Radiofrequency Ablation and Laser Ablation of Benign Thyroid Nodules Are Similarly Effective at 6 Months in a Prospective, Randomized Trial

Clinical ThyroidologyVol. 32, No. 6 Thyroid NodulesFree AccessRadiofrequency Ablation and Laser Ablation of Benign Thyroid Nodules Are Similarly Effective at 6 Months in a Prospective, Randomized TrialAudun Braaten and Martin BiermannAudun BraatenSection for Interventional Radiology, Department of Radiology, Haukeland University Hospital, Bergen, NorwaySearch for more papers by this author and Martin BiermannNuclear Medicine/PET Center, Department of Radiology, Haukeland University Hospital, Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, NorwaySearch for more papers by this authorPublished Online:5 Jun 2020https://doi.org/10.1089/ct.2020;32.279-283AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Review of: Cesareo R, Pacella CM, Pasqualini V, Campagna G, Iozzino M, Gallo A, Lauria Pantano A, Cianni R, Pedone C, Pozzilli P, Taffon C, Crescenzi A, Manfrini S, Palermo A 2020 Laser ablation versus radiofrequency ablation for benign non-functioning thyroid nodules: Six-month results of a randomized, parallel, open-label, trial (LARA trial). Thyroid. Epub 2020 Mar 17. PMID: 32056501.SUMMARYBackgroundThyroid nodules are a common clinical problem, with a prevalence of about 50% in patients >50 years of age. While most thyroid nodules are benign and require only periodic monitoring (1), some cause compressive symptoms or may be cosmetically displeasing. Thyroid surgery, which is the main therapeutic approach for thyroid nodules with local symptoms, may be associated with neck scars, and—if performed bilaterally—with hypothyroidism and hypoparathyroidism. Minimally invasive image-guided ablation is becoming increasingly common as an alternative to surgery for treating benign nonfunctioning thyroid nodules.The present study is a prospective, randomized trial comparing radiofrequency ablation (RFA) and laser ablation (LA) in the hands of the same interventional radiologist (2).MethodsBetween January 2016 and November 2018, a total of 60 patients with a benign nonfunctioning thyroid nodule were randomly assigned to either RFA or LA based on the following inclusion criteria: age >18 years; solitary thyroid nodule or dominating nodule in a multinodular goiter; nodule volume ≥5 ml; solid portion >80%; compressive symptoms or cosmetic concerns, or an increase in nodule volume >20% in 1 year regardless of symptoms; exclusion of malignancy using one single fine-needle aspiration and one thyroid core needle biopsy; normal serum levels of thyroid hormones, thyroid-stimulating hormone (TSH) and calcitonin; absence of antithyroglobulin antibodies and antithyroid peroxidase antibodies; and written informed consent. Exclusion criteria were ultrasound features suggestive of malignancy; previous treatments for thyroid nodule(s); pregnancy; and hyperfunctioning lesions evaluated biochemically or on [99mTc]pertechnetate scintigraphy.Ultrasound was performed using a 7.5- to 12-MHz linear probe. The volume of thyroid nodules was calculated by the ellipsoid formula. Core needle biopsy was performed by a 21-gauge double-action spring-activated needle using 1.1- or 1.6-cm excursion. After local anesthesia was administered, the needle was inserted into the nodule under ultrasound guidance, and the spring was activated to sample the peripheral and subperipheral tissues, moving from the center to the periphery of the nodule. One needle pass was performed per lesion. Samples were fixed in 10% buffered formalin. All patients underwent laryngoscopy before the ablation procedure. For ablation, patients were placed in the supine position with full neck extension. Perithyroidal injection of mepivacaine and ropivacaine (approximately 5 ml) was used for pain control.RFA was based on the “moving shot” technique using a transisthmic approach. An 18-gauge 10-cm electrode with a 1-cm active tip (RF Medical, South Korea) was applied using 55 W of power and adequate exposure time to induce transient multiple hyperechoic zones in the nodule.For LA, 21-gauge introducer needles were inserted with direct nodule puncture along the nodule’s longest axis using a dedicated linear ultrasound transducer with a needle-guiding attachment (EchoLaser, Elesta, Florence, Italy). Subsequently, a 300-µm flat-tipped quartz optical fiber was advanced up to the introducer needle tip. The introducer needle was then withdrawn to expose at least 5 mm of the fiber tip in direct contact with the tissue. The fibers were then connected with a laser source operating at 1064 nm. The number of 21-gauge applicators was based on the size and shape of the nodule. Each treatment was performed with a fixed power of 3 W, but illumination time differed on a case-by-case basis according to the size and shape of the nodule. After the first illumination, the applicators were withdrawn until the whole target was illuminated.The primary end points of the trial were thyroid nodule volume reduction expressed as a percentage of nodule volume at baseline and the proportion of nodules with more than 50% reduction. Both of these end points were assessed at 6 months after ablation. Differences between treatment groups were evaluated using nonparametric tests with a significance level of p < 0.05 (two-sided). The sample size of 2×30 patients was estimated to have 90% power to detect a 10% difference in nodule volume reduction.ResultsThe 60 patients were randomly assigned to RFA or LA. The mean (±SD) age was 56±13 years. The mean thyroid