (17.8%)   Mixed 69 (26.1%) Evaluation of response to treatment on   Solid 148 (56.1%) ablated dominant nodules   Ablation time (sec) 587 (51–3113)   Total energy delivered (Kcal) 4.34 (0.47–19.35) Several parameters were systematically collected to   Energy delivered per nodules (Kcal) 2.64 (0.21–16.89) evaluate the response to RFA, as shown in Fig. 1. The  Non-target nodule IAR was associated with technique efficacy, defined   Number of nodules per patient as the ratio between the ablated volume and the    0 33 (17.8%) volume of the ablated nodules (18). It was evaluated    1 93 (50.3%) at 1 month by CEUS.    2 49 (26.5%)    3 8 (4.3%) The volume reduction rate (VRR) was used to determine    4 2 (1.1%) the extent of shrinkage of the ablated nodule (19)   Maximum diameter (mm) 5.8 (3.0–18.8) and was evaluated by US at each follow-up point.   Volume (mL) 0.05 (0.01–2.17) Regrowth of ablated dominant nodules was defined as   Left 107 (48.0%) the volume of the ablated nodules increasing by ≥50%   Right 99 (44.4%) compared to the minimum recorded volume measured   Isthmus 17 (7.6%) during the follow-up (20, 21).   Cystic 46 (20.6%)   Mixed 126 (56.5%)   Solid 51 (22.9%) Evaluation of resolution on clinical problems In addition, the cosmetic and symptomatic scores of MNG, multinodular goiter; BMI, body mass index; FT3, free MNG patients were systematically recorded in the same triiodothyronine; FT4, free thyroxine; TSH: thyroid stimulating hormone. value in parentheses is the range. manner during each visit from baseline until the last visit. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 3 Treatment efficacy at each follow-up point. Data are presented as median (range). Cosmetic Symptomatic n Volume of ADN (mL) VRR (%) Regrowth (%) Volume of TG (mL) score score Baseline 185 6.30 (0.64–59.50) – 0 (0) 26.37 (7.87–127.91) 4 (1–4) 1 (0–4) a a a a 1 month 185 3.19 (0.25–32.66) 39.25 (0–89.90) 0 (0) 18.38 (7.87–96.63) 2 (1–4) 1 (0–3) a,b a,b a 6 months 170 1.04 (0.03–22.31) 78.47 (17.97–99.42) 0 (0) 15.10 (7.32–51.09) 1 (1–4)a 0 (0–2) a,b,c a,b,c a 12 months 178 0.50 (0–18.21) 90.90 (25.29–100) 0 (0) 12.48 (6.48–37.77) 1 (1–3)a 0 (0–1) a,b,c,d a,b,c,d a a 24 months 89 0.09 (0–8.44) 98.25 (37.27–100) 0 (0) 11.17 (6.54–20.86) 1 (1–2) 0 (0–1) a,b,c,d a,b,c,d a a 36 months 36 0.06 (0–4.19) 99.20 (51.89–100) 0 (0) 10.20 (6.54–13.40) 1 (1–2) 0 (0–1) a,b,c,d a,b,c,d a a 48 months 14 0.06 (0–3.77) 99.31 (64.00–100) 0 (0) 9.56 (7.44–13.53) 1 (1) 0 (0) a,b,c,d a,b,c,d a a 60 months 10 0.05 (0–0.67) 99.33 (96.40–100) 0 (0) 8.87 (7.71–12.19) 1 (1) 0 (0) a b c d P < 0.05 versus baseline; P < 0.05 vs 1 month; P < 0.05 vs 6 months; P < 0.05 vs 12 months. ADN, ablated dominant nodules; IAR, initial ablation ratio; TG, thyroid gland; VRR, volume reduction rate. Stable disease (SD) contained non-target or new nodules Evaluation of development on all nodules developed to <1 cm with ACR TI-RADS≤3, and these After complete ablation of the dominant nodules, nodules developed relatively slowly and were small. when considering the need for retreatment due to Complete relief (CR) contained complete necrosis of the development of non-target nodules (remaining all ablated nodules without any active nodules in the small benign nodules, ACR TI-RADS ≤ 3 and ≤ 20 mm) entire thyroid. Furthermore, when the MNG patients and/or new nodules, a comprehensive assessment of with non-target and/or new nodules showed PD and were all nodules should be performed. Focusing on the risks deemed suitable for RFA, retreatment was considered. of retreatment, we classified and defined all nodule burdens after RFA in three directions, as shown in Table 1. Evaluation of complications Progressive disease (PD) may increase the retreatment Complications were recorded based on the criteria risk. It includes non-target nodules enlarged to ≥ 1 cm with ACR TI-RADS ≤3, or new nodules developed of the Society of Interventional Radiology (SIR) (22, to ≥1 cm with ACR TI-RADS ≤3, which represent the trends 23). SIR classifications A–B were regarded as minor of causing cosmetic and/or symptomatic problems; or complications, and SIR classifications C–F were regarded non-target or new nodules developed to ACR TI-RADS ≥4. as major complications. Figure 3 Trends of (A) VRR on ablated nodules, (B) cosmetic score, and (C) symptomatic score on MNG patients in the whole observation period. Compared with that at baseline, the cosmetic score and symptom score of MNG patients significantly decreased at 1-, 6-, 12-, 24-, 36-, 48- and 60 months, *P < 0.05. VRR, volume reduction rate. Table 4 The development of unablated and new nodules after RFA. End point Patients (n, %)/ Nodules, n Nodule type Baseline ACR TI-RADS Maximum diameter Change in nodule size PD 18 (9.7%)  16 Non-target ACR TI-RADS ≤ 3 ≤3 ≥1 cm With enlargement  9 New Undetected ≤3 ≥1 cm – SD 126 (68.1%)  151 Non-target ACR TI-RADS ≤ 3 ≤3 < 1 cm Any  30 Non-target ACR TI-RADS ≤ 3 ≤3 ≥1 cm Without enlargement  32 New Undetected ≤3 <1 cm – CR 41 (22.2%)  26 Non-target ACR TI-RADS ≤ 3 Undetected The enlargement of the non-target nodule was defined as a 20% increase in ≥2 diameters with a minimum increase of 2 mm, or a 50% increase in volume. ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; CR, complete relief; PD, progressive disease; SD, stable disease. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Results A total of 185 MNG patients (mean age, 43.48 years; 148 women and 37 men) with 487 nodules were included in the study, and the median follow-up period was 22 months (range, 12–60 months) as of the data cutoff. The demographic characteristics of all patients and nodules were summarized in Table 2. Before treatment, the initial cosmetic and symptomatic scores of these 185 patients were 4 (range: 1–4) and 1 (range: 0–4), respectively. To solve these problems, 264 dominant nodules (54.4%) with a maximum diameter of 30 mm (range, 20–66 mm) were completely ablated by single-session RFA. Of these, 114 (61.6%) patients had one ablated dominant nodule, 63 (34.1%) patients had two ablated nodules, and the remaining 8 (4.3%) patients had three ablated dominant nodules. The median ablation time and energy were 587 s (range: 51–3113 s) and 4.34 kcal (range: 0.47–19.35 kcal), respectively, and the ablation energy per nodule was 2.64 kcal (range: 0.21–16.89 kcal). After the procedure, 223 nodules (45.6%) with a median largest diameter of 5.9 mm (range: 3.0–18.8 mm) were non-target nodules, and 152 (82.2%) patients had ≥1 non-target nodule. Treatment efficacy in VRR The IAR of all target nodules was 100% confirmed by CEUS at 1 month. When we analyzed the trend of the ablated nodule volume after the procedure, significant shrinkage was observed during the follow-up period (P < 0.05). Specifically, the ablated nodule volume at one month was significantly lower than that at baseline (P < 0.05) and the median VRR achieved 39.25% (range: 0%–89.90%). Further significantly progressive VRR was seen during the first two years ( P < 0.05), which was 98.25% (range: 37.27%–100%) at 24 months. Until 36 months, the nodule volume recorded did not significantly differ from that at 24 months and remained Figure 4 stable thereafter. The ablated nodule volumes at each (A) The number of nodules developed with PD and (B) the largest ultrasound evaluation were presented in Table 3. The diameter of 16 enlarged non-target nodules at each follow-up point. respective changes in VRR are shown in Fig. 3A. In These non-target nodules were significantly enlarged in largest diameter at the 12-, 24-, 36-, 48-, and 60-month follow-ups compared with particular, none of the ablated nodules regrew during baseline, *P < 0.05. PD, progressive disease. the observation period. Statistical analysis Treatment efficacy in cosmetic and SPSS statistical software, version 25.0 (IBM Corp.), was symptomatic scores. used to perform the statistical analysis. Qualitative variables are expressed as numbers (percentages), Both cosmetic and symptomatic scores. improved after and quantitative variables are expressed as RFA (Table 3 and Fig. 3). The cosmetic scores improved medians (ranges) or means ± standard deviations. significantly from 4 at baseline to 2 at the 1-month Quantitative variables were compared using t-test assessment (P < 0.05), and all patients had a cosmetic or Mann–Whitney U test, and qualitative variables score of 1 at 48 months after RFA (Fig. 3B). Similarly were compared using Fisher’s exact test or the chi-square (Fig. 3C), the symptomatic scores were significantly test. Two-sided P-values < 0.05 were considered improved at one month (P < 0.05) and no patient statistically significant. complained of any symptoms after 48 months. