Evaluation of radiofrequency ablation for papillary thyroid microcarcinoma with trachea-adjacent location versus trachea-distant location: a propensity score matching study

Evaluation of radiofrequency ablation for papillary thyroid microcarcinoma with trachea-adjacent location versus trachea-distant location: a propensity score matching study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of radiofrequency ablation for papillary thyroid microcarcinoma with trachea-adjacent location versus trachea-distant location: a propensity score matching study Haoyu Jing, Lin Yan, Jing Xiao, Xinyang Li, Bo Jiang, Zhen Yang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2937812/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare those with PTMC distant from the trachea. Methods This retrospective study reviewed patients who underwent RFA for solitary low-risk PTMC between June 2014 and July 2020. Patients were categorized into A group (PTMC adjacent to the trachea) (n = 211) and D group (PTMC distant from the trachea) (n = 790). The volume, volume reduction ratio (VRR), tumor disappearance, complication, and disease progression were assessed and compared between groups. Factors affecting disease progression were evaluated by Cox regression analysis. Results After a mean follow-up time of 30.0 ± 16.5 months, the overall VRR and tumor disappearance rate were 99.2 ± 4.6% and 87.5%, respectively. After propensity score matching, no significant differences were observed between the groups in the latest volume (0.8 ± 4.0 mm 3 vs 0.6 ± 3.5 mm 3 , p = 0.631), VRR (99.5 ± 2.3% vs 99.5 ± 2.8%, p = 0.638), and tumor disappearance rate (87.6% vs 88.0%, p = 0.845). In addition, no differences could be found between groups in the incidence of disease progression (2.9% vs 3.3%, p = 0.624) and complication (0.5% vs 0.5%, p = 1.000). Tracheal adjacency was not associated with disease progression (p = 0.671). Conclusion RFA is an effective and safe alternative approach for eligible patients with PTMC located adjacent to the trachea and PTMC distant from the trachea. Ablation techniques Radiofrequency ablation Papillary thyroid microcarcinoma Ultrasonography Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Thyroid carcinoma is the most common endocrine malignancy worldwide, responsible for more than 586,000 new cases in 2020 and ranking 9th in terms of incidence among all cancers (Sung et al. 2021 ). The global incidence of thyroid carcinoma has increased dramatically over the last few decades, whereas mortality due to this cancer has remained steady or even declined (Miranda-Filho et al. 2021 ; Pizzato et al. 2022 ; Li, Brito, and Vaccarella 2020 ). This unusual phenomenon has been attributed to the prevalence of papillary thyroid microcarcinoma (PTMC), which is defined as papillary thyroid carcinoma (PTC) with a maximal diameter (MD) of no more than 1.0 cm (Haugen et al. 2016 ). PTMC exhibits a favorable progression with a 10-year survival rate of over 99% (Tuttle, Haugen, and Perrier 2017 ; Haugen et al. 2016 ). A considerable proportion of thyroid cancer cases have been found in close proximity to the trachea, with no intervening thyroid tissue. Approximately 38.0% of PTCs and 26.0% of all thyroid cancers are detected as trachea-adjacent (Ito et al. 2016 ; Chung et al. 2020 ). Trachea-adjacent PTCs pose a risk for tracheal invasion, particularly when an obtuse angle is observed between the tumor and the trachea, which is associated with a higher risk of tracheal invasion (Chung et al. 2020 ). Immediate surgical intervention is necessary upon identification of tracheal invasion (Haugen et al. 2016 ). However, the optimal treatment strategy for PTCs abutting the trachea without clinical or imaging tracheal invasion is unclear. Thyroidectomy has conventionally been the primary treatment for PTMC (Haugen et al. 2016 ). Although surgery can effectively remove the primary tumor, it is associated with potential impacts on the quality of life (such as scarring, lifelong thyroid hormone replacement, and recurrent laryngeal nerve injury) (Nickel et al. 2019 ). Active surveillance (AS) is now considered an alternative management strategy by the American Thyroid Association guidelines for low-risk PTC (T1aN0M0) to avoid overtreatment (Haugen et al. 2016 ). The Japan Association of Endocrine Surgery recommends AS for low-risk PTMCs simply touching the trachea (Sugitani et al. 2021 ). However, patients who opt for AS may experience psychological anxiety about disease progression throughout the follow-up, and many ultimately select delayed surgical resection (Oh et al. 2018 ). Thermal ablation (TA) has been demonstrated as an effective, safe, and minimally invasive treatment modality for benign thyroid neoplasms and thyroid cancers (Choi and Jung 2020 ; Cesareo et al. 2022 ; Xue, Teng, and Wang 2022 ). Studies have shown favorable results for TA in treating PTC (Yan, Lan, et al. 2021 ; Xiao et al. 2021 ; Cho et al. 2020 ; Xue, Teng, and Wang 2022 ). Moreover, several studies have investigated the efficacy of ablation for PTCs with specific locations in the thyroid. For instance, Song et al. evaluated the efficacy of TA for PTMC located in the isthmus and found that TA had similar outcomes compared with total thyroidectomy (Song et al. 2020 ; Song et al. 2021 ). Another study by Zheng et al. provided information on the effectiveness of TA for PTMC touching the capsule (Zheng, Dou, Han, et al. 2023 ). To our knowledge, no studies have investigated the efficacy and safety of TA for PTC adjacent to the trachea. Therefore, the present study aimed to evaluate the efficacy and safety of TA for solitary PTMC adjacent to the trachea and compared the outcomes with PTMC distant from the trachea. Materials and methods Patients The Institutional Review Board of our institution approved this retrospective study. All the patients underwent radiofrequency ablation (RFA) at our institution (a tertiary academic center) and were provided written informed consent before treatments. Ablation is recommended for eligible patients who refuse surgery and AS, and a comprehensive discussion about the pros and cons was conducted before ablation. The inclusion criteria were: (1) core-needle biopsy or fine needle aspiration pathologically diagnosed PTC; (2) a unifocal tumor with a maximum diameter ≤ 10 mm; (3) no clinical or imaging evidence of gross extrathyroidal extension (ETE) (Tuttle, Haugen, and Perrier 2017 ), lymph node metastasis (LNM) and distant metastasis;(4) tumor adjacent to the trachea (no thyroid tissue between the thyroid cancer and the trachea on imaging) or tumor distant from the trachea (distance between tumor and the trachea ≥ 2 mm). The exclusion criteria were: (1) patients with evidence of aggressive PTC by biopsy; (2) history of neck irradiation (3) underwent RFA or Surgical Resection before; (4) obtuse angle between tumor and the trachea (Supplementary Fig. 1); (5) other malignant diseases; and (6) a follow-up time < 12 months. The patients were classified into two groups: the A group (A group) comprised patients with PTMC located adjacent to the trachea, while the D group (D group) consisted of patients with PTMCs located distant from the trachea. Supplement Fig. 1 . Angles between PTCs and the trachea. a, acute angle; b, almost right angle; c, obtuse angle Between June 2014 and July 2020, 1386 patients with PTMC underwent RFA at our institution. After the exclusion of patients with multiple PTMCs (n = 192), a distance between tumor and the trachea greater than 0mm and less than 2 mm (n = 113), surgical resection history (n = 9), obtuse angle between the tumor and the trachea (n = 4) and a follow-up time < 12 months (n = 67), finally, 211 patients were enrolled in A group and 790 patients were enrolled in D group (Fig. 1 ). Pre-RFA assessment Before treatment, all patients underwent thorough laboratory tests and imaging examinations. Laboratory tests included complete blood count, coagulation tests, and thyroid function. Ultrasound (US) and Contrast-enhance ultrasound (CEUS) (SonoVue, Bracco International) were executed to assess tumor size ( \(volume=\pi abc/6\) , a: transverse diameter; b: vertical diameter; c: anteroposterior diameter), location, relation to the capsule, tumor vascularity, and cervical lymph node. CEUS enhancement modes of tumors were divided into hypo-enhancement, iso-enhancement, and hyper-enhancement as compared to the thyroid parenchyma intensity at peak enhancements. CT was performed to detect tracheal invasion, LNM, and distant metastasis. When cervical lymph nodes were suspected, US-guided core-needle biopsy was carried out to determine their metastatic status. RFA Procedure Communication was performed prior to the treatment to reduce nervousness and promote cooperation. Patient’s posture and sterilization procedures were performed in compliance with previously published protocols (Yan, Lan, et al. 2021 ; Song et al. 2021 ). All procedures were carried out under local anesthesia, induced by the administration of 1% lidocaine, which was injected into both the subcutaneous puncture site and the anterior capsule of the thyroid. The ablation was executed using an 18-gauge bipolar RF applicator with a 0.9 cm active tip (CelonProSurge micro 100-T09, Olympus Surgical Technologies Europe) and was powered by a bipolar radiofrequency ablation generator (CelonLabPOWER, Olympus Surgical Technologies Europe). The ablation power was set at 4–9 W. Several techniques and methods were utilized to prevent thermal injury during the process (Fig. 2 ). Firstly, the moving-shot technique was employed by dividing the target tumor into multiple small ablation units, and ablating them one by one, starting from the deepest portion and moving towards the most superficial (J.H. Kim et al. 2018 ). In cases where tumors were located in close proximity to the trachea, ablation was initiated from the portion closest to the trachea. Secondly, the trans-isthmic approach was utilized by inserting the ablation needle into the target tumor in the lateral thyroid lobe via the isthmus moving from midline-to-lateral direction (J.H. Kim et al. 2018 ). Additionally, the hydrodissection technique was performed for tumors adjacent to the trachea or those within 5 mm from other critical neck structures (Yan, Zhang, et al. 2021 ). To achieve this, normal saline was injected using a 23-gauge needle to create a distance of ≥ 5 mm from critical structures. Furthermore, the leverage pry-off