Interventional procedure overview of percutaneous ultrasound-guided microwave ablation for symptomatic benign thyroid nodules
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Summary of key evidence on percutaneous ultrasound-guided microwave ablation for symptomatic benign thyroid nodules
Study 1 Zheng (2018)
Study type | Systematic review and meta-analysis |
Country | China (n=6), Germany (n=3) |
Recruitment period | Search period: inception to June 2018 |
Study population and number | n=1,461 patients with 1,845 BTNs across 9 studies (cooled MWA: n=1,408 patients with 1,784 BTNs, uncooled MWA n=53 with 61 BTNs) |
Age and sex | Mean age 42 to 66 years, 50% to 91% female |
Patient selection criteria | Inclusion criteria: Human studies published in English language demonstrating the clinical value of MWA for BTNs, studies reporting results of volume reduction at 3-, 6- or 12-month follow up, or complications. Exclusion criteria: Overlapping studies, case reports, case series with fewer than 8 patients, review articles, editorials, letters, comments, conference proceedings. |
Technique | 6 studies used cooled MWA carried out at 2450 MHz and 4 studies used uncooled MWA carried out at 902-928 MHz (1 study used both cooled and uncooled MWA). 5 studies used a moving-shot technique, 5 studies used a hydrodissection approach and 3 studies used a transisthmic approach. |
Follow up | 3 to 24 months – meta-analysis done up to 12 months |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Reported follow up was short; 1/9 studies reported a follow up of greater than 12 months and maximum follow up for uncooled microwave ablation (uMWA) was 6 months. The majority of efficacy outcomes are reported only at 3 months.
Study design issues: Relevant studies were identified using MEDLINE, EMBASE and the Cochrane Library, and to identify other suitable articles, the bibliographies of the returned articles were also screened. Two independent reviewers extracted relevant study data and assessed the quality of the included studies using the Methodological Index for Non-Randomised Studies (MINORS) evaluation tool. Disagreements were resolved by consensus with a third reviewer.
The primary efficacy outcome was mean % VRR. Mean VRR % and SDs from studies where this was not reported were estimated from medians and interquartile ranges as outlined in Hozo (2005).
Meta-analytic pooling of VRR and proportions of complications was done using the inverse-variance method for calculating weights. Pooled VRR and pooled proportions of complications were summarised using a fixed-effect model in the case of zero or non-significant heterogeneity. In the case of significant heterogeneity, a random-effects model was used. Heterogeneity among studies was assessed by using chi-square testing and I² statistics (in which 0–40%, is defined as not significant; 30–60%, may represent moderate heterogeneity; 50–90% - may represent substantial heterogeneity; 75–100% - may represent considerable heterogeneity).
Publication bias was visually assessed by funnel plots, and statistical significance was evaluated by Egger's test (with statistical significant set at p=0.05).
Study population issues: The mean initial nodule volume was 15.0 ml (range 2.1–102.1 ml) across all studies, but the mean initial nodule volume of cooled microwave ablation (cMWA) (11.3 ml; range, 2.1–99.0 ml) was lower than that of uMWA (47.8 mL; range, 19.8–102.1 ml; p <0.01).
Significant publication bias was noted at 3-month follow up (p<0.01) for % VRR and for cMWA group in subgroup analysis. (p = 0.03). Significant heterogeneity was noted for complications in cMWA and across all MWA, as well as in percentage VRR for overall VRR and both cMWA and uMWA in subgroup analysis.
Other issues: 1 study included in this systematic review is also included in the Cui (2019) systematic review (Study 2) and the Guo (2021) systematic review (Study 3).
Key efficacy findings
Number of patients analysed: 1,461 (9 studies, cMWA: n=1,408 patients, uMWA n=53)
Overall reduction in nodule volume
Length of follow up | VRR of BTNs at 3-month follow up (95% CI) | I2 value | P value (publication bias) |
3 months | 54.3% (45.3% – 63.3%) | 97.6% | <0.01 |
6 months | 73.5% (66.7% – 80.3%) | 94.9% | 0.14 |
12 months | 88.6% (84.9% – 92.4%) | 92.7% | 0.72 |
Overall reduction in nodule volume by MWA type:
Type of MWA | Pooled VRR of BTNs at 3‑month follow up (95% CI) | I2 value | P value (publication bias) |
cMWA | 58.4% (49.3% - 67.4%) | 97.0% | 0.03 |
uMWA | 45.3% (29.5% - 61.1%) | 92.7% | 0.07 |
There was no statistically significant difference between cMWA and uMWA in pooled VRR (P = 0.07).
Key safety findings
262 complications of MWA were reported among 1,845 thyroid nodules in 1,461 patients (72 major complications and 190 minor complications).
Type of MWA | Pooled proportion (95% CI) (number of cases) | I2 value | P value for publication bias |
cMWA | 29.7% (18.8% - 40.5%) | 97.4% | 0.40 |
uMWA | 97.8% (94.0% - 100%) | 0% | 0.11 |
All MWA | 52.4% (29.8% - 74.9%) | 99.5% | 0.08 |
There was a statistically significant difference between cMWA and uMWA in overall incidence of complications (P <0.01).
Type of MWA | Pooled proportion (95% CI) (number of cases) | I2 value | P value for publication bias |
cMWA | 4.9% (2.4% - 7.4%) | 69.9% | 0.58 |
uMWA | 5.0% (0% - 10.8%) | 0% | 0.07 |
All MWA | 4.8% (2.7% - 7.0%) | 55.9% | 0.42 |
Type of MWA | Pooled proportion (95% CI) (number of cases) | I2 value | P value for publication bias |
cMWA | 21.0% (13.2% - 28.8%) | 98.0% | 0.45 |
uMWA | 97.8% (94.0% - 100%) | 0% | 0.11 |
All MWA | 48.3% (31.2% - 65.4%) | 99.7% | 0.09 |
There was a statistically significant difference between cMWA and uMWA in incidence of minor complications (P <0.01).