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 5 Characteristics of four patients qualified the indications of retreatment. Patient A Patient B Patient C Patient D Patients’ characteristics  Age (years) 27 29 38 14  Sex Female Female Female Female  BMI (kg/m ) 26.35 28.28 21.48 16.94  Thyroid function status Normal Normal Normal Normal  Pregnancy during follow-up Yes No No No  Underlying diseases No No Liver transplant No First treatment of DN  n 1 2 2 2  Maximum diameter at baseline (mm) 48 52; 22 43; 25 39; 36  Volume at baseline (mL) 20.52 11.76; 1.87 26.46; 1.57 5.71; 7.16  Follow-up time (month) 24 60 24 36  VVR at endpoint (%) 97.80 96.23; 100 92.97; 100 95.90; 99.27 PD nodules  Nodules type ENTN ENTN ENTN ENTN  ACR TI-RADS at endpoint 3 3 2 2  Maximum diameter (mm)   At baseline 17.9 8.7 9.4 13.3   At endpoint 30.6 21.3 20.4 43.1  Volume (mL)   At baseline 1.09 0.18 0.21 1.00   At endpoint 8.70 2.39 1.86 13.17 BMI, body mass index; VRR, volume reduction rate; PD, progressive disease; ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; DN, dominant nodules; ENTN, enlarged non-target nodule. these nodules developed PD and qualified for re-treatment. The development of all nodules Retreatment When we evaluated the development of all nodules A total of four patients (2.2%, 4/185) qualified for based on the risk of retreatment (Table 4), we found retreatment (Table 5) due to the PD of non-target nodules. that the vast majority of patients (90.3%, 167/185) had A typical case was shown in Fig. 5. slow or no progression without a high possibility of retreatment. In particular, 22.2% of patients (41/185) Complications showed the best development result, CR, in which no other nodules were presented within the entire Five cases (2.7%, 5/185, Table 6) had voice change, thyroid. However, 9.7% of patients (18/185) developed which gradually and spontaneously recovered within PD and showed 25 enlarged, non-target nodules and 3 months (minor complications, SIR classification A). new nodules measuring ≥1 cm with ACR TI-RADS ≤ 3, No delayed or life-threatening complications occurred increasing the risk of the potential need for retreatment during the follow-up. due to cosmetic and/or symptomatic problems. As for the thyroid function, the thyroid-stimulating The details related to PD are presented in Fig. 4. With hormone (TSH) level changed from 1.12 μIU/mld (range: respect to the time of progression, it showed a trend 0.01–6.39 μIU/mld) at baseline to 1.39 μIU/mld (range: of increase from fast to slow and continued over time. 0.01–8.87 μIU/mld) at the endpoint, and the number of Specifically, most of the patients (61.1%, 11/18) with TSH abnormalities changed from 12 patients (6.5%) to half of the nodules (56.0%, 14/25) progressed rapidly 5 patients (2.7%). within the first year of follow-up. Gradual progression occurred during the subsequent four years. Considering Discussion the enlarged size of 16 non-target nodules, significant spontaneous enlargement from 9.7 mm (range: 5.3– 17.9mm) at baseline to 17.4 mm (range: 13.4–21.3mm) Our results demonstrated that MNG is positively affected was observed with the rates of 2.8 mm/year at 60 months. by RFA at a mean follow-up time of 22 months with an All nine new nodules developed to ≥1 cm with ACR obvious and long-lasting shrinkage of dominant nodules, TI-RADS ≤ 3. During the follow-up period, no non-target significant improvements in cosmetic and symptom or new nodules developed to ACR TI-RADS ≥ 4. scores, a low incidence of complications, and a 2.2% of R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 retreatment rate due to the progression of all nodule loads after RFA. The major aim of RFA is to eliminate, or at least reduce, clinical discomfort and avoid further invasive treatment. For a disease such as MNG, in which a pathological process involves the whole thyroid gland (24), this discomfort is not only associated with the presence of dominant nodules but also associated with whole thyroid swelling or all nodule burdens. Therefore, a comprehensive assessment of the efficacy of the procedure for the treatment of the entire thyroid should be important and necessary for MNG patients. In recent years, following previous studies of RFA for MNG or retrosternal goiter, although RFA is recognized as an effective procedure for shrinking ablated nodules, with VRRs of approximately 70% to 80% at 6 to 12 months (12, 13, 14, 15), data on the improvement of cosmetic outcomes and the relief of symptoms related to whole thyroid swelling or the presence of all nodule loads in a large sample are still rare. Based on this, we selected 185 MNG patients who underwent a single session of RFA and were followed up for 22.38 ± 13.75 months (range, 12–60 months), and the final results confirmed the persistent elimination of aesthetic and symptomatic concerns, which became significant starting from one month and progressed until reaching the endpoint. Additionally, the size of the ablated dominant nodules was significantly shrunken, with a VRR of 78.47% (range, 17.97%–99.42%) and 89.20% (range, 25.29%–100%) at 6 and 12 months after the procedure, respectively, which was also consistent with the aforementioned studies. Although the treatment response of the ablated target nodules is a key indicator of treatment effectiveness, the ‘unequivocal progression or appearance’ of non-target or new lesions also denotes a possible trend of the overall level of substantial worsening, which is closely related to continued therapy (25). Early attempts to evaluate the recurrence and retreatment of MNG patients in some previous surgical studies have confirmed that these problems are of great concern, and recurrence was Figure 5 defined as the presence of a nodule larger than or equal to A case qualified for retreatment due to the PD of a non-target nodule. 3 mm or 5 mm on US (3, 23, 26, 27, 28, 29, 30), with studies Female, 27 years, BMI 26.35 kg/m , TSH 1.31 uIU/mL. (A) finding recurrence rates ranging from 2.0% to 60.6% and Ultrasonography before RFA showed three nodules in both lobes of the reoperation rates from 1.6% to 8.0% (25, 26, 27, 28, 29). thyroid: one in the left lobe, size, 43 × 19 × 48 mm (red arrow); and the However, these definitions were not fully applicable to other two in the right, size, 17.9 × 9.9 × 11.7 mm (white arrow), and 8.0 × RFA for the following reasons: (i) discrepancies in the 6.0 × 5.8 mm. The patient received RFA to treat the dominant nodule in definitions of recurrence made it difficult to compare the the left lobe, and the other 2 nodules were non-target nodules. (B) The results among research groups, (ii) recurrence in surgery ablated dominant nodule was completely ablated in one session (red studies only focused on new nodules, but for RFA, non- arrow) which was confirmed by CEUS. (C–E) The ablated dominant nodule target nodules also had to be evaluated; (iii) some 5 mm in the left lobe showed significant shrinkage during the follow-up (red or 3 mm nodules that were recognized as indicating arrow) and achieved a volume reduction rate of 97.80% at 24 months (red recurrence were actually ‘non-measurable,’ because the arrow). Both non-target nodules in the right lobe showed PD. The smaller accuracy and reproducibility of the US measurements lesion was enlarged from 8.0 × 6.0 × 5.8 mm at baseline to 10.3 × 5.9 × 10.9 mm at 24 months, and the larger one enlarged from 17.9 × 9.9 × and the clinical significance could not be guaranteed ( 25); 11.7 mm at baseline to 30.6 × 25.5 × 21.3 mm (white arrow) at 24 months and (iv) it is debatable whether nodules <1 cm can be causing cosmetic problems. This patient qualified the indications of defined as a recurrence. To address inconsistencies in the retreatment due to this larger non-target nodule. The schematic was evaluation criteria in solid tumors (25), based on the risk of drawn by Figdraw. retreatment, our study first self-defined CR, SD, and PD to R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 6 Complications of RFA during the follow-up. nonclinical causes, such as geographical distance. Further prospective studies are still needed to validate Complications Values, n (%) our results. In addition, supporting evidence on whether Major complications 0 (0) the number of dominant nodules ablated by a single  Permanent voice change (>3 months) 0 (0) RFA session affects outcomes remains scarce, but this  Airway obstruction 0 (0) issue was not explored in our study. The core factors  Infection 0 (0) of nodule regrowth cannot be distinguished by routine  Permanent hypoparathyroidism (>3 months) 0 (0) US, including the difference between ablation zones and  Rupture of the ablated nodules 0 (0) recurrent or active nodules. Therefore, a discriminable parameter of regrowth, such as an ablated nodule Minor complications 5 (2.7) volume increase of ≥50%, was used in this study. Finally,  Transient voice change (≤3 months) 5 (2.7) different ablation volumes of target nodules may have  Hematoma 0 (0) a major impact on the outcome of RFA for MNG, but  Transient hypoparathyroidism (≤3 months) 0 (0) only patients with completely ablated dominant nodules were included in this study. Therefore, our results have a limited scope of application and may not be generalized assess the development of all nodule burdens, especially to all institutions. non-target and new nodules, after complete ablation of target nodules. CR is defined as the disappearance of all In summary, for selected MNG patients with 2–5 benign active nodules during the follow-up period. SD suggests nodules in the thyroid, more than 50% normal thyroid the persistent complete necrosis of target nodules without tissue and well-defined target dominant nodules that the tendency of worsening of non-target or new lesions. were completely ablated in a single session of RFA, PD is defined as non-target and new nodules showing the current study showed that RFA has a reasonable substantial worsening that requires close surveillance effect in that it significantly improves the cosmetic evaluation or possible continued therapy, even for outcomes and symptoms, effectively shrinks dominant target lesions showing the best treatment response. nodules, and has low rates of PD and retreatment based According to our criteria, the vast majority of patients on all nodule burdens. were in a progression-free state after complete ablation of all dominant nodules by a single session of RFA, and more importantly, the overall progression rate was