method was employed to elevate or depress the ablation needle using either the hands of the operator or the patient’s trachea as a fulcrum (Yang et al. 2019 ). Owing to the thinness of the capsule between the tumor and the trachea, the capsule was ablated together during the ablation (Song et al. 2020 ). CEUS was performed following RFA to evaluate the ablation effect. Additional ablation was performed if any enhancement was seen on CEUS. Follow-up Following the ablation, all patients underwent follow-ups at 1, 3, 6, and 12 months after ablation and every 6–12 months after that. At each follow-up, US, CEUS, and laboratory tests were performed. Figure 3 depicts a typical case of RFA treatment for PTMC adjacent to the trachea and after-RFA follow-up. Unless the ablation zone disappeared, core-needle biopsy was performed to assess the efficacy of the ablation 3 or 6 months following the procedure. If residual cancer, new thyroid cancer, or LNM was suspected, a biopsy was also carried out. CT was performed annually. PET or bone scans were performed if distant metastases were noticed. Evaluation criteria Technical success was defined as the complete non-enhancement in the target tumor at CEUS at the end of ablation. Evaluation of technique efficacy consisted of volume, the volume reduction rate (VRR, calculated as \(VRR=[\text{i}\text{n}\text{i}\text{t}\text{i}\text{a}\text{l} \text{v}\text{o}\text{l}\text{u}\text{m}\text{e} - \text{f}\text{i}\text{n}\text{a}\text{l} \text{v}\text{o}\text{l}\text{u}\text{m}\text{e}]\times 100/\text{i}\text{n}\text{i}\text{t}\text{i}\text{a}\text{l} \text{v}\text{o}\text{l}\text{u}\text{m}\text{e}\) ), tumor disappearance rate, and disease progression. Tumor disappearance was defined as the ablation area of PTC completely disappeared on US or the ablation area remained scar-like on US, but there was non-enhancement on CEUS. Disease progression was defined as (1) persistently detected lesion at the ablation zone confirmed by biopsy; (2) new malignant thyroid tumor confirmed pathologically; (3) pathologically confirmed LNM; (4) distant metastasis detected by imaging; and (5) death due to PTC. Complications were identified based on the standard for image-guided thyroid ablation (Mauri et al. 2019 ). Statistical Analysis Statistical analysis was performed using the SPSS statistical software version 25.0 and R software version 3.6.2 ( www.r-project.org ). A 1:1 propensity score matching (PSM) method was applied to reduce potential biases between groups. The matching factors included age, sex, MD, volume, the mode of CEUS, and follow-up time. Patients were matched using nearest neighbor matching with a caliper of 0.20 without replacement. Continuous variables were presented as mean ± SD and analyzed using Wilcoxon signed rank test or Mann-Whitney U test. Categorical variables were presented as numbers with percentages and compared using Chi-square or Fisher’s exact test. Progression-free survival curves and tumor disappearance rate curves were generated using the Kaplan-Meier method, and between-group differences were compared using the log-rank test. Cox proportional hazards regression model was used to identify the variables affecting the disease prognosis. Two-sided p-values < 0.05 were considered statistically significant. Results Demographic and Tumor Characteristics A total of 211 patients (163 females, 48 males; mean age: 43.0 years ± 10.2, range 23.0–72.0 years) were enrolled in A group and 790 patients (623 females, 167 males; mean age: 43.7 years ± 10.1, range 18.0–78.0 years) were enrolled in D group. The mean follow-up time was 30.0 ± 16.5 months (range, 12.0–96.4 months). The MD and volume in the A group were significantly larger than those in the D group before PSM was conducted (6.7 ± 2.0 mm vs. 6.1 ± 1.9 mm, 131.1 ± 105.4 mm 3 vs. 101.8 ± 92.7 mm 3 ; all p < 0.001). After 1:1 PSM, 418 patients (209 for each group) were ultimately included. Baseline characteristics between the two groups were comparable and showed no significant between-group difference (Table 1 ). Table 1 Baseline characteristics of patients before and after propensity score matching Parameter Before PSM After PSM A group (n = 211) D group (n = 790) p value A group (n = 209) D group (n = 209) p value Age (years) 43.0 ± 10.2 43.7 ± 10.1 0.205 43.1 ± 10.1 42.3 ± 10.5 0.556 Sex 0.613 0.111 Female 163(77.3) 623(78.9) 161(77.0) 174(83.3) Male 48(22.7) 167(21.1) 48(23.0) 35(16.7) MD (mm) 6.7 ± 2.0 6.1 ± 1.9 < 0.001 6.7 ± 2.0 6.7 ± 2.0 0.870 Volume(mm 3 ) 131.1 ± 105.4 101.8 ± 92.7 < 0.001 130.4 ± 105.6 127.5 ± 106.4 0.631 Follow-up time(months) 28.8 ± 14.9 30.3 ± 16.9 0.251 28.89 ± 14.94 30.2 ± 15.07 0.362 CEUS 0.377 0.381 Hypo-enhancement 198(93.8) 727(92.0) 196(93.8) 200(95.7) Iso-/hyper-enhancement 13(6.2) 63(8.0) 13(6.2) 9(4.3) Note: Data are presented as mean ± SD or number (percentages); CEUS, contrast-enhanced ultrasound; MD, maximal diameter; PSM, propensity score matching. 1. Changes in tumor characteristics All target tumors showed complete non-enhancement at CEUS after RFA, and the technical success rate was 100%. The overall volume and VRR were 0.9 ± 4.8 mm 3 and 99.2 ± 4.6% at the last follow-up. Table 2 presents the mean volume at each follow-up point. After PSM, the volume in the D group was greater than that in the A group after RFA (p 0.05). The mean VRR in the A group was higher than that in the D group at 1-month and 6-month follow-ups (all p 0.05). In the most recent follow-up, the mean VRR in the A group was 99.5 ± 2.3% (range 80.3–100.0%), and in the D group, it was 99.5 ± 2.8% (range 77.1–100%), without a difference between the two groups (p = 0.638). Table 2 Changes in volume of PTMCs in A and D groups at each follow-up point Time Before PSM After PSM Total A group (n = 211) D group (n = 790) p value A group (n = 209) D group (n = 209) p value Baseline 108.0 ± 96.2 131.1 ± 105.4 101.8 ± 92.7 < 0.001 130.4 ± 105.6 127.5 ± 106.4 0.572 1 month 439.2 ± 1973.6 * 341.0 ± 319.6 * 464.4 ± 2205.7 * 0.942 336.6 ± 314.2 * 431.4 ± 437.6 * 0.067 3 months 141.8 ± 222.0 138.3 ± 170.0 142.8 ± 233.7 0.074 136.7 ± 169.5 177.3 ± 277.2 0.902 6 months 52.1 ± 109.4 * 40.7 ± 66.4 * 55.2 ± 118.0 * 0.883 39.4 ± 65.4 * 78.7 ± 164.5 * 0.157 12 months 16.9 ± 52.6 * 17.2 ± 56.3 * 16.8 ± 51.6 * 0.947 24.2 ± 117.1 * 22.0 ± 69.7 * 0.436 24 months 5.1 ± 22.3 * 5.0 ± 16.7 * 5.1 ± 23.5 * 0.998 5.0 ± 16.7 * 5.0 ± 30.3 * 0.913 36 months 0.9 ± 4.8 * 0.8 ± 4.0 * 0.9 ± 4.9 * 0.807 0.8 ± 4.0 * 0.6 ± 3.5 * 0.631 Notes: Data are presented as mean ± SD; * , statistically significant difference (P value < 0.05 versus baseline); PSM, propensity score matching. Table 3 Changes in volume reduction ratio of PTMCs in A and D groups at each follow-up point Time Before PSM After PSM Total A group (n = 211) D group (n = 790) p value A group (n = 209) D group (n = 209) p value 1 month -487.4 ± 2174.7 -298.7 ± 573.2 -535.7 ± 2418.2 < 0.001 -299.5 ± 576.0 -423.4 ± 697.6 0.004 3 months -71.2 ± 302.4 -38.3 ± 202.9 -79.8 ± 322.7 0.179 -38.3 ± 204.1 -66.9 ± 233.2 0.257 6 months 36.5 ± 170.2 62.1 ± 72.6 29.8 ± 187.2 0.028 62.5 ± 72.9 40.1 ± 94.0 0.033 12 months 82.7 ± 59.7 83.3 ± 58.6 82.5 ± 60.1 0.922 73.1 ± 152.4 83.6 ± 44.1 0.512 24 months 94.6 ± 25.0 95.6 ± 16.2 94.4 ± 26.8 0.972 95.6 ± 16.2 96.6 ± 19.6 0.889 36 months 99.2 ± 4.6 99.5 ± 2.3 99.1 ± 5.0 0.805 99.5 ± 2.3 99.5 ± 2.8 0.638 Notes: Data are presented as mean ± SD. PSM: propensity score matching At the last follow-up, 876 (87.5%) tumors completely disappeared on CEUS before PSM. After PSM, 87.8% (367/418) tumors completely disappeared, among which 87.6% tumors (183/209) were in the A group, and 88.0% tumors (184/209) were in the D group. From the Kaplan-Meier curves in Fig. 4 , it can be seen that the tumor disappearance rate between A and D groups was not significantly different (p = 0.845). 2. Disease progression Prior to PSM, the overall incidence of disease progression was 3.3% (33/1001), which included 2.3% (23/1001) new thyroid cancer, 0.5% (5/1001) residual cancer, and 0.5% (5/1001) LNM (Table 4 ). The mean time of disease progression was 30.3 ± 22.9 months. The disease progression rate in the A group was comparable to that in the D group (3.3% vs 3.3%, P = 0.700). Furthermore, there was no evidence of a difference between groups in the incidence of new thyroid cancer (2.4% vs. 2.3%, p = 0.815), LNM (0.5% vs. 0.5%, p = 0.972), and residual cancer (0.5% vs. 0.5%, p = 0.961). After PSM, the disease progression rate was 3.1% (13/418), and the mean time of disease progression was 26.9 ± 16.2 months. No significant difference between groups regarding disease progression was evident (2.9% vs. 3.3%; p = 0.624), which was similar to the results before PSM (Table 4 ). It also be found in Fig. 5 , the progression-free survival curves between the two groups were not significantly different before or after PSM. As shown in Table 4 , the results revealed no statistically significant difference between groups in the incidence of new thyroid cancer (2.4% vs. 2.4%; p = 0.815), residual cancer (0.5% vs. 0.5%; p = 0.999), or LNM (0 vs. 0.5%; p = 0.607). Furthermore, from the data in Table 5, it can be seen that tracheal adjacency was not independently associated with disease progression according to the multivariable Cox regression analysis before and after PSM (all p > 0.05). Table 4 Comparison of outcomes between A and D groups. Outcomes Before PSM After PSM A group (n = 211) D group (n = 790) HR (95%CI) p value A group (n = 209) D group (n = 209) HR (95%CI) p value Disease progression 7(3.3) 26(3.3) 1.2(0.5, 2.7) 0.700 6(2.9) 7(3.3) 1.3(0.4, 3.9) 0.624 Residual cancer 1(0.5) 4(0.5) 1.0(0.1, 8.5) 0.961 1(0.5) 1(0.5) 1.0(0.1, 15.9) 0.999 New cancer 5(2.4) 18(2.3) 1.3(0.5, 3.5) 0.609 5(2.4) 5(2.4) 1.2(0.3, 4.0) 0.815 Ipsilateral lobe 1(0.5) 7(0.8) 0.6(0.2, 1.9) 0.715 1(0.5) 2(1.0) 1.5(0.2, 17.0) 0.732 Contralateral lobe 4(1.9) 11(1.3) 1.5(0.2, 12.0) 0.373 4(1.9) 3(1.4) 0.7(0.2, 3.1) 0.618 LNM 1(0.5) 4(0.5) 1.0(0.1, 8.6) 0.972 0(0) 1(0.5) 68.3(0, 141707.6) 0.607 Ipsilateral neck 1(0.5) 4(0.5) 1.0(0.1, 8.6) 1.000 0(0) 1(0.5) 68.3(0, 141707.6) 0.607 Contralateral neck 0(0) 0(0) … … 0(0) 0(0) … … Notes: Data are presented as number (percentages); CI, confidence interval; HR: hazard ratio; LNM, lymph node metastasis; PSM, propensity score matching. Among the 33 patients who experienced disease progression, 4 underwent surgical resection, 5 selected AS, and 24 underwent additional RFA. For the patients who chose AS, the tumor sizes remained stable, and no signs of local progression were found. All patients who selected additional RFA or surgery were successfully treated without any disease progression. For patients who chose additional RFA, 62.5% of their lesions completely disappeared throughout the follow-up, and the remaining lesions had biopsy at 3–6 months after additional RFA with negative results. 