Ultrasound-Guided Radiofrequency Ablation for Papillary Thyroid Microcarcinoma: Efficacy and Safety in a Cross-Country Multicenter Retrospective Study

One year follow-up of US-Guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma: The first experience in Taiwan

Papillary thyroid microcarcinoma (PTMC) has a high incidence and a good prognosis. Surgical operation for all PTMC might be an overtreatment. The objective of this study was to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating low-risk PTMC. Ninety-eight PTMC in 92 patients were included in this study. US and contrast-enhanced ultrasound (CEUS) examinations were performed before ablation. RFA was performed using the moving-shot technique. The ablation area exceeded the tumor edge to prevent marginal residue and recurrence. Patients were followed at 1, 3, 6, and 12 months and every six months thereafter. US and CEUS examinations were used to evaluate the ablation area. At three months after ablation, US-guided core-needle biopsy (CNB) was performed in the center, at the edge of the ablation area, and in the surrounding thyroid parenchyma to exclude recurrence. The mean tumor volume was 118.8 ± 106.9 mm3. The mean volume reduction ratio (VRR) was 0.47 ± 0.27, 0.19 ± 0.16, 0.08 ± 0.11, 0.04 ± 0.10, and 0 at 1, 3, 6, 12, and 18 months after RFA, respectively. Significant differences in the VRR were found between every two follow-up times before six months (p < 0.01), and no significant differences in the VRR were found between six months and after 12 months (p = 0.42). Of all the nodules, 10 (41.7%) resolved in six months, and 23 (95.8%) resolved in 12 months. No residual or recurrent tumor tissue was detected in RFA area or in residual thyroid tissue during follow-up. No suspicious metastatic lymph nodes were detected. The histological pathology results of US-guided CNB confirmed the absence of residual or recurrent tumor. No major complications were encountered. RFA can effectively eliminate low-risk PTMC with a very small complication rate. RFA may be an alternative strategy for the treatment of PTMC.

Ultrasound-Guided Radiofrequency Ablation of Low-Risk Papillary Thyroid Microcarcinoma: a Prospective Study

To investigate and compare the clinical outcomes of radiofrequency ablation (RFA) for multifocal papillary thyroid microcarcinoma (PTMC) versus unifocal PTMC in a large cohort. Patients with low-risk PTMC (n = 487) who underwent RFA were included in this retrospective study and divided into the unifocal group (U group) (n = 432) and the multifocal group (M group) (n = 55) according to the number of lesions. After 1:1 propensity score matching (PSM), volume, volume reduction ratio (VRR), the development of local tumor progression including lymph node metastasis (LNM), recurrent PTMC and persistent lesions, and recurrence-free survival (RFS) rate were evaluated and compared between the two groups. The different impacts of multifocality on recurrence after RFA for PTMC were investigated by Cox analysis. During a mean follow-up time of 49.25 ± 12.98 months, the overall VRR was 99.40 ± 4.43% and the overall incidence of local tumor progression was 3.70% (18/487). No complications occurred after RFA. After PSM, no significant differences were found in volume (0.11 ± 0.69 mm3 vs 0 mm3, p = 0.441), VRR (99.87 ± 0.78% vs 100%, p = 0.441), complete disappearance rate (95.61% vs 89.09%, p = 0.201), incidence of local tumor progression (5.45% vs 5.45%, p = 1.000), LNM (1.82% vs 0%, p = 0.317), recurrent PTMC (1.82% vs 5.45%, p = 0.611), persistent lesions (1.82% vs 0%, p = 0.317), and RFS rate (96.36% vs 94.55%, p = 0.632) between the M group and U group. The association between multifocality and local tumor recurrence also remained nonsignificant (p = 0.619). No distant metastasis or delayed surgery occurred. The impact of multifocality on the prognosis after RFA for low-risk PTMC was little. RFA might be a promising treatment for both unifocal and multifocal PTMC in properly selected patients after sufficient preoperative evaluation. • No significant differences are found in the local tumor progression between the unifocal PTMC and multifocal PTMC. • Multifocality is not associated with higher recurrence after RFA for low-risk PTMC. • RFA is a promising alternative for both unifocal and multifocal PTMC.