nodule volume was 25±22 ml. Mean procedure time was 23 ± 8 minutes for LA and 16 ± 13 minutes for RFA (P not significant). Six months after the procedure, thyroid nodule volume was reduced by 64% (mean; 95% CI, 57–71) after RFA and by 53% (95% CI, 47–59) after LA (P = 0.02). Greater than 50% volume reduction was achieved in 87% of patients after RFA and in 67% after LA (P not significant). Compressive symptoms were alleviated by 2 points on a 10-point scale, and cosmetic concerns improved by 2 points on a 4-point scale in both groups.Intraprocedural dysphonia occurred in one patient in each group. Fiberoptic laryngoscopy showed no impairment of laryngeal motility, and symptoms resolved within a few days. Three and two patients experienced hematoma, six and five local pain, and one and two transient thyrotoxicosis after RFA and LA, respectively. None required hospitalization.ConclusionsIn this randomized, prospective trial, RFA and LA for solitary nonfunctioning thyroid nodules were equally safe and effective. Both led to a similar reduction in compressive symptoms and cosmetic concerns. However, RFA resulted in greater thyroid nodule shrinkage than LA.COMMENTARYThyroid nodules are a frequent clinical problem in any thyroid clinic. While hyperfunctioning nodules can be treated by radioactive iodine and cystic nodules by instillation of ethanol or other sclerosing agents, the preferred treatment for symptomatic solid nonfunctioning thyroid nodules is surgery (1). From a cosmetic viewpoint, the main disadvantage of surgery is the cervical neck scars it causes. One approach is minimally invasive surgery that uses alternative access routes, such as the transoral or transaxillary approach (3).An alternative approach is the use of image-guided interventions. While ultrasound-guided ethanol instillation of solid nodules can lead to significant reduction in nodule volume (4), ethanol may seep into adjacent cervical tissues, causing pain and/or local nerve damage. Ethanol instillation is therefore recommended only for the treatment of cystic nodules (5).Thermal ablation methods include RFA, LA (6), microwave (7), and high-intensity focal ultrasound (7, 8). The Italian group Minimally-Invasive Treatments of the Thyroid (MITT) recently issued a consensus statement regarding thermal ablation (9). Thermal ablation may be proposed as first-line treatment for solid symptomatic nonfunctioning benign thyroid nodules. Thermal ablation is an option for hyperfunctioning nodules in patients who refuse, or are not eligible for, surgery or radioiodine treatment. Before performing thermal ablation of a solid nodule, duplicate cytologic confirmation that the nodule is benign is required. Single confirmation is adequate in sonographically low-risk nodules (i.e., EU-TIRADS ≤3) and in hyperfunctioning nodules. In cases of thyroid nodule regrowth, repeat cytology is suggested before a second ablation. Predominantly cystic nodules should undergo ultrasound-guided aspiration, and if relapse occurs, ethanol instillation should be pursued (9). While the statements regarding indication and follow-up are relatively detailed, no conclusion was drawn regarding the preferred mode of thermal therapy (9).A recent meta-analysis on thermal ablation included 12 studies with 1186 nodules treated with RFA and 2009 with LA (10). Volume reduction rates at 6 months, 1 year, and 2 years were 68%, 75%, and 87% for RFA and 48%, 52%, and 45% for LA. However, LA was preferentially conducted in larger nodules for which there was less volume reduction (10). The relevance of the present study is that it compares the two thermal ablation methods in the hands of the same interventional radiologist in a prospective, randomized design. While the two methods were similarly safe and effective, RFA achieved a significantly greater degree of nodule shrinkage at 6 months after the procedure, in line with the pooled results of the meta-analysis (2).When introducing a thermal ablation method in a given institution, a number of aspects need to be considered: the initial investment for the equipment, the running costs per procedure, and training requirements. RFA and LA entail similar costs per procedure, but have both a considerable learning curve (6). In cases of thyroid nodules that are located close to the recurrent laryngeal nerve (RLN), hydrodissection with instillation of saline solution between the thyroid capsule and the carotid artery may help protect the RLN from thermal damage (11).Depending on the volume of ablative procedures, most institutions will best be served by using only one method for thermal ablation. In our department, RFA is mainly used for palliative treatment of malignant liver lesions, and we have concluded that the number of patients with symptomatic solid thyroid nodules that are not amenable to surgery is too low to justify the establishment of thermal ablation as an alternative mode of therapy.The present study has the following limitations: (i) Follow-up time was limited to 6 months. (ii) The number of patients included was aimed at comparing the efficacy, rather than the safety, of the procedure. (iii) Core biopsy of the ablated nodules was performed to correlate of ablation effect with nodule composition but was not a necessary part of the procedure.In conclusion, RFA and LA were similarly safe and effective for the ablation of solid nonfunctioning thyroid nodules in this study. There was improvement in compressive symptoms and/or cosmetics in both groups.References1. 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