Major complication | Percentage incidence (cMWA) | Percentage incidence (uMWA) (n=53) | Percentage incidence (overall) (n=1,461) |
Transient voice change | 3.7% (54/1408) | 0% (0/53) | 3.7% (54/1461) |
Transient hoarseness | 0.21% (3/1408) | 0% (0/53) | 0.21% (3/1461) |
Ipsilateral vocal cord palsy | 0.07% (1/1408) | 0% (0/53) | 0.07% (1/1461) |
Horner's syndrome | 0.07% (1/1408) | 1.9% (1/53) | 0.1% (2/1461) |
Thyroid dysfunction | 0.41% (6/1408) | 0% (0/53) | 0.41% (6/1461) |
Nodule rupture | 0.27% (4/1408) | 0% (0/53) | 0.27% (4/1461) |
Sympathetic nerve injury | 0.07% (1/1408) | 0% (0/53) | 0.07% (1/1461) |
Graves' disease | 0% (0/1408) | 1.9% (1/53) | 0.07% (1/1461) |
Percentage incidence (cMWA) | Percentage incidence (uMWA) (n=53) | Percentage incidence (overall) (n=1,461) | |
Pain | 5.4% (77/1408) | 100% (53/53) | 8.9% (130/1461) |
Skin burn | 0.21% (3/1408) | 0% (0/53) | 0.21% (3/1461) |
Haemorrhage | 1.9% (27/1408) | 0% (0/53) | 1.8% (27/1461) |
Vomiting | 0.07% (1/1408) | 0% (0/53) | 0.07% (1/1461) |
First-degree burn | 0% (0/1408) | 47.2% (25/53) | 1.7% (25/1461) |
Hyperthyroidism | 0.07% (1/1408) | 1.9% (1/53) | 0.1% (2/1461) |
Haematoma | 0% (0/1408) | 3.7% (2/53) | 0.1% (2/1461) |
Percentage incidence (cMWA) | Percentage incidence (uMWA) | Percentage incidence (overall) | |
Heat sensation | 0.57% (8/1408) | 0% (0/53) | 0.55% (8/1461) |
Superficial haematomas | 0.64% (9/1408) | Exact number not reported* | Unknown* |
Coughing | 0.07% (1/1408) | 0% (0/53) | 0.07% (1/1461) |
Choking and coughing | 0.85% (12/1408) | 0% (0/53) | 0.82% (12/1461) |
Mild bleeding | 0.28% (4/1408) | 0% (0/53) | 0.27% (4/1461) |
Fever | 0.92% (13/1408) | 0% (0/53) | 0.89% (13/1461) |
*Paper states "almost all patients" in 1 study of 30 patients
Study 2 Cui (2019)
Study type | Systematic review and meta-analysis |
Country | China (n=6), Germany (n=1) |
Recruitment period | Search date: not reported |
Study population and number | n=1,146 patients with BTNs or papillary thyroid microcarcinoma (BTNs: n=1,085 patients with 1,159 nodules across 5 studies, papillary thyroid microcarcinoma: n = 61 patients with 67 nodules across 2 studies) |
Age and sex | Not reported |
Patient selection criteria | Inclusion criteria: Human studies published in English language demonstrating the clinical value of MWA for benign thyroid nodules and papillary thyroid microcarcinoma; studies in which clinical outcomes for nodules treated with US-guided MWA were reported (such as nodule volume, symptom score, cosmetic score); follow up of at least 3 months. Exclusion criteria: Abstracts, case reports, case series, in vitro studies, animal studies. In the case of multiple articles by the same author being returned, articles that were not the most up to date or reported incomplete data were excluded. |
Technique | Of the 7 selected articles, 2 studies used multiple rounds of MWA, while a single round of MWA was used in the other studies. |
Follow up | 3-12 months |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Follow-up length varied between studies. 6/7 studies had a follow up of greater than 12 months, while 1 study had a follow up of 3 months.
Study design issues: Relevant studies were identified using PubMed, EMBASE, Cochrane, and Web of Science. Some additional studies were found through a manual search that included references from other studies, and any duplicate publications were excluded. One reviewer extracted relevant study data and 2 further reviewers verified the accuracy of the extracted data.
The primary efficacy outcomes of this study included changes in nodule volume, symptom scores, and cosmetic scores. The included articles estimated nodule volumes using the formula for the volume of an ellipsoid: V=π/6*(abc) where a, b, and c are the largest diameters in the x-, y-, and z-dimensions. The primary safety outcome was the rate of major and minor complications as defined by the Society of Interventional Radiology. Major complications included transient or permanent voice change, hypoparathyroidism, oesophageal injury, dysphagia, infection, and nodule rupture, while minor complications included unbearable pain (severe pain that need medication to relieve it), skin burns, haematoma, and vomiting.
For the continuous data, the SMD was calculated for all outcomes as all of the analysed outcomes used the same unit scale. A 95% CI was calculated for each SMD. The odds ratio (OR) and 95% CI were calculated for one dichotomous outcome. P values were considered significant if less than 0.05. When possible, subgroup analyses were done for all outcomes for "benign thyroid nodules" and "papillary thyroid microcarcinomas".
Meta-analysis was done using the Cochrane Review Manager (RevMan) Version 5.3 and used a pre-treatment to post-treatment comparison, with all subjects serving as their own controls. Each treatment outcome was assessed and recorded as an absolute value or change from the baseline using the last available timepoint. Efficacy and safety outcomes included in the meta-analysis were summarised using a fixed-effect model in the case of zero or non-significant heterogeneity. In the case of significant heterogeneity (p≤0.05), a random-effects model was used. Heterogeneity within studies was assessed using the I² statistic (in which a value of 25% illustrates low heterogeneity; 50% illustrates moderate heterogeneity and 75% illustrates high heterogeneity).
The quality of the included studies in terms of risk of bias was assessed using the Cochrane Collaboration's tool. 3/7 studies had high levels of selection bias and 2/7 studies had issues with blinding participants and personnel (performance bias).
Other issues: 1 study included in this systematic review is also included in the Guo (2021) systematic review, and a second study is included in both the Guo (2021) systematic review (Study 3) and the Zheng (2018) systematic review (Study 1).
Key efficacy findings
Number of patients analysed: 1,146 (1,226 nodules)
Reduction in nodule volume (benign nodule subgroup analysis)
% VRR after MWA treatment = 75% (SMD: 0.99, 95% CI 0.91-1.08; 5 studies, n=1,159 nodules; I2=0%, p<0.00001)
Symptom score change
Symptom score after MWA treatment = SMD: 1.51 (95% CI -0.40-3.42; 2 studies, n=766 nodules; I2=100%, p<0.12)
All studies reporting symptom score contained patients with benign nodules only.
Cosmetic score change
Cosmetic score after MWA treatment = SMD: 1.20 (95% CI 0.87-1.52; 3 studies, n=876 nodules; I2=83%, p<0.00001)
All studies reporting cosmetic score contained patients with benign nodules only.
Key safety findings
Complication | % incidence (number of nodules) | Incidence as % of patients* |
Transient or permanent voice change | 4.6 (58/1226) | 5.1 (58/1146) |
Nodule rupture | 0.5 (6/1226) | 0.5 (6/1146) |
Unbearable pain | 2.2 (28/1226) | 2.4 (28/1146) |
Skin burns | 0.08 (1/1226) | 0.08 (1/1146) |
*Calculated values
Complication | % incidence (number of nodules) | Incidence as % of patients* |
Haematoma | 3.8 (46/1226) | 4.0 (46/1146) |
*Calculated values
Study 3 Guo (2021)
Study type | Systematic review and meta-analysis |
Country | China (n=3), Germany (n=2) |
Recruitment period | Search period: inception to September 2020 |
Study population and number | n=1,768 patients with 1,894 BTNs across 5 studies (MWA: 869 patients with 938 BTNs, RFA: 899 patients with 956 BTNs) |
Age and sex | MWA: Mean age 47.1 to 57.0 years, 53% to 78% female RFA: Mean age 46.3 to 54 years, 55% to 78% female |
Patient selection criteria | Inclusion criteria: Human studies published in English language comparing the clinical results of RFA and MWA in treatment of BTNs, studies reporting results of volume reduction at 3-, 6- or 12-month follow up and complications. Exclusion criteria: Overlapping/duplicated studies, review articles, conference abstracts, case reports, letters, animal studies, studies with insufficient data to calculate VRR. |
Technique | Not reported |
Follow up | 3 to 14 months |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Reported follow up was short; meta-analysis was done up to 12 months (with 1/5 studies reporting a follow up of greater than 12 months and 2/5 studies only reporting a follow up of 3 months).
Study design issues: Relevant studies were identified using MEDLINE, EMBASE and the Cochrane Library, and data was extracted by 2 independent reviewers. The quality of the included studies was assessed by using the Cochrane Collaboration's tool in RevMan 5.3. Most of the studies showed unclear risks in blinding of participants and personnel (performance bias), and blinding of outcome assessment (detection bias).
