Abstract
Purpose
This study aimed to compare the efficacy and safety of ultrasound-guided RFA and MWA in the treatment of unifocal PTMC.
Methods
This retrospective study included 512 patients with 512 unifocal papillary thyroid microcarcinomas (PTMCs) who underwent RFA (n = 346) and MWA (n = 166) between January 2021 and December 2021. The volumes of the ablation areas were measured during follow-up, and the volume reduction rates were evaluated. The ablation duration, volume of hydrodissection, and ablation-related complications were also compared between the groups.
Results
All lesions received complete ablation and no local or distant recurrences were observed in the two groups. A larger volume of isolation liquid was used for RFA than for MWA (p = 0.000). Hoarseness occurred in seven patients who underwent RFA (p = 0.102). At the 1-week follow-up, the mean volume of the areas ablated by RFA was smaller than that of the areas ablated by MWA (p = 0.049). During follow-ups at months 3, 9, 12, 15, and 18, the mean volumes of the ablated areas were larger in the RFA group than in the MWA group (all, p < 0.05). The mean volume of the ablated lesions increased slightly at the 1-week follow-up and then decreased at 1 month after ablation in both groups. The absorption curve of the ablated lesions in the RFA group was similar to that in the MWA group.
Conclusions
RFA and MWA are both efficient and safe methods for treating unifocal PTMC. They may be alternative techniques for patients who are not eligible or are unwilling to undergo surgery.
Introduction
Recently, with the rapid development of ultrasound imaging, the detection rate of thyroid nodules and the incidence of papillary thyroid microcarcinoma (PTMC) have significantly increased [Citation1]. Currently, the treatment of PTMC involves several approaches. Surgical interventions such as thyroidectomy or lobectomy are traditional treatment options for patients with PTMC. However, because of the indolent nature of PTMC and its excellent prognosis, there has been a growing trend toward minimally invasive techniques, such as ultrasound-guided thermal ablation, for its treatment [Citation2, Citation3].
There are several types of thermal ablation based on different energy sources [Citation4]. Radiofrequency ablation (RFA) is the most common and widely used thermal ablation technique. It involves the introduction of a high-frequency alternating current through an electrode, generating high temperatures that cause coagulative necrosis of the target tissue and destroy the tumor. Another ablation technique, microwave ablation (MWA), uses microwave energy to generate high temperatures, leading to coagulative necrosis of cells and destruction of tumor tissue. Both RFA and MWA offer the advantages of minimal invasiveness and reduced recovery time in patients with small low-risk PTMCs. Ongoing research and clinical studies continue to refine ablation strategies for papillary microcarcinomas of the thyroid, with a focus on optimizing patient outcomes and quality of life. Even though several literatures reported RFA or MWA treating PTMC, they included small volume of lesions or reported different ablation parameters with more complication rate. Therefore, this study aimed to compare the efficacy and safety of RFA and MWA for unifocal PTMC in a large volume of patients.
Materials and methods
Ethics statements
This study was approved by the ethics committee of Ruijin Hospital (protocol number: KY2017-125). Written informed consent was obtained from each patient before initiating the ablation procedure.
Study design and patients
Between January 2021 and December 2021, 585 patients with unifocal PTMC were treated with RFA and MWA by our team and screened for this retrospective study. All nodules were evaluated for suspected PTMC by ultrasound examination.
The inclusion criteria were as follows: 1) solitary PTMC cytologically diagnosed by fine-needle aspiration biopsy (FNAB) or highly suspected PTMC on ultrasonography (US), and 2) patients who were not eligible or were unwilling to undergo surgery. The exclusion criteria were as follows: 1) PTMC coexisting with other types of thyroid malignancies, 2) nodules located in the isthmus, 3) lymph node metastasis in the neck or distant metastasis detected by US or other imaging modalities, and 4) incomplete patient information and ultrasonographic or histological data.
In total, 512 nodules were included in our study (). Preoperative examinations were performed before the patients underwent ablation.
Figure 1. Research flowchart.