3. Safety None of the patients experienced any life-threatening or permanent complications during or after RFA. One patient had hoarseness (recovered within 2 months), 3 patients experienced cough, and 1 patient experienced hematoma (relieved within a week) after RFA. The overall incidence of complication in the study was 0.5% (5/1001), including 0.9% (2/211) in the A group vs. 0.4% (3/790) in the D group (p = 0.285). After PSM, the incidence of complication in A and D group were 0.5% (1/209) and 0.5% (1/209), respectively (p = 1.000). Discussion Our study is the first to explore the effectiveness and safety of RFA as a treatment modality for PTMC located adjacent to the trachea. We have compared the clinical outcomes of PTMCs with trachea-adjacent location and trachea-distant location, respectively. Technical success in our study was 100%, and the complication rate was less than 1%. During a mean follow-up period of 30.0 ± 16.5 months, we found no significant differences in volume, VRR, tumor disappearance rate, or disease progression rate between PTMCs with trachea-adjacent location and trachea-distant location. The trachea-adjacent location was not associated with disease progression in univariate and multivariate Cox regression analyses. Our study has revealed the effectiveness and safety of RFA as a treatment modality for PTMC located adjacent to the trachea. Statements on the optimum management strategy for low-risk PTMC remain controversial. The currently available management strategies for low-risk PTMC include surgical resection, thermal ablation, and active surveillance, and each strategy has pros and cons (Chou et al. 2022 ; H.J. Kim, Cho, and Baek 2021 ; Sun et al. 2022 ). RFA, as a form of thermal ablation, is becoming an increasingly attractive option, especially for patients unsuitable for or reluctant to surgical resection and patients with great anxiety about AS (Choi and Jung 2020 ; Xue, Teng, and Wang 2022 ). Many studies investigating RFA for the treatment of PTC obtained promising outcomes(Yan et al. 2022 ; Zhang et al. 2020 ; Cho et al. 2020 ; Cao et al. 2021 ). In a recent meta-analysis, the VRR and tumor disappearance rate for PTMC at 12 months after RFA were 93.3% and 64%; the incidence of residual cancer, new thyroid cancer, and LNM after RFA were 0.3%, 2.5%, and 1.0%, respectively(Xue, Teng, and Wang 2022 ). In the current study, we explored a total of 1001 patients with solitary PTMC who underwent RFA with a follow-up time of 30.0 ± 16.5 months. The VRR, tumor disappearance rate, and disease progression rate for PTMC were respectively 99.0%, 87.5%, and 3.3%. These findings were in line with previous studies(Yan, Lan, et al. 2021 ; Wei et al. 2022 ; Xue, Teng, and Wang 2022 ; Cho et al. 2021 ), which further strengthens the argument that RFA could be an effective treatment option for low-risk PTMC. Some researchers have questioned the feasibility of RFA for PTMCs adjacent to the trachea, stating the possibility of minimal ETE and an elevated risk of disease progression in tumors touching the medial capsular surrounding the trachea. However, the eighth edition of the AJCC guideline has exclued minimal ETE from the T stage classification due to little evidence of its impact on disease-related mortality and persistence/recurrence prediction in PTC (Tam et al. 2018 ; Tuttle, Haugen, and Perrier 2017 ). A prior study by Song et al. assessed the effectiveness of RFA for PTMC in the isthmus and reported a 100% tumor disappearance rate, with 0% incidence of LNM and 0.8% residual cancer, suggesting that RFA is an effective treatment option for PTMC in the isthmus (Song et al. 2020 ). Following that, Song et al. compared the clinical outcomes of RFA with total thyroidectomy for PTMCs in the isthmus, revealing that RFA can match total thyroidectomy in terms of treatment efficacy (Song et al. 2021 ). More recently, a prospective study by Zheng et al. focused on ablation for PTC with sonographic minimal ETE. The study demonstrated that ablation is similarly effective as surgery for T1N0M0 PTC cases with sonographic minimal ETE (Zheng, Dou, Liu, et al. 2023 ). However, to date, no study has explored the outcomes of TA for PTMCs adjacent to the trachea. In this study, we compared the efficacy of RFA for PTMCs with trachea-adjacent and trachea-distant locations after controlling for confounding factors using PSM. The tumor disappearance rate and VRR for PTMCs adjacent to the trachea were 87.6% and 99.5%, respectively, showing no significant differences from PTMCs distant from the trachea. Additionally, no significant differences could be observed in the incidence of new cancer, residual cancer, or LNM between PTMCs with trachea-adjacent and trachea-distant locations. The Kaplan-Meier analysis further revealed no significant differences in progression-free survival between PTMCs abutting the trachea and PTMCs distant from the trachea. We analyzed whether trachea-adjacent location was a risk factor affecting disease progression using univariable and multivariable analysis based on the Cox proportional hazards regression model, and no evidence was found to indicate that trachea-adjacent location influences disease progression. These results indicate that RFA is an effective treatment for ineligible patients with low-risk PTMC adjacent to the trachea. The overall incidence of complications in the study was found to be 0.5%, which was lower than previous reported rates (2.0–3.6%) (van Dijk et al. 2022 ; Choi and Jung 2020 ; Cho et al. 2021 ). There was no statistically significant difference in complication incidence between PTMC adjacent to the trachea and those distant from the trachea before and after PSM (p > 0.05). The common complication observed after surgery was permanent recurrent laryngeal nerve injury, with prior studies reporting an incidence ranging from 2.3–3% (Ferrari et al. 2016 ; Hayward et al. 2013 ). In contrast, in this study, no patient experienced any permanent complications after ablation, and only one patient experienced hoarseness, which resolved within two months. For patients with tumors located adjacent to the “danger triangle”, ablation was performed with caution and close monitoring of the patient’s condition during. A case reported by Morvan demonstrated tracheal necrosis after RFA for a benign thyroid nodule under general anesthesia (Morvan et al. 2022 ). However, at our institution, local anesthesia was routinely performed for thyroid tumor ablation to enable real-time patient feedback and facilitate necessary adjustments. Although the retrospective nature of this study could lead to an underestimation of the complication incidence, we identified several critical factors for reducing complications. Firstly, a comprehensive pre-ablation evaluation was paramount, involving the use of US, CEUS, and CT scans to assess tumor characteristics and determine the most appropriate ablation route. In addition, the combined use of multiple techniques and methods, including hydrodissection and leverage pry-off methods, was essential, particularly when dealing with tumors located adjacent to the trachea. The hydrodissection technique was implemented to increase the distance between the tumor margin and critical neck structures. The distance was further increased by the application of leverage pry-off method. With the application of moving-shot technique and the trans-isthmic approach, thermal injury to surrounding structures could be minimized. This study has several limitations. Firstly, it was a retrospective study conducted at a single center, which may have resulted in selection bias. Secondly, the incidence of complications may be underestimated due to the retrospective nature. Thirdly, the identification of aggressive pathologic subtypes of PTMC may not have been accurate as PTMCs were diagnosed by core-needle biopsy or fine needle aspiration. Furthermore, the study’s sample size and follow-up time were insufficient for such an indolent tumor. Finally, further large cohort prospective studies performed in multi-centers with longer follow-ups are needed. In conclusion, our results demonstrate that there was no difference in clinical outcomes between PTMC located adjacent to the trachea and those located distantly. RFA is an effective and safe alternative approach for managing eligible low-risk PTMC adjacent to the trachea. Declarations Acknowledgements The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Conflict of interest The authors have no relevant financial or non-financial interests to disclose. 