The preliminary study on the microwave ablation of multifocal papillary thyroid microcarcinoma

doi:10.21203/rs.3.rs-2582416/v1

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The preliminary study on the microwave ablation of multifocal papillary thyroid microcarcinoma

https://doi.org/10.21203/rs.3.rs-2582416/v1

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published 01 Jan, 2024

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Purpose

To evaluate the feasibility, efficiency, and safety of MWA for PTMC.

Methods

This was a retrospective study, the date of patients who underwent MWA for multifocal PTMC from October 2016 to December 2021 were reviewed. After ablation, the changes in tumor size and volume, as well as the rate of technical success, tumor disappearance, disease progression, and complications were assessed. According to the tumor location, the cases were further divided into unilateral multifocal disease (UMD) subgroup and bilateral multifocal disease (BMD) subgroup. And further analyses were carried out.

Results

There was a total of 94 cases enrolled in the present study, which included 24 males and 70 females. The median age was 40 years (22–66 years); the median follow-up time was 14 months (6–48 months). Complete ablation was achieved in all enrolled cases. Therefore, the technical success rate was 100%. Due to expanding ablation, the MD and volume of the ablation zone increased at the 1st and 3rd months after ablation and decreased from 12th month after ablation (p < 0.05 for all). The total complete tumor disappearance rate was (45/94, 47.87%), including, 40.625% (13/32) in the UMD subgroup vs. 51.61% (32/62) in the BMD subgroup (p = 0.312). The total disease progression rate was 4 (4/94, 4.26%), including 6.25% (2/32) in the UMD subgroup vs. 3.23% (2/62) in the BMD subgroup (p = 0.881). The overall complication rate was 4.26% (4/94).

Conclusion

This preliminary study indicates that MWA is a safe and effective treatment for multifocal PTMC.

multifocal

PTMC

MWA

safety

The incidence of thyroid cancer has increased rapidly in last decades, ranking in the 9th place for incidence in 2020(1). Papillary thyroid carcinoma (PTC) is the most common pathological subtype in the thyroid malignancy (2). Papillary thyroid microcarcinoma (PTMC) is defined as a PTC measuring less than 1cm in its maximum diameter. The incidence of PTMC increased the most at a total of 441% from 1983 to 2006 or by 19.2% per year (3). In generally, most of PTMCs are low risk with favorable prognosis(4). Tumor multifocality is frequently observed in PTMC, roughly 20%-40%(5). According to the guidelines, the first recommend therapy is surgery (6). However, due to the cosmetic problems and lifelong hormone replacement, most patients refuse to accept the traditional surgery. Active surveillance (AS) is suggested as a safe strategy for management of PTMC(7, 8). However, because of the anxiety induce by PTMC, few case could accept and adhere this management.

In recent years, minimally invasive image-guide ablation techniques such as microwave ablation (MWA), radiofrequency ablation (RFA), laser ablation (LA) have been developed. The outcomes of thermal ablation for unifocal PTMC were proved to be promising according to the previous studies(9–11).However, the study on MWA of multifocal PTMC has seldom been reported.

Therefore, in present study, the clinical outcomes of MWA on multifocal PTMCs were summarized and the result in unilateral and bilateral multifocal PTMC were further compared between subgroups.

The retrospective research was approved by the China-Japan Friendship Hospital Ethics Committee. All patients were provided with informed consent before undergoing MWA treatment. The requirement for written informed consent of patients for publication of data was waived by the ethics committees because the personal details were kept confidential.

Patients

The medical records of cases with multifocal PTC who underwent MWA treatment from October 2016 to December 2021 are reviewed. The inclusion criteria were as follows: 1) all nodules treated with MWA had fine-needle aspiration biopsy cytology proven PTMC; 2) no lymph node metastasis (LNM) or extrathyroidal extension (ETE) on us or CT pre-ablation; 3) ineligibility or refusal to undergo surgery; and 4) follow-up time ≥ 6 months. The exclusion criteria were as follows: 1) thyroid malignant tumor beyond PTC; 2) unifocal lesion; 3) associated with tumor located in other organs; 4) recurrent laryngeal nerve palsy. The enrolled cases were divided into unilateral multifocal disease (UMD) and bilateral multifocal disease (BMD) subgroups according to the tumor location for further analysis.

Preoperative examination

All patients underwent the routine US examination including nodules’ size, volume(v = πabc/6), blood flow distribution and location, which carried out with the GE LOGIQ E9 (GE healthcare, Pittsburgh, PA, USA). The laboratory examinations (blood routine test, coagulation and thyroid function) and neck and chest CT scans were carried before MWA.