Preablation evaluations
Personal history was obtained from patients and recorded, and laboratory examinations, including thyroid function, liver/kidney function, and routine blood tests and virus indicator analysis, were performed. Preoperative imaging including electronic laryngoscopy and electrocardiography was performed. The ultrasonographic characteristics of the thyroid nodules were observed. The size, location, margin (regular/irregular), composition (solid/cystic), echogenicity (hypoechoic/hyperechoic), and presence of calcification (none/micro/macro/both) were recorded. Color Doppler US was also performed to analyze the blood supply (low/intermediate/high) of the nodules. The location of each nodule was described as the lower, middle, or upper pole. The distance between the thyroid nodule and the capsule was also measured. FNABs were obtained by two radiologists with more than 10 years of experience in thyroid US imaging. The nodule size was calculated using the equation V = pABC/6 (where V is the volume, A is the largest dimension, and B and C are the other two perpendicular dimensions).
Ablation procedure
Radiologists with more than 10 years of experience in interventional US performed MWA and RFA. The ablation procedure was performed using a 5–12-MHz linear array transducer with ultrasound equipment (Resona 9, Mindray, China). A multiparametric monitoring device was used to monitor the heart rate, blood pressure, and partial pressure of oxygen. Patients were placed in the supine position, and the anterior thyroid area was exposed and sterilized. Local anesthesia was administered using 2% lidocaine. Hydrodissection was performed with 0.9% normal saline to prevent injury to the trachea, large vessels, and laryngeal recurrent nerves. For RFA, an 18-gauge RF generator (STARmed, Seoul, Korea) with an active tip of 10 mm was percutaneously inserted into the lesion under ultrasound guidance. A power output of 65 W was used. For MWA, a small skin incision was made with the patient under local anesthesia. A 19-gauge cooled-shaft needle microwave antenna (MTC3; Weijing Medical, Nanjing, China) was percutaneously inserted into the lesion under ultrasound guidance. A power output of 30 W was used for the PTMC. All procedures were performed using the transisthmic approach with a fixed technique.
Ablation ceased when the gasification and hypoechoic areas covered and completely exceeded the edge of the lesion by at least 2 mm. Perfusion of the ablated area was assessed using contrast-enhanced ultrasonography (CEUS) to determine whether supplementary ablation was needed ( and ). During CEUS, a bolus of 2.4-ml microbubble contrast agent (Sonovue, Bracco, Milan, Italy) was injected through the dorsal vein, followed by injection of 5 ml of normal saline. The timer was started immediately and lasted for 2 min. The entire process was recorded and stored on the hard drive of the ultrasound instrument. At the end of the treatment, the needle tract was ablated, and the antenna was withdrawn from the outside of the thyroid envelope.
Figure 2. A case of RFA. (A) A 34-year-old female patient with a suspected lesion located in the right lobe of the thyroid, which was confirmed as PTMCs by FNAB; (B) After US-guided RFA, the ablated lesion was evaluated with CEUS;(C) In the 1st week follow up, the ablated lesion appeared as a well-defined heterogeneous echogenic area on the grayscale US; (D) On the final follow-up, the ablated area was almost completely absorbed.
Figure 3. A case of MWA. (A) A 37-year-old female patient with a suspected lesion located in the right lobe of the thyroid, which was confirmed as PTMCs by FNAB; (B) After US-guided MWA, the ablated lesion was evaluated with CEUS; (C) In the first week follow up, the ablated lesion appeared as a well-defined heterogeneous echogenic area on the grayscale US with a central hypoechoic ablated needle channel; (D) On the final follow-up, the ablated area was almost completely absorbed.
Postablation evaluations
All patients underwent thyroid ultrasound and thyroid function examinations (fT3, fT4, and thyroid stimulating hormone levels) at week 1 and months 1, 3, 9, 12, 15, 18 and 22 after ablation. Contrast-enhanced US was performed at each time point to verify the treatment effectiveness. Ablation effectiveness was defined as the absence of enhancement in any area of the original tumor. The volume of the ablated area was measured, and the volume reduction rate (VRR) was calculated as follows: =(V1h–Vfollow-up)/V1h (where V1h is the volume at 1 h after ablation, and Vfollow-up is the volume at each time point of follow-up). Fine-needle aspiration (FNA) was performed for imaging-suspected recurrence or lymph node metastasis (LNM). Computed tomography of the neck and chest was performed annually to monitor for distant metastases.
Study endpoints
Complete ablation, local or distant recurrence, LNM or distant metastasis, and death due to PTMC were the primary endpoints. Changes in the lesion volume and complication rates were the secondary endpoints. Complications were recorded according to standardized terminology and reporting criteria for image-guided thyroid ablation [Citation5].
Statistical analysis
Quantitative data are described as mean ± standard deviation and were compared using the independent samples t-test. Categorical data were compared the χ2 test or Fisher exact test. The statistical software SPSS, version 23.0 (IBM Corp., Armonk, NY, USA) was used to perform the data analysis. A P-value < 0.05 was considered to indicate statistical significance.