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Angles between PTCs and the trachea. a, acute angle; b, almost right angle; c, obtuse angle Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2937812","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":200869405,"identity":"efe1e33e-f7b0-499c-8ac3-5ab319d4b048","order_by":0,"name":"Haoyu Jing","email":"","orcid":"","institution":"Chinese PLA Medical School","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Haoyu","middleName":"","lastName":"Jing","suffix":""},{"id":200869406,"identity":"2dc1f891-ff70-4363-ac34-aeed308f1b6d","order_by":1,"name":"Lin Yan","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Yan","suffix":""},{"id":200869407,"identity":"a2600483-25ac-494d-a44d-5ced59c0cc70","order_by":2,"name":"Jing Xiao","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Xiao","suffix":""},{"id":200869408,"identity":"89c2809a-0bfc-4c2f-9d09-c5e96f87a747","order_by":3,"name":"Xinyang Li","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xinyang","middleName":"","lastName":"Li","suffix":""},{"id":200869409,"identity":"5cc17e73-600c-4e3b-ae6a-ff4b34007365","order_by":4,"name":"Bo Jiang","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Jiang","suffix":""},{"id":200869410,"identity":"7cc2bcf6-8b03-4674-9efd-77999459d548","order_by":5,"name":"Zhen Yang","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Yang","suffix":""},{"id":200869411,"identity":"075ca719-89f8-4c90-83c6-2d9bc19edd35","order_by":6,"name":"Yingying Li","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yingying","middleName":"","lastName":"Li","suffix":""},{"id":200869412,"identity":"1fd0c42b-a6d2-4d4d-8b6d-d0828053e724","order_by":7,"name":"Mingbo Zhang","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mingbo","middleName":"","lastName":"Zhang","suffix":""},{"id":200869413,"identity":"603759bc-d8c5-4779-942a-df0ad8d4b8cf","order_by":8,"name":"Yukun Luo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArklEQVRIie3PsQoCMQyA4RyFukTraNGHCHQQ4dBXKQh1cfARCvcS9UVuzuGuD+ByIDj3dge5wT1ugv2nDPkIASiVfrAZaNV7qtGYKCQatKZ8CiubWE7ApnypKXopWQTvkG5IwFUejjLCD6Q7rlVU9tyKyCG6kWwiazWVkiXSFYm9mAS2ifgbgs9AmfZoU9fIfjGT4Hr/2u6Mabo8SAjM/WeqomR/PMPCxVKpVPrf3l66MjT8/3wKAAAAAElFTkSuQmCC","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yukun","middleName":"","lastName":"Luo","suffix":""}],"badges":[],"createdAt":"2023-05-15 13:16:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2937812/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2937812/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":37193915,"identity":"efdb15bc-2922-4326-bf87-c3375df69b7a","added_by":"auto","created_at":"2023-05-18 13:24:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":176636,"visible":true,"origin":"","legend":"\u003cp\u003eThe flowchart of patient enrollment\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-2937812/v1/007d3448c7277bcc5bda16e0.png"},{"id":37193920,"identity":"93705bb6-577e-44d8-aa85-46c98565615b","added_by":"auto","created_at":"2023-05-18 13:24:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":831533,"visible":true,"origin":"","legend":"\u003cp\u003eThe US images of the ablation procedure performed on a 31-year-old female with papillary thyroid carcinoma adjacent to the trachea. a, US image of the tumor (arrowheads) before ablation; b, The hydrodissection technique (arrows) was applied wherein normal saline was injected into the space between the tumor (arrowheads) and the trachea as well as space between the anterior thyroid capsule and superficial soft tissue; c, The ablation needle (arrows) was inserted into the target tumor via the isthmus moving from midline-to-lateral direction; the ablation was initiated from the deepest portion of the tumor and the portion closest to the trachea; during ablation, the tumor was elevated upward away from the trachea with the operator's finger serving as the fulcrum(utilizing the leverage pry-off method) to further increase the distance (double side arrow) between the tumor and the trachea; d, The ablation needle (arrows) was moved towards to the superficial portion of the tumor (arrowheads)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-2937812/v1/26c369be80bd730033fdfdc5.png"},{"id":37195015,"identity":"8de74ff6-1f3a-40aa-bd96-bf603da7843a","added_by":"auto","created_at":"2023-05-18 13:32:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1969026,"visible":true,"origin":"","legend":"\u003cp\u003eThe US and CEUS images obtained in a 64-year-old male with papillary thyroid carcinoma adjacent to the trachea in the right thyroid lobe. a, b Transverse and longitudinal planes of US images of the tumor (arrows) before RFA; c, d CEUS images showed non-enhancement in the ablation area (arrows) immediately after RFA; e, f CEUS images of the ablation area (arrows) at 1-month follow-up; g, h CEUS images of the ablation area (arrows) at 3-months follow-up; i, j The ablation area displayed scar-like non-enhancement (arrows) at 12-month follow-up; k, l The ablation area completely disappeared at the 18-month follow-up\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-2937812/v1/11aef88e236fb5ce473705aa.png"},{"id":37193918,"identity":"3039dc74-9434-4a22-82d9-750300398c03","added_by":"auto","created_at":"2023-05-18 13:24:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":183599,"visible":true,"origin":"","legend":"\u003cp\u003eGraph shows Kaplan-Meier curves for tumor disappearance rate between A and D groups after propensity score matching\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-2937812/v1/bc15f5119192981dd2b9157c.png"},{"id":37193916,"identity":"803d18d5-d2b3-486c-af13-199c960c2662","added_by":"auto","created_at":"2023-05-18 13:24:39","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":350830,"visible":true,"origin":"","legend":"\u003cp\u003eGraph shows Kaplan-Meier curves for progression-free survival between the A group and D group. a, Before propensity score matching; b, After propensity score matching\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-2937812/v1/e21e6afe2db1a7cb6794bd83.png"},{"id":37198689,"identity":"0bc7c4ac-6c59-417a-ac92-752e55d16c73","added_by":"auto","created_at":"2023-05-18 14:14:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3766440,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2937812/v1/2a6476fb-0eec-4817-9c5c-368c3ab2ada7.pdf"},{"id":37193919,"identity":"612fc9be-f3ae-41b0-ae63-84a12c4b127b","added_by":"auto","created_at":"2023-05-18 13:24:39","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2293132,"visible":true,"origin":"","legend":"\u003cp\u003eSupplement fig 1. Angles between PTCs and the trachea. a, acute angle; b, almost right angle; c, obtuse angle\u003c/p\u003e","description":"","filename":"Supplementaryfig1.tif","url":"https://assets-eu.researchsquare.com/files/rs-2937812/v1/97ce475c3916b930749a9a68.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of radiofrequency ablation for papillary thyroid microcarcinoma with trachea-adjacent location versus trachea-distant location: a propensity score matching study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThyroid carcinoma is the most common endocrine malignancy worldwide, responsible for more than 586,000 new cases in 2020 and ranking 9th in terms of incidence among all cancers (Sung et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The global incidence of thyroid carcinoma has increased dramatically over the last few decades, whereas mortality due to this cancer has remained steady or even declined (Miranda-Filho et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Pizzato et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Li, Brito, and Vaccarella \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). This unusual phenomenon has been attributed to the prevalence of papillary thyroid microcarcinoma (PTMC), which is defined as papillary thyroid carcinoma (PTC) with a maximal diameter (MD) of no more than 1.0 cm (Haugen et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). PTMC exhibits a favorable progression with a 10-year survival rate of over 99% (Tuttle, Haugen, and Perrier \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Haugen et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA considerable proportion of thyroid cancer cases have been found in close proximity to the trachea, with no intervening thyroid tissue. Approximately 38.0% of PTCs and 26.0% of all thyroid cancers are detected as trachea-adjacent (Ito et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Chung et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Trachea-adjacent PTCs pose a risk for tracheal invasion, particularly when an obtuse angle is observed between the tumor and the trachea, which is associated with a higher risk of tracheal invasion (Chung et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Immediate surgical intervention is necessary upon identification of tracheal invasion (Haugen et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). However, the optimal treatment strategy for PTCs abutting the trachea without clinical or imaging tracheal invasion is unclear. Thyroidectomy has conventionally been the primary treatment for PTMC (Haugen et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Although surgery can effectively remove the primary tumor, it is associated with potential impacts on the quality of life (such as scarring, lifelong thyroid hormone replacement, and recurrent laryngeal nerve injury) (Nickel et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Active surveillance (AS) is now considered an alternative management strategy by the American Thyroid Association guidelines for low-risk PTC (T1aN0M0) to avoid overtreatment (Haugen et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). The Japan Association of Endocrine Surgery recommends AS for low-risk PTMCs simply touching the trachea (Sugitani et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). However, patients who opt for AS may experience psychological anxiety about disease progression throughout the follow-up, and many ultimately select delayed surgical resection (Oh et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Thermal ablation (TA) has been demonstrated as an effective, safe, and minimally invasive treatment modality for benign thyroid neoplasms and thyroid cancers (Choi and Jung \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Cesareo et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Xue, Teng, and Wang \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Studies have shown favorable results for TA in treating PTC (Yan, Lan, et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Xiao et al. \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Cho et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Xue, Teng, and Wang \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Moreover, several studies have investigated the efficacy of ablation for PTCs with specific locations in the thyroid. For instance, Song et al. evaluated the efficacy of TA for PTMC located in the isthmus and found that TA had similar outcomes compared with total thyroidectomy (Song et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Song et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Another study by Zheng et al. provided information on the effectiveness of TA for PTMC touching the capsule (Zheng, Dou, Han, et al. \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). To our knowledge, no studies have investigated the efficacy and safety of TA for PTC adjacent to the trachea.\u003c/p\u003e \u003cp\u003eTherefore, the present study aimed to evaluate the efficacy and safety of TA for solitary PTMC adjacent to the trachea and compared the outcomes with PTMC distant from the trachea.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003e The Institutional Review Board of our institution approved this retrospective study. All the patients underwent radiofrequency ablation (RFA) at our institution (a tertiary academic center) and were provided written informed consent before treatments. Ablation is recommended for eligible patients who refuse surgery and AS, and a comprehensive discussion about the pros and cons was conducted before ablation.