MWA procedure

All US-guided procedures were performed by radiologists with more than 3 years experience for thyroid nodules ablation. Patients were supine in the operating bed, and their necks were fully exposed and routinely sterilized. Lidocaine (1%) was injected on the proposed puncture side for local anesthesia. For protecting surrounding vital organs, normal saline as isolation fluid was injected along the thyroid capsule corresponding to the PTC tumor location through an 18-gauge needle guided by US. The 17G MWA antenna with a 0.35-cm radiation tip (Intelligent Basic Type Eco or Kangyou Microwave Tumor Ablation Systems, Nanjing, China) was percutaneously inserted into the PTC lesion under US guidance. The multiple points ablation strategy was applied. That is, in one-point ablation, fixed applicator ablation was performed with a power of 30 W and radiation time of 15–20 s. Then, the antenna tip was moved to the next point guided by ultrasound, and the next ablation was performed with the same radiation time. Subsequent ablation was performed until the overlap ablation zone covered the whole nodule. The strategy of extending ablation was performed, which referred to the ablation zone covering the whole PTC lesion and extending at least 2 mm from the lesion margin. For bilateral nodule ablation, if there were no voice changes and no abnormal vocal cord movements on US after one side ablation, MWA was immediately performed on the contralateral side. If there were any signs of recurrent laryngeal nerve (RLN) injury, the ablation was stopped, and the second session was suspended until RLN function recovered. For ablation order in BMD subgroup, the PTMC locating in safe side was firstly ablated, which generally refer to the PTMC nodule is far from RLN. The PTMC nodule closed to RLN in contralateral was ablated lastly. In UMD subgroup, the nodule in deep position was firstly ablated for avoiding hyperechogenicity caused by gasification affects the US field. After ablation, Ultrasound Contrast (CEUS) was employed immediately to evaluate the ablated effect. If any nodule enhancement inside the ablation zone was found on CEUS or the distant of the expanding distant was < 2 mm, a complementary ablation was performed immediately.

Post-ablation observation and follow-up

After ablation, the patient was placed in the observing room for approximately 30 minutes to monitor complications. The follow-up time is 3 months within the first year and every 6 months thereafter. The routine follow-up included neck ultrasound examination and thyroid function every time, neck and chest CT scans once a year. If local recurrence, new one or LNM was suspicious, CEUS and FNA were further performed to make a definite diagnosis. The size of the ablation zones and volume reduction ratio (VRR) were calculated and recorded. VRR= (primary volume-final volume)/primary volume.

Statistical analysis

Descriptive statistics are presented as the mean ± standard deviation (SD) or median for continuous data according to whether the data were normally distributed. Categorical variables are presented as percentages. Paired t-tests or Wilcoxon signed rank tests were used to compare changes in thyroid function, size and volume of tumors between pre- and post-ablation. All statistical analyses were performed using SPSS statistics software (version 26.0); a P value < 0.05 was considered statistically significant. Univariable and multivariable analyses were performed by using a Cox proportional hazard model to identify the variable associated with disease progression.

Demographic characteristics

The demographic characteristics are summarized in Table 1. Data from 94 patients was reviewed and summarized. The median age was 40 years old. The follow-up time ranged from 10 to 48 months (median 14 months). The number of tumors ranged from 2 to 5 (median 2). There are 32 patients in the UMD subgroup and 62 patients in the BMD subgroup. No significant differences were found between the UMD and BMD subgroups regarding age (p = 0.290), sex rate (p = 0.679), or tumor number (p = 0.057).

Table 1

the patients’ baseline in UMD and BMD subgroup
Variable	Total (n = 94)	UMD* (n = 32)	BMD* (n = 62)	P value
Age (years)	40.00	42.78 ± 1.557	39.00	0.290
Female (%)	70 (74.47)	23	47	0.679
Male (%)	24 (25.53)	9	15
Follow-up time (months)	12.000	12.000	12.000	0.546
Ablation time (s)	135.00	128.31 ± 9.242	140	0.037
BRAF^V600E mutation
Positive	79(84.04)	29(90.63)	50(80.65)	0.211
Negative	15(15.96)	3(9.37)	12(19.35)
Maximum diameter	0.700	0.656 ± 0.0324	0.7000	0.386
multifocality	2.00	2.00	2.00	0.057
*UMD, unilateral multifocal disease; BMD, bilateral multifocal disease

Tumor characteristics in subgroups

In the UMD subgroup, the number of tumors was 68 in 36 cases. Among them, 28 patients had 2 tumors and 4 patients had 3 tumors. In the BMD subgroup, the number of tumors was 149 in 42 cases. Among them, 44 patients had 2 tumors, 12 patients had 3 tumors, 5 patients had 4 tumors and 1 patient had 5 tumors. There was no difference between UMD and BMD subgroups regarding the MD and primary tumor volume (p > 0.05 for both).