Purpose To evaluate the effect of Hashimoto's thyroiditis (HT) on the extent of ablation zone in ultrasound (US)-guided radiofrequency ablation (RFA) for early stages of papillary thyroid microcarcinoma (PTMC). Method We selected 772 patients with 797 PTMCs who underwent with RFA from August 2017 to August 2020. They were subdivided into two groups as follows: (i) 216 patients (224 PTMCs) with HT in the ‘HT + PTMC’ group and (ii) 556 patients (573 PTMCs) with healthy thyroid in the ‘PTMC’ group. We assessed the extent (maximum diameter and volume) of the ablation zone by contrast-enhanced ultrasound (CEUS) immediately, one day, and 1 week following RFA. Results The ablation zone of the ‘HT + PTMC’ group was smaller than that of the ‘PTMC’ group at 1 week of RFA (maximum diameter: 14.6 ± 3.1 mm vs. 15.2 ± 3.2 mm and volume: 0.932 ± 0.498 mL vs. 1.028 ± 0.540 mL, respectively, p < .05). However, there were no differences before, immediately, and one day post-RFA (p > .05). Life-threatening complications did not develop in any of the patients. Conclusion RFA-treated PTMCs were smaller in size in patients with HT than in those with a healthy thyroid at 1 week of RFA. However, the exact mechanism underlying this phenomenon and its clinical significance warrant further investigation.

Objective: Papillary thyroid microcarcinoma (PTMC) has a good prognosis and a long survival time. Health-related quality of life (HRQoL) is vital for PTMC patients during their survivorship. Ultrasound (US)-guided radiofrequency ablation (RFA), which has high efficacy and safety, is recommended as an alternative treatment to surgery for the patients with low-risk PTMC. However, the assessment of QoL of patients with PTMC has not been specially reported. The purpose of our study was to compare the HRQoL of patients with PTMC who underwent RFA and those who underwent surgery.Methods: From October 2019 to December 2019, 88 PTMC patients were enrolled in our study, including 54 in RFA group and 34 in surgery group. We used three questionnaires which included the 36-item short form health survey (SF-36), thyroid cancer-specific quality of life (THYCA-QOL), and Fear of Progression Questionnaire-Short Form (FoP-Q-SF) for each patient to evaluate their scores of HRQoL. The scores were compared after adjusting for age, sex, medical expense, and follow-up time.Results: According to the SF-36, the scores of the domain for the role limitation due to physical problems and emotional problems (RP, RE) as well as Physical Component Summary (PCS) showed a significant negative linear association between the RFA group and surgery group: RP coefficient [coef]−22.613 [confidence interval (CI) −33.504 to −11.723], p < 0.001, RE (coef: −21.901 [CI −36.737 to −7.064], p = 0.004), and PCS (coef: −8.312 [CI −13.694 to −2.930], p = 0.003). The THYCA-QOL showed that the scores of the surgery group were higher than that of the RFA group regarding scars (coef: 10.246 [CI 1.330 to 19.162], p = 0.025 according to the multivariate analysis), suggesting a higher level of complaint in the surgery group. There was no statistically significant difference in the scores of FoP-Q-SF between the two groups.Conclusions: In patients with PTMC, US-guided RFA offers advantage over surgery in terms of HRQoL, which supports the role of RFA as an alternative strategy to surgery.

The current study sought to explore the effects of ultrasound (US)-guided radiofrequency ablation (RFA) on papillary thyroid microcarcinoma (PTMC) and influencing factors. PTMC patients were assigned to observation (US-guided RFA) and control (surgical operation) groups. A series of operation-related indexes (operation time, intraoperative bleeding, wound closure time, hospital stay, and expenses), visual analogue scale score, lesion size, and thyroid function-related indexes (thyroid-stimulating hormone [TSH], free triiodothyronine*** [FT3], free thyroxine [FT4]), inflammatory factors, and thyroglobulin antibody (TgAb) were assessed and compared. After a 6-month follow-up period, the complications and recurrence were recorded, in addition to analyses of postoperative recurrence cumulative incidence and evaluation of recurrence risk factors. Operation-related indexes of the observation group were relatively decreased compared with the control group. In addition, the lesion volume in the observation group was lower compared to that in the control group at the 6th month after operation, whereas the volume reduction rate was higher. There were no significant differences in regard to thyroid function-related indexes in the observation group before/after operation. After operation, serum TSH levels and inflammatory factors, and TgAb levels were all diminished, while the FT3 and FT4 levels were both elevated in the observation group relative to the control group, and postoperative recurrence cumulative incidence was lower in the observation group. TSH and TgAb were established as the independent risk factors for recurrence after RFA in PTMC patients. Our findings highlighted that US-guided RFA exhibits better efficacy, safety, and postoperative recovery and lower recurrence risk for PTMC.