\u003c/p\u003e \u003cp\u003eThe inclusion criteria were: (1) core-needle biopsy or fine needle aspiration pathologically diagnosed PTC; (2) a unifocal tumor with a maximum diameter\u0026thinsp;\u0026le;\u0026thinsp;10 mm; (3) no clinical or imaging evidence of gross extrathyroidal extension (ETE) (Tuttle, Haugen, and Perrier \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), lymph node metastasis (LNM) and distant metastasis;(4) tumor adjacent to the trachea (no thyroid tissue between the thyroid cancer and the trachea on imaging) or tumor distant from the trachea (distance between tumor and the trachea\u0026thinsp;\u0026ge;\u0026thinsp;2 mm). The exclusion criteria were: (1) patients with evidence of aggressive PTC by biopsy; (2) history of neck irradiation (3) underwent RFA or Surgical Resection before; (4) obtuse angle between tumor and the trachea (Supplementary Fig.\u0026nbsp;1); (5) other malignant diseases; and (6) a follow-up time\u0026thinsp;\u0026lt;\u0026thinsp;12 months. The patients were classified into two groups: the A group (A group) comprised patients with PTMC located adjacent to the trachea, while the D group (D group) consisted of patients with PTMCs located distant from the trachea.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSupplement Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Angles between PTCs and the trachea. a, acute angle; b, almost right angle; c, obtuse angle\u003c/p\u003e \u003cp\u003eBetween June 2014 and July 2020, 1386 patients with PTMC underwent RFA at our institution. After the exclusion of patients with multiple PTMCs (n\u0026thinsp;=\u0026thinsp;192), a distance between tumor and the trachea greater than 0mm and less than 2 mm (n\u0026thinsp;=\u0026thinsp;113), surgical resection history (n\u0026thinsp;=\u0026thinsp;9), obtuse angle between the tumor and the trachea (n\u0026thinsp;=\u0026thinsp;4) and a follow-up time\u0026thinsp;\u0026lt;\u0026thinsp;12 months (n\u0026thinsp;=\u0026thinsp;67), finally, 211 patients were enrolled in A group and 790 patients were enrolled in D group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePre-RFA assessment\u003c/h3\u003e\n\u003cp\u003eBefore treatment, all patients underwent thorough laboratory tests and imaging examinations. Laboratory tests included complete blood count, coagulation tests, and thyroid function. Ultrasound (US) and Contrast-enhance ultrasound (CEUS) (SonoVue, Bracco International) were executed to assess tumor size (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(volume=\\pi abc/6\\)\u003c/span\u003e\u003c/span\u003e, a: transverse diameter; b: vertical diameter; c: anteroposterior diameter), location, relation to the capsule, tumor vascularity, and cervical lymph node. CEUS enhancement modes of tumors were divided into hypo-enhancement, iso-enhancement, and hyper-enhancement as compared to the thyroid parenchyma intensity at peak enhancements. CT was performed to detect tracheal invasion, LNM, and distant metastasis. When cervical lymph nodes were suspected, US-guided core-needle biopsy was carried out to determine their metastatic status.\u003c/p\u003e\n\u003ch3\u003eRFA Procedure\u003c/h3\u003e\n\u003cp\u003eCommunication was performed prior to the treatment to reduce nervousness and promote cooperation. Patient\u0026rsquo;s posture and sterilization procedures were performed in compliance with previously published protocols (Yan, Lan, et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Song et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). All procedures were carried out under local anesthesia, induced by the administration of 1% lidocaine, which was injected into both the subcutaneous puncture site and the anterior capsule of the thyroid. The ablation was executed using an 18-gauge bipolar RF applicator with a 0.9 cm active tip (CelonProSurge micro 100-T09, Olympus Surgical Technologies Europe) and was powered by a bipolar radiofrequency ablation generator (CelonLabPOWER, Olympus Surgical Technologies Europe). The ablation power was set at 4\u0026ndash;9 W. Several techniques and methods were utilized to prevent thermal injury during the process (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Firstly, the moving-shot technique was employed by dividing the target tumor into multiple small ablation units, and ablating them one by one, starting from the deepest portion and moving towards the most superficial (J.H. Kim et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). In cases where tumors were located in close proximity to the trachea, ablation was initiated from the portion closest to the trachea. Secondly, the trans-isthmic approach was utilized by inserting the ablation needle into the target tumor in the lateral thyroid lobe via the isthmus moving from midline-to-lateral direction (J.H. Kim et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Additionally, the hydrodissection technique was performed for tumors adjacent to the trachea or those within 5 mm from other critical neck structures (Yan, Zhang, et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). To achieve this, normal saline was injected using a 23-gauge needle to create a distance of \u0026ge;\u0026thinsp;5 mm from critical structures. Furthermore, the leverage pry-off method was employed to elevate or depress the ablation needle using either the hands of the operator or the patient\u0026rsquo;s trachea as a fulcrum (Yang et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Owing to the thinness of the capsule between the tumor and the trachea, the capsule was ablated together during the ablation (Song et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). CEUS was performed following RFA to evaluate the ablation effect. Additional ablation was performed if any enhancement was seen on CEUS.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003eFollowing the ablation, all patients underwent follow-ups at 1, 3, 6, and 12 months after ablation and every 6\u0026ndash;12 months after that. At each follow-up, US, CEUS, and laboratory tests were performed. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e depicts a typical case of RFA treatment for PTMC adjacent to the trachea and after-RFA follow-up. Unless the ablation zone disappeared, core-needle biopsy was performed to assess the efficacy of the ablation 3 or 6 months following the procedure. If residual cancer, new thyroid cancer, or LNM was suspected, a biopsy was also carried out. CT was performed annually. PET or bone scans were performed if distant metastases were noticed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eEvaluation criteria\u003c/h3\u003e\n\u003cp\u003eTechnical success was defined as the complete non-enhancement in the target tumor at CEUS at the end of ablation. Evaluation of technique efficacy consisted of volume, the volume reduction rate (VRR, calculated as \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(VRR=[\\text{i}\\text{n}\\text{i}\\text{t}\\text{i}\\text{a}\\text{l} \\text{v}\\text{o}\\text{l}\\text{u}\\text{m}\\text{e} - \\text{f}\\text{i}\\text{n}\\text{a}\\text{l} \\text{v}\\text{o}\\text{l}\\text{u}\\text{m}\\text{e}]\\times 100/\\text{i}\\text{n}\\text{i}\\text{t}\\text{i}\\text{a}\\text{l} \\text{v}\\text{o}\\text{l}\\text{u}\\text{m}\\text{e}\\)\u003c/span\u003e\u003c/span\u003e), tumor disappearance rate, and disease progression. Tumor disappearance was defined as the ablation area of PTC completely disappeared on US or the ablation area remained scar-like on US, but there was non-enhancement on CEUS. Disease progression was defined as (1) persistently detected lesion at the ablation zone confirmed by biopsy; (2) new malignant thyroid tumor confirmed pathologically; (3) pathologically confirmed LNM; (4) distant metastasis detected by imaging; and (5) death due to PTC. Complications were identified based on the standard for image-guided thyroid ablation (Mauri et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n \u003cp\u003eStatistical analysis was performed using the SPSS statistical software version 25.0 and R software version 3.6.2 (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.r-project.org\u003c/span\u003e\u003c/span\u003e). A 1:1 propensity score matching (PSM) method was applied to reduce potential biases between groups. The matching factors included age, sex, MD, volume, the mode of CEUS, and follow-up time. Patients were matched using nearest neighbor matching with a caliper of 0.20 without replacement. Continuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and analyzed using Wilcoxon signed rank test or Mann-Whitney U test. Categorical variables were presented as numbers with percentages and compared using Chi-square or Fisher\u0026rsquo;s exact test. Progression-free survival curves and tumor disappearance rate curves were generated using the Kaplan-Meier method, and between-group differences were compared using the log-rank test. Cox proportional hazards regression model was used to identify the variables affecting the disease prognosis. Two-sided p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Tumor Characteristics\u003c/h2\u003e \u003cp\u003eA total of 211 patients (163 females, 48 males; mean age: 43.0 years\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2, range 23.0\u0026ndash;72.0 years) were enrolled in A group and 790 patients (623 females, 167 males; mean age: 43.7 years\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1, range 18.0\u0026ndash;78.0 years) were enrolled in D group. The mean follow-up time was 30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5 months (range, 12.0\u0026ndash;96.4 months). The MD and volume in the A group were significantly larger than those in the D group before PSM was conducted (6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0 mm vs. 6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 mm, 131.1\u0026thinsp;\u0026plusmn;\u0026thinsp;105.4 mm\u003csup\u003e3\u003c/sup\u003e vs. 101.8\u0026thinsp;\u0026plusmn;\u0026thinsp;92.7 mm\u003csup\u003e3\u003c/sup\u003e; all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After 1:1 PSM, 418 patients (209 for each group) were ultimately included. Baseline characteristics between the two groups were comparable and showed no significant between-group difference (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of patients before and after propensity score matching\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;211)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;790)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eA group (n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e42.