Declaration of interest 9.7% and the rate of need for retreatment due to PD was The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported. much lower (2.2%, 4/185), which were not higher than previous surgical studies. This can mainly be attributed to the different minimum nodule size criteria of clinically Funding relevant negative development: contrary to most surgical This work was supported by the fifth Five-Year Project of the Third studies in which a nodule diameter of 5 mm or greater Affiliated Hospital of Sun Yat-Sen University (grant 2023WW102), the was the criterion for recurrence, our study used a larger 5010 Clinical Research Project of Sun Yat-sen University (grant 2022010), nodule diameter as a criterion for PD (1 cm or greater). the Key Scientific and Technological Program of Guangzhou City (grant The main basis for our revision is that only nodules ≥1 201802020023), the Natural Science Foundation of Guangdong Province (grant 2020A1515010425), the National Natural Science Foundation of cm might have the greater potential to cause clinical China (grant 81971632), the Key Scientific and Technological Projects of discomfort or be clinically significant cancers ( 4), and it Guangdong Province (grant 2019B020235002), and the Key Scientific and is also supported by many guidelines that recommend Technological Projects of Guangdong Province (grant 2018B030332001-1). against the biopsy of nodules smaller than 1 cm (4, 6, 31). Therefore, we believe that this criterion and the rate of PD may be more consistent with the clinical course and Author contribution statement significance of MNG. Meanwhile, to endocrinologists, RG contributed to literature research, data collection, formal analysis, and manuscript drafting. BZ contributed to clinical studies, formal analysis, surgeons, and MNG patients, this also suggests that a and manuscript drafting. TW contributed to clinical studies and statistical single-session RFA may not expose MNG patients to a high analysis. YL contributed to clinical studies. TY contributed to statistical retreatment rate after complete ablation of dominant analysis. YH contributed to data collection. JQ contributed to data nodules, so that the originally expected need for multiple collection. ZY, WX, and JR contributed to study design and manuscript treatments may not be a reason to limit the clinical editing, and JR is the guarantor of integrity of the entire study. application of RFA for MNG. All authors provided clinical feedback in interpreting the results, contributed critically to subsequent revisions, and approved the final We should also consider the limitations of this study. version of the manuscript. First, although all patients had a follow-up of over 12 months, the number of patients showed a progressive reduction over time, particularly after 36 months. The Acknowledgements reasons may include the patients skipping the periodic The authors thank all the participating teams of this study and Springer visits due to the complete remission of MNG or other Nature Author Services for improving and proofreading the manuscript. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 study of 72 patients. European Radiology 2023 33 752–762. (https:// doi.org/10.1007/s00330-022-09052-3) References 13 Chiang PL, Lin WC, Chen HL, Luo SD, Chen MH, Chen WC, Chang YH, 1 Kobaly K, Kim CS & Mandel SJ. Contemporary management of Chou CK, Su YY, Tung YC, et al. Efficacy and safety of single-session thyroid nodules. Annual Review of Medicine 2022 73 517–528. radiofrequency ablation for intrathoracic goiter: preliminary results (https://doi.org/10.1146/annurev-med-042220-015032) and short-term evaluation. International Journal of Hyperthermia 2 Wong R, Farrell SG & Grossmann M. Thyroid nodules: diagnosis 2021 38 976–984. (https://doi.org/10.1080/02656736.2021.1942241) and management. Medical Journal of Australia 2018 209 92–98. 14 Lang BHH & Fung MMH. Safety and efficacy of single-session (https://doi.org/10.5694/mja17.01204) radiofrequency ablation treatment for benign non-toxic 3 Yetkin G, Uludag M, Onceken O, Citgez B, Isgor A & Akgun I. multinodular goiter. World Journal of Surgery 2022 46 1704–1710. Does unilateral lobectomy suffice to manage unilateral nontoxic (https://doi.org/10.1007/s00268-022-06527-8) goiter? Endocrine Practice 2010 16 36–41. (https://doi.org/10.4158/ 15 Hong MJ, Baek JH, Choi YJ, Lee JH, Lim HK, Shong YK & Hong SJ. EP09140.OR) Radiofrequency ablation is a thyroid function–preserving treatment 4 Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, for patients with bilateral benign thyroid nodules. Journal of Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Vascular and Interventional Radiology 2015 26 55–61. (https://doi. et al. 2015 American Thyroid Association management guidelines org/10.1016/j.jvir.2014.09.015) for adult patients with thyroid nodules and differentiated thyroid 16 Myung SK, Lee CW, Lee J, Kim J & Kim HS. Risk factors for thyroid cancer: the American Thyroid Association guidelines task force on cancer: a hospital-based case-control study in Korean adults. thyroid nodules and differentiated thyroid cancer. Thyroid 2016 26 Cancer Research and Treatment 2017 49 70–78. (https://doi. 1–133. (https://doi.org/10.1089/thy.2015.0020) org/10.4143/crt.2015.310) 5 White ML, Doherty GM & Gauger PG. Evidence-based surgical 17 Spiezia S, Garberoglio R, Milone F, Ramundo V, Caiazzo C, management of substernal goiter. World Journal of Surgery 2008 32 Assanti AP, Deandrea M, Limone PP, Macchia PE, Lombardi G, et al. 1285–1300. (https://doi.org/10.1007/s00268-008-9466-3) Thyroid nodules and related symptoms are stably controlled two 6 Kim JH, Baek JH, Lim HK, Ahn HS, Baek SM, Choi YJ, Choi YJ, years after radiofrequency thermal ablation. Thyroid 2009 19 Chung SR, Ha EJ, Hahn SY, et al. 2017 Thyroid radiofrequency 219–225. (https://doi.org/10.1089/thy.2008.0202) ablation guideline: Korean society of thyroid radiology. Korean 18 Wang N, Zheng B, Wu T, Tan L, Lian Y, Ma Y, Guo R, Xu S, Zeng L, Journal of Radiology 2018 19 632–655. (https://doi.org/10.3348/ Xu W, et al. Thyroid dysfunction following radiofrequency ablation for kjr.2018.19.4.632) benign thyroid nodules: more likely to occur within one-week and in 7 Dobnig H, Zechmann W, Hermann M, Lehner M, Heute D, high-risk population. International Journal of Hyperthermia 2021 38 Mirzaei S, Gessl A, Stepan V, Höfle G, Riss P, et al. Radiofrequency 1060–1068. (https://doi.org/10.1080/02656736.2021.1950849) ablation of thyroid nodules: ‘Good Clinical Practice 19 Jeong WK, Baek JH, Rhim H, Kim YS, Kwak MS, Jeong HJ & Lee D. Recommendations’ for Austria. Wiener Medizinische Wochenschrift Radiofrequency ablation of benign thyroid nodules: safety and 2019 170 6–14. (https://doi.org/10.1007/s10354-019-0682-2) imaging follow-up in 236 patients. European Radiology 2008 18 8 Thyroid Cancer Committee of China Anti-cancer Association, 1244–1250. (https://doi.org/10.1007/s00330-008-0880-6) Interventional Ultrasound Committee of Chinese College of 20 Mauri G, Pacella CM, Papini E, Solbiati L, Goldberg SN, Ahmed M & Interventionalists, Tumor Ablation Committee of Chinese College Sconfienza LM. Image-guided thyroid ablation: proposal for of Interventionalists, Tumor Interventional Therapy Committee of standardization of terminology and reporting criteria. Thyroid 2019 China Anti-cancer Association, Tumor Minimally-Invasive Treatment 29 611–618. (https://doi.org/10.1089/thy.2018.0604) of China Anti-cancer Association and Thyroid Tumor Ablation 21 Chen MH, Lin WC, Luo SD, Chiang PL, Chen YS, Chen WC, Lin AN, Experts Group of Chinese Medical Doctor Association. Chinese Wang CK, Baek JH & Chen HL. Residual, regrowth, and new growth Expert Consensus and Operational Guidelines on Thermal Ablation of radiofrequency ablation for benign thyroid nodules of different for Thryoid Benign Nodules, Microcarcinoma and Metastatic volumes: two-year follow-up results. International Journal of Cervical Lymph Nodes. China Cancer 2018 27 768–773. (https://doi. Hyperthermia 2022 39 1172–1178. (https://doi.org/10.1080/0265673 org/10.11735/j.issn.1004-0242.2018.10.A006) 6.2022.2112305) 9 Papini E, Monpeyssen H, Frasoldati A & Hegedüs L. 2020 European 22 Sacks D, McClenny TE, Cardella JF & Lewis CA. Society of Thyroid Association clinical practice guideline for the use of image- guided ablation in benign thyroid nodules. European Thyroid Interventional Radiology clinical practice guidelines. Journal of Vascular and Interventional Radiology 2003 14 S199–S202. (https:// Journal 2020 9 172–185. (https://doi.org/10.1159/000508484) doi.org/10.1097/01.rvi.0000094584.83406.3e) 10 Papini E, Pacella CM, Solbiati LA, Achille G, Barbaro D, Bernardi S, Cantisani V, Cesareo R, Chiti A, Cozzaglio L, et al. Minimally-invasive 23 Ahmed M, Solbiati L, Brace CL, Breen DJ, Callstrom MR, treatments for benign thyroid nodules: a Delphi-based consensus Charboneau JW, Chen MH, Choi BI, Baère T de, Dodd GD, et al. Image-guided tumor ablation: standardization of terminology and statement from the Italian minimally-invasive treatments of the reporting criteria—A 10-year update. Radiology 2014 273 241–260. thyroid (MITT) group. International Journal of Hyperthermia 2019 36 375–381. (https://doi.org/10.1080/02656736.2019.1575482) (https://doi.org/10.1148/radiol.14132958) 11 Bartolotta TV, Midiri M, Runza G, Galia M, Taibbi A, Damiani L, 24 Rienzo-Madero B de, Sabra JP, Gand E, Donatini G & Kraimps JL. Unilateral benign multinodular versus solitary goiter: long-term Palermo Patera G & Lagalla R. Incidentally discovered thyroid contralateral