The primary efficacy outcome was mean percentage VRR. Mean VRR and SDs from studies where this was not reported were estimated from medians and interquartile ranges as outlined in Wan (2014). Ablation-related major and minor complications were as defined by the Society of Interventional Radiology.
The pooled VRRs were calculated using an inverse-variance weighting model. Standard mean differences (SMD) with 95% CIs were used to analyse symptomatic and cosmetic scores; risk difference (RD) with 95% CI was utilised to analyse complications.
Heterogeneity within the studies was estimated using the chi-square test, with p < 0.05 suggesting significant heterogeneity, and the I2 statistic (with 0%–40% suggesting mild heterogeneity, 30%–60% suggesting moderate heterogeneity, 50%–90% suggesting substantial heterogeneity, and 75%–100% suggesting considerable heterogeneity). Meta-analyses were using a fixed-effect model in the case of zero or non-significant heterogeneity. In the case of significant heterogeneity, a random-effects model was used.
Study population issues: The preoperative mean nodule volume did not significantly differ between RFA (9.0 ml, 95% CI: 2.1-15.9 ml) and MWA (8.5 ml, 95%CI: 2.2–14.9 ml; p=0.923).
Other issues: 1 study included in this systematic review is also included in the Cui (2019) systematic review, and a second study is included in both the Cui (2019) systematic review (Study 2) and the Zheng (2018) systematic review (Study 1).
Key efficacy findings
Number of patients analysed: 1,768 (MWA: 869 patients with 938 BTNs, RFA: 899 patients with 956 BTNs)
Overall reduction in nodule volume (n=number of nodules):
VRR % of BTNs (95% CI) for MWA (n=938 at 3 months, n=866 at 6/12 months) | VRR % of BTNs (95% CI) for RFA (n=956 at 3 months, n=861 at 6/12 months) | P value for significant difference | |
3 months (5 studies) | 54% (48- 60%) I2 = 93%, p<0.01 | 56% (49-63%) I2 = 98%, p<0.01 | 0.668 |
6 months (3 studies) | 75% (70-80%) I2 = 89%, p<0.01 | 81% (77-85%) I2 = 92%, p<0.01 | 0.08 |
12 months (3 studies) | 80% (77-83%) I2 = 74%, p<0.01 | 86% (82-91%) I2 = 95%, p<0.01 | 0.036 |
Symptom improvement (n=number of nodules):
SMD (95% CI) for MWA (n=866) | SMD (95% CI) for RFA (n=861) | P value for significant difference | |
6 months (3 studies) | 1.12 (0.38-1.87) I2=97%, p<0.01 | 1.17 (0.36-1.98) I2=97%, p<0.01 | 0.93 |
12 months (3 studies) | 1.45 (0.34-2.56) I2=98%, p<0.01 | 1.46 (0.29-2.62) I2=98%, p<0.01 | 0.93 |
Cosmetic improvement (n=number of nodules):
SMD (95% CI) for MWA (n=866) | SMD (95% CI) for RFA (n=861) | P value for significant diff. | |
6 months (3 studies) | 0.94 (0.84-1.04) I2 = 0%, p=0.38 | 0.87 (0.77-0.97) I2 = 0%, p=0.46 | 0.334 |
12 months (3 studies) | 1.15 (0.83-1.47) I2 = 81%, p<0.01 | 1.21 (0.66-1.76) I2 = 87%, p<0.01 | 0.872 |
Key safety findings
Major complications
Risk difference between RFA and MWA across all studies (major complications) = -0.02 (95% CI 0.04 to 0.00, I2=0%, p=0.107)
Major complications (RFA) | Major complications (MWA) | |
Cheng, 2017 | Transient voice change (29/649) Nodule rupture (2/649) | Transient voice change (35/603) Nodule rupture (4/603) Sympathetic nerve injury (1/603) |
Hu, 2019 | Transient voice change (2/72) | Transient voice change (4/100) |
Korkusuz, 2018 | None | None |
Vorländer, 2018 | None | Sympathetic nerve injury (1/24) |
Yue, 2016 | Transient voice change (4/102) | Transient voice change (5/102) |
All | Transient voice change (35/899) Nodule rupture (2/899) Total major complications: 37/899 | Transient voice change (44/869) Nodule rupture (4/869) Sympathetic nerve injury (2/869) Total major complications: 40/869 |
Minor complications
Risk difference between RFA and MWA across all studies (minor complications) = 0.00 (95% CI -0.01 to 0.02, I2=0%, p=0.661)
Study 4 Honglei (2021)
Study type | Non-randomised comparative study |
Country | China |
Recruitment period | 2017-2019 |
Study population and number | n=267 patients with 1,075 BTNs (132 patients with 530 thyroid cystadenoma, 134 patients with 543 nodular goitre, 1 patient with both thyroid cystadenoma and nodular goitre) |
Age and sex | Mean age 50.1±11.7 years, 80% female |
Patient selection criteria | Inclusion criteria: BTNs associated with symptoms (neck discomfort due to lump; general examination found thyroid lump causing psychological discomfort; and dysphagia), nodules classified as TIR1-TIR3 on fine-needle aspiration, growing nodule size as confirmed by follow up. Exclusion criteria: Irradiation and/or surgery on the head and neck, malignant nodules, pregnancy, lactation, non-adherent patients. |
Technique | Patients were placed in a dorsal decubitus position with the arms extended to the side of the body, and the neck in hyperextension. A 2450 MHz MWA system (KY-2000, Kangyou Medical, China) MWA system and accompanying microwave antennas (KY‑2450A-1, Kangyou Medical, China) were used with a continuous output of 40W. Ablation time depended on the size and number of nodules. |
Follow up | Mean 23 months (outcomes reported to 15 months) |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Thyroid function tests, antibodies against Tg, thyrotropin receptors, and thyroid peroxidase were measured 24 hours after MWA, as well as every 3 months for a year. Follow up using ultrasound was carried out every 3 months for at least 1 year.
Study design issues: This non-randomised, single-centre, retrospective study assessed safety and efficacy of MWA using ultrasound guidance for BTNs (specifically thyroid cystadenoma and nodular goitre). The primary efficacy outcomes measured were nodule area and % VRR, and the primary safety outcome measured was the rate of complications.
Study population issues: The baseline nodule area did not statistically significantly differ between patients with nodular goitre (mean area 4.7±3.51 cm2) and thyroid cystadenoma (mean area 5.87±3.75 cm2; p = 0.48). The mean nodule area across all patients was 5.28±3.63 cm2.