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.556\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.613\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e163(77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e623(78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e161(77.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e174(83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48(22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e167(21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48(23.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35(16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMD (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.870\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume(mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131.1\u0026thinsp;\u0026plusmn;\u0026thinsp;105.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101.8\u0026thinsp;\u0026plusmn;\u0026thinsp;92.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130.4\u0026thinsp;\u0026plusmn;\u0026thinsp;105.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e127.5\u0026thinsp;\u0026plusmn;\u0026thinsp;106.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.631\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up time(months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.3\u0026thinsp;\u0026plusmn;\u0026thinsp;16.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.89\u0026thinsp;\u0026plusmn;\u0026thinsp;14.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.362\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.381\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypo-enhancement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e198(93.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e727(92.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e196(93.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e200(95.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIso-/hyper-enhancement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63(8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9(4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eNote: Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or number (percentages);\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCEUS, contrast-enhanced ultrasound;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eMD, maximal diameter;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePSM, propensity score matching.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e1. Changes in tumor characteristics\u003c/h3\u003e\n\u003cp\u003eAll target tumors showed complete non-enhancement at CEUS after RFA, and the technical success rate was 100%. The overall volume and VRR were 0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 mm\u003csup\u003e3\u003c/sup\u003e and 99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6% at the last follow-up. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the mean volume at each follow-up point. After PSM, the volume in the D group was greater than that in the A group after RFA (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Except for the volume after RFA, there were no significant differences in the volume between the A and D groups in any of the follow-ups (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The mean VRR in the A group was higher than that in the D group at 1-month and 6-month follow-ups (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There was no difference in VRR between the two groups at other follow-up points (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the most recent follow-up, the mean VRR in the A group was 99.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3% (range 80.3\u0026ndash;100.0%), and in the D group, it was 99.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8% (range 77.1\u0026ndash;100%), without a difference between the two groups (p\u0026thinsp;=\u0026thinsp;0.638).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in volume of PTMCs in A and D groups at each follow-up point\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;211)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;790)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eA group (n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108.0\u0026thinsp;\u0026plusmn;\u0026thinsp;96.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e131.1\u0026thinsp;\u0026plusmn;\u0026thinsp;105.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.8\u0026thinsp;\u0026plusmn;\u0026thinsp;92.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e130.4\u0026thinsp;\u0026plusmn;\u0026thinsp;105.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e127.5\u0026thinsp;\u0026plusmn;\u0026thinsp;106.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.572\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e439.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1973.6\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e341.0\u0026thinsp;\u0026plusmn;\u0026thinsp;319.6\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e464.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2205.7\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.942\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e336.6\u0026thinsp;\u0026plusmn;\u0026thinsp;314.2\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e431.4\u0026thinsp;\u0026plusmn;\u0026thinsp;437.6\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141.8\u0026thinsp;\u0026plusmn;\u0026thinsp;222.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e138.3\u0026thinsp;\u0026plusmn;\u0026thinsp;170.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e142.8\u0026thinsp;\u0026plusmn;\u0026thinsp;233.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e136.7\u0026thinsp;\u0026plusmn;\u0026thinsp;169.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e177.3\u0026thinsp;\u0026plusmn;\u0026thinsp;277.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.1\u0026thinsp;\u0026plusmn;\u0026thinsp;109.4\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.7\u0026thinsp;\u0026plusmn;\u0026thinsp;66.4\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.2\u0026thinsp;\u0026plusmn;\u0026thinsp;118.0\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.883\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39.4\u0026thinsp;\u0026plusmn;\u0026thinsp;65.4\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e78.7\u0026thinsp;\u0026plusmn;\u0026thinsp;164.5\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.9\u0026thinsp;\u0026plusmn;\u0026thinsp;52.6\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.2\u0026thinsp;\u0026plusmn;\u0026thinsp;56.3\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.8\u0026thinsp;\u0026plusmn;\u0026thinsp;51.6\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.947\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.2\u0026thinsp;\u0026plusmn;\u0026thinsp;117.1\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22.0\u0026thinsp;\u0026plusmn;\u0026thinsp;69.7\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.436\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;22.3\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;23.5\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;30.3\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.913\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.807\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.631\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNotes: Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003csup\u003e*\u003c/sup\u003e, statistically significant difference (P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 versus baseline);\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePSM, propensity score matching.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in volume reduction ratio of PTMCs in A and D groups at each follow-up point\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;211)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;790)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eA group (n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-487.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2174.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-298.7\u0026thinsp;\u0026plusmn;\u0026thinsp;573.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-535.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2418.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-299.5\u0026thinsp;\u0026plusmn;\u0026thinsp;576.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-423.4\u0026thinsp;\u0026plusmn;\u0026thinsp;697.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-71.2\u0026thinsp;\u0026plusmn;\u0026thinsp;302.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-38.3\u0026thinsp;\u0026plusmn;\u0026thinsp;202.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-79.8\u0026thinsp;\u0026plusmn;\u0026thinsp;322.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-38.3\u0026thinsp;\u0026plusmn;\u0026thinsp;204.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-66.9\u0026thinsp;\u0026plusmn;\u0026thinsp;233.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.5\u0026thinsp;\u0026plusmn;\u0026thinsp;170.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.1\u0026thinsp;\u0026plusmn;\u0026thinsp;72.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.8\u0026thinsp;\u0026plusmn;\u0026thinsp;187.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62.5\u0026thinsp;\u0026plusmn;\u0026thinsp;72.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e40.1\u0026thinsp;\u0026plusmn;\u0026thinsp;94.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82.7\u0026thinsp;\u0026plusmn;\u0026thinsp;59.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.3\u0026thinsp;\u0026plusmn;\u0026thinsp;58.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82.5\u0026thinsp;\u0026plusmn;\u0026thinsp;60.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.922\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e73.1\u0026thinsp;\u0026plusmn;\u0026thinsp;152.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e83.6\u0026thinsp;\u0026plusmn;\u0026thinsp;44.