reoperation rates after lobectomy. Surgery 2019 165 nodules: incidence, and greyscale and colour Doppler pattern in an adult population screened by real-time compound spatial 75–79. (https://doi.org/10.1016/j.surg.2018.04.074) sonography. Radiologia Medica 2006 111 989–998. (https://doi. 25 Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, org/10.1007/s11547-006-0097-1) Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al.. New 12 Li Y, Li X, Xiao J, Yan L, Li M, Zhang M & Luo Y. Ultrasound-guided response evaluation criteria in solid tumours: revised RECIST microwave ablation combined with ethanol injection for the guideline (version 1.1). European Journal of Cancer 2009 45 treatment of solitary nodular retrosternal goiter: a prospective 228–247. (https://doi.org/10.1016/j.ejca.2008.10.026) R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 26 Barczyński M, Konturek A, Hubalewska-Dydejczyk A, Gołkowski F, 29 Rayes N, Steinmüller T, Schröder S, Klötzler A, Bertram H, Cichoń S & Nowak W. Five-year Follow-up of a Randomized Clinical Denecke T, Neuhaus P & Seehofer D. Bilateral subtotal Trial of Total thyroidectomy versus Dunhill Operation versus thyroidectomy versus hemithyroidectomy plus subtotal resection bilateral Subtotal thyroidectomy for Multinodular Nontoxic Goiter. (Dunhill procedure) for benign goiter: long-term results of a World Journal of Surgery 2010 34 1203–1213. (https://doi. prospective, randomized study. World Journal of Surgery 2013 37 org/10.1007/s00268-010-0491-7) 84–90. (https://doi.org/10.1007/s00268-012-1793-8) 27 Barczyński M, Konturek A, Hubalewska-Dydejczyk A, Gołkowski F & 30 Zatelli MC, Lamartina L, Meringolo D, Arvat E, Damiani L, Grani G, Nowak W. Ten-year follow-up of a randomized clinical trial Nervo A, Durante C & Giacomelli L. Thyroid nodule recurrence of total thyroidectomy versus Dunhill operation versus bilateral following lobo-isthmectomy: incidence, patient’s characteristics, subtotal thyroidectomy for multinodular non-toxic goiter. World and risk factors. Journal of Endocrinological Investigation 2018 41 Journal of Surgery 2018 42 384–392. (https://doi.org/10.1007/ 1469–1475. (https://doi.org/10.1007/s40618-018-0946-5) s00268-017-4230-1) 31 Shin JH, Baek JH, Chung J, Ha EJ, Kim JH, Lee YH, Lim HK, Moon WJ, 28 Bellantone R, Lombardi CP, Boscherini M, Raffaelli M, Tondolo V, Na DG, Park JS, et al. Ultrasonography diagnosis and imaging- Alesina PF, Corsello SM, Fintini D & Bossola M. Predictive factors for based management of thyroid nodules: revised Korean society of recurrence after thyroid lobectomy for unilateral non-toxic goiter in thyroid radiology consensus statement and recommendations. an endemic area: results of a multivariate analysis. Surgery 2004 Korean Journal of Radiology 2016 17 370–395. (https://doi. 136 1247–1251. (https://doi.org/10.1016/j.surg.2004.06.054) org/10.3348/kjr.2016.17.3.370) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Thyroid Journal Bioscientifica

Two-year prognosis of multinodular goiter following radiofrequency ablation based on all nodule burdens

Download PDF
11 pages

Loading next page...
 
/lp/bioscientifica/two-year-prognosis-of-multinodular-goiter-following-radiofrequency-JAuDPo4KTX

References (31)

Publisher
Bioscientifica
Copyright
© the author(s)
ISSN
2235-0640
eISSN
2235-0802
DOI
10.1530/etj-23-0134
Publisher site
See Article on Publisher Site

Abstract

Objective: Few studies use all nodule burdens to specify the prognosis of multinodular goiter (MNG) following radiofrequency ablation (RFA), so this study addresses this question for MNG after completely ablating dominant nodules. Methods: The RFA indications for MNG include 2–5 benign nodules with over 50% normal tissue on ultrasound, 1–3 well-defined benign dominant nodules on cytology, largest diameter ≥20 mm and/or with clinical complaints, and patient refusal or unable to undergo surgery. A retrospective study of 185 MNG patients with completely ablated dominant nodules in a single-session RFA was conducted. The efficacy and complications were evaluated at 1, 6, 12 months, and yearly thereafter. Based on retreatment risks, progressive disease (PD), stable disease (SD), and complete relief (CR) were introduced to assess all nodule load changes. PD was clarified as having new/non-target nodules that newly appeared to ACR TI-RADS≥4, or new/enlarged non-target nodules ≥1 cm. Results: The initial ablation ratios of target nodules were 100% at one month. During a mean 22.38 ± 13.75 months (range, 12–60 months), the volume reduction rate of ablated nodules was 98.25% at 24 months without regrowth. Cosmetic and symptomatic scores decreased to 1 and 0, respectively, after 48 months. Of the patients, 9.7% (18/185) had PD and the retreatment rate was 2.2% (4/185). The complication rate was 2.7% (5/185). Conclusion: RFA provides cosmetic and symptomatic relief for an average of two years. RFA is a useful minimally invasive treatment modality for selected MNG patients. Keywords: radiofrequency ablation; nodular goiter; efficacy; retreatment Published by Bioscientifica Ltd. This work is licensed under a Creative Commons https://etj.bioscientifica.com Attribution 4.0 International License. © 2024 the author(s) R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 condition of non-target nodules may change and new Introduction nodules may appear, possible retreatment may be inevitable. However, to our knowledge, no systematic Thyroid nodules (TNs) are commonly detected via study has focused on the actual magnitude of this high-resolution ultrasonography (US) and affect problem, and little is known. Given our experience, we approximately 70% of the general population (1, 2). hypothesized that RFA might be clinically efficacious Although most are benign TNs (BTNs) and asymptomatic, for MNG patients whose dominant TNs were a noticeable but small percentage will progressively completely ablated. If this is proven to be the case, enlarge and cause cosmetic and/or symptomatic this may suggest the possibility of RFA for selected problems necessitating surgical resection (3, 4, 5). suitable MNG patients. However, surgical interventions for TNs are somewhat Therefore, in this retrospective study, we evaluated disadvantageous in that the risks of trauma, scar the prognosis of MNG based on all nodule burdens for formation, and mild to severe complications are high, patients whose dominant nodules were completely as is the prevalence of hypothyroidism. As a result, ablated in a single session of RFA. nonsurgical and minimally invasive interventions like radiofrequency ablation (RFA) have been widely used and recognized as highly effective and Materials and methods safe treatment options for BTNs in many authoritative guidelines (6, 7, 8, 9, 10). Institutional guidelines for RFA and However, it is well recognized that over half of the patient selection patients with BTNs are MNG, which presents as two or more nonpalpable or palpable nodules within This retrospective study was approved by the Ethics an enlarged thyroid (11). This condition poses some Committee of the Third Affiliated Hospital of Sun challenges for RFA (9, 10), because, unlike surgery, Yat-sen University (no. (2015)2-215), and all patients which allows the removal of the entire lobe or provided written informed consent for treatment. gland in MNG patients, RFA is only indicated for the In our institute, by combining many guidelines for treatment of well-defined dominant nodules of MNG thermal ablation (6, 7, 8, 9, 10), the indications for according to current guidelines (9, 10). Although MNG patients to receive RFA were as follows: (i) with four clinical trials have shown favorable results on a total of two to five nodules and at least 50% normal the shrinkage of ablated dominant nodules in MNG tissue left (Fig. 1A); (ii) with benign-appearing of patients (12, 13, 14, 15), evidence supporting the all TNs on ultrasound (ACR TI-RADS ≤3); (iii) with no efficacy of RFA in improving cosmetic outcomes and intra-thoracic extension on CT or MR imaging; (iv) relieving symptoms associated with whole thyroid with one to three well-defined dominant nodules ( Fig. swelling or all nodule burdens in a large sample 1A, blue nodule), which were confirmed as Bethesda remains scarce. In addition, considering that the class II on cytology, with a largest diameter ≥20 mm Figure 1 Diagram of the indications of RFA for MNG and observed indicators during the follow-up. (A) In the thyroid, the total number of nodules was less than five and at least 50% of normal tissue was left. All thyroid nodules had a benign appearance on ultrasound (ACR TI-RADS ≤3). RFA was performed for the dominant target nodules (red arrows), which were confirmed as Bethesda class II on cytology, with a largest diameter ≥20 mm and/or complaints of symptomatic or cosmetic problems, and the remaining small benign nodules (ACR TI-RADS ≤3 and ≤20 mm) except for dominant target nodules were non-target nodules (red nodules). (B–C) At 1 month, the IAR of ablated dominant nodules was measured by CEUS (red arrows). During the follow-up, the development of all thyroid nodules, including the VRR (red arrows) of ablated dominant nodules and the development of non-target (red nodules) and new nodules (green nodule), was monitored. The schematic was drawn by Figdraw. ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; CEUS, contrast-enhanced ultrasonography; IAR, initial ablation ratio; RFA, radiofrequency ablation; US, ultrasound; VRR, volume reduction rate. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 and/or complaining of cosmetic or symptomatic problems; and (v) refusal or unable to undergo thyroidectomy due to underlying diseases. The following were contraindications for RFA: (i) severe cardiopulmonary insufficiency and coagulation disorders; (ii) nodules with massive calcifications. Between December 2017 and December 2021, all 214 consecutive patients with MNG who qualified for the above criteria underwent the single-session RFA at the Third Affiliated Hospital of Sun Yat-sen University, Figure 2 and their complete medical records were reviewed. Flowchart of the retrospective study. MNG, multinodular goiter; RFA, We included subjects who fulfilled the following radiofrequency ablation. criteria: (i) complete ablation of all the dominant nodules in one session (The initial ablation ratios classified in terms of the proportion of its solid component (IAR) were 100% confirmed by contrast-enhanced US (17): (i) >75%, solid; (ii) 25%–75%, mixed; and (iii) <25%, (CEUS) at 1 month after RFA); (ii) no high-risk factors cystic. The total volume of the thyroid gland included the of thyroid cancer, including a family history of thyroid left lobe, the right lobe, and the volume of target dominant cancer, a history of hereditary syndromes indicating nodules in the isthmus (18). Moreover, in the clinical a predisposition to thyroid cancer, or a history of assessment, the patients were asked to provide their radiation exposure to the head and neck in childhood cosmetic grading scores and symptomatic grading scores. (16); (iii) no previous history of thyroid surgery or The cosmetic score is assessed by radiologists using the radioactive iodine treatment; and (iv) underwent following scale (6): (i) no visible or palpable mass, (ii) more than 1 year of follow-up. Based on our selection no cosmetic problem but palpable mass, (iii) cosmetic criteria, 29 patients were excluded due to their problem on swallowing only, (iv) a readily detected previous history of thyroid surgery or radioactive iodine cosmetic problem. The symptom score was obtained by treatment. Ultimately, 185 patients were included (Fig. 2). a questionnaire concerning five clinical symptoms ( 13): compression, cough, difficulty swallowing, voice change, and pain. Each positive symptom was allocated 1 point, Pre-RFA evaluation so that the symptom scores ranged from 0 to 5. All patients were subjected to US examination, clinical assessment, and thyroid function tests before RFA. RFA procedure Once fine-needle aspiration biopsy was performed to confirm the benignity of all target dominant When we ablated multiple nodules, to avoid causing nodules. The number, location, composition, size, and serious damage to the recurrent laryngeal nerves, all ACR TI-RADS score of all TNes were determined the dominant nodules in the ipsilateral thyroid lobe were ablated first, starting with the largest nodule, via US examination. The composition of the nodule was Table 1 The definitions of the criteria about all nodule burdens for MNG after RFA. Definitions PD Complete necrosis of ablated nodules and either non-target nodules enlarged to ≥1 cm with ACR TI-RADS ≤3; or new nodules developed to ≥1 cm with ACR TI-RADS ≤3; or non-target nodules or new nodules developed to ACR TI-RADS ≥4 SD Complete necrosis of ablated nodules and either unenlarged non-target nodules with ACR TI-RADS ≤3 or non-target nodules or new nodules developed to <1 cm with ACR TI-RADS ≤3 CR Complete necrosis of ablated nodules without other nodules Enlargement of the non-target nodule was defined as a 20% increase in ≥2 diameters with a minimum increase of 2 mm or a 50% increase in volume; Qualifying criteria of PD may increase the risk of retreatment. ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; CR, complete relief; MNG, multinodular goiter; PD, progressive disease; RFA, radiofrequency ablation; SD, stable disease. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 2 Baseline characteristics of all 185 MNG patients and until all the suitable dominant nodules of the unilateral thyroid lobe were completely ablated sequentially. 487 nodules. Data are presented as mean ± S.D. or as median In subsequent observation, the radiologist providing (range) or n (%). treatment subjectively assessed the patients’ voices for 10 min to determine the functional integrity of the Baseline characteristics Values recurrent laryngeal nerve of the treated side. Ablation Patients’ characteristics of the dominant nodules in the contralateral lobe was  Age (years) 43.38 ± 13.78 performed in the same manner.  Sex (Female) 148 (80.0%)  BMI (kg/m ) 22.10 ± 2.78 One radiologist with 7 years of experience completed all  FT3 (pmol/L) 4.40 (3.01–8.21) RFA procedures using the VRS01 RFA system (STARmed,  FT4 (pmol/L) 13.11 (9.34–22.62) Korea) and initiated internal cooling of the 18G  TSH (uIU/mL) 1.12 (0.01–6.39) electrodes with 10 mm or 7 mm active tips under the  Follow-up time (months) 22.38 ± 13.75 (12–60) guidance of the same US equipment. Local anesthesia,  Underlying diseases a lateral approach, a moving-shot technique, and a   Hypertension 9 (4.9%) hydrodissection approach (5% glucose) were used   Diabetes 6 (3.2%) during the RFA treatment.   Coronary heart disease 3 (1.6%) In particular, CEUS was performed preoperatively,   Liver transplant 3 (1.6%) intraoperatively, and immediately postoperatively to   Renal transplant 6 (3.2%)  Cosmetic score 4 (1–4) identify the active tissue of the dominant nodules. If there  Symptomatic score 1 (0–4) were areas of enhancement in the ablated nodule during Nodule characteristics the RFA procedure, supplementary ablation guided by  Number of nodules per patient CEUS was performed until the whole target nodule was   2 100 (54.1%) completely ablated.   3 58 (31.3%)   4 22 (11.9%) Follow-up evaluation   5 5 (2.7%)  Ablated target nodule For follow-up, patients underwent periodic US   Number of nodules per patient examination, clinical assessment, and thyroid function    1 114 (61.6%) tests at 1, 6, 12 months after RFA and then yearly    2 63 (34.1%) thereafter. All US examinations were performed by    3 8 (4.3%) three or four experienced radiologists, and another   Maximum diameter (mm) 30 (20–66) radiologist subsequently analyzed both cross-sectional   Volume (mL) 6.30 (0.64–59.50) and longitudinal dynamic images of the whole thyroid   Left 114 (43.2%) gland at each visit and included nodules with a largest   Right 130 (49.2%) diameter ≥3 mm for analysis.   Isthmus 20 (7.6%)   Cystic 47 (17.8%)   Mixed 69 (26.1%) Evaluation of response to treatment on   Solid 148 (56.1%) ablated dominant nodules   Ablation time (sec) 587 (51–3113)   Total energy delivered (Kcal) 4.34 (0.47–19.35) Several parameters were systematically collected to   Energy delivered per nodules (Kcal) 2.64 (0.21–16.89) evaluate the response to RFA, as shown in Fig. 1. The  Non-target nodule IAR was associated with technique efficacy, defined   Number of nodules per patient as the ratio between the ablated volume and the    0 33 (17.8%) volume of the ablated nodules (18). It was evaluated    1 93 (50.3%) at 1 month by CEUS.    2 49 (26.5%)    3 8 (4.3%) The volume reduction rate (VRR) was used to determine    4 2 (1.1%) the extent of shrinkage of the ablated nodule (19)   Maximum diameter (mm) 5.8 (3.0–18.8) and was evaluated by US at each follow-up point.   Volume (mL) 0.05 (0.01–2.17) Regrowth of ablated dominant nodules was defined as   Left 107 (48.0%) the volume of the ablated nodules increasing by ≥50%   Right 99 (44.4%) compared to the minimum recorded volume measured   Isthmus 17 (7.6%) during the follow-up (20, 21).   Cystic 46 (20.6%)   Mixed 126 (56.5%)   Solid 51 (22.9%) Evaluation of resolution on clinical problems In addition, the cosmetic and symptomatic scores of MNG, multinodular goiter; BMI, body mass index; FT3, free MNG patients were systematically recorded in the same triiodothyronine; FT4, free thyroxine; TSH: thyroid stimulating hormone. value in parentheses is the range. manner during each visit from baseline until the last visit. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 3 Treatment efficacy at each follow-up point. Data are presented as median (range). Cosmetic Symptomatic n Volume of ADN (mL) VRR (%) Regrowth (%) Volume of TG (mL) score score Baseline 185 6.30 (0.64–59.50) – 0 (0) 26.37 (7.87–127.91) 4 (1–4) 1 (0–4) a a a a 1 month 185 3.19 (0.25–32.66) 39.25 (0–89.90) 0 (0) 18.38 (7.87–96.63) 2 (1–4) 1 (0–3) a,b a,b a 6 months 170 1.04 (0.03–22.31) 78.47 (17.97–99.42) 0 (0) 15.10 (7.32–51.09) 1 (1–4)a 0 (0–2) a,b,c a,b,c a 12 months 178 0.50 (0–18.21) 90.90 (25.29–100) 0 (0) 12.48 (6.48–37.77) 1 (1–3)a 0 (0–1) a,b,c,d a,b,c,d a a 24 months 89 0.09 (0–8.44) 98.25 (37.27–100) 0 (0) 11.17 (6.54–20.86) 1 (1–2) 0 (0–1) a,b,c,d a,b,c,d a a 36 months 36 0.06 (0–4.19) 99.20 (51.89–100) 0 (0) 10.20 (6.54–13.40) 1 (1–2) 0 (0–1) a,b,c,d a,b,c,d a a 48 months 14 0.06 (0–3.77) 99.31 (64.00–100) 0 (0) 9.56 (7.44–13.53) 1 (1) 0 (0) a,b,c,d a,b,c,d a a 60 months 10 0.05 (0–0.67) 99.33 (96.40–100) 0 (0) 8.87 (7.71–12.19) 1 (1) 0 (0) a b c d P < 0.05 versus baseline; P < 0.05 vs 1 month; P < 0.05 vs 6 months; P < 0.05 vs 12 months. ADN, ablated dominant nodules; IAR, initial ablation ratio; TG, thyroid gland; VRR, volume reduction rate. Stable disease (SD) contained non-target or new nodules Evaluation of development on all nodules developed to <1 cm with ACR TI-RADS≤3, and these After complete ablation of the dominant nodules, nodules developed relatively slowly and were small. when considering the need for retreatment due to Complete relief (CR) contained complete necrosis of