Treatment outcomes in patients with papillary thyroid cancer undergoing radiofrequency ablation of metastatic lymph nodes
Original Article

Treatment outcomes in patients with papillary thyroid cancer undergoing radiofrequency ablation of metastatic lymph nodes

Alexandra LaForteza1 ORCID logo, Emily Persons2, Mohammad Hussein1,3, Xinyi Luo1, Peter P. Issa2, Jessan Jishu2, Mohamed Shama1, Eman Toraih1,4, Emad Kandil1

1Division of General, Endocrine and Oncological Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA; 2School of Medicine, Tulane University, New Orleans, LA, USA; 3Ochsner Clinic Foundation, New Orleans, LA, USA; 4Medical Genetics, Histology and Cell Biology Department, School of Medicine, Suez Canal University, Ismailia, Egypt

Contributions: (I) Conception and design: A LaForteza, E Kandil, PP Issa, E Persons; (II) Administrative support: E Kandil, M Shama, E Toraih; (III) Provision of study materials or patients: E Kandil, A LaForteza, PP Issa, X Luo; (IV) Collection and assembly of data: A LaForteza, J Jishu, E Persons; (V) Data analysis and interpretation: E Toraih, M Hussein; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Emad Kandil, MD, MBA, FACS, FACE. Division of General, Endocrine and Oncological Surgery, Department of Surgery, School of Medicine, Tulane University, 1430 Tulane Ave, New Orleans, LA 70112, USA. Email: ekandil@tulane.edu.

Background: Lymph node metastases in papillary thyroid cancer (PTC) increases recurrence risk and negatively impact survival. Traditional treatments like re-operation and radioactive iodine (RAI) have downsides. Radiofrequency ablation (RFA) is an emerging non-surgical therapeutic option, but there is seldom data on its efficacy and safety specifically for metastatic lymph nodes. We aimed to evaluate clinical outcomes of RFA applied to cervical lymph nodes in patients with PTC metastasis in North American population.

Methods: This was a single-institution retrospective analysis of 68 PTC patients with lymph nodes who underwent percutaneous RFA from January 2020 to December 2022. Volume reduction ratio (VRR), changes in thyroglobulin (Tg) levels, lymph node regrowth rate, and complications were assessed. Treatment response and outcomes were analyzed.

Results: Median lymph node maximum diameter was 12.9 mm and median volume was 0.27 mL at baseline. After RFA, median VRR was 79.5% [interquartile range (IQR), 50–89.7%]. Post-RFA, Tg to an average of 0.2 ng/mL (IQR, 0–0.6 ng/mL). In the 19 patients (27.9%) with undetectable Tg after RFA, median VRR was 86% (IQR, 73–94%). Quantitative Tg decrease strongly correlated with VRR percentage (r=0.82, P<0.001). Lymph node regrowth was seen in 5 patients (7.4%) over median 18 months follow-up. Only one patient experienced transient thermal injury associated with Horner’s syndrome and symptoms resolved within 1 month.

Conclusions: In patients with PTC and metastatic cervical lymph nodes, RFA provided marked volume reduction and meaningful biochemical response without major complications. Excellent radiographic control was achieved in most patients. RFA demonstrates early promise as an emerging non-surgical therapeutic option for PTC patients with metastatic lymph nodes.

Keywords: Radiofrequency ablation (RFA); lymph node; thyroglobulin; thyroid cancer

Submitted Jul 08, 2024. Accepted for publication Oct 11, 2024. Published online Oct 26, 2024.

doi: 10.21037/gs-24-285

Highlight box

Key findings

• In a single institution study, radiofrequency ablation (RFA) of metastatic cervical lymph nodes reduced elevated thyroglobulin levels 0.4 ng/mL [interquartile range (IQR), 0.1–1.57 ng/mL] to undetectable levels in 19 patients.

• The median volume reduction ratio of metastatic lymph nodes after RFA was 79.5% (IQR, 50.0–89.7%).

What is known and what is new?

• Patients with recurrent papillary thyroid cancer (PTC) require additional surgery for repeat neck dissection and/or adjuvant radioactive iodine therapy.

• We evaluated RFA approach aimed at treating metastatic cervical lymph nodes.

What is the implication, and what should change now?

• RFA is a promising non-surgical option for treatment of cervical lymph nodes in patients with metastatic PTC.