Background: Despite reports describing favorable short-term results for thermal ablation of thyroid cancer, there remains a need to evaluate long-term results because of its indolent characteristics. The purpose of this study was to evaluate the long-term efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC) over a follow-up period of more than five years. Methods: From a cohort of patients under surveillance after US-guided RFA for primary low-risk PTMC, those with a record of follow-up data of more than five years were selected for this study. Before RFA, all patients underwent US and computed tomography to evaluate the PTMC and the presence of neck metastasis. RFA was performed using thyroid-dedicated electrodes. Follow-up US was performed 6 and 12 months after initial RFA, and then every 12 months. The status of ablated tumors was evaluated according to volume reduction, local tumor progression, newly developed cancers, lymph node (LN) or distant metastasis, and delayed surgery during follow-up. Complications during the procedure and follow-up period were evaluated. Results: A total of 84 nodules from 74 patients were included in this study. All patients tolerated RFA, and the mean follow-up duration was 72 months. After RFA, complete disappearance rates of 98.8% and 100% were achieved at 24 and 60-month follow-up, respectively. Additional ablations were performed in 13 of 84 tumors. The mean number of RFA sessions was 1.2. There were four newly developed cancers in three patients, and these were also treated with RFA and completely disappeared. During the follow-up period, there was no local tumor progression, no LN or distant metastasis, and no patients underwent delayed surgery. The major complication rate was 1.4% (1/74), and there was no delayed complication or procedure-related death. Conclusions: RFA is effective for treating low-risk PTMC patients, without occurrence of local tumor progression, LN or distant metastasis, delayed complications, procedure-related death, or delayed surgery over more than five years of follow-up.

Simple SummaryUltrasound (US)-guided minimally-invasive techniques, such as radiofrequency ablation (RFA) have emerged as an alternative treatment to surgery for benign and malignant thyroid nodules. Based on a systematic literature search, here we report the long-term outcomes of thyroid RFA. Available data show that US-guided RFA significantly reduced benign thyroid nodules and destroyed most PTMC, and this was generally maintained for at least 5 years after the initial treatment. Further studies addressing the risk of regrowth in patients with benign thyroid nodules, as well as the risk of recurrence in patients with PTMC are needed.Background: US-guided minimally-invasive techniques, such as radiofrequency ablation (RFA) have emerged as an alternative treatment for benign and malignant thyroid nodules. This systematic review aims to provide an overview on the long-term outcomes of US-guided RFA in patients with benign and malignant thyroid nodules. Methods: We systematically searched PubMed/MEDLINE, EMBASE, and Scopus to identify articles reporting the outcomes of thyroid RFA after a follow-up of at least 3 years. Results: A total of 20 studies met the inclusion criteria and were included in the review. In patients with benign thyroid nodules, RFA significantly reduced nodule volume and this was generally maintained for the following 5 years. However, a small but not negligible proportion of nodules regrew and some of them required further treatments over time. In patients with malignant nodules, RFA has been used not only to treat differentiated thyroid cancer (DTC) neck recurrences, but also to treat papillary thyroid microcarcinoma (PTMC). In most patients with PTMC, RFA led to complete disappearance of the tumor. When it was compared to surgery, RFA was not inferior in terms of oncologic efficacy but it had a lower complication rate. However, RFA did not allow for final pathology, disease staging and accurate risk stratification. Conclusions: US-guided RFA significantly reduces benign thyroid nodules and destroys most PTMC, and this is generally maintained for at least 5 years after the initial treatment. Further studies addressing the risk of regrowths in patients with benign thyroid nodules, as well as the risk of recurrence in patients with PTMC are needed.