the development of non-target nodules (remaining all ablated nodules without any active nodules in the small benign nodules, ACR TI-RADS ≤ 3 and ≤ 20 mm) entire thyroid. Furthermore, when the MNG patients and/or new nodules, a comprehensive assessment of with non-target and/or new nodules showed PD and were all nodules should be performed. Focusing on the risks deemed suitable for RFA, retreatment was considered. of retreatment, we classified and defined all nodule burdens after RFA in three directions, as shown in Table 1. Evaluation of complications Progressive disease (PD) may increase the retreatment Complications were recorded based on the criteria risk. It includes non-target nodules enlarged to ≥ 1 cm with ACR TI-RADS ≤3, or new nodules developed of the Society of Interventional Radiology (SIR) (22, to ≥1 cm with ACR TI-RADS ≤3, which represent the trends 23). SIR classifications A–B were regarded as minor of causing cosmetic and/or symptomatic problems; or complications, and SIR classifications C–F were regarded non-target or new nodules developed to ACR TI-RADS ≥4. as major complications. Figure 3 Trends of (A) VRR on ablated nodules, (B) cosmetic score, and (C) symptomatic score on MNG patients in the whole observation period. Compared with that at baseline, the cosmetic score and symptom score of MNG patients significantly decreased at 1-, 6-, 12-, 24-, 36-, 48- and 60 months, *P < 0.05. VRR, volume reduction rate. Table 4 The development of unablated and new nodules after RFA. End point Patients (n, %)/ Nodules, n Nodule type Baseline ACR TI-RADS Maximum diameter Change in nodule size PD 18 (9.7%)  16 Non-target ACR TI-RADS ≤ 3 ≤3 ≥1 cm With enlargement  9 New Undetected ≤3 ≥1 cm – SD 126 (68.1%)  151 Non-target ACR TI-RADS ≤ 3 ≤3 < 1 cm Any  30 Non-target ACR TI-RADS ≤ 3 ≤3 ≥1 cm Without enlargement  32 New Undetected ≤3 <1 cm – CR 41 (22.2%)  26 Non-target ACR TI-RADS ≤ 3 Undetected The enlargement of the non-target nodule was defined as a 20% increase in ≥2 diameters with a minimum increase of 2 mm, or a 50% increase in volume. ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; CR, complete relief; PD, progressive disease; SD, stable disease. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Results A total of 185 MNG patients (mean age, 43.48 years; 148 women and 37 men) with 487 nodules were included in the study, and the median follow-up period was 22 months (range, 12–60 months) as of the data cutoff. The demographic characteristics of all patients and nodules were summarized in Table 2. Before treatment, the initial cosmetic and symptomatic scores of these 185 patients were 4 (range: 1–4) and 1 (range: 0–4), respectively. To solve these problems, 264 dominant nodules (54.4%) with a maximum diameter of 30 mm (range, 20–66 mm) were completely ablated by single-session RFA. Of these, 114 (61.6%) patients had one ablated dominant nodule, 63 (34.1%) patients had two ablated nodules, and the remaining 8 (4.3%) patients had three ablated dominant nodules. The median ablation time and energy were 587 s (range: 51–3113 s) and 4.34 kcal (range: 0.47–19.35 kcal), respectively, and the ablation energy per nodule was 2.64 kcal (range: 0.21–16.89 kcal). After the procedure, 223 nodules (45.6%) with a median largest diameter of 5.9 mm (range: 3.0–18.8 mm) were non-target nodules, and 152 (82.2%) patients had ≥1 non-target nodule. Treatment efficacy in VRR The IAR of all target nodules was 100% confirmed by CEUS at 1 month. When we analyzed the trend of the ablated nodule volume after the procedure, significant shrinkage was observed during the follow-up period (P < 0.05). Specifically, the ablated nodule volume at one month was significantly lower than that at baseline (P < 0.05) and the median VRR achieved 39.25% (range: 0%–89.90%). Further significantly progressive VRR was seen during the first two years ( P < 0.05), which was 98.25% (range: 37.27%–100%) at 24 months. Until 36 months, the nodule volume recorded did not significantly differ from that at 24 months and remained Figure 4 stable thereafter. The ablated nodule volumes at each (A) The number of nodules developed with PD and (B) the largest ultrasound evaluation were presented in Table 3. The diameter of 16 enlarged non-target nodules at each follow-up point. respective changes in VRR are shown in Fig. 3A. In These non-target nodules were significantly enlarged in largest diameter at the 12-, 24-, 36-, 48-, and 60-month follow-ups compared with particular, none of the ablated nodules regrew during baseline, *P < 0.05. PD, progressive disease. the observation period. Statistical analysis Treatment efficacy in cosmetic and SPSS statistical software, version 25.0 (IBM Corp.), was symptomatic scores. used to perform the statistical analysis. Qualitative variables are expressed as numbers (percentages), Both cosmetic and symptomatic scores. improved after and quantitative variables are expressed as RFA (Table 3 and Fig. 3). The cosmetic scores improved medians (ranges) or means ± standard deviations. significantly from 4 at baseline to 2 at the 1-month Quantitative variables were compared using t-test assessment (P < 0.05), and all patients had a cosmetic or Mann–Whitney U test, and qualitative variables score of 1 at 48 months after RFA (Fig. 3B). Similarly were compared using Fisher’s exact test or the chi-square (Fig. 3C), the symptomatic scores were significantly test. Two-sided P-values < 0.05 were considered improved at one month (P < 0.05) and no patient statistically significant. complained of any symptoms after 48 months. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 5 Characteristics of four patients qualified the indications of retreatment. Patient A Patient B Patient C Patient D Patients’ characteristics  Age (years) 27 29 38 14  Sex Female Female Female Female  BMI (kg/m ) 26.35 28.28 21.48 16.94  Thyroid function status Normal Normal Normal Normal  Pregnancy during follow-up Yes No No No  Underlying diseases No No Liver transplant No First treatment of DN  n 1 2 2 2  Maximum diameter at baseline (mm) 48 52; 22 43; 25 39; 36  Volume at baseline (mL) 20.52 11.76; 1.87 26.46; 1.57 5.71; 7.16  Follow-up time (month) 24 60 24 36  VVR at endpoint (%) 97.80 96.23; 100 92.97; 100 95.90; 99.27 PD nodules  Nodules type ENTN ENTN ENTN ENTN  ACR TI-RADS at endpoint 3 3 2 2  Maximum diameter (mm)   At baseline 17.9 8.7 9.4 13.3   At endpoint 30.6 21.3 20.4 43.1  Volume (mL)   At baseline 1.09 0.18 0.21 1.00   At endpoint 8.70 2.39 1.86 13.17 BMI, body mass index; VRR, volume reduction rate; PD, progressive disease; ACR TI-RADS, American College of Radiology Thyroid Imaging, Reporting and Data System; DN, dominant nodules; ENTN, enlarged non-target nodule. these nodules developed PD and qualified for re-treatment. The development of all nodules Retreatment When we evaluated the development of all nodules A total of four patients (2.2%, 4/185) qualified for based on the risk of retreatment (Table 4), we found retreatment (Table 5) due to the PD of non-target nodules. that the vast majority of patients (90.3%, 167/185) had A typical case was shown in Fig. 5. slow or no progression without a high possibility of retreatment. In particular, 22.2% of patients (41/185) Complications showed the best development result, CR, in which no other nodules were presented within the entire Five cases (2.7%, 5/185, Table 6) had voice change, thyroid. However, 9.7% of patients (18/185) developed which gradually and spontaneously recovered within PD and showed 25 enlarged, non-target nodules and 3 months (minor complications, SIR classification A). new nodules measuring ≥1 cm with ACR TI-RADS ≤ 3, No delayed or life-threatening complications occurred increasing the risk of the potential need for retreatment during the follow-up. due to cosmetic and/or symptomatic problems. As for the thyroid function, the thyroid-stimulating The details related to PD are presented in Fig. 4. With hormone (TSH) level changed from 1.12 μIU/mld (range: respect to the time of progression, it showed a trend 0.01–6.39 μIU/mld) at baseline to 1.39 μIU/mld (range: of increase from fast to slow and continued over time. 0.01–8.87 μIU/mld) at the endpoint, and the number of Specifically, most of the patients (61.1%, 11/18) with TSH abnormalities changed from 12 patients (6.5%) to half of the nodules (56.0%, 14/25) progressed rapidly 5 patients (2.7%). within the first year of follow-up. Gradual progression occurred during the subsequent four years. Considering Discussion the enlarged size of 16 non-target nodules, significant spontaneous enlargement from 9.7 mm (range: 5.3– 17.9mm) at baseline to 17.4 mm (range: 13.4–21.3mm) Our results demonstrated that MNG is positively affected was observed with the rates of 2.8 mm/year at 60 months. by RFA at a mean follow-up time of 22 months with an All nine new nodules developed to ≥1 cm with ACR obvious and long-lasting shrinkage of dominant nodules, TI-RADS ≤ 3. During the follow-up period, no non-target significant improvements in cosmetic and symptom or new nodules developed to ACR TI-RADS ≥ 4. scores, a low incidence of complications, and a 2.2% of R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 retreatment rate due to the progression of all nodule loads after RFA. The major aim of RFA is to eliminate, or at least reduce, clinical discomfort and avoid further invasive treatment. For a disease such as MNG, in which a pathological process involves the whole thyroid gland (24), this discomfort is not only associated with the presence of dominant nodules but also associated with whole thyroid