UNIVERSITÀ DI PISA
Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in
Medicina e Chirurgia
Scuola di Specializzazione in Radiodiagnostica
Direttore: Prof. Carlo Bartolozzi
TESI DI SPECIALIZZAZIONE
The efficacy of Radiofrequency Ablation in the treatment of benign
thyroid nodules and recurrent well-differentiated thyroid carcinomas
Relatore:
Chiar.mo Prof. Carlo Bartolozzi
Candidata:
Dr.ssa Benedetta Pontillo Contillo
INDEX
ABSTRACT 2
INTRODUCTION 5
MATERIALS AND METHODS 8
•
Patients8
•
Pre-ablation assessment8
•
Procedure9
•
Follow-up10
•
Statistical analysis11
RESULTS 12
DISCUSSION 18
CONCLUSION
25
REFERENCES 26
ABSTRACT
Purpose: The aim of our study was to evaluate in our experience the effectiveness of
the Radiofrequency Ablation (RFA) in the treatment of benign thyroid nodules and locally recurrent thyroid malignancies.
Materials and methods: The study includes 23 patients, 15 with nodular goiter (NG)
with contraindication or refusing surgery and 8 with inoperable recurrent well-differentiated thyroid cancer (RTC). RFA was performed in a single session under ultrasound guidance, under local anesthesia and mild sedation using 18- or 19-gauge
internally cooled, single tipped electrode with 7- and 10-mm active tips. The pre- and
post-treatment evaluations included: contrast-enhanced ultrasound (CEUS) and unenhanced Computed Tomography (CT) study for the GNs, completed with contrast media in patients with RTCs. Of each lesion the initial volume (V), the vascularity and the proportion of the solid component were assessed; for NGs we also evaluated thyroid function, local symptoms (according to a score of 0-10 severity) and a cosmetic score defined by the radiologist according to a 1-4 scale (not palpable, palpable but not visible, visible only during swallowing and visible in any position). The follow-up in 21/23 patients ranged between 6 and 18 months; 2/8 patients with RTCs did not undergo 6-months follow-up, respectively for systemic progression of disease and onset of severe comorbidity. Volume Reduction Rate was assessed during the follow-up and therapeutic success was defined as a> 50% VRR. Residual vital tissue was also assessed by using CEUS or post-contrastographic CT examinations. Complications were also evaluated.
For NGs we also tried whether there was a correlation between VRR at 6 months follow-up and some parameters such as age, gender, mean energy per millilitre of pre-treatment nodule volume, nodule initial volume, initial nodule solidity and initial nodule vascularity.
Results: Mean V of lesions before treatment was 29.5 ± 24.7 mL for NGs (range:
5.5-90ml), and 4.7 ± 3.5 ml (range: 0.8 to 8.8 ml) for RTCs.
The mean VRR at 6, 12 and 18 months were respectively 74.3%, 79.8% and 82.3% for NGs. At last follow-up, the therapeutic success rate of NGs was 100% (15/15). The overall recurrence rate was 0% (0/15).
We found that volume, residual vital tissue, cosmetic score and symptom score of NGs were significantly lower at last follow-up than before treatment (P <0.0005 for all comparison). Initial nodule volume, vascularity and energy delivered per millilitre of pre-treatment nodule volume demonstrated to be were significantly related to
6-months VRR (P < 0.0001 for all analysis).
The VRR of RTCs was 68.4%, 66.4% and 64.4% during the follow-up at 6, 12 and 18 months. At last follow-up, the therapeutic success rate for RTCs was 83% (5/6) with overall regrowth and/or recurrence rate of 0% (0/6).
In no case of NG treated with RFA was observed dysphonia; 3/6 patients with paratracheal RCT, closely adjacent to the danger triangle of the recurrent laryngeal nerve, have reported dysphonia (permanent in 2 cases and transient in 1 patient).
Conclusions: RFA demonstrated in our experience to be an effective and safe
interventional technique and may represent a viable alternative to surgery in selected patients.