Key efficacy findings
Number of patients analysed: 267
Changes in nodule volume (number of nodules)
Nodular goitre (n=133) | Thyroid cystadenoma | Total | P value | |
Baseline nodule area (cm2) | 4.7±3.51 | 5.87±3.75 | 5.28±3.63 | 0.4842 |
Mean nodule area (cm2) – 3 months | 2.34±2.52 | 2.44±2.26 | 2.39±2.35 | 0.2450 |
% VRR – 3 months | 50.22±27.7 | 59.29±22.3 | 54.74±24.9 | - |
Mean nodule area (cm2) – 6 months | 0.82±0.30 | 1.14±1.27 | 0.98±1.14 | <0.05 |
% VRR – 6 months | 82.56±16.5 | 84.31±14.2 | 81.44±17.1 | - |
Mean nodule area (cm2) – 9 months | 0.57±0.15 | 0.79±0.19 | 0.68±0.27 | <0.05 |
% VRR – 9 months | 90.3±4.4 | 91.4±3.2 | 89.8±6.9 | - |
Mean nodule area (cm2) – 12 months | 0.20±0.08 | 0.21±0.10 | 0.20±0.10 | <0.05 |
% VRR – 12 months | 91.2±3.5 | 93.5±1.3 | 92.9±2.0 | - |
Mean nodule area (cm2) – 15 months | 0.18±0.06 | 0.22±0.09 | 0.16±0.07 | <0.05 |
% VRR – 15 months | 92.0±2.4 | 93.8±1.0 | 93.3±1.8 | - |
Follow up | TSH uIU/ml | FT3 pmol/l | FT4 pmol/L | T.abs | P value |
Baseline | 1.92±0.64 | 4.66±0.61 | 11.40±3.1 | Negative | - |
3 months | 2±0.9 | 4.78±1.1 | 13.37±1.2 | Negative | Not significant |
6 months | 1.77±0.7 | 4.1±0.4 | 12.40±1.1 | Negative | Not significant |
9 months | 1.8±0.99 | 4.18±1.20 | 14.40±2.1 | Negative | Not significant |
1 year | 1.88±1.0 | 3.89±0.21 | 12.40±0.9 | Negative | Not significant |
FT3=free triiodothyronine, FT4=free thyroxine, T.abs=thyroid antibodies test, TSH=thyroid-stimulating hormone
All thyroid function tests at baseline and post-ablation showed no statistically significant difference in thyroid function following MWA.
Key safety findings
Complication | Number of cases (% of patients) |
Nausea | 5/267 (1.85) |
Skin burn | 4/267 (1.48) |
Cough | 3/267 (1.11) |
Vomiting | 2/267 (0.74) |
Local oedema | 2/267 (0.74) |
Transient voice change | 2/267 (0.74) |
All complications | 18/267 (6.69) (95% CI 0.039 – 0.095) |
Study 5 Jin (2021)
Study type | Non-randomised comparative study |
Country | China |
Recruitment period | 2018-2019 |
Study population and number | n=943 patients with BTNs (n=532 MWA, n=411 RFA); 578 matched patients n=289 MWA, n=289 RFA |
Age and sex | MWA: Median age 48 years (range 35 to 88 years), sex not reported RFA: Median age 52 years (range 39 to 91 years), sex not reported |
Patient selection criteria | Inclusion criteria: Patients aged 18 to 80 years inclusive, 2 sets of fine-needle aspiration cytology (FNAC) results confirming benign nature of nodules, maximum diameter of BTNs ≥ 2 cm. Exclusion criteria: Basic function disorders (including disorders in respiratory, circulatory, or metabolic systems), abnormal coagulation functions, abnormal liver or kidney function, allergy to local anaesthetic, BTNs less than 2 mm from thyroid capsule, more than 5 BTNs, addiction to smoking or drinking, non-completion of QoL questionnaire at baseline or follow up. |
Technique | MWA: A 2450 MHz MWA system (MTI-5DT, Changcheng Co. Ltd. Nanjing, Jiangsu Province, China) was applied to BTNs. RFA: An RFA system (S-1500, Maide Co.Ltd. Shanghai, China) was applied to BTNs, with different active tips (5, 7, 10 mm) applied according to diameter of nodules. |
Follow up | 18 months |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Patients returned to hospital for ultrasound examination at the 1st, 3rd, 6th, 12th, and 18th postoperative month, and also filled out QoL questionnaires at the same time points.
Study design issues: This was a retrospective non-randomised comparative study. To balance group characteristics (including age, gender, number of BTNs, average volume of BTNs, Body mass index (BMI), and preoperative QoL scores,) a 1:1 propensity score matching was done. After 1:1 propensity score matching, 289 pairs of patients were matched.
The primary efficacy outcomes were mean VRR and QoL, and the primary safety outcome was the rate of complications. To calculate effect size for QoL-related parameters, ordinal logistic regression and binary logistic regression were used to calculate odds ratios. The Mann–Whitney U test was used to compare continuous variables and Fischer's exact test to compare small percentages.
The QoL questionnaire that patients filled out was made by the Korean Thyroid Association and translated into Chinese by the researchers. The QoL questionnaire was composed of 41 items divided into 4 parts, evaluating the spiritual wellbeing, psychological wellbeing, social wellbeing, and physical wellbeing. Each item was scored between 1 and 10, resulting in a possible score range between 0 and 410.
Study population issues: Following propensity score matching, baseline characteristics did not significantly differ between MWA and RFA. The preoperative median nodule volume was 9.2 ml for both groups (range 5.6-18.9 ml) and the median preoperative quality of life as measured by the QoL questionnaire provided was 271/410 (range 181 to 410). However, baseline characteristics are given for all patients eligible for the study (n=532 in the MWA group and n=411 in the RFA group) instead of the paired patients (n=289 in each group) in whom outcomes are reported.
Key efficacy findings
Number of patients analysed: 578 (n=289 MWA, n=289 RFA)
Mean VRR % (min, max) MWA (n=289) | Mean VRR % (min, max) RFA (n=289) | P value | |
1 month | 15.3 (8.2, 22.4) | 15.4 (8.2, 22.6) | 0.32 |
3 months | 47.9 (37.7, 58.1) | 48.2 (36.9, 59.5) | 0.72 |
6 months | 67.8 (59.9, 75.7) | 68.1 (60.0, 76.2) | 0.91 |
12 months | 79.3 (76.1, 82.5) | 80.1 (78.3, 81.9) | 0.56 |
18 months | 91.7 (88.5, 94.9) | 89.2 (84.4, 94.0) | 0.58 |
Cases of BTN recurrence
There was 1 BTN recurrence in a patient with a preliminary BTN volume of 10.28 ml (treatment group not stated). The patient had a secondary ablation treatment. After 6 months, VRR of this BTN reached 67.2% and no recurrence was found.