Introduction

Papillary thyroid cancer (PTC), although generally associated with good prognosis, recurs in up to 30% of patients (1). Regional lymph node metastases are present in 20–50% of patients with PTC (2). The presence of lymph node metastasis has consistently been shown to negatively impact outcomes—increasing the risk of locoregional recurrence, disease-specific mortality, and overall mortality (3-5). Therefore, treatment of metastatic cervical lymph nodes is a clinically important issue in the management of PTC.

Traditionally, treatment options for recurrent or persistent metastatic lymph nodes have included additional surgery for repeat neck dissection and/or adjuvant radioactive iodine (RAI) therapy (6). However, the morbidity associated with repeat neck surgery can be substantial. Complication rates from revision central and lateral neck dissection have been reported up to 14% and 37% (7,8). RAI therapy also carries risks such as radiation thyroiditis, sialadenitis, and secondary malignancies (9,10). Additionally, RAI uptake can be poor in small volume metastatic disease, limiting its efficacy for microscopic foci (11).

Over the past decade, thermal ablation has emerged as a promising non-surgical treatment option for locoregional control in recurrent thyroid cancers. Approaches using laser, microwave, and radiofrequency modalities have been studied for ablation of recurrent disease in cervical lymph nodes (12-14). Radiofrequency ablation (RFA) has shown promise given its established safety record, efficacy for tumor destruction, and ability to overcome the limitations of surgery and RAI therapy (15-18). Its minimally invasive percutaneous approach also allows treatment of disease not amenable to surgical resection without morbidity of open surgery. Studies evaluating RFA for primary or locally recurrent PTC nodules in the thyroid bed have shown volume reduction ratio (VRR) exceeding 50–96% and ability to normalize thyroglobulin (Tg) levels in up to 89% of cases (14,19,20).

Given the important prognostic and survival implications of lymph node metastases in PTC, investigation into the efficacy and clinical impact of emerging non-surgical therapies is essential for recurrent disease. In this study, we review outcomes after RFA applied for treatment of cervical lymph nodes in patients with recurrent PTC. The goals were to (I) assess the volumetric response to RFA and impact on serum Tg levels and (II) analyze volume reduction and biochemical response based on various demographic and clinicopathological factors to determine if specific disease characteristics are associated with treatment response. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-24-285/rc).

Methods

Study population

This study was approved by the Institutional Review Board of Tulane University (No. 2023-452) and individual consent for this retrospective analysis was waived. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). We performed a retrospective review of 68 PTC patients with cervical lymph nodes who underwent ultrasound guided percutaneous RFA at Tulane Medical Center between January 2020 and December 2022. All patients included in this study had a previous thyroidectomy with documented pathology of PTC. Those included present with evidence of recurrent non extensive disease in a single lymph node. The selective group of patients who were candidates for RFA were at high risk for another surgery or were not interested in a second surgery. Patients underwent prior biopsies to confirm recurrent disease and that included routine Tg washout consistent with elevated Tg levels. Patients in this study were treated by a single high-volume fellowship-trained endocrine surgeon (E.K.). All patients had a single RFA treatment and response was recorded. The data that was collected were stripped from patient identifying information. At follow up appointments, suspicious lymph nodes were identified based on elevated Tg levels (>0.1 ng/mL) and abnormal ultrasound findings such as cystic change, calcifications, hypervascularity, round shape, loss of fatty hilum, or peripheral vascularity. Patients underwent fine needle aspiration (FNA) and RFA of lymph nodes.

Our protocol at our institution included follow-up visit every 6 months up to 24 months. The following outcomes were assessed: VRR based on pre- and post-procedure ultrasound evaluation, changes in Tg levels pre-procedure and at last follow-up, rate of lymph node regrowth on follow-up ultrasound, short-term and 1-year complications, and length of follow-up with ultrasound or Tg monitoring.

RFA technique procedure

The radiofrequency technique has been published previously (21-23). First, patients were swabbed with povidone-iodine, draped, and local anesthetic was applied. All patients were treated with an 18-gauge STARmed (Seoul, Korea) internally cooled electrode with an active tip of 5 mm. Direct short-axis approach was used to proceed with ablation with the moving-shot technique for all patients (24). Patient monitoring following RFA was typically for 30 minutes to ensure no immediate complication. At clinic follow-up visit, patient lymph node dimensions were collected as well as reports of symptoms.