INTRODUCTION
Thyroid nodules are very common in clinical practice, being their prevalence largely dependent on screening modality. It varies from 4-7% for palpable nodules to 20-76% for nodules detected by ultrasound (US) investigation, especially due to the wide use in clinical practice of high-resolution US technique [1-3], according to the prevalence reported at autopsy that ranges from 50 and 65%.
The clinical significance of thyroid nodules lies in their possible association with thyroid disfunction and compressive symptoms, but it is primarily due to their malignant potential [1,4].
Thyroid malignancies represent only 4-6,5% of all biopsied nodules and 1% of all cancers [1,4]; differentiated thyroid carcinoma, including papillary and follicular subtypes, is the most common and constitues 90% of all thyroid malignancies.
Serum thyrotropin (TSH) and thyroid US are pivotal in the evaluation of thyroid nodules, as they provide important information regarding thyroid nodule functionality and the presence of features suspicious for malignancy.
Although no imaging modality may accurately predict the nature of every nodule, high-resolution US is the most sensitive, easily available and cost-effective diagnostic tool available for risk stratification for malignancy in thyroid nodules. However, fine-needle aspiration biopsy (FNAB) currently represents the best diagnostic test to preoperatively assess nodules nature [1,3,5].
Regarding to treatment, benign asymptomatic nodules are usually managed by observation only and follow-up while the primary thyroid cancer is always the prerogative of surgery.
If the nodule is benign but causes cosmetic problems or symptoms such as dysphagia, foreign body sensation and hyperthiroidism or if the lesion is a local recurrence of thyroid carcinoma, a treatment is required and surgery is usually a better choice to remove the nodule effectively. The problem is that whereas thyroid surgery is widely available and safe in many centres, it still carries a 2 to 10% risk of complications, it is costly, and it may not be appropriate for a surgical high risk individual or for someone refusing surgery [6]. If recurrent thyroid cancer is detected several years after primary surgical intervention, significant risks may be associated with comorbidity and with scars from previous operations; this group of patients has undergone total thyroidectomy, radioactive iodine ablation and many have also had lymph node dissections, thus cervical anatomic planes are distorted. A nonsurgical and minimally invasive treatment modality is needed as an alternative in these patients. When it refers to benign thyroid nodule but with compressive symptoms, surgical intervention has some disadvantages such as leaving scar tissue in the neck, for which the patient refuses surgery; moreover, surgery is not always feasible because the patient has important comorbidities or may not be intubated for the presence of severe tracheal compression by the goiter. Radioiodine therapy and suppressive therapy also presented some disadvantages.
Thus, a nonsurgical, minimally invasive alternative for these patients is required, being the US-guided ablative therapy no needing for general anesthesia, no scarring, requiring earlier recovery to normal lifestyle, and burdened with fewer complications. Ethanol Ablation (EA) [7,8] and Laser Ablation (LA) [9] have been tried previously in such scenarios.
Since 1998, Radiofrequency Ablation (RFA) has also been introduced to ablate thyroid malignancies and benign thyroid nodules [10]. Since that time, several papers have been published about RFA in thyroid glands, demonstrating the efficacy and safety of RFA for treating benign non-functioning, autonomously functioning thyroid nodules [11-16] and local recurrence from well differentiated malignancies [17-20]. The efficacy of RFA for reducing benign nodule volume and relieving nodule-related clinical problems has been recently confirmed by the prospective comparison study by Baek et al. using a control group [21] and by Lim et al. that reported a mean volume reduction rate of 93.4% in a four-years follow-up period [22].
In patients with locally recurrent thyroid cancer RFA also demonstrated to be effective for maintaining locoregional control of their cancer [17–20], being reported a mean volume reduction of 56–93% [19, 20].
The aim of our study was to determine the efficacy of Ultrasound-guided Radiofrequency Ablation in our experience in the treatment of symptomatic benign thyroid nodules and recurrent well-differentiated thyroid cancers.