Background: Active surveillance (AS) of papillary thyroid microcarcinomas (PTMC) is emerging as an alternative to immediate surgery. While thermal ablation has also shown promise for low-risk PTMC, it has not been prospectively studied in patients appropriate for AS. This study aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for tumor control and quality of life (QoL) management in patients with PTMC who favored AS over immediate surgery. Methods: This prospective clinical trial was conducted at a single tertiary referral hospital from 2018 to 2021. Of 227 adult patients aged ≤60 years with low-risk unifocal PTMC favoring AS over immediate surgery, 100 patients underwent RFA for their management. The primary endpoint was the disease progression rate, and secondary endpoints were technical success, volume reduction rate (VRR), complication rates, and QoL. Results: The median age of the study population was 42 years (range, 27-59 years), and 83% (83/100, [CI: 66.1-100]) were female. The median follow-up was 30 months (range, 12-56 months). All 100 patients underwent RFA with technical success. Most of the ablation zones showed continuous volume reduction, and 95.9% (94/98, [CI: 77.5-100.0]) showed complete disappearance at the last follow-up. The median VRR was 100.0% at 1-year follow-up and persisted throughout the last follow-up. The cumulative disease progression rate among 98 patients who underwent at least 1-year follow-up was 3.1% (3/98, [CI: 0.6-9.0]); one patient had lymph node metastasis (treated with surgery), and two patients had new PTMC (1 treated with RFA, 1 ongoing AS). Major complications were not observed. Psychological (baseline vs. last follow-up, 7.3 vs. 8.0, p = 0.002) and social (8.0 vs. 8.7, p = 0.005) QoL scores significantly improved during follow-up without compromising physical QoL (8.6 vs. 8.5, p = 0.99). Conclusions: RFA can be a reasonable strategy for effectively and safely controlling tumors and improving QoL in non-elderly patients with low-risk PTMC appropriate for AS. Clinical Trial registration: This trial is registered with ClinicalTrials.gov: NCT03432299.

Objective To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea. Methods Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated. Results A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73). Conclusion For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.

Purpose To assess the impact of Hashimoto’s thyroiditis (HT) on radiofrequency ablation (RFA) outcomes for papillary thyroid microcarcinoma (PTMC). Methods A retrospective study of 391 PTMC patients treated with RFA from March 2017 to August 2020, divided by HT accompanied or not. Ablation area size, volume reduction ratio (VRR), lesion disappearance, complications, and recurrences were analyzed. Results 391 patients (mean age, 41.3 ± 11.2 [SD]; 317 women, 110 with HT) were evaluated. The follow-up time was 2 years. HT+ PTMC patients (Group A) exhibited larger ablation diameters at 1st and 3rd month post-RFA. In comparison, PTMC patients (Group B) had larger diameters at 1st and 3rd months but smaller at 6th months, returning to baseline around 6th month in Group B and 9th month in Group A. VRRs in Group B were greater than Group A at 3rd, 6th, 9th, 12th and 15th month, all p < 0.05). The Kaplan-Meier curves revealed a slower lesion disappearance rate in A (12th) compared to B group (9th). Complication and recurrence rates were similar for both groups (4.4% and 0.8% overall, Group B vs Group A: 4.3% vs 4.6%, p = 0.905; 0.4% vs 1.8%, p = 0.192). Conclusion HT delays the resorption of PTMC lesions following RFA, but it does not impact the procedure’s effectiveness or safety. Regardless of HT status, RFA remains a viable alternative to surgery for PTMC.

To date there is no study on the feasibility of radiofrequency ablation (RFA) for papillary thyroid microcarcinomas (PTMCs) with BRAF V600E mutation. This study was designed to evaluate the efficiency, safety, and prognosis of ultrasound (US)-guided percutaneous RFA for unifocal PTMCs with BRAF V600E mutation. Sixty patients with 60 unifocal BRAF V600E mutation-positive PTMCs who received US-guided RFA between January 2020 and December 2021 were retrospectively analyzed. The mean maximum PTMC tumor diameter was 5.8 ± 1.7 mm (range, 2.5-10.0 mm). All PTMCs were pathologically confirmed by fine needle aspiration or core needle biopsy, and BRAF V600E mutation was confirmed to be positive by real-time fluorescent quantitative polymerase chain reaction. Contrast-enhanced ultrasound (CEUS) was performed immediately after RFA to evaluate whether PTMCs were extendedly ablated. Ultrasound was performed 1, 3, 6, and 12 months after RFA and every 6 months thereafter to evaluate the changes in the ablation zone, local recurrence, and cervical lymph node metastasis (LNM). The complications were recorded and evaluated. Extended ablation was achieved in all enrolled patients. The ablation zone sizes increased immediately after RFA compared with those of tumors before treatment. One month later, the ablation zone sizes were smaller than immediately after RFA. At the last follow-up assessment, 42 nodules (70.0%) completely disappeared and the ablation zones of 18 nodules (30.0%) showed fissure-like changes. No local recurrence or cervical LNM was detected. Voice change (1.7%) was the only major complication. RFA is effective and safe in treating unifocal PTMCs with BRAF V600E mutation, especially when surgery is not feasible or refused by patients who are unwilling to continue active surveillance.