Technical success

After ablation, complete ablation referring to that by ultrasound evaluation the PTMC were completed enveloped by zone of ablation was performed in all enrolled cases in one season. The ablation time in one case ranged 32s from 632s (median 135s) in present study, which included 128.31 ± 9.242s in the UMD subgroup and 42-632s (median 140s) in the BMD subgroup. The ablation time was slightly longer in BMD subgroup than UMD subgroup (p = 0.037).

All targeted tumors were ablated successfully according to the preoperative plan. No ablation was suspended due to RLN injury after ablation in one side. Therefore, the technical success rate of MWA ablation was 100% (94/94).

Treatment efficiency

Due to the expanding ablation strategy, the volume of post-MWA tumor at 1st and 3rd month were significantly larger than that of pre-MWA tumor (0.901cm³ vs. 0.113cm³, p < .001 for both). The VRR at 1 and 3 months was − 700% and − 196.381%, respectively. At 6th month, the volume of post-MWA ablation zone was roughly same as the primary tumor. However, the volume of post-MWA tumor at 12th month was much smaller than that of pre-MWA tumor (p = 0.005). (Table 2) According to the statistic results, there is no significantly different regarding thyroid function between that before ablation and 1 month after ablation (p > 0.05).

Table 2

the volume of tumors post-ablation at each follow-up time point
Follow-up time(months)	Volume (cm³)	P value	VRR(%)
Pre-MWA(n = 94)	0.113
Post-MWA
1 (n = 94)	0.901	< .001	-700.000
3 (n = 94)	0.313	< .001	-196.381
6 (n = 94)	0.092	0.915	15.476
12 (n = 74)	0.020	< .001	80.556
18 (n = 43)	0.000	0.001	74.978
24 (n = 33)	0.000	0.010	86.006
36 (n = 18)	0.000	0.001	100.000
48 (n = 11)	0.000	0.013	33.824

At the end of follow-up time, the ablation zone in 45 cases (45/94, 47.87%) had completely disappeared. In the UMD subgroup, the ablation zone in 13 cases (13/32, 40.625%) had completely disappeared. Among them, 3 (3/32, 9.375%) patients had a tumor disappearance at 6th month, 4 (4/32, 12.5%) patients at 12th month, 2 (2/32, 6.25%) patients at 18th month, 1 (1/32, 3.125%) patient at 24th month, 2 (2/32, 6.25%) patients at 36th month, and 1 (1/32,3.125%) patient at 48th month. In the BMD subgroup, the ablation zone in 32 cases (32/62, 51.61%) had completely disappeared. Among them, 13 (13/62, 20.97%) patients had a tumor disappearance at 6th month, 14 (14/62, 22.58%) patients at 12th month, 1 (1/62, 1.61%) patient at 18th month, 3 (3/62, 4.84%) patients at 24th month, and 1 (1/62, 1.61%) at 36th month. There was no difference in rate of tumor disappearance between UMD and BMD subgroups (p = 0.312).

During the follow up period, no local recurrence happened. Disease progression occurred in 4 (4/94, 4.26%) cases, which includes new tumor encountered in 4 (4/94, 4.26%) cases and lymph node metastasis (LNM) in 1 (1/94, 1.06%) case. In the UMD subgroup, 2 (2/32, 6.25%) patients had disease progression. Both of them developed new tumor. In the BMD subgroup, 2 (2/62, 3.23%) cases developed disease progression. One of them developed new tumor, and another one had a new tumor and LNM simultaneously. No differences were found in diseases progression between UMD and BMD subgroups (p = 0.881). Among the 4 patients who had a disease progression, no one was older than 55 years old, 1 patient accompanied by Chronic lymphocytic Thyroiditis (CLT), 3 patients’ primary tumor had BRAF^V600E mutation, and 3 patients’ gender were female. Cox regression analysis showed that no risk factors was significantly associated with disease progression regarding to multifocality age, sex, size of tumor, CLT, and BRAF^V600E mutation.