MATERIALS AND METHODS
Patients
Twenty-three nodules in 23 patients judged ineligible for surgery or refusing surgery
were treated with single-session US-guided RFA at our Institution. Fiftheen out of 23
lesions were benign nodules in patients (12 females, 3 males; mean ± SD age, 57,8 ±
9,9 years; range, 39-73 years) with nodular goiter (NG) reporting cosmetic and/or
symptomatic problems. Eight patients (2 females, 4 males; mean ± SD age, 68 ± 9,8
years; range, 53-83 years) presented with regional recurrence from well-differentiated
thyroid carcinoma (RTC). Citologically confirmation of benign or malignant nature,
respectively, was obtained on two separate US-guided FNAB for each patient.
Pre-ablation assessment
All patients were evaluated by baseline and contrast-enhanced ultrasound (CEUS)
examination (7,5 MHz, MyLab Twice, Esaote, Italy).
Unenhanced and post-contrastographic computed tomography (CT) examination
(Light Speed VCT, General Electric, USA) of the neck was also performed for all
RTCs; baseline CT scan was also done for large benign nodules (> 20 mL).
The volume of each nodule was calculated before RF ablation as V= πabc/6 (where V
is volume, a is the largest diameter, and b and c the two other orthogonal diameters).
Nodule vascularization was assessed before treatment by evaluating lesions contrast
enhancement using three-point scale, with grade 1, 2 and 3 defined respectively as
diffusely low, inhomogeneously moderate and diffusely high vascularity.
medium uptake, was also evaluated. Fluid component of mixed type nodules was
previously aspirated in order to obtain only predominantly solid lesions (solid
component > 85%). Furthermore, all patients with NG were asked to rate pressure
symptoms on a 10-cm visual analogue scale (0–10 cm), and the physician recorded a
cosmetic grade (1, no palpable mass; 2, invisible but palpable mass; 3, mass visible on swallowing only; and 4, easily visible mass) [23-25]. Laboratory examinations for
patients with NG included measurements of serum thyrotropin, total triiodothyronine
and free thyroxine concentrations.
Procedure
A written informed consent document, explaining possible complications, was obtained from all patients before the procedure.
RF ablation was performed on inpatients who had been hospitalized during the
previous afternoon and discharged the morning after treatment.
Platelet count and blood coagulation tests, including prothrombin time and activated
partial thromboplastin time were required to be normal.
Before ablation, an intravenous route was made via the antecubital vein of the arm for the intravenous administration of sedative drugs, being the procedure performed under mild sedation. The patients were treated with 2% lidocaine for local anesthesia at the puncture site. To prevent unnecessary scar formation, the skin was not incised. All RF ablations were performed by using a RF generator (VIVA RF generator, STARmed, Korea) and 18- or 19-gauge internally cooled, single tipped electrode
with 7- or 10-mm active tip. In this study we treated only one nodule per patient; if the patient had a multinodular goiter, we treated the nodule of most cosmetic or symptomatic concern. Under US guidance, we performed RF ablation of benign nodules using transisthmic approach and moving shot technique, as previously
described [11,12,21,23]. Small regional recurrences of thyroid cancer were treated by mostly using a vertical approach being the electrode fixed during ablation. One puncture of the skin and thyroid capsule was made in all patients.
During the procedure, we payed special attention to the preservation of surrounding
important organs to prevent significant complication such as nerve injury.
Ablation was begun with 30–35 Watt of RF power. If a transient hyperechoic zone
did not form at the electrode tip within 5–10 s, RF power was increased in 5 W
increments to a maximum of 45 W, depending on the size of the active tip and the
internal characteristics of each nodule.
CEUS examinations were performed during procedure to better assess residual vascularized tissue. The ablation procedure was terminated when all conceptual units had become unenhancing zones. Immediate complications were evaluated
periprocedurally.
Follow-up
Patients were followed-up by US and CT examinations as in the pre-ablation
assessment. Mean follow-up period was 10,4 months for NGs and 13 months for
RTCs (range between 6 and 18 months).
Volume - Final Volume/Initial Volume) x100] were assessed. Therapeutic success
was defined as a >50 % VRR.
Residual vital tissue was also assessed by using CEUS or post-contrastografic CT
examinations.