Quality of life
Mean value for MWA (n=289) (min, max) | Mean value for RFA (n=289) (min, max) | Adjusted effect size (95% CI) | P value | |
Postoperative QoL score across all time points (min, max) | 341.57 (334.25, 348.89) | 343.91 (335.20, 352.62) | 1.02 (0.78 to 1.52) | 0.32 |
QoL (1 month postoperative) | 291.38 (284.1, 298.66) | 293.46 (286.65, 300.27) | 0.81 (0.72 to 1.03) | 0.59 |
QoL (3 months postoperative) | 310.59 (301.83, 319.35) | 312.49 (304.93, 320.05) | 0.71 (0.56 to 0.91) | 0.68 |
QoL (6 months postoperative) | 337.86 (329.93, 345.79) | 341.58 (332.67, 350.46) | 1.09 (0.71 to 1.25) | 0.81 |
QoL (12 months postoperative) | 352.19 (340.27, 364.11) | 353.78 (340.96, 366.59) | 0.82 (0.56 to 1.26) | 0.38 |
QoL (18 months postoperative) | 372.89 (360.08, 385.70) | 373.19 (360.68, 385.70) | 0.32 (0.13 to 0.58) | 0.67 |
Overall QoL score*: Total physical wellbeing | 93.2 (85.88, 100.52) | 92.9 (86.32, 99.48) | 1.52 (1.32 to 1.89) | 0.78 |
Overall QoL score*: Total psychological wellbeing | 91.7 (81.92, 101.48) | 93.9 (83.34, 104.46) | 1.38 (1.09 to 3.56) | 0.39 |
Overall QoL score*: Total spiritual wellbeing | 91.32 (79.4, 103.04) | 92.97 (79.78, 106.16) | 1.52 (1.32 to 1.86) | 0.38 |
Overall QoL score*: Total social wellbeing | 72.56 (63.44, 81.68) | 73.91 (62.34, 85.48) | 1.08 (1.03 to 1.95) | 0.24 |
*Max score in each category not reported (but overall max 410)
% MWA (n=289) (number of patients) | % RFA (n=289) (number of patients) | Adjusted effect size | P value | |
Proportion of QoL scores >400 | 59 (170/289) | 58 (167/289) | 0.38 (0.31 to 0.49) | 0.38 |
Proportion of QoL scores =410 | 12 (34/289) | 13 (38/289) | 0.59 (0.21 to 0.89) | 0.42 |
Proportion of QoL scores 300-400 | 20 (58/289) | 19 (55/289) | 0.41 (0.18 to 0.97) | 0.50 |
Proportion of QoL scores 200-300 | 12 (35/289) | 13 (38/289) | 0.95 (0.52 to 1.39) | 0.41 |
Proportion of QoL scores <200 | 9 (26/289) | 10 (29/289) | 0.28 (0.11 to 0.59) | 0.17 |
Key safety findings
MWA group (n=289) % rate (number of patients) | RFA group (n=289) % rate (number of patients) | P value | |
|---|---|---|---|
0.34 (1/289) | 0 | 0.12 | |
Skin burn and pain (all) | 0.69 (2/289) | 1.03 (3/289) | 0.37 |
Skin burn and pain (mild) | 0.35 (1/289) | 0.35 (1/289) | - |
Skin burn and pain (moderate) | 0.35 (1/289) | 0.35 (1/289) | - |
Skin burn and pain (severe) | 0 | 0.35 (1/289) | - |
Hoarseness | 0.35 (1/289) | 0.69 (2/289) | 0.72 |
Cough after drinking | 0.35 (1/289) | 0.35 (1/289) | 0.49 |
All complications | 1.73 (5/289) | 2.06 (6/289) | 0.73 |
Study 6 Luo (2021)
Study type | Case series |
Country | China |
Recruitment period | 2014-2017 |
Study population and number | n=171 patients with BTNs |
Age and sex | Mean age 47.0±14.2 years |
Patient selection criteria | Patients with BTNs confirmed via core-needle (18-gauge) biopsy; nodules with a largest diameter larger than 3 cm; BTNs with a fluid component <80% as seen with an ultrasound assessment; normal serum free thyroxine (FT4) level and a corresponding normal or low thyrotropin (TSH) level; no vocal cord immobility, as confirmed via a laryngoscope. |
Technique | A 2450 MHz MWA system (KY-2000, Kangyou Medical, Nanjing, China) was applied to BTNs with power output from 20-30W.The hydrodissection technique was applied to prevent damage to critical adjacent structures, and MWA was done using the moving-shot technique. For nodules with a diameter ≤5 cm, MWA was done in one session, while for nodules with a diameter >5 cm, MWA was done in 2 or 3 sessions. |
Follow up | 3 years |
Conflict of interest/source of funding | No conflict of interest. Funding supported by various grants. |
Analysis
Follow-up issues: Ultrasound examination was done in all patients at the time of the 1-, 3-, 6-, 12-, 24, and 36-month follow-up examinations by 2 radiologists. Upon ultrasound examination, changes in nodule volume, therapeutic success rate, and improvement of symptomatic and cosmetic problems were checked.
20/171 (11.6%) patients were lost to follow up at 24 months and 31/171 (18.1%) patients were lost to follow up after 36 months.
Study design issues: This was a retrospective case series aiming to evaluate efficacy of MWA by nodule composition.
Therapeutic success was defined as a VRR > 50% at the 12-month follow up. Technical efficiency was defined as a VRR ≥50% of the initial nodule volume at each follow-up time point. Recurrence was defined as a nodule volume increase >50% over the smallest recorded volume.
In statistical analyses, groups were compared using the Mann–Whitney U test and chi-square tests were used to compare categorical variables (where p values less than or equal to 0.05 were considered to indicate a statistically significant difference).
Study population issues: The mean diameter of these nodules was 4.3±1.3 cm, and the mean volume was 21.2±18.9 ml. Of the nodules, 58 (32.2%), 85 (47.2%), and 37 (20.6%) had volumes ≤10, 10.0–30, and ≥ 30 ml, respectively.
For the fluid component assessment, 87 (48.3%) were solid (≤10% fluid component), 74 (41.1%) were predominantly solid (11%–50% fluid component), and 19 (10.6%) were predominantly cystic nodules (51%–90% fluid component); none of the nodules were cystic (>90% fluid component).
Key efficacy findings
Number of patients analysed = 171 (151 at 24 months, 140 at 36 months)
Overall effect of procedure (n=number of nodules)
Technical success (n=number of nodules)
All nodules (n=180) | |
Mean duration of ablation (min) | 14.7±8.2 |
Technical success | 97.8% (176/180) |
Total energy (kJ) | 19.9±12.1 |
Median nodule volume (n=number of nodules)
Follow up | Median nodule volume in ml (n=180) |
Baseline | 21.2±18.9 |
1 month | 10.6±9.5* |
3 months | 6.2±6.0*# |
6 months | 3.9±5.1*♦ |
12 months | 2.4±3.2*#♦^ |
* = p < 0.001 versus baseline values respectively,
# = p < 0.001 versus 1-month values respectively,
♦ = p < 0.001 versus 3-month values respectively,
^ = p < 0.05 versus 6-month values respectively.
Mean VRR % (n=number of nodules)
Mean VRR % (n=180) | |
1 month | 47.1±20.2 |
3 months | 68.2±18.1 |
6 months | 79.7±15.9 |
12 months | 87.4±12.3 |
24 months (n=151 patients) | 90.1 |
36 months (n=140 patients) | 93.2 |
Efficacy by nodule diameter (n=number of nodules)
Technical success by nodule diameter
Initial nodule diameter ≤10 ml (n=58) | Initial nodule diameter 10–30 ml (n=85) | Initial nodule diameter ≥30 ml (n=37) | |
Mean duration of ablation (min) | 14.9±6.5 | 15.3±9.0 | 15.8±9.5 |
Technical success | 96.6% (56/58) | 97.6% (83/85) | 100% (37/37) |
Total energy (kJ) | 20.2±9.0 | 21.5±14.5 | 17.4±9.5 |
Median nodule volume by initial nodule diameter (n=number of nodules)
Follow up | Median nodule volume (ml) for nodules with initial diameter ≤10 ml (n=58) | Median nodule volume (ml) for nodules with initial diameter 10–30 ml (n=85) | Median nodule volume (ml) for nodules with initial diameter ≥30 ml (n=37) |
Baseline | 11.5±4.7 | 15.1±8.5 | 22.8±8.2 |
1 month | 7.5±1.9* | 11.4±8.1* | 27.9±13.1* |
3 months | 4.5±1.7*# | 6.7±5.6*# | 14.8±10.9*# |
6 months | 3.0±1.6*#♦ | 4.1±3.8*#♦ | 10.1±12.4*#♦ |
12 months | 1.2±1.1*#♦^ | 2.5±3.0*#♦^ | 5.6±6.3*#♦^ |
* = p < 0.001 versus baseline values respectively,
# = p < 0.001 versus 1-month values respectively,
♦ = p < 0.001 versus 3-month values respectively,
^ = p < 0.05 versus 6-month values respectively.