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.512\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94.6\u0026thinsp;\u0026plusmn;\u0026thinsp;25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.6\u0026thinsp;\u0026plusmn;\u0026thinsp;16.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94.4\u0026thinsp;\u0026plusmn;\u0026thinsp;26.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95.6\u0026thinsp;\u0026plusmn;\u0026thinsp;16.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e96.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.889\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e99.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.805\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e99.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e99.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.638\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNotes: Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003ePSM: propensity score matching\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt the last follow-up, 876 (87.5%) tumors completely disappeared on CEUS before PSM. After PSM, 87.8% (367/418) tumors completely disappeared, among which 87.6% tumors (183/209) were in the A group, and 88.0% tumors (184/209) were in the D group. From the Kaplan-Meier curves in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, it can be seen that the tumor disappearance rate between A and D groups was not significantly different (p\u0026thinsp;=\u0026thinsp;0.845).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003e2. Disease progression\u003c/h3\u003e\n\u003cp\u003ePrior to PSM, the overall incidence of disease progression was 3.3% (33/1001), which included 2.3% (23/1001) new thyroid cancer, 0.5% (5/1001) residual cancer, and 0.5% (5/1001) LNM (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The mean time of disease progression was 30.3\u0026thinsp;\u0026plusmn;\u0026thinsp;22.9 months. The disease progression rate in the A group was comparable to that in the D group (3.3% vs 3.3%, P\u0026thinsp;=\u0026thinsp;0.700). Furthermore, there was no evidence of a difference between groups in the incidence of new thyroid cancer (2.4% vs. 2.3%, p\u0026thinsp;=\u0026thinsp;0.815), LNM (0.5% vs. 0.5%, p\u0026thinsp;=\u0026thinsp;0.972), and residual cancer (0.5% vs. 0.5%, p\u0026thinsp;=\u0026thinsp;0.961). After PSM, the disease progression rate was 3.1% (13/418), and the mean time of disease progression was 26.9\u0026thinsp;\u0026plusmn;\u0026thinsp;16.2 months. No significant difference between groups regarding disease progression was evident (2.9% vs. 3.3%; p\u0026thinsp;=\u0026thinsp;0.624), which was similar to the results before PSM (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). It also be found in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the progression-free survival curves between the two groups were not significantly different before or after PSM. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, the results revealed no statistically significant difference between groups in the incidence of new thyroid cancer (2.4% vs. 2.4%; p\u0026thinsp;=\u0026thinsp;0.815), residual cancer (0.5% vs. 0.5%; p\u0026thinsp;=\u0026thinsp;0.999), or LNM (0 vs. 0.5%; p\u0026thinsp;=\u0026thinsp;0.607). Furthermore, from the data in Table\u0026nbsp;5, it can be seen that tracheal adjacency was not independently associated with disease progression according to the multivariable Cox regression analysis before and after PSM (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of outcomes between A and D groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eBefore PSM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eAfter PSM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;211)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;790)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003cp\u003e(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eA group (n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eD group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003cp\u003e(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease progression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.2(0.5, 2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6(2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.3(0.4, 3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.624\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResidual cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0(0.1, 8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.0(0.1, 15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNew cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.3(0.5, 3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.2(0.3, 4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.815\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIpsilateral lobe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6(0.2, 1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2(1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.5(0.2, 17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.732\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eContralateral lobe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5(0.2, 12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4(1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.7(0.2, 3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.618\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLNM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0(0.1, 8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68.3(0, 141707.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIpsilateral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0(0.1, 8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68.3(0, 141707.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eContralateral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026hellip;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026hellip;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026hellip;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026hellip;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eNotes: Data are presented as number (percentages);\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eCI, confidence interval;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eHR: hazard ratio;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eLNM, lymph node metastasis;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePSM, propensity score matching.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong the 33 patients who experienced disease progression, 4 underwent surgical resection, 5 selected AS, and 24 underwent additional RFA. For the patients who chose AS, the tumor sizes remained stable, and no signs of local progression were found. All patients who selected additional RFA or surgery were successfully treated without any disease progression. For patients who chose additional RFA, 62.5% of their lesions completely disappeared throughout the follow-up, and the remaining lesions had biopsy at 3\u0026ndash;6 months after additional RFA with negative results.\u003c/p\u003e\n\u003ch3\u003e3. Safety\u003c/h3\u003e\n\u003cp\u003eNone of the patients experienced any life-threatening or permanent complications during or after RFA. One patient had hoarseness (recovered within 2 months), 3 patients experienced cough, and 1 patient experienced hematoma (relieved within a week) after RFA. The overall incidence of complication in the study was 0.5% (5/1001), including 0.9% (2/211) in the A group vs. 0.4% (3/790) in the D group (p\u0026thinsp;=\u0026thinsp;0.285). After PSM, the incidence of complication in A and D group were 0.5% (1/209) and 0.5% (1/209), respectively (p\u0026thinsp;=\u0026thinsp;1.000).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study is the first to explore the effectiveness and safety of RFA as a treatment modality for PTMC located adjacent to the trachea. We have compared the clinical outcomes of PTMCs with trachea-adjacent location and trachea-distant location, respectively. Technical success in our study was 100%, and the complication rate was less than 1%. During a mean follow-up period of 30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5 months, we found no significant differences in volume, VRR, tumor disappearance rate, or disease progression rate between PTMCs with trachea-adjacent location and trachea-distant location. The trachea-adjacent location was not associated with disease progression in univariate and multivariate Cox regression analyses. Our study has revealed the effectiveness and safety of RFA as a treatment modality for PTMC located adjacent to the trachea.\u003c/p\u003e \u003cp\u003eStatements on the optimum management strategy for low-risk PTMC remain controversial. The currently available management strategies for low-risk PTMC include surgical resection, thermal ablation, and active surveillance, and each strategy has pros and cons (Chou et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; H.J. Kim, Cho, and Baek \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Sun et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). RFA, as a form of thermal ablation, is becoming an increasingly attractive option, especially for patients unsuitable for or reluctant to surgical resection and patients with great anxiety about AS (Choi and Jung \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Xue, Teng, and Wang \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Many studies investigating RFA for the treatment of PTC obtained promising outcomes(Yan et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Zhang et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Cho et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Cao et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). In a recent meta-analysis, the VRR and tumor disappearance rate for PTMC at 12 months after RFA were 93.3% and 64%; the incidence of residual cancer, new thyroid cancer, and LNM after RFA were 0.3%, 2.5%, and 1.0%, respectively(Xue, Teng, and Wang \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). In the current study, we explored a total of 1001 patients with solitary PTMC who underwent RFA with a follow-up time of 30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5 months. The VRR, tumor disappearance rate, and disease progression rate for PTMC were respectively 99.0%, 87.5%, and 3.3%. These findings were in line with previous studies(Yan, Lan, et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Wei et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Xue, Teng, and Wang \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Cho et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2021\u003c/span\u003e), which further strengthens the argument that RFA could be an effective treatment option for low-risk PTMC.