Cosmetic and symptom scores and thyroid function tests were evaluated during the
follow-up period in the same manner as before ablation.
For NGs we also tried whether there was a correlation between VRR at 6 months
follow-up and some parameters such as age, gender, mean energy per millilitre of
pre- treatment nodule volume, initial nodule volume, initial nodule solidity and initial
nodule vascularity.
Regrowth and/or recurrence were defined as increases in nodule volume >50%
compared with previous US examination [26,27]. Complications were assessed
according to clinical signs and symptoms.
Statistical analysis
All data were analysed using the statistical software package JMP for Windows
(http://www.jmp.com). Continuous data are reported as mean ± SD (range). Wilcoxon signed rank tests were used to compare changes in nodule volume and in
residual vital tissue before RF ablation and at each follow-up. Changes in cosmetic
and symptom scores of NGs before treatment and at last follow-up were also
evaluated by using Wilcoxon signed rank tests.
Multiple linear regression analysis were utilized for NGs to determine a correlation
energy per millilitre of pre- treatment nodule volume, initial nodule volume, initial
nodule solidity and initial nodule vascularity. We did not perform statystical analysis
for RTCs because of the limited population.
Differences were considered statistically significant when the P value was less than
0.05.
RESULTS
The baseline characteristics of the NGS and RTCs, and the initial cosmetic and
symptom scores of the patients are summarised in Table 1 and Table 2, respectively.
Tab.1 Baseline characteristics of benign thyroid nodules and patients’ cosmetic and symptom scores
Tab.2 Baseline characteristics of local recurrences of well-differentiated thyroid carcinomas
Follow-up period ranged between 6 and 18 months, with the mean ± SD follow-up
13 ± 5,4 months (range, 6– 18 months) for RTCs.
Changes in thyroid nodule volume and residual vital tissue of NGs at each follow-up
are shown in Fig. 1. Cosmetic and symptom scores improvement at last follow-up is
illustrated in Fig. 2. The mean ± SD nodule volumes in NGs at 6, 12 and 18 months
follow-up were 7,4±8,6 ml, 4,1±2,8 ml and 4,6±2,7 ml, respectively. We found that
volume (7,2± 8,7 ml; range 0,6-37,4 ml), residual vital tissue (2,4±4,8 ml; range
0-19,3 ml), cosmetic score (1,8±0,5) and symptom score (0,5±1,2) of NGs were
significantly lower at last follow-up than before treatment (P<0,0001 for volume and
residual vital tissue comparison; P=0,0001 and P=0,0002 for symptom and cosmetic
scores comparison, respectively).
Fig. 1 Changes of thyroid
nodule volume and residual vital tissue before RF ablation and at each follow-up
The mean ± SD VRRs of NGs at 6 months, 12 months and 18 months follow-up were
74,3±9,7 % (range, 56,5–90%), 79,8± 8 % (range, 62,6–89%) and 83,0± 5,3 %
Fig. 2 Changes of
symptom and cosmetic scores before RF ablation and at last follow-up.
At last follow-up, the therapeutic success rate for NGs was 100% (15/15) and the
complete necrosis (considered as the absence of residual vital tissue) was obtained in
5/15 patients (33.3 %). The overall recurrence rate was 0% (0/15).
Fig. 3 Changes of Volume
Reduction Rate (VRR) before RF ablation and at each follow-up
Mean total energy delivered per nodule in NGs was 36173,7±18087,3 J (range, 2303–
(E/ml) was 1615,4±725,6 J (range, 132,4–2572,9 J).
Multiple linear regression analysis showed that initial nodule volume, vascularity and
energy delivered per millilitre of pre-treatment nodule volume were significantly
related to 6-months VRR (P<0,0001 for all analysis). Statistically significant
relationship between VRR and above-mentioned factors are shown in Fig. 4-6.
No patients experienced hypothyroidism nor hyperthyroidism after procedure. A
patient suffering from hyperthyroidism because of a Plummer nodule returned to be
euthyroid after one week to treatment and after the immediate withdrawal of therapy
with methimazole. The overall complication rate in NGs was 0% (0/15).