swelling or all nodule burdens. Therefore, a comprehensive assessment of the efficacy of the procedure for the treatment of the entire thyroid should be important and necessary for MNG patients. In recent years, following previous studies of RFA for MNG or retrosternal goiter, although RFA is recognized as an effective procedure for shrinking ablated nodules, with VRRs of approximately 70% to 80% at 6 to 12 months (12, 13, 14, 15), data on the improvement of cosmetic outcomes and the relief of symptoms related to whole thyroid swelling or the presence of all nodule loads in a large sample are still rare. Based on this, we selected 185 MNG patients who underwent a single session of RFA and were followed up for 22.38 ± 13.75 months (range, 12–60 months), and the final results confirmed the persistent elimination of aesthetic and symptomatic concerns, which became significant starting from one month and progressed until reaching the endpoint. Additionally, the size of the ablated dominant nodules was significantly shrunken, with a VRR of 78.47% (range, 17.97%–99.42%) and 89.20% (range, 25.29%–100%) at 6 and 12 months after the procedure, respectively, which was also consistent with the aforementioned studies. Although the treatment response of the ablated target nodules is a key indicator of treatment effectiveness, the ‘unequivocal progression or appearance’ of non-target or new lesions also denotes a possible trend of the overall level of substantial worsening, which is closely related to continued therapy (25). Early attempts to evaluate the recurrence and retreatment of MNG patients in some previous surgical studies have confirmed that these problems are of great concern, and recurrence was Figure 5 defined as the presence of a nodule larger than or equal to A case qualified for retreatment due to the PD of a non-target nodule. 3 mm or 5 mm on US (3, 23, 26, 27, 28, 29, 30), with studies Female, 27 years, BMI 26.35 kg/m , TSH 1.31 uIU/mL. (A) finding recurrence rates ranging from 2.0% to 60.6% and Ultrasonography before RFA showed three nodules in both lobes of the reoperation rates from 1.6% to 8.0% (25, 26, 27, 28, 29). thyroid: one in the left lobe, size, 43 × 19 × 48 mm (red arrow); and the However, these definitions were not fully applicable to other two in the right, size, 17.9 × 9.9 × 11.7 mm (white arrow), and 8.0 × RFA for the following reasons: (i) discrepancies in the 6.0 × 5.8 mm. The patient received RFA to treat the dominant nodule in definitions of recurrence made it difficult to compare the the left lobe, and the other 2 nodules were non-target nodules. (B) The results among research groups, (ii) recurrence in surgery ablated dominant nodule was completely ablated in one session (red studies only focused on new nodules, but for RFA, non- arrow) which was confirmed by CEUS. (C–E) The ablated dominant nodule target nodules also had to be evaluated; (iii) some 5 mm in the left lobe showed significant shrinkage during the follow-up (red or 3 mm nodules that were recognized as indicating arrow) and achieved a volume reduction rate of 97.80% at 24 months (red recurrence were actually ‘non-measurable,’ because the arrow). Both non-target nodules in the right lobe showed PD. The smaller accuracy and reproducibility of the US measurements lesion was enlarged from 8.0 × 6.0 × 5.8 mm at baseline to 10.3 × 5.9 × 10.9 mm at 24 months, and the larger one enlarged from 17.9 × 9.9 × and the clinical significance could not be guaranteed ( 25); 11.7 mm at baseline to 30.6 × 25.5 × 21.3 mm (white arrow) at 24 months and (iv) it is debatable whether nodules <1 cm can be causing cosmetic problems. This patient qualified the indications of defined as a recurrence. To address inconsistencies in the retreatment due to this larger non-target nodule. The schematic was evaluation criteria in solid tumors (25), based on the risk of drawn by Figdraw. retreatment, our study first self-defined CR, SD, and PD to R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 Table 6 Complications of RFA during the follow-up. nonclinical causes, such as geographical distance. Further prospective studies are still needed to validate Complications Values, n (%) our results. In addition, supporting evidence on whether Major complications 0 (0) the number of dominant nodules ablated by a single  Permanent voice change (>3 months) 0 (0) RFA session affects outcomes remains scarce, but this  Airway obstruction 0 (0) issue was not explored in our study. The core factors  Infection 0 (0) of nodule regrowth cannot be distinguished by routine  Permanent hypoparathyroidism (>3 months) 0 (0) US, including the difference between ablation zones and  Rupture of the ablated nodules 0 (0) recurrent or active nodules. Therefore, a discriminable parameter of regrowth, such as an ablated nodule Minor complications 5 (2.7) volume increase of ≥50%, was used in this study. Finally,  Transient voice change (≤3 months) 5 (2.7) different ablation volumes of target nodules may have  Hematoma 0 (0) a major impact on the outcome of RFA for MNG, but  Transient hypoparathyroidism (≤3 months) 0 (0) only patients with completely ablated dominant nodules were included in this study. Therefore, our results have a limited scope of application and may not be generalized assess the development of all nodule burdens, especially to all institutions. non-target and new nodules, after complete ablation of target nodules. CR is defined as the disappearance of all In summary, for selected MNG patients with 2–5 benign active nodules during the follow-up period. SD suggests nodules in the thyroid, more than 50% normal thyroid the persistent complete necrosis of target nodules without tissue and well-defined target dominant nodules that the tendency of worsening of non-target or new lesions. were completely ablated in a single session of RFA, PD is defined as non-target and new nodules showing the current study showed that RFA has a reasonable substantial worsening that requires close surveillance effect in that it significantly improves the cosmetic evaluation or possible continued therapy, even for outcomes and symptoms, effectively shrinks dominant target lesions showing the best treatment response. nodules, and has low rates of PD and retreatment based According to our criteria, the vast majority of patients on all nodule burdens. were in a progression-free state after complete ablation of all dominant nodules by a single session of RFA, and more importantly, the overall progression rate was Declaration of interest 9.7% and the rate of need for retreatment due to PD was The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported. much lower (2.2%, 4/185), which were not higher than previous surgical studies. This can mainly be attributed to the different minimum nodule size criteria of clinically Funding relevant negative development: contrary to most surgical This work was supported by the fifth Five-Year Project of the Third studies in which a nodule diameter of 5 mm or greater Affiliated Hospital of Sun Yat-Sen University (grant 2023WW102), the was the criterion for recurrence, our study used a larger 5010 Clinical Research Project of Sun Yat-sen University (grant 2022010), nodule diameter as a criterion for PD (1 cm or greater). the Key Scientific and Technological Program of Guangzhou City (grant The main basis for our revision is that only nodules ≥1 201802020023), the Natural Science Foundation of Guangdong Province (grant 2020A1515010425), the National Natural Science Foundation of cm might have the greater potential to cause clinical China (grant 81971632), the Key Scientific and Technological Projects of discomfort or be clinically significant cancers ( 4), and it Guangdong Province (grant 2019B020235002), and the Key Scientific and is also supported by many guidelines that recommend Technological Projects of Guangdong Province (grant 2018B030332001-1). against the biopsy of nodules smaller than 1 cm (4, 6, 31). Therefore, we believe that this criterion and the rate of PD may be more consistent with the clinical course and Author contribution statement significance of MNG. Meanwhile, to endocrinologists, RG contributed to literature research, data collection, formal analysis, and manuscript drafting. BZ contributed to clinical studies, formal analysis, surgeons, and MNG patients, this also suggests that a and manuscript drafting. TW contributed to clinical studies and statistical single-session RFA may not expose MNG patients to a high analysis. YL contributed to clinical studies. TY contributed to statistical retreatment rate after complete ablation of dominant analysis. YH contributed to data collection. JQ contributed to data nodules, so that the originally expected need for multiple collection. ZY, WX, and JR contributed to study design and manuscript treatments may not be a reason to limit the clinical editing, and JR is the guarantor of integrity of the entire study. application of RFA for MNG. All authors provided clinical feedback in interpreting the results, contributed critically to subsequent revisions, and approved the final We should also consider the limitations of this study. version of the manuscript. First, although all patients had a follow-up of over 12 months, the number of patients showed a progressive reduction over time, particularly after 36 months. The Acknowledgements reasons may include the patients skipping the periodic The authors thank all the participating teams of this study and Springer visits due to the complete remission of MNG or other Nature Author Services for improving and proofreading the manuscript. R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 study of 72 patients. European Radiology 2023 33 752–762. (https:// doi.org/10.1007/s00330-022-09052-3) References 13 Chiang PL, Lin WC, Chen HL, Luo SD, Chen MH, Chen WC, Chang YH, 1 Kobaly K, Kim CS & Mandel SJ. Contemporary management of Chou CK, Su YY, Tung YC, et al. Efficacy and safety of single-session thyroid nodules. Annual Review of Medicine 2022 73 517–528. radiofrequency ablation for intrathoracic goiter: preliminary results (https://doi.org/10.1146/annurev-med-042220-015032) and short-term evaluation. International Journal of Hyperthermia 2 Wong R, Farrell SG & Grossmann M. Thyroid nodules: diagnosis 2021 38 976–984. (https://doi.org/10.1080/02656736.2021.1942241) and management. Medical Journal of Australia 2018 209 92–98. 