\u003c/p\u003e \u003cp\u003eSome researchers have questioned the feasibility of RFA for PTMCs adjacent to the trachea, stating the possibility of minimal ETE and an elevated risk of disease progression in tumors touching the medial capsular surrounding the trachea. However, the eighth edition of the AJCC guideline has exclued minimal ETE from the T stage classification due to little evidence of its impact on disease-related mortality and persistence/recurrence prediction in PTC (Tam et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Tuttle, Haugen, and Perrier \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). A prior study by Song et al. assessed the effectiveness of RFA for PTMC in the isthmus and reported a 100% tumor disappearance rate, with 0% incidence of LNM and 0.8% residual cancer, suggesting that RFA is an effective treatment option for PTMC in the isthmus (Song et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Following that, Song et al. compared the clinical outcomes of RFA with total thyroidectomy for PTMCs in the isthmus, revealing that RFA can match total thyroidectomy in terms of treatment efficacy (Song et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). More recently, a prospective study by Zheng et al. focused on ablation for PTC with sonographic minimal ETE. The study demonstrated that ablation is similarly effective as surgery for T1N0M0 PTC cases with sonographic minimal ETE (Zheng, Dou, Liu, et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). However, to date, no study has explored the outcomes of TA for PTMCs adjacent to the trachea. In this study, we compared the efficacy of RFA for PTMCs with trachea-adjacent and trachea-distant locations after controlling for confounding factors using PSM. The tumor disappearance rate and VRR for PTMCs adjacent to the trachea were 87.6% and 99.5%, respectively, showing no significant differences from PTMCs distant from the trachea. Additionally, no significant differences could be observed in the incidence of new cancer, residual cancer, or LNM between PTMCs with trachea-adjacent and trachea-distant locations. The Kaplan-Meier analysis further revealed no significant differences in progression-free survival between PTMCs abutting the trachea and PTMCs distant from the trachea. We analyzed whether trachea-adjacent location was a risk factor affecting disease progression using univariable and multivariable analysis based on the Cox proportional hazards regression model, and no evidence was found to indicate that trachea-adjacent location influences disease progression. These results indicate that RFA is an effective treatment for ineligible patients with low-risk PTMC adjacent to the trachea.\u003c/p\u003e \u003cp\u003eThe overall incidence of complications in the study was found to be 0.5%, which was lower than previous reported rates (2.0\u0026ndash;3.6%) (van Dijk et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Choi and Jung \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Cho et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). There was no statistically significant difference in complication incidence between PTMC adjacent to the trachea and those distant from the trachea before and after PSM (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The common complication observed after surgery was permanent recurrent laryngeal nerve injury, with prior studies reporting an incidence ranging from 2.3\u0026ndash;3% (Ferrari et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Hayward et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). In contrast, in this study, no patient experienced any permanent complications after ablation, and only one patient experienced hoarseness, which resolved within two months. For patients with tumors located adjacent to the \u0026ldquo;danger triangle\u0026rdquo;, ablation was performed with caution and close monitoring of the patient\u0026rsquo;s condition during. A case reported by Morvan demonstrated tracheal necrosis after RFA for a benign thyroid nodule under general anesthesia (Morvan et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). However, at our institution, local anesthesia was routinely performed for thyroid tumor ablation to enable real-time patient feedback and facilitate necessary adjustments. Although the retrospective nature of this study could lead to an underestimation of the complication incidence, we identified several critical factors for reducing complications. Firstly, a comprehensive pre-ablation evaluation was paramount, involving the use of US, CEUS, and CT scans to assess tumor characteristics and determine the most appropriate ablation route. In addition, the combined use of multiple techniques and methods, including hydrodissection and leverage pry-off methods, was essential, particularly when dealing with tumors located adjacent to the trachea. The hydrodissection technique was implemented to increase the distance between the tumor margin and critical neck structures. The distance was further increased by the application of leverage pry-off method. With the application of moving-shot technique and the trans-isthmic approach, thermal injury to surrounding structures could be minimized.\u003c/p\u003e \u003cp\u003eThis study has several limitations. Firstly, it was a retrospective study conducted at a single center, which may have resulted in selection bias. Secondly, the incidence of complications may be underestimated due to the retrospective nature. Thirdly, the identification of aggressive pathologic subtypes of PTMC may not have been accurate as PTMCs were diagnosed by core-needle biopsy or fine needle aspiration. Furthermore, the study\u0026rsquo;s sample size and follow-up time were insufficient for such an indolent tumor. Finally, further large cohort prospective studies performed in multi-centers with longer follow-ups are needed.\u003c/p\u003e \u003cp\u003eIn conclusion, our results demonstrate that there was no difference in clinical outcomes between PTMC located adjacent to the trachea and those located distantly. RFA is an effective and safe alternative approach for managing eligible low-risk PTMC adjacent to the trachea.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cem\u003eConflict of interest\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cem\u003eHuman and animal rights statement\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis article does not contain any studies with animals performed by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cem\u003eInformed consent\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCao, X. 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Liang. 2023. \u0026quot;Microwave ablation vs. surgery for papillary thyroid carcinoma with minimal sonographic extrathyroid extension: a multicentre prospective study.\u0026quot; \u003cem\u003eEur Radiol\u003c/em\u003e 33 (1): 233-243. https://doi.org/10.1007/s00330-022-08962-6. https://www.ncbi.nlm.nih.gov/pubmed/35771248.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ablation techniques, Radiofrequency ablation, Papillary thyroid microcarcinoma, Ultrasonography","lastPublishedDoi":"10.21203/rs.3.rs-2937812/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2937812/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare those with PTMC distant from the trachea.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study reviewed patients who underwent RFA for solitary low-risk PTMC between June 2014 and July 2020. Patients were categorized into A group (PTMC adjacent to the trachea) (n\u0026thinsp;=\u0026thinsp;211) and D group (PTMC distant from the trachea) (n\u0026thinsp;=\u0026thinsp;790). The volume, volume reduction ratio (VRR), tumor disappearance, complication, and disease progression were assessed and compared between groups. Factors affecting disease progression were evaluated by Cox regression analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter a mean follow-up time of 30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5 months, the overall VRR and tumor disappearance rate were 99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6% and 87.5%, respectively. After propensity score matching, no significant differences were observed between the groups in the latest volume (0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 mm\u003csup\u003e3\u003c/sup\u003e vs 0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5 mm\u003csup\u003e3\u003c/sup\u003e, p\u0026thinsp;=\u0026thinsp;0.631), VRR (99.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3% vs 99.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8%, p\u0026thinsp;=\u0026thinsp;0.638), and tumor disappearance rate (87.6% vs 88.0%, p\u0026thinsp;=\u0026thinsp;0.845). In addition, no differences could be found between groups in the incidence of disease progression (2.9% vs 3.3%, p\u0026thinsp;=\u0026thinsp;0.624) and complication (0.5% vs 0.5%, p\u0026thinsp;=\u0026thinsp;1.000). Tracheal adjacency was not associated with disease progression (p\u0026thinsp;=\u0026thinsp;0.671).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eRFA is an effective and safe alternative approach for eligible patients with PTMC located adjacent to the trachea and PTMC distant from the trachea.\u003c/p\u003e","manuscriptTitle":"Evaluation of radiofrequency ablation for papillary thyroid microcarcinoma with trachea-adjacent location versus trachea-distant location: a propensity score matching study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-05-18 13:24:35","doi":"10.21203/rs.3.rs-2937812/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8c7ccab5-bb7e-46d3-9503-62e44849b7ce","owner":[],"postedDate":"May 18th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-05-18T14:14:28+00:00","versionOfRecord":[],"versionCreatedAt":"2023-05-18 13:24:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2937812","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2937812","identity":"rs-2937812","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}