Results
Patients’ baseline characteristics
The characteristics of the enrolled patients are listed in , and their ultrasonographic characteristics are shown in . Among the 512 participants, 346 nodules received RFA (mean patient age, 37.32 ± 9.81 years, 283 females) and 166 nodules received MWA (mean patient age, 38.29 ± 9.93 years, 128 females). FNAB was not performed before ablation in 23 nodules, which all received RFA. The distribution of Bethesda categories differed between the two groups. The number of patients diagnosed as having Bethesda V/VI thyroid tumors was higher in the MWA group than in the RFA group. There were no differences between the groups in terms of sex, age, gene mutation, coexisting thyroid disease, or history of subtotal thyroidectomy/lobectomy.
Table 1. Baseline characteristics of the patients between the two groups.
Table 2. Ultrasonographic characteristics of the nodules between the two groups.
The nodule size was larger in the RFA group than in the MWA group. Compared with the MWA group, the RFA group had more nodules located in the upper and lower poles and immediately adjacent to the thyroid capsule. There were no significant differences between the two groups in composition, echogenicity, margin, size, presence of calcification, and blood supply.
Oncological outcomes
All lesions received complete ablation as evaluated by grayscale US and CEUS at 1 h after ablation and at each follow-up time point. No local or distant recurrences were observed in all these patients. The mean volume of the ablated areas was measured using US at each follow-up. At the 1-week follow-up, the mean volume of the areas ablated by RFA was slightly smaller than those ablated by MWA. During the follow-ups at months 3, 9, 12, 15, and 18, the mean volumes of the ablated areas were larger in the RFA group than in the MWA group, whereas during the first week of follow-up, they were lower in the RFA group than in the MWA group. The mean volume of the ablated lesions increased slightly at the 1-week follow-up and then decreased at 1 month after ablation in both groups (). There was a higher VRR in the MWA group at follow-up months 3, 6, and 9. The absorption curve of the ablated lesions in the RFA group coincided with that in the MWA group, which showed almost complete absorption at the end of follow-up (). At the end of follow-up, all ablated lesions completely disappeared or only scar strips remained ( and ). There were no statistically significant differences in volume or VRR at the end of the follow-up period.
Figure 4. The diagram displayed the VRR at each follow-up after RA or MWA. “**” indicates P < 0.01, “*” indicates P < 0.05.
Table 3. Volumes of the ablated lesions between the two groups.
Treatment parameters and complications between the RFA and MWA groups
The ablation duration for RFA was longer than that for MWA in patients with PTMCs (p = 0.000). A larger volume of isolation liquid was used for RFA than for MWA (p = 0.000). Hoarseness occurred in seven patients who underwent RFA (p = 0.102) (). No ablation-related complications were observed in either group. All patients experiencing hoarseness recovered within 3 months after undergoing ablation.
Table 4. Treatment parameters and complications in the two groups.
Discussion
In recent years, thermal ablation has become increasingly popular for the treatment of PTMC.
Studies have confirmed that thermal ablation is a safe and feasible method for treating PTMC with the advantages of reduced trauma, shorter hospitalization time, and better quality of life. According to the 2020 guidelines of the Chinese Medical Doctor Association [Citation6] and the 2021 guidelines of the European Thyroid Association and Cardiovascular and Interventional Radiological Society [Citation7], thermal ablation is recommended for the treatment of unifocal PTMC. Liang et al. reported that MWA is feasible for the treatment of PTMC with ultrasound-detected capsular invasion [Citation8]. Additionally, Zhang et al. showed that percutaneous laser ablation (PLA) is a safe and effective technique for treating PTMC [Citation9]. A previous meta-analysis suggested that RFA is a safe and efficient method for the treatment of low-risk PTMCs [Citation10]. However, limited data has compared the effects and treatment responses to different thermal ablations on PTMCs. Our study showed similar complication rates and postoperative recovery times between RFA and MWA for the treatment of unifocal PTMC.