VRR

Lymph node volume was determined by dimensions of width, length, and height measured by ultrasonography imaging. VRR was defined per previous literature as (V0 − V1)/V0] × 100, where V0 and V1 represent the initial and follow-up volume, respectively.

Statistical analysis

Categorical variables were reported as counts and percentages while continuous variables were reported as mean ± standard deviation or median with interquartile range. Comparison of VRR based on clinicopathological factors was performed using the Mann-Whitney U test. A P value <0.05 was considered statistically significant. Statistical analysis was performed using SPSS (v28.0).

Results

Characteristics of the study population

Demographics and clinicopathological details of the 68 patients who underwent RFA are shown in Table 1. The mean age was 55.2±13.8 years. The majority were female (85.3%) and White (58.8%). There were 32 patients (47.1%) who had a previous lymph node dissection and 26 patients (38.2%) who underwent radioiodine treatment. There were 10 (14.7%) level 2 lymph nodes treated by RFA, 42 (61.8%) level 3 lymph nodes, 9 (13.2%) level 4, 4 (5.9%) level 5, 1 (1.5%) level 6, and 2 (2.9%) central. The surgical pathology of patients’ previous total or completion thyroidectomy underwent genetic testing for common markers. The majority of patients (39.7%) had BRAF V600E mutation, while there were other mutations such as KRAS, HRAS, NRAS. Median baseline maximum lymph node diameter was 12.9 mm and median volume was 0.27 mL.

Table 1

Baseline patient and lymph node characteristics

Characteristics Values
Demographic data
   Age, years 55.2±13.8
      <55 31 (45.6)
      ≥55 37 (54.4)
   Sex
      Female 58 (85.3)
      Male 10 (14.7)
   Race
      White 40 (58.8)
      Black 24 (35.3)
      Asian 4 (5.9)
Clinicopathological data
   Hashimoto thyroiditis (positive) 15 (22.1)
   Diagnosis
      Papillary thyroid microcarcinoma 14 (20.6)
      Papillary thyroid cancer 51 (75.0)
      Follicular thyroid cancer 3 (4.4)
   Lymph node dimensions
      Baseline maximum diameter (cm) 1.29 (1.03–1.69)
      Baseline volume (mL) 0.27 (0.13–0.53)

Data are presented as count (percentage), mean ± standard deviation, or median (interquartile range). Follow-up was performed by either ultrasound or thyroglobulin levels. Tg, thyroglobulin.

Dynamic changes of thyroglobulin following RFA

Pre-RFA, the median Tg level was 0.4 ng/mL (IQR, 0.1–1.57 ng/mL), and postoperative it was 0.2 ng/mL (IQR, 0–0.6 ng/mL). There were 19 patients with elevated Tg levels that became undetectable (<0.1 ng/mL) during the median post-RFA 18-month follow-up period (IQR, 12–24 months).

Volume reduction following RFA of lymph nodes

After RFA, the median VRR was 79.5% (IQR, 50.0–89.7%) (Table 2). VRR did not significantly differ based on age, sex, race, side, diagnosis, genetic mutations, TNM staging, type of thyroid surgery, lymph node dissection, or RAI treatment. Lymph node regrowth occurred in 5 patients (7.4%) over the 18 months (IQR, 12–24 months) follow-up period.

Table 2

Outcomes before and after RFA treatment

Parameter Values
Laboratory data
   Serum thyroglobulin level, ng/mL
    Baseline 0.4 [0.1–1.57]
    Postoperative 0.2 [0.0–0.6]
Outcomes
   Volume reduction ratio, % 79.5 [50.0–89.7]
   Lymph node regrowth (positive) 5 (7.4)
   Follow-up, months 18 [12–24]

Data are presented as count (percentage) or median [interquartile range]. RFA, radiofrequency ablation.

Complications

There was one complication involving transient thermal injury resulting in Horner’s syndrome. The symptoms resolved within 1 month. No other adverse events, major complications, or mortality occurred.