Fig. 4,5,6 Multiple linear regression analysis showed
a statistically significant correlation between the 6-months VRR and some parameters such as the initial nodule volume, the initial nodule vascularity and the energy delivered per millilitre of pre-treatment nodule.
Two out of 8 patients with RTCs did not perform 6-months follow-up because of systemic disease progression and the occurrence of severe comorbidity, respectively. Five out 6 patients presented with lesions in the surgical bed. Clinical findings, changes in nodule volume and VRR for each RTC at each follow-up are reported in Table 3 and 4. Changes in thyroid nodule volume for each RTC at 6-months,
12-months and 18-12-months follow-up are shown in Fig. 7. The mean ± SD lesion volumes
in RTCs at each follow-up were 1,6±1,7 ml, 2±1,8 ml and 2,4±1,8 ml, respectively.
Fig. 7
Tab. 3
Fig. 7, Tab. 3 Characteristics and changes in nodule volume of each RTC at each follow-up
Changes of VRRs of each RTC at 6 months, 12 months and 18 months follow-up are
66,4± 11,5 % (range, 46,6–75 %) and 64,4± 12,5 % (range, 46,6–73,3 %) at 6, 12 and
18 months follow-up, respectively.
At last follow-up, the therapeutic success rate for RTCs was 83% (5/6) and the
complete necrosis (considered as the absence of vascularized tissue) was obtained in
3/6 patients (50%). The overall regrowth and/or recurrence rate was 0% (0/6).
Fig. 8
Tab. 4
Fig. 8, Tab. 4 Characteristics and changes in VRR of each RTC at each follow-up
The overall complication rate in RTCs was 50% (3/6); major complications were
triangle of recurrent laryngeal nerve (two reported permanent voice change and one
presented transient dysphonia, both due to recurrent nerve injury). No patient
experienced a life-threatening or delayed complication during follow-up.
DISCUSSION
Thyroid nodular disease is very common. The prevalence of thyroid nodules has been reported as 20-76% at ultrasound examination, according to the prevalence reported at autopsy that ranges from 50 and 65% [1-3,28].
If the nodule is malignant or benign but causes compressive symptoms, surgery is usually a better choice to remove the nodule effectively. If the patient has primary thyroid cancer, surgery is always the first choice, but if recurrent thyroid cancer is detected several years after primary surgical intervention, significant risks may be associated with comorbidity and with scars from previous operations; this group of patients has undergone total thyroidectomy, radioactive iodine ablation and many have also had lymph node dissections, thus cervical anatomic planes are distorted. A nonsurgical and minimally invasive treatment modality is needed as an alternative in these patients. When it refers to benign thyroid nodule but with compressive symptoms, surgical intervention has some disadvantages such as leaving scar tissue in the neck; moreover, in some patients with NG, surgery is not feasible because the patient has important comorbidities or may not be intubated for the presence of severe tracheal compression by the goiter. It calls for a nonsurgical, minimally invasive alternative for these patients, being the US-guided ablative therapy no
needing for general anesthesia, no scarring, requiring earlier recovery to normal lifestyle, and burdened with fewer complications.
Ethanol Ablation (EA) [7,8] and laser Ablation (LA) [9] have been tried previously in such scenarios.
Radiofrequency has also been introduced to ablate thyroid malignancies and benign thyroid nodules. In 1998, the first paper about radiofrequency ablation in thyroid disease was published by Solbiati et al [10]. Since that time, several papers have been published about radiofrequency ablation (RFA) in thyroid glands, demonstrating the efficacy and safety of RFA for treating benign non-functioning, autonomously functioning thyroid nodules [11–16] and local recurrence from well differentiated malignancies [17-20].
In our study we treated with RFA only solid or mainly solid nodules, both benign and malignant. The fluid component of mixed type benign nodules was previously aspirated in order to obtain only predominantly solid or solid lesions (solid
component > 85%).