RFA and MWA techniques involve inducing coagulative necrosis in tissues under high-temperature conditions, leading to the metabolic breakdown of the necrotic area. This serves to reduce the volume of nodules and clear tumor cells [Citation11, Citation12]. RFA involves destruction of the target tissue through a combination of heat and convective heat. It uses an oscillating high-frequency alternating current (200–1200 kHz) to rapidly vibrate and generate friction in the polar molecules of the RFA needle tip. This results in an increase in temperature and heat generation, causing cellular necrosis and achieving the purpose of extinguishing the tumor [Citation11, Citation13]. MWA relies on generating an electromagnetic field with wavelengths of 0.03–30 cm and frequencies of 900–2500 MHz. This induces oscillations in molecules such as water, creating friction, and subsequently increasing local temperatures. Unlike RFA, MWA does not require direct contact with conductive tissue, and its heat dissipation is not affected by coolants. Consequently, it can deliver more heat in a shorter period, making it useful for treating larger tumors. This might explain why the ablation duration was shorter in the MWA group than in the RFA group in our study, which was also consistent with a previous study’s finding [Citation14]. The ablation zone of MWA was larger than that of RFA, with less impact from the heat-sink effect, leading to a reduced treatment time. Although MWA is gaining popularity in applications involving organs such as the liver, lungs, and bones [Citation15–17], there may be certain drawbacks in its application for thyroid and central lymph node treatment, which may potentially lead to increased pain and a higher incidence of complications. Nevertheless, with the continuous advancement of medical equipment, many of these limitations can be optimized [Citation11, Citation18, Citation19].
Theoretically, MWA has a weaker heat-sink effect and is more powerful than RFA. Numerous scholars have conducted comparative studies on the efficacy of RFA and MWA; however, controversy remains. In Jin et al.’s study [Citation20], 289 pairs of patients with benign thyroid nodules were divided into RFA and MWA groups. The results revealed no significant differences between the two groups in terms of the operative time, intraoperative blood loss, duration of hospital stay, total cost, quality of life scores, complication rates, or volume reduction rate. Vorländer’s study [Citation21] revealed that both RFA and MWA methods were suitable for treating thyroid nodules, with no significant differences in the application time, energy delivery, and volume reduction. Another study compared the efficacy and safety of RFA and MWA for the treatment of benign thyroid nodules and demonstrated that the VRRs, therapeutic success rates, symptoms, cosmetic scores, and complications related to treatment for the two techniques are equivalent [Citation22]. In Cerit’s study [Citation23], 80 patients underwent either RFA or MWA for benign thyroid nodules, and follow-up after the procedure indicated the effectiveness of both methods. However, RFA demonstrated better nodule volume reduction than MWA. Peng et al. [Citation23] compared the efficacy and safety of ultrasound-guided MWA and RFA for benign thyroid nodules, and they concluded that for larger thyroid nodules, MWA exhibited superior treatment efficiency and effectiveness compared with RFA. For nodules located near the “danger triangle” region, RFA was safer than MWA. Another study by Guo et al. [Citation24] confirmed that both RFA and MWA are effective and safe methods for treating thyroid nodules. However, RFA demonstrated a greater reduction in nodule volume at 12 months than MWA, suggesting a potentially superior long-term effect in reducing the nodule volume. Our study showed a better VRR with RFA for treating unifocal PTMC at several follow-up points; however, the VRR curve of ablated lesions after RFA coincided with that of MWA.
The occurrence rates of complications, including hoarseness, hematoma, and skin burns, were low for the thermal ablation of PTMC. In a study by Hu et al. [Citation25], the hoarseness occurrence rates after MWA and RFA were 4% and 2.8%, respectively. Peng et al. [Citation23] reported that the occurrence rates of hoarseness after MWA and RFA were 12.35% and 6.35%, respectively. Korkusuz et al. [Citation26] suggested that radiofrequency ablation provides better control over heat, reducing the risk of damage to surrounding nerves and making it more suitable for thyroid nodules in critical areas. In our study, hoarseness occurred in seven (2.02%) patients in the RFA group, whereas no complications occurred in the MWA group. This may be due to selection bias in the two groups.
This study has several limitations. First, as aforementioned selection bias exists in this retrospective study. Second, the sample size of the MWA group was also small because of selection bias; thus, the data may not adequately represent the differences between the two groups in terms of complications and effects. Finally, the recurrence rate could not be evaluated because of the short follow-up period.
In conclusion, RFA and MWA are both efficient and safe methods for the interventional treatment of unifocal PTMC. They may be alternative techniques for patients who are not eligible or are unwilling to undergo surgery.
Data availability statement
There are ethical restrictions on sharing of de-identified data for this study. The ethics committee has not agreed to the public sharing of data as we do not have the participants’ permission to share their anonymous data
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Reference
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