Discussion

RFA has recently become a popular nonsurgical option in treating thyroid cancer (25). International studies have shown that RFA of cervical metastatic lymph nodes is a safe management option with low complication rates (26-28). However, there are limited USA based studies of RFA of cervical lymph node metastasis in thyroid cancer. In a study that utilized RFA to treat cervical lymph node metastasis showed that 87% of patients demonstrated loss of hypervascularity on Doppler imaging, and over 95% drop of Tg levels after RFA (29). Other studies have evaluated thermal ablation demonstrating safety and efficacy of RFA for recurrent PTC in the thyroid bed, with 50–96% volume reduction and normalization of Tg levels in 29–89% (14,30,31).

In this retrospective study evaluating outcomes after ultrasound-guided percutaneous RFA for cervical lymph nodes in 68 patients who were at high risk for metastatic PTC, we found an excellent radiographic response with median 79.5% volume reduction. RFA also provided meaningful biochemical response, achieving undetectable Tg levels in 27.9% of patients previously exhibited elevated Tg levels. This suggests thermal ablation achieves comparable response rates for both intrathyroidal and nodal metastatic disease.

Notably, we found no significant difference in VRR based on patient demographic factors, primary tumor characteristics like size or mutations, or details of prior therapy including type of surgery or RAI treatment. The consistency of response across subgroups suggests most PTC patients with suspicious nodes are likely to benefit from RFA regardless of disease extent or previous treatments. We did observe a trend toward greater VRR in older patients and lower rates in those with invasive primary tumor behavior reflected in extrathyroidal extension or lateral neck disease. However, these did not reach statistical significance likely due to small sample size. Larger studies could help clarify if certain disease presentations are more amenable to RFA treatment.

The standard remains for surgical resection of metastatic cervical lymph nodes. However, certain patients who meet the criteria for RFA show reasonable control in size and biochemical improvement (32). In our cohort, nearly all patients (92.6%) showed no evidence of radiographic lymph node regrowth over a median 18 months follow-up. Durable local control for this length of time is very promising, as most recurrences happen within the first 1–2 years after initial therapy (33). Only 15–20% of low risk PTC patients suffer recurrence beyond 2 years (34). Our findings suggest RFA may offer lasting regional control, but further study with longer follow-up is necessary. Further future multi-institutional studies are warranted to examine the long-term outcomes in studies similar to our current study and others from Asia with comparable results seen on Table 3 (26-28).

Table 3

Existing literature

Author Year Country Treatment Findings
Lim et al. (26) 2015 Korea RFA Recurrent tumor volume reduction of 95.1%±12.3% (range, 41.2–100%). Serum Tg significantly decreased in 44.8% of patients
Guang et al. (27) 2017 China RFA The mean volume reduction rate of metastatic cervical LNs at 24 months was 94.9%±5.3% (range, 78.2–100.0%). Significant decrease in serum Tg
Yan et al. (28) 2021 China RFA The mean volume reduction of metastatic cervical LNs was 99.28%±2.27%. Significant decrease in serum Tg

Tg, thyroglobulin; RFA, radiofrequency ablation; LNs, lymph nodes.

This study had several limitations including retrospective design and lack of comparison group managed with traditional surgery/RAI therapies. As thermal ablation for metastatic nodes represents a novel approach in PTC, comparison studies will be important to directly quantify oncologic and clinical impact against current standards of care. Our results lay early groundwork suggesting RFA provides meaningful local control, but survival outcomes, risk reduction for future recurrence, and impact on quality of life remain to be clarified.

Conclusions

Although surgical resection maintains the standard of metastatic cervical lymph nodes, RFA is a promising non-surgical option for regional control of metastatic cervical lymph nodes in patients who are not candidates for surgery. Our study showed notable volume reduction and over a quarter of patients achieving undetectable Tg levels. Thermal ablation achieved radiographic control without major complications over median 18 months follow-up. Additional randomized trials with long-term oncological outcomes are warranted to further define the role of RFA relative to repeat neck dissection or RAI therapy for lymph node metastases in PTC.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-24-285/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-285/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-285/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-285/coif). E.K. serves as an Editor-in-Chief of Gland Surgery from May 2024 to April 2026. E.K. receives consulting fees from TaeWoong (STARmed). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of Tulane University (No. 2023-452) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: LaForteza A, Persons E, Hussein M, Luo X, Issa PP, Jishu J, Shama M, Toraih E, Kandil E. Treatment outcomes in patients with papillary thyroid cancer undergoing radiofrequency ablation of metastatic lymph nodes. Gland Surg 2024;13(10):1752-1758. doi: 10.21037/gs-24-285

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