As shown by many reports RFA is more effective than EA in the treatment of solid or mainly solid benign nodules, suggesting that solid components might be more resistant to ethanol diffusion and that the vascularity of solid nodules favors the drainage of ethanol; thus, the success of the procedure [29-34] results to be limited and multiple injections of a larger amount of ethanol are required to obtain a satisfactory degree of volume reduction. This may lead to greater patient discomfort or to adverse effects of the procedure.
Some reports [12,31] demonstrated that RF ablation may be also effective and safe in the treatment of benign predominantly cystic nodules being the volume reduction rate quite similar (93.1% in EA and 92.2% for RF ablation) at the 6-month follow-up [35].
Nevertheless, RFA has several disadvantages compared to EA, including its high cost and technical difficulty. Therefore, EA remains the first-line modality in the treatment of cystic or mainly cystic thyroid nodules [36-39]; according to these findings, we did not perform RFA for cystic or predominantly cystic benign nodules. Previous studies also suggested the usefulness of EA in the treatment of regional recurrent thyroid malignancies [40,41], but RF ablation demonstrated to be more effective than EA for these lesions even when it was used to treat larger lesions [18,42]. Compared with EA, RFA has also an advantage in number of treatment sessions. The reason for the better efficacy of RF ablation may be due to the solidity of recurrences and to the nonuniform ethanol diffusion unable to induce necrosis to the lesion border.
Regarding to LA, RFA results demonstrated to be superior to that of laser ablation in a long-term follow-up, being the VRR 90–92% in RFA versus 48% in LA in a three-years follow-up [22,23,43] and more recently, Lim et al. [22] also compared changes in
volume of benign nodules treated with RFA to those of LA; they observed a gradual volume reduction in RFA treated nodules during follow-up, whereas nodules treated with LA tended to increase in volume at last follow-up [21,43-45] with the latter
possibly due to the regrowth of undertreated peripheral portions of nodules [23,44,46]. RFA also seems to be safer than laser ablation [47].
The efficacy of RF ablation for reducing benign nodule volume and relieving nodule-related clinical problems was recently confirmed by the prospective comparison study by Baek et al. and using a control group [21]. In five, representative studies, reduction of the nodule volume after RF ablation ranged from 33– 58% at one month and from 51–85% at six months postablation [12,14,21,46]. More recently, the mean volume reduction rate based on 111 patients with 126 benign thyroid nodules has been reported to be 93.4% four years following RF ablation [22].
In patients with locally recurrent thyroid cancer RFA also demonstrated to be effective for maintaining locoregional control of cancer [17-20], being reported a mean volume reduction of 56–93% [19,20], and with 42–58% of the nodules disappearing completely [17,18,20].
The results of our study correspond well to those study results.
The present evaluation of 23 patients demonstrated that RF ablation resulted in significant reductions in the volumes of 15 benign thyroid nodules, as well as improving cosmetic and/or symptomatic problems for NGs. We found that the efficacy of RF ablation in the treatment of benign nodules was influenced by the initial volume (being the VRR higher for smaller lesions) and vascularity of the nodules, resulted RFA to be more effective in nodule with low grade of vascularization. Energy delivered per millilitre of pre-treatment nodule volume also demonstrated to be significantly related to 6-months VRR, suggesting an adequate energy supply.
We suggest that the efficacy of RF ablation is explained by the moving shot technique and straight internally cooled electrodes. For the moving shot technique, we divided thyroid nodules into multiple small conceptual ablation units and then performed ablation in the nodule in a unit-by-unit manner by moving the electrode [12,23,24,46]. This technique enabled more detailed ablation of each conceptual unit and of the periphery of the nodule showing the capacity to completely ablate the entire nodule unlike other stationary ablation methods such as in laser ablation. Theoretically, this technique will ablate nodules more completely because the tumor shape is usually ellipsoid rather than round [23].
We treated all nodules in a single-session ablation, according to several previous studies [11,13,48,49] reporting that single-session RF ablation was sufficient for
treatment of thyroid nodules, reducing nodule volume and improving cosmetic problems and nodule-related symptoms. In our study no benign nodule presented a regrowth during the follow-up period.