Mean VRR % by initial nodule diameter (n=number of nodules)
Mean VRR % for nodules with initial diameter ≤10 ml (n=58) | Mean VRR % for nodules with initial diameter 10–30 ml (n=85) | Mean VRR % for nodules with initial diameter ≥30 ml (n=37) | |
1 month | 40.6±23.2 | 45.9±20.9 | 42.2±24.5 |
3 months | 61.1±20.8††† | 62.6±22.0††† | 58.8±32.9††† |
6 months | 74.6±19.1††† | 77.2±17.5††† | 74.0±32.9††† |
12 months | 84.7±13.0††† | 85.7±15.3††† | 86.6±14.7††† |
††† = p < 0.001 versus VRR(%) at 1-month follow up after ablation, respectively
Solid nodules (n=87) | Predominantly solid nodules (n=74) | Predominantly cystic nodules (n=19) | |
Mean duration of ablation (min) | 14.8±7.7 | 15.2±8.5 | 10.7±7.4 |
Technical success | 96.6% (84/87) | 98.6% (73/74) | 100% (19/19) |
Total energy (kJ) | 20.2±11.4 | 20.5±12.9 | 14.2±12.5 |
Median nodule volume by nodule composition (n=number of nodules)
Follow up | Median nodule volume (ml), solid nodules (n=87) | Median nodule volume (ml), predominantly solid nodules (n=74) | Median nodule volume (ml), predominantly cystic nodules (n=19) |
Baseline | 17.3±15.2 | 24.4±20.5 | 26.5±2.4 |
1 month | 9.7±7.9* | 11.8±10.7* | 9.7±9.6* |
3 months | 5.8±5.0*# | 6.8±5.5*# | 5.5±5.3*# |
6 months | 3.6±2.6*#♦ | 4.4±3.3*#♦ | 3.7±4.6*#♦ |
12 months | 2.2±2.1*#♦^ | 2.5±3.1*#♦^ | 2.8±3.9*#♦^ |
* = p < 0.001 versus baseline values respectively,
# = p < 0.001 versus 1-month values respectively,
♦ = p < 0.001 versus 3-month values respectively,
^ = p < 0.05 versus 6-month values respectively.
Mean VRR % by nodule composition (n=number of nodules)
Mean VRR %, solid nodules (n=87) | Mean VRR %, predominantly solid nodules (n=74) | Mean VRR %, predominantly cystic nodules (n=19) | |
|---|---|---|---|
1 month | 31.1±26.9 | 38.5±31.8 | 35.0±34.3 |
3 months | 56.4±22.2††† | 65.2±22.6††† | 73.3±17.3††† |
6 months | 72.6±19.6††† | 78.3±20.6††† | 83.9±10.8††† |
12 months | 83.3±15.8††† | 87.4±13.5††† | 88.9±10.1††† |
††† = p < 0.001 versus VRR(%) at 1-month follow up after ablation, respectively
Key safety findings
Rate of complications
Number (%) | Comments | |
Nodule rupture | 3/171 (1.7%) | Symptoms improved within 1–2 weeks after treatment with nonsteroidal anti-inflammatory drugs such as ibuprofen for 1 or 2 weeks. Lesions gradually regressed without further treatment |
Hoarseness | 4/171 | All patients recovered within 1 month |
Slight pain at the ablative site was also reported by most patients on the first day after MWA.
Study 7 Shi (2019)
Study type | Non-randomised comparative study |
Country | China |
Recruitment period | 2015-2018 |
Study population and number | n=318 patients with 328 treated benign thyroid nodules; 320 matched nodules (n=160 nodules treated with MWA and n=160 nodules treated with laser ablation (LA)) |
Age and sex | MWA: Mean age 42.9±17.7 years, 70.6% female LA: Mean age 44.5±21.4 years, 75.0% female |
Patient selection criteria | Inclusion criteria: Patients with nodules >50% solid and benign, confirmed by cytologic examination or histopathological biopsy; neck symptoms, cosmetic problems, or refused surgery or clinical observations, requirement for minimally invasive interventional therapy with absolute informed consent; serum levels of thyrotropin and thyroid hormone within normal limits. Exclusion criteria: Medication or additional treatment for thyroid nodules; incomplete data; follow up shorter than 6 months. |
Technique | MWA was done with a KY-2000 2450 MHz microwave system (KY-2000, Kangyou Medical, Nanjing, China), equipped with a 16-gauge, Teflon-coated, internal-cooled microwave antenna with a 3-mm active tip and a 10-cm shaft. The power output was 30W. LA was done with an ultrasonic laser integrated system produced by Italian Esaote Medical, and Echolaser X4 laser treatment system. The device comprised a 1,064-µm diode laser unit with a maximum of 4 laser sources, each with an individual energy emission setting and independent activation, 0.3-mm optic fibre, 21-gauge Chiba needle, and a foot pedal. Power output used was 3W. Patients were positioned supine with the neck fully exposed. The target nodule location and its adjacent structures were evaluated under ultrasound and the puncture route was pre-designed. All procedures were done under aseptic conditions and local anaesthesia with 1% lidocaine. When the nodule was located at the upper or lower pole of the thyroid or adjacent to important structures such as the vagus nerve, trachea, or oesophagus, hydrodissection was chosen to prevent accidental injury. |
Follow up | MWA: 14.3±6.5 months LA: 14.1±6.2 months |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Volume of the ablated nodules, symptom scores, cosmetic score and thyroid function were all measured 3, 6, and 12 months during the first year of follow up, and every 6 months thereafter.
Study design issues: This retrospective, non-randomised comparative study aimed to examine efficacy and safety of percutaneous ultrasound-guided microwave and laser ablation. Prior to ablation, the nodules were classified as either large or small (nodular volume ≥13 or <13 ml, respectively).
1:1 propensity score matching was done to balance baseline characteristics of the MWA and LA groups.
After the 1:1 match, qualitative variables were analysed using the chi-squared test or Fisher's exact test. Quantitative variables were analysed by Student's t-test. A p value of <0.05 was considered statistically significant.
The main efficacy outcomes were % VRR, symptom score reduction and cosmetic score reduction. Symptom scores ranged from 0 (none) to 10 (most severe) and were self-assessed based on pain or discomfort, foreign body sensation, and compression. The cosmetic scores were evaluated by an experienced physician and ranged from 1 to 4 as follows: 1, no palpable mass; 2, palpable mass but no cosmetic problems; 3, cosmetic problem on swallowing only or detected by an experienced physician; and 4, a readily detected cosmetic problem.
Complications associated with the MWA and LA ablations were in accordance with the report standard of the Society of Interventional Radiology. Major complications were considered voice changes, sympathetic nerve injury, and nodule rupture with or without infection. Minor complications included haemorrhage or hematoma, vomiting, skin burns, and thyroid function changes. Side effects included pain, coughing, and mild fever during the perioperative and follow-up periods.
Patient population issues: The baseline mean nodule volume was 12.7±5.1 ml in the MWA group and 13.1±4.7 ml in the LA group (p=0.466), the baseline symptom score was 5.8±2.5 in the MWA group and 6.0±1.9 in the LA group (p=0.421), and cosmetic score was 3.0±0.8 in the MWA group and 2.9±0.9 in the LA group (p=0.294). Baseline values by nodule size were not reported.