To compare the abilities of ultrasonography (US) and Computed Tomography (CT) to identify calcifications and to predict probability of malignancy for Papillary Thyroid Carcinoma (PTC) and Papillary Thyroid Microcarcinoma (PTMC). We reviewed 1008 cases of PTC/PTMC with calcifications reported by pre-operative US, CT, or post-operative pathology. The size of the thyroid nodule was obtained from the US report and the maximum diameter (d) was documented. According to the nodule size (d), the PTC and PTMC groups were each divided into two subgroups, as follows: large PTC group (d ≥ 2 cm), small PTC group (1 cm < d < 2 cm), large PTMC group (0.6 cm ≤ d ≤ 1 cm), and small PTMC group (d < 0.6 cm). In the 1008 patients, the ratio of females to males was 2.29 and the mean age was 40.9 years (standard deviation: 11.7 years). Of the 1008 records, 92.8% were found to have calcifications according to the US report, while 50.4% showed calcifications according to the CT report. This difference between US and CT reports was statistically significant (p < 0.0005). The percentages of US reports showing calcifications were similar for all four PTC and PTMC subgroups (93.7%, 94.3%, 92.1%, and 85.1%, respectively; p = 0.052), while the percentages of CT reports showing calcifications were significantly different among the PTC and PTMC subgroups (62.3%, 52.2%, 45.4%, and 31.3%, respectively; p < 0.0005). As for the prediction of malignancy, US was superior to CT in all four subgroups (large PTC group: 97.1% vs. 54.1%, small PTC group: 94.8% vs. 42.9%, large PTMC group: 97.2% vs. 32.0%, small PTMC group: 95.5% vs. 14.9%; p < 0.0005 for all pairwise comparisons). No significant difference was observed in terms of the ability of US to predict the malignancy of PTC versus PTMC (p = 0.31), while CT showed significant superiority in diagnosing PTC versus PTMC (p < 0.0005). The predictive value of CT for PTC declined as the nodule size decreased (p < 0.05 for all pairwise comparisons). Our results showed that US detected calcifications and predicted the malignancy of all nodule sizes of thyroid papillary carcinoma equally well, while the performance of CT declined with the reduction of nodule size.

Background We comprehensively evaluate the efficacy and safety of US-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) via a systematic review and meta-analysis. Methods We searched the PubMed, Embase and Cochrane Library databases for studies published during the time between the establishment of the database through October 2021. We included a 10 non-randomized controlled trial (non-RCT) that reported the application of US-guided RFA in PTMC. The sample size of patients totaled 1279. We evaluated the ablation efficacy by analyzing the volume reduction rate (VRR), complete disappearance rate (CDR) and recurrence rate of PTMC treated by RFA. We analyzed all data using STATA version 15.1 (Stata Corporation, College Station, TX). Results Our pooled results proved RFA treatment significantly reduces the volume of tumors (Weighted Mean Difference [WMD] = −103.20, 95% CI: −111.93 – −94.48, p = 0.000). We also found the VRR at 12 months after RFA was 93.27% (95% CI: 84.68–101.86), and the CDR at 12 months after RFA was 64% (95% CI: 39–89%). Additionally, pooled results showed the incidence of mPTC residue in ablation area, newly discovered mPTC and lymph node metastases after RFA treatment were respectively 0.3% (95% CI: −0.1–0.7%), 2.5% (95% CI: 1.1–3.9%) and 1.0% (95% CI: 0.2–1.9%), and the incidence of complications after RFA treatment was 1.8% (95% CI: 0.7–3.2%). Conclusions US-guided RFA is effective and safe for treating PTMC. It could be an excellent alternative to the existing treatment options.