The advantage of straight internally cooled electrodes is easy movement [46], and the advantage of an internally cooling technique is preventing carbonization [50]. This electrode is shorter and thinner than that of a conventional electrode used in the liver, and was designed for easy control and minimal normal tissue injury.
On the basis of previous studies [11,12,51] we proposed use of the transisthmic approach. An electrode approach is made from the medial to the lateral aspect of a targeted nodule, the short axis of the nodule, and RFA is performed in a transverse ultrasound view. This method has several advantages over the long-axis approach
(caudocranial or craniocaudal direction) and the vertical approach [13,31,52,53], firstly that the electrode passes through sufficient thyroid parenchyma to prevent a change in the position of the electrode tip during swallowing or talking. Another advantage is clear visualization of the relations of the thyroid nodule, electrode tip, and recurrent laryngeal nerve to one another in order to minimize the risk of injury to the recurrent laryngeal nerve.
For the 8 RTCs we treated, both transisthmic approach and vertical method were used, by choosing as the case. We did not perform moving shot technique in the treatment of RTCs but the electrode was held fixed during the treatment. In this way we have exploited the heating effect due to the presence of perilesional fibrosis linked to previous surgery and radiation therapy in the neck.
According to other investigators [17,42] we reported no recurrent disease at RF sites in our small group of patients with RTCs with a mean follow-up of 13 months. However, some authors [19] experienced tumoral regrowth in 2 of 15 treated cases, including one where complete ablation was initially obtained. The factors that cause tumor regrowth are unclear. Park at al. [19] demonstrated that there was no marked difference in techniques such as ablation time or RF power output between the masses that responded to therapy versus the ones that did not in their study.
They hypothesized that is likely that regrowth is related to tumour biological behaviours. Thus, RFA is only recommended in the treatment of histologically well-differentiated tumours, and there is no evidence of efficacy of RFA in the treatment
of poorly differentiated tumours or in medullary cancers. According to these findings, we included in our study only recurrences from well-differentiated thyroid cancers. A therapeutic success was obtained in 5 out of 6 patients (83%) because 1/6 RTC presented a VRR <50%; this is explained by the fact that the end point of our study, as previously suggested [17–20], was volume reduction and local control of cancer in patients with RTCs.
One patient was lost from follow-up to the onset of severe lung infection and respiratory failure and another patient presented disease progression in other sites except the RF site and has been managed with systemic therapy in another Institution. Three of our patients had dysphonia after treatment of a recurrence in the surgical bed. Dupuy et al. [17] and Monchik et al. [18] also reported that one patient had dysphonia after treatment of a surgical bed tumor. These findings suggest that RFA is less safe in the surgical bed than in the lateral aspect of the neck. During RFA of the lateral aspect of the neck, the vagus nerve can be damaged, especially when the nerve is close to the tumor. At ultrasound examination, however, the vagus nerve is well visualized within the carotid sheath, usually posterolateral to the common carotid artery and posteromedial to the internal jugular vein. Careful attention to the vagus nerve during ablation can prevent vagus nerve injury [54,55]. In contrast, in the surgical bed, the recurrent laryngeal nerve is not visualized at ultrasound examination, and the nerve is more vulnerable to thermal injury.
Our study had several limitations. The first limitation was a relatively short-term follow-up period. Nodule regrowth may be possible during longterm follow-up
periods, thus further results should be verified. Another limitation was that our sample size was small and might not be reflective of a larger population of symptomatic thyroid nodules and recurrent thyroid cancers.
In addition, selection bias is inevitable. Regarding to RTCs, we treated small lesions likely providing more favourable results. Further works are needed to fully evaluate the RFA in inoperable RTCs because of the indolent nature of the disease and low mortality rate.
CONCLUSION
Although surgery is the standard treatment of symptomatic benign thyroid nodules and locally metastatic thyroid cancer, RFA is effective for symptoms relief and locoregional control of recurrences. RFA reduced the tumor volume significantly and demonstrated also to be a safe procedure. However, RFA is less safe for central than for lateral neck tumors, and we recommend that caution be exercised in the treatment of lesions that may be in close proximity to the recurrent laryngeal nerve.
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