Key efficacy findings
Number of patients analysed = 320 (n=160 MWA, n=160 LA)
Nodule volume reduction (all nodules)
Follow up | % VRR for MWA (n=160) | % VRR for LA (n=160) | P value |
3 months | 54±40 | 56±28 | 0.605 |
6 months | 70±22 | 75±26 | 0.064 |
12 months | 75 ± 30 | 79±33 | 0.257 |
Last follow up | 83±32 | 88±25 | 0.120 |
Nodule volume reduction by nodule size (n=number of nodules)
Follow up | % VRR, MWA - large nodules (n=85) | % VRR, LA - large nodules (n=75) | P value | % VRR, MWA - small nodules (n=85) | % VRR, LA - small nodules (n=75) | P value |
3 months | 55±37 | 57±31 | 0.703 | 53 ±41 | 55±27 | 0.725 |
6 months | 68±24 | 77±31 | 0.036 | 72±21 | 73±26 | 0.796 |
12 months | 72±25 | 81±30 | 0.035 | 77±24 | 76±33 | 0.832 |
Last follow-up | 79±26 | 87±25 | 0.042 | 85 ± 25 | 89±28 | 0.358 |
Symptom and cosmetic score, all nodules (n=number of nodules)
Follow up | Symptom score for MWA (n=160) | Symptom score for LA (n=160) | Cosmetic score for MWA (n=160) | Cosmetic score for LA (n=160) |
3 months | 5.5±1.8 | 5.8±2.0 | 2.8±1.1 | 2.8±1.0 |
6 months | 4.6±2.2 | 4.7±2.1 | 2.2±0.9 | 2.3±1.1 |
12 months | 4.2±1.8 | 4.1±1.9 | 1.8±1.2 | 1.9±1.0 |
Last follow up | 3.5±1.6 | 3.6±1.9 | 1.5±0.8 | 1.6±0.7 |
Symptom score by nodule size (n=number of nodules)
Follow up | Symptom score, MWA - large nodules (n=85) | Symptom score, LA - large nodules (n=75) | Symptom score, MWA - small nodules (n=85) | Symptom score, LA - small nodules (n=75) |
3 months | 5.8±1.9 | 6.2±2.0 | 5.1±1.7 | 5.2±1.8 |
6 months | 5.0±2.2 | 5.2±1.9 | 4.4±2.0 | 4.3±2.3 |
12 months | 4.5±1.6 | 4.7±1.7 | 4.0±1.8 | 3.8±2.0 |
Last follow-up | 3.9±1.9 | 4.0±1.8 | 3.2±1.5 | 3.2±1.8 |
Cosmetic score by nodule size (n=number of nodules)
Follow up | Cosmetic score, MWA - large nodules (n=85) | Cosmetic score, LA - large nodules (n=75) | Cosmetic score, MWA - small nodules (n=85) | Cosmetic score, LA - small nodules (n=75) |
3 months | 3.0±0.8 | 3.0±1.0 | 2.5±1.2 | 2.6±1.1 |
6 months | 2.4±1.1 | 2.5±1.2 | 2.0±0.9 | 2.0±1.3 |
12 months | 2.0±1.3 | 2.2±0.9 | 1.7 ± 0.7 | 1.7±0.8 |
Last follow-up | 1.6±1.0 | 1.8±0.8 | 1.4±0.7 | 1.4±0.5 |
Key safety findings
Complications observed after MWA and LA – number of nodules (%)
MWA (n=160) | LA (n=160) | P value | |
Voice change | 2 (1.3) | 3 (1.88) | 0.937 |
Haematoma | 5 (3.1) | 2 (1.3) | 0.813 |
Pain | 20 (12.5) | 39 (24.4) | 0.135 |
Complications by nodule size
MWA, large nodules (n=85) | LA, large nodules (n=75) | P value, large nodules | MWA, small nodules (n=85) | LA, small nodules (n=75) | P value, small nodules | |
Voice change | 2 (2.4) | 1 | 0.914 | 0 | 2 | 0.818 |
Haematoma | 3 | 1 | 0.829 | 2 (2.4) | 1 | 0.908 |
Pain | 10 | 23 | 0.162 | 10 | 16 | 0.491 |
Study 8 Jin (2018)
Study type | Non-randomised comparative study |
Country | China |
Recruitment period | 2015-2017 |
Study population and number | n=212 patients with BTNs (n=106 treated with MWA and n=106 treated by conventional thyroidectomy) |
Age and sex | MWA: Mean age 39.6±9.3 years, 74% female Thyroidectomy: Mean age 45.4±11.2 years, 74% female |
Patient selection criteria | Inclusion criteria: Patients with nodules over 2 mm apart from the thyroid capsule; maximum diameter of the TN ≥ 2 cm; existence of cosmetic problems or compressive symptoms; cytological conformation of the benign nature of the nodule through US‑guided fine-needle aspiration cytology; serum levels of thyrotropine and thyroid hormone within normal levels. Exclusion criteria: Whole or a large part of the TN is located behind the sternum; abnormal function of the vocal cords on the opposite side of the TN; serious coagulation disorders; serious cardiopulmonary diseases; history of chemotherapy or radiotherapy. |
Technique | Patients were placed in a supine position with their necks fully exposed. MWA was done with a MTI-5DT microwave system (Changcheng Medical Instruments Cooperation, Nanjing, China). For conventional thyroidectomy, a 4–6 cm incision was made on the superior border of the sternum. The thyroid goitre was dissected with an ultrasound knife (Johnson & Johnson Inc., New Brunswick, NJ, USA). |
Follow up | MWA: Mean 12.8 ± 5.1 months Thyroidectomy: Mean 12.7 ± 2.8 months |
Conflict of interest/source of funding | None |
Analysis
Follow-up issues: Serum concentrations of thyrotropine, triiodothyronine, free thyroxine, thyroglobulin, IL-6, TNF-a and CRP were detected at 12 h after the operation. US assessments were done at 1, 3, 6 and 12 months after treatment.
Study design issues: This retrospective, non-randomised comparative study aimed to compare ultrasound (US)-guided percutaneous MWA and conventional thyroidectomy in benign thyroid nodules treatment.
280 patients were initially selected for study, and 106 pairs matched after 1:1 propensity score matching was done. After the 1:1 match, qualitative variables were analysed using the chi-squared test. One-way analysis of variance was used to compare the normal distribution quantitatively. A p value of < 0.05 was considered statistically significant.
The main efficacy outcomes were % VRR and nodule volume where TN volume = ¼ p*a*b*c/6 (where a is the largest diameter, b and c are the other 2 perpendicular diameters) and VRR(%) = ¼ [(baseline volume - final volume)*100]/baseline volume.
Patient population issues: The baseline median nodule volume was 5.7 ml (IQR 3.8-10.3) in the MWA group and 5.5 ml (IQR 3.5-9.6) in the thyroidectomy group (p=0.531). The baseline median nodule diameter was 28.6 mm (IQR 24.1–35.3) in the MWA group and 28.2 mm (IQR 23–35.9) in the thyroidectomy group (p=0.56).
Key efficacy findings
Number of patients analysed = 212 (n=106 MWA, n=106 thyroidectomy)
Nodule volume reduction for MWA group (n=106)
Volume cm3 | % VRR | |
Baseline | 2.50 (0.30–5.00) | - |
1 month | 2.12 (1.21–2.79) | 15.2±2.3 |
3 months | 1.31 (0.89–1.91) | 47.6±3.6% |
6 months | 0.82 (0.32–1.21) | 67.2±6.8% |
12 months | 0.51 (0.00–1.00) | 79.6±10.2% |
Key safety findings
Percentage incidence of complications
Incidence in MWA (n=106) | Thyroidectomy (n=106) | |
Vocal cord paralysis | 0.94% (1/106) | 6.6% (7/106) |
Skin burn | 0.94% (1/106) | 0 |
All patients recovered from complications within 3 months of their procedure.