Further ablations were employed to successfully manage all of these new tumors and LNM, and no disease progression occurred in the last follow-up period.

Assessment of treatment safety

Complications were encountered in 4 (4/94, 4.26%) cases in present study. Among them, hoarseness as an exclusive major complication occurred in 3 cases (3/94,3.19%). The symptoms disappeared within 4 months without any therapy. 1 patient developed a stuffy nose, bloodshot eyes and facial redness as minor complications and obviously improved within 7 days after ablation.

PTMC is recognized as a low risk disease according to the literature (4, 6). However, multifocal PTCs have been associated with increased risk of disease progression after initial treatment(12–15). How to manage the multiple PTMCs is still controversial(16). Surgery is recommended as the first-line therapy (17). But the damage for patients’ thyroid function should be concerned. AS could not be accepted for most of patients. It has been verified that the MWA could be used for unifocal PTMC as a safe and effective method(18). Whether the thermal ablation could be managed multiple malignant tumor? In clinical, minimally invasive thermal ablation has been widely used in treatment for multifocal hepatocellular carcinoma (HCC) and multifocal renal cell carcinoma (RCC)(19, 20). The present study evaluated the feasibility, safety and efficiency of MWA for multifocal PTMCs.

The results showed that all patients underwent successfully complete ablation, suggesting MWA is a feasible treatment for multifocal PTMCs. Because the PTMC nodule in safe side was firstly ablated and the one close RLN in contralateral was managed lastly in present study. Although there are 4 cases encountered RLN injury, the complete ablation was achieved in all enrolled cases.

There is no local recurrence in present study during the follow up period, indicating that MWA could utterly inactive target tumors and the efficiency is 100%. In addition, there was no difference regarding thyroid function between pre-ablation and post-ablation, which demonstrates that MWA has no influence on thyroid function, even in cases of expanding ablation for multifocal PTC nodules simultaneously.

At the end of follow up period, the rate of tumor disappearance was 47.87%, which includes 40.625% in UMD subgroup and 51.61% in the BMD subgroup. The tumor disappearance rate in present study is consistent with that of MWA in unifocal PTC(21). these results demonstrate the MWA of PTC has similar tumor disappearance both in multifocal or unifocal PTC. In addition, there is no difference regarding tumor disappearance between the two subgroups.

During the follow up period, 4 patients developed disease progression. Among them, 2 (6.25%, 2/32) patients were in the UMD subgroup and 2 (3.23%, 2/62) patients were in the BMD subgroup. According to the previous study, multifocal bilateral PTMCs associated with higher risk of disease progression than multifocal unilateral PTMCs(22). However, no differences were found between the two subgroups in present study. Further analysis, the rate of LNM was similar with previous study about MWA on unifocal PTC(21). The rate of new tumor is higher than that in studies with unifocal PTC. The underlying reason maybe that there are tiny PTC nodule which is too small to discover on US before ablation. During follow up, a few of them develop the new one. Fortunately, all new ones, as well as LNM were further ablated and there was no disease progression in the last of follow up.

In the present study, the only major complication was slightly RLN injury. The rate of complication was similar to the results of unifocal PTC studies(21). In our experience, the isolation technique is a key factor to ensure the safety of ablation, which has been successfully employed in MWA of unifocal PTC(21). All symptoms disappeared within four months without any therapy, illustrating that MWA is a safe therapy for multifocal PTMC nodules.

There were still a few limitations in present study. First, it was a single-center retrospective study, which might have resulted in some selection biases. Second, the sample capacity is relatively small and the follow up time is relative short. The definite conclusion needs the further study with larger sample and longer follow up time.

The present preliminary study indicate that it is feasible, safe and effective for MWA of multifocal PTMC.

Acknowledgements

We thank all participants for their support in this study.

Author Disclosure Statement

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Funding

National Natural Science Foundation of China (62176268).

National High Level Hospital Clinical Research Funding (2022-NHLHCRF-PY-07)

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Journal Publication

published 01 Jan, 2024

Read the published version in Academic Radiology →

Version 1

posted

You are reading this latest preprint version

The preliminary study on the microwave ablation of multifocal papillary thyroid microcarcinoma

Status:

Journal Publication

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Materials And Methods

Patients

Preoperative examination

MWA procedure

Post-ablation observation and follow-up

Statistical analysis

Results

Demographic characteristics

Tumor characteristics in subgroups

Technical success

Treatment efficiency

Assessment of treatment safety

Discussion

Declarations

References

Status:

Journal Publication

Version 1