14 Lang BHH & Fung MMH. Safety and efficacy of single-session (https://doi.org/10.5694/mja17.01204) radiofrequency ablation treatment for benign non-toxic 3 Yetkin G, Uludag M, Onceken O, Citgez B, Isgor A & Akgun I. multinodular goiter. World Journal of Surgery 2022 46 1704–1710. Does unilateral lobectomy suffice to manage unilateral nontoxic (https://doi.org/10.1007/s00268-022-06527-8) goiter? Endocrine Practice 2010 16 36–41. (https://doi.org/10.4158/ 15 Hong MJ, Baek JH, Choi YJ, Lee JH, Lim HK, Shong YK & Hong SJ. EP09140.OR) Radiofrequency ablation is a thyroid function–preserving treatment 4 Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, for patients with bilateral benign thyroid nodules. Journal of Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Vascular and Interventional Radiology 2015 26 55–61. (https://doi. et al. 2015 American Thyroid Association management guidelines org/10.1016/j.jvir.2014.09.015) for adult patients with thyroid nodules and differentiated thyroid 16 Myung SK, Lee CW, Lee J, Kim J & Kim HS. Risk factors for thyroid cancer: the American Thyroid Association guidelines task force on cancer: a hospital-based case-control study in Korean adults. thyroid nodules and differentiated thyroid cancer. Thyroid 2016 26 Cancer Research and Treatment 2017 49 70–78. (https://doi. 1–133. (https://doi.org/10.1089/thy.2015.0020) org/10.4143/crt.2015.310) 5 White ML, Doherty GM & Gauger PG. Evidence-based surgical 17 Spiezia S, Garberoglio R, Milone F, Ramundo V, Caiazzo C, management of substernal goiter. World Journal of Surgery 2008 32 Assanti AP, Deandrea M, Limone PP, Macchia PE, Lombardi G, et al. 1285–1300. (https://doi.org/10.1007/s00268-008-9466-3) Thyroid nodules and related symptoms are stably controlled two 6 Kim JH, Baek JH, Lim HK, Ahn HS, Baek SM, Choi YJ, Choi YJ, years after radiofrequency thermal ablation. Thyroid 2009 19 Chung SR, Ha EJ, Hahn SY, et al. 2017 Thyroid radiofrequency 219–225. (https://doi.org/10.1089/thy.2008.0202) ablation guideline: Korean society of thyroid radiology. Korean 18 Wang N, Zheng B, Wu T, Tan L, Lian Y, Ma Y, Guo R, Xu S, Zeng L, Journal of Radiology 2018 19 632–655. (https://doi.org/10.3348/ Xu W, et al. Thyroid dysfunction following radiofrequency ablation for kjr.2018.19.4.632) benign thyroid nodules: more likely to occur within one-week and in 7 Dobnig H, Zechmann W, Hermann M, Lehner M, Heute D, high-risk population. International Journal of Hyperthermia 2021 38 Mirzaei S, Gessl A, Stepan V, Höfle G, Riss P, et al. Radiofrequency 1060–1068. (https://doi.org/10.1080/02656736.2021.1950849) ablation of thyroid nodules: ‘Good Clinical Practice 19 Jeong WK, Baek JH, Rhim H, Kim YS, Kwak MS, Jeong HJ & Lee D. Recommendations’ for Austria. Wiener Medizinische Wochenschrift Radiofrequency ablation of benign thyroid nodules: safety and 2019 170 6–14. (https://doi.org/10.1007/s10354-019-0682-2) imaging follow-up in 236 patients. European Radiology 2008 18 8 Thyroid Cancer Committee of China Anti-cancer Association, 1244–1250. (https://doi.org/10.1007/s00330-008-0880-6) Interventional Ultrasound Committee of Chinese College of 20 Mauri G, Pacella CM, Papini E, Solbiati L, Goldberg SN, Ahmed M & Interventionalists, Tumor Ablation Committee of Chinese College Sconfienza LM. Image-guided thyroid ablation: proposal for of Interventionalists, Tumor Interventional Therapy Committee of standardization of terminology and reporting criteria. Thyroid 2019 China Anti-cancer Association, Tumor Minimally-Invasive Treatment 29 611–618. (https://doi.org/10.1089/thy.2018.0604) of China Anti-cancer Association and Thyroid Tumor Ablation 21 Chen MH, Lin WC, Luo SD, Chiang PL, Chen YS, Chen WC, Lin AN, Experts Group of Chinese Medical Doctor Association. Chinese Wang CK, Baek JH & Chen HL. Residual, regrowth, and new growth Expert Consensus and Operational Guidelines on Thermal Ablation of radiofrequency ablation for benign thyroid nodules of different for Thryoid Benign Nodules, Microcarcinoma and Metastatic volumes: two-year follow-up results. International Journal of Cervical Lymph Nodes. China Cancer 2018 27 768–773. (https://doi. Hyperthermia 2022 39 1172–1178. (https://doi.org/10.1080/0265673 org/10.11735/j.issn.1004-0242.2018.10.A006) 6.2022.2112305) 9 Papini E, Monpeyssen H, Frasoldati A & Hegedüs L. 2020 European 22 Sacks D, McClenny TE, Cardella JF & Lewis CA. Society of Thyroid Association clinical practice guideline for the use of image- guided ablation in benign thyroid nodules. European Thyroid Interventional Radiology clinical practice guidelines. Journal of Vascular and Interventional Radiology 2003 14 S199–S202. (https:// Journal 2020 9 172–185. (https://doi.org/10.1159/000508484) doi.org/10.1097/01.rvi.0000094584.83406.3e) 10 Papini E, Pacella CM, Solbiati LA, Achille G, Barbaro D, Bernardi S, Cantisani V, Cesareo R, Chiti A, Cozzaglio L, et al. Minimally-invasive 23 Ahmed M, Solbiati L, Brace CL, Breen DJ, Callstrom MR, treatments for benign thyroid nodules: a Delphi-based consensus Charboneau JW, Chen MH, Choi BI, Baère T de, Dodd GD, et al. Image-guided tumor ablation: standardization of terminology and statement from the Italian minimally-invasive treatments of the reporting criteria—A 10-year update. Radiology 2014 273 241–260. thyroid (MITT) group. International Journal of Hyperthermia 2019 36 375–381. (https://doi.org/10.1080/02656736.2019.1575482) (https://doi.org/10.1148/radiol.14132958) 11 Bartolotta TV, Midiri M, Runza G, Galia M, Taibbi A, Damiani L, 24 Rienzo-Madero B de, Sabra JP, Gand E, Donatini G & Kraimps JL. Unilateral benign multinodular versus solitary goiter: long-term Palermo Patera G & Lagalla R. Incidentally discovered thyroid contralateral reoperation rates after lobectomy. Surgery 2019 165 nodules: incidence, and greyscale and colour Doppler pattern in an adult population screened by real-time compound spatial 75–79. (https://doi.org/10.1016/j.surg.2018.04.074) sonography. Radiologia Medica 2006 111 989–998. (https://doi. 25 Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, org/10.1007/s11547-006-0097-1) Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al.. New 12 Li Y, Li X, Xiao J, Yan L, Li M, Zhang M & Luo Y. Ultrasound-guided response evaluation criteria in solid tumours: revised RECIST microwave ablation combined with ethanol injection for the guideline (version 1.1). European Journal of Cancer 2009 45 treatment of solitary nodular retrosternal goiter: a prospective 228–247. (https://doi.org/10.1016/j.ejca.2008.10.026) R Guo et al. European Thyroid Journal (2024) 13 e230134 https://doi.org/10.1530/ETJ-23-0134 26 Barczyński M, Konturek A, Hubalewska-Dydejczyk A, Gołkowski F, 29 Rayes N, Steinmüller T, Schröder S, Klötzler A, Bertram H, Cichoń S & Nowak W. Five-year Follow-up of a Randomized Clinical Denecke T, Neuhaus P & Seehofer D. Bilateral subtotal Trial of Total thyroidectomy versus Dunhill Operation versus thyroidectomy versus hemithyroidectomy plus subtotal resection bilateral Subtotal thyroidectomy for Multinodular Nontoxic Goiter. (Dunhill procedure) for benign goiter: long-term results of a World Journal of Surgery 2010 34 1203–1213. (https://doi. prospective, randomized study. World Journal of Surgery 2013 37 org/10.1007/s00268-010-0491-7) 84–90. (https://doi.org/10.1007/s00268-012-1793-8) 27 Barczyński M, Konturek A, Hubalewska-Dydejczyk A, Gołkowski F & 30 Zatelli MC, Lamartina L, Meringolo D, Arvat E, Damiani L, Grani G, Nowak W. Ten-year follow-up of a randomized clinical trial Nervo A, Durante C & Giacomelli L. Thyroid nodule recurrence of total thyroidectomy versus Dunhill operation versus bilateral following lobo-isthmectomy: incidence, patient’s characteristics, subtotal thyroidectomy for multinodular non-toxic goiter. World and risk factors. Journal of Endocrinological Investigation 2018 41 Journal of Surgery 2018 42 384–392. (https://doi.org/10.1007/ 1469–1475. (https://doi.org/10.1007/s40618-018-0946-5) s00268-017-4230-1) 31 Shin JH, Baek JH, Chung J, Ha EJ, Kim JH, Lee YH, Lim HK, Moon WJ, 28 Bellantone R, Lombardi CP, Boscherini M, Raffaelli M, Tondolo V, Na DG, Park JS, et al. Ultrasonography diagnosis and imaging- Alesina PF, Corsello SM, Fintini D & Bossola M. Predictive factors for based management of thyroid nodules: revised Korean society of recurrence after thyroid lobectomy for unilateral non-toxic goiter in thyroid radiology consensus statement and recommendations. an endemic area: results of a multivariate analysis. Surgery 2004 Korean Journal of Radiology 2016 17 370–395. (https://doi. 136 1247–1251. (https://doi.org/10.1016/j.surg.2004.06.054) org/10.3348/kjr.2016.17.3.370)

Journal

European Thyroid Journal – Bioscientifica

Published: Jan 30, 2024

Keywords: radiofrequency ablation

There are no references for this article.