Study 9 Fu (2021)
Study type | Case series |
Country | China |
Recruitment period | 2018-2020 |
Study population and number | n=115 patients with 115 BTNs |
Age and sex | Mean age 44.3±9.3 years for males (range 30-74), mean age 43.8±10.8 years for females (range 19-68 years), 85% female |
Patient selection criteria | Inclusion criteria: Patients with BTNs confirmed twice by cytological diagnosis; no suspicion of malignancy; compression symptoms, foreign body sensation or neck discomfort; patient request to undergo thermal ablation due to anxiety about condition; patients refusing traditional surgery or patients unable to undergo surgery. Exclusion criteria: Previous ablation of thyroid nodules; severe cardiac or pulmonary disease or coagulation dysfunction; severe adhesions between the nodules and oesophagus, trachea, and large blood vessels that could not be effectively separated; abnormally high calcitonin; incomplete medical follow up; unilateral multiple nodules |
Technique | Patients were placed in the supine position with hyper-extended neck. A 2450 MHz MWA system (KY-2000, Kangyou Medical, China) MWA system was used with a continuous output of 30W, and the procedure was done using the moving-shot technique. |
Follow up | 12 months |
Conflict of interest/source of funding | No conflict of interest reported. Funded by National Natural Science Foundation of China. |
Analysis
Follow-up issues: Ultrasonography was done 1, 3, 6, and 12 months after the procedure, and thyroid function was re-examined 1 month after the procedure.
Study design issues: This single-centre, retrospective study assessed safety and efficacy of MWA using ultrasound guidance for BTNs and examined factors linked to efficacy.
The primary efficacy outcomes measured were nodule volume and % VRR, and the primary safety outcome measured was the rate of complications. "Cured" patients were defined as a VRR of >90% after 12-month follow up.
Study population issues: A total of 171 patients (with 247 nodules) were selected in this research, with 115 patients meeting the criteria. The baseline nodule volume in the cohort of 115 patients was 5.30±8.56 ml.
Key efficacy findings
Number of patients analysed: 115
Mean nodule volume in ml (±SD)* | Mean % VRR (±SD)* | |
Baseline | 5.30±8.56 | - |
1 month | 2.62±4.45 | 41.96±21.66 |
3 months | 1.48±2.42 | 68.64±18.85 |
6 months | 0.89±1.70 | 83.56±14.05 |
12 months | 0.58±1.32 | 91.43±10.35 |
*Both mean nodule volume and % VRR were statistically significant (p<0.05) at all time points.
Differences in thyroid function before and after treatment was not statistically significant (p > 0.05).
In a univariate analysis of parameters, there were statistically significant (p<0.05) differences in maximum BTN diameter, preoperative volume, echo, internal composition, blood flow distribution, enhancement mode, and immediate volume after ablation between cured (VRR >90%) and non-cured (VRR ≤90%) nodules. Multivariate logistic regression analysis showed that internal composition of the BTNs, enhancement mode, and the immediate volume after ablation were statistically significant in the determination of the ablation efficacy (p<0.05).
Key safety findings
Rate of complications
% incidence (no. of patients) | Comments on resolution | |
Neck pain | 9.56 (11/115) | Resolved within 5 days of procedure |
Hoarseness (short-term) | 2.61 (3/115) | Resolved within 1 day of procedure |
Hoarseness (long term) | 0.87 (1/115) | Resolved 3 months after procedure |
Haematoma | 3.48 (4/115) | Resolved 2-7 days after procedure |
Fever | 1.74 (2/115) | Resolved 3 days after procedure |
Skin burn | 0.87 (1/115) | - |
Oesophageal burn | 0.87 (1/115) | - |
Study 10 Zhao (2021)
Study type | Case series |
Country | China |
Recruitment period | 2015-2017 |
Study population and number | n=53 patients with BTNs |
Age and sex | Mean age 49±12 years, 75% female |
Patient selection criteria | Inclusion criteria: Patients with a single BTN reporting pressure symptoms and/or cosmetic problems; largest diameter of solid nodule > 2 cm; confirmation of benignancy with repeated fine-needle aspiration (FNA) cytology; serum thyroid hormone and thyrotropin levels within normal ranges; single MWA treatment. Exclusion criteria: Substernal nodules or nodules that were difficult to monitor during the MWA procedure; serious coagulopathy; pregnancy; patients with incomplete imaging data or follow-up time <36 months. |
Technique | Patients were placed in a supine position with their necks fully exposed. MWA was done with a 2450 MHz MWA system (KY-2000, Kangyou Medical, China) MWA system was used with a continuous output of 30W, and the procedure was done using the mobile ablation method. |
Follow up | 3 years |
Conflict of interest/source of funding | No conflict of interest. Study funded by Capital's Funds for Health Improvement and Research |
Analysis
Follow-up issues: Postprocedural follow up was carried out at 1, 2, and 3 years after treatment. At each follow up, US examination, thyroid serum tests, and calculation of symptoms/cosmetics scores were carried out.
Study design issues: Case series with long-term follow up. The main efficacy outcomes were % VRR, symptom score reduction and cosmetic score reduction. Symptom scores ranged from 0 (none) to 10 (most severe) and were self-assessed based on pain or discomfort, foreign body sensation, and compression. The cosmetic scores were evaluated by an experienced physician and ranged from 1 to 4 as follows: 1, no palpable mass; 2, palpable mass but no cosmetic problems; 3, cosmetic problem on swallowing only or detected by an experienced physician; and 4, a readily detected cosmetic problem. Therapeutic success was defined as a reduction of more than 50% in nodule volume following ablation.
T-test (for normal distribution data) or Mann–Whitney U test (for skewed data) was used to compare numerical data, and chi-square analysis was used to compare categorical data. A p value <.05 was considered statistically significant
Patient population issues: The baseline mean nodule volume was 7.8±11.42 ml, the baseline symptom score was 4.93±2.16, and cosmetic score was 2.94±1.03.
Key efficacy findings
Number of patients analysed: 53
Reduction in nodule volume, symptom score and cosmetic score
Mean nodule volume in ml (±SD) | Mean % VRR (±SD) | Symptom score | Cosmetic score | |
Baseline | 7.8±11.42 ml (range 28‑75) | - | 4.93±2.16 | 2.94±1.03 |
1 year | 2.71±6.49 (range 0-35.1) | 72.15±22.01 (range 10-100) | 1.30±1.96* | 1.60±0.89* |
2 years | 1.56±4.04 range (22.9) | 83.40±21.07 (range 26-100) | 1.16±1.74 | 1.24±0.64 |
3 years | 1.49±4.00 (range 18.1) | 84.64±18.11 (range 30-100) | 0.85±1.52 | 0.99±1.01 |
*Both mean nodule volume and % VRR were statistically significant (p<0.05) at all time points.
Reduction in nodule volume by nodule size
Nodule size | <10 ml | 10-30 ml | >30 ml | P value |
VRR (%) | 71.03±16.35 | 72.19±19.79 | 72.86±4.27 | 0.967 |
Energy volume (J/ml) | 941.61 | 892.90 | 751.15 | 0.235 |
Key safety findings
Rate of complications
Side effect/complication | % incidence (no. of patients) |
Pain | 60.3 (32/53) |
Swelling | 49.1 (26/53) |
Hoarseness | 1.8 (1/53) |
Fever | 1.8 (1/53) |
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