A Meta-Analysis of Clinical Outcomes After Radiofrequency Ablation and Microwave Ablation for Lung Cancer and Pulmonary Metastases

ORIGINAL ARTICLE

CLINICAL PRACTICE MANAGEMENT

A Meta-Analysis of Clinical Outcomes After Radiofrequency Ablation and Microwave Ablation for Lung Cancer and Pulmonary Metastases Zhuhui Yuan, MBBS a, Yang Wang, MBBS a, Jim Zhang, MD b, Jiasheng Zheng, MD c, Wei Li, MD, PhD a Abstract Purpose: We conducted a meta-analysis assessing clinical outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) for treating lung cancer. Methods: Databases were searched up to 2017 to identify high-quality studies. The results were presented as pooled estimates with 95% confidence intervals (CIs). Results: Fifty-three studies were included, and up to 3,432 patients were pooled. The estimated 1-, 2-, 3-, 4-, and 5-year overall survival (OS) rates were higher for RFA-treated patients compared with those treated by MWA. The median OS, median progression-free survival (PFS), median local tumor PFS, complete ablation rate, and adverse events did not differ significantly. Subgroup analyses by tumor type showed that the median OS for RFA-treated patients with pulmonary metastases was higher than that of the MWA-treated patients. Conclusion: Thermal ablation, both RFA and MWA, is an effective approach for treating lung cancer with low risk of adverse events. RFA is associated with longer survival than MWA, and patients with pulmonary metastases showed better survival after RFA compared with MWA-treated patients. Key Words: Microwave ablation, radiofrequency ablation, primary lung cancer, pulmonary metastases, meta-analysis J Am Coll Radiol 2018;-:---. Copyright
2018 American College of Radiology

INTRODUCTION Radiofrequency ablation (RFA) is the predominant method to date among the ablation therapies for cancers and has been successfully applied to either primary or a Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China. b Biomedical Application Manager Greater China R&D, Shanghai, China. c Center of Interventional Oncology and Liver Diseases, Beijing You’an Hospital, Capital Medical University, Beijing, China. Corresponding author and reprints: Dr Wei Li, Cancer Center, Beijing Ditan Hospital, Capital Medical University, No.8 Jingshun East Street, Chaoyang district, Beijing 100015, China; e-mail: [email protected]. Zhuhui Yuan and Yang Wang contributed equally to this manuscript. This work was supported by Beijing Talents Project; Funding for High-Level Talents in Beijing Municipal Health System (Grant No. 2014-3-088); National Major Scientific Instruments and Equipment Development Project (Grant No. ZDYZ2015-2); Beijing Natural Science Foundation (Grant No. 7142078); National Twelve-Five Key Technology Support Program (Grant No. 2012BAI15B08); Beijing You’an Hospital Hepatic Disease & HIV Fund (Grant No. 20150203), and the National Natural Science Foundation of China (Grant No. H1617/81472328). The authors state that they have no conflicts of interest related to the material discussed in this article.

ª 2018 American College of Radiology 1546-1440/18/$36.00 n https://doi.org/10.1016/j.jacr.2018.10.012

metastatic tumors of less than 3 cm to 3.5 cm in size [1]. With the development of local thermal ablation, there is also growing evidence supporting the use of microwave ablation (MWA) to produce tissue-heating effects in lung tumors. However, the two approaches differ in several aspects associated with complete tumor necrosis: the energy yielded by a microwave antenna penetrates the target lesion uniformly and is less influenced by lesion conductivity. Likewise, carbonization and desiccation induced by thermal energy could be counteractive to RFA and increase tissue resistivity. Besides, blood flow could wash out the desired energy. RFA is vulnerable to this effect when the target lesion is near vessels. By contrast, the heat deposition of MWA is based on water rather than blood. Theoretically, although MWA is more optimal than RFA, the differing efficacies of the two approaches remain debated. This article focuses on providing such a desired systematic comparison based on the available evidence.

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This study was performed based on the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement [2].

METHODS AND MATERIALS A comprehensive literature search spanning 2010 to 2017 was performed in five databases: MEDLINE, Embase, the Cochrane Library, Web of Science, and ClinicalTrials. gov. The searched terms are listed in Appendix 1. The reference lists of target articles were also reviewed to further identify potentially relevant studies. The research was performed independently by two observers (Z.H.Y. and Y.W.) using a predetermined research strategy. Inclusion and Exclusion Criteria The inclusion criteria were: (1) the study had human subjects; (2) the patients had lung cancer, including primary or metastatic cancer, of all stages and all subtypes; (3) the studies reported clinical outcome after RFA or MWA; (4) the studies reported survival status after treatment (at 1, 2, 3, 4, and 5 years); (5) the studies were either prospective or retrospective randomized controlled trials (RCTs) and non-RCTs. We included studies published in English that reported on RFA and MWA for treating lung cancer. After title and abstract review, we excluded studies that were not directly relevant to RFA and MWA, such as cryoablation and laser ablation for treating lung cancer, and duplicate publications. When encountering duplicate trials published by the same group, only the latest or most complete reports were deemed eligible. Review articles, editorial reviews,

comments, posters, case reports, and letters were also excluded. Literature focusing on the outcome of the treatment without survival data was excluded. Figure 1 summarizes the literature search and screening. Metaanalysis was performed by combining the results of the selected articles with overall survival (OS), progressionfree survival (PFS), local tumor PFS (LTPFS), and complete ablation (CA) data.

Data Extraction and Quality Assessment Two researchers (Z.H.Y. and Y.W.) performed the literature screening and data extraction independently based on a predefined data form, and all disagreements were discussed and resolved by consensus. The following information was extracted from each study: the first author, publication year, study design, sample size, baseline patient characteristics, tumor characteristics, treatment modalities, ablation type(s) (RFA, MWA, or both), duration of follow-up, details of treatment efficacy, and the occurrence of adverse events (AEs). No attempt was made to obtain missing data from the authors. Survival rates were calculated using the Kaplan-Meier approach in the few studies reporting original data. In studies that did not report survival rates explicitly but that provided Kaplan-Meier survival curves, survival data were extracted from the survival curves. The AEs occurring for each therapeutic measure were added up instead of estimated with pooled analysis, and proportions and 95% confidence intervals (CIs) were calculated using a binomial distribution. The Quality Appraisal Tool for case series [3] and the Newcastle-Ottawa Scale for cohort studies [4] were assigned to each of these studies to assess

Fig 1. Flowchart of literature search and review.

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Table 1. Comparison of True SEs and Estimated SEs Survival Rates Gobara (2016) [19] OS survival rates True SEs* Estimated SEs† PFS survival rates True SEs Estimated SEs de Baère (2015) [22] OS survival rates True SEs Estimated SEs PFS survival rates True SEs Estimated SEs Koizumi (2015) [49] OS survival rates True SEs Estimated SEs

Median Follow-Up Time (Months)

Sample Size

1 Year

2 Years

3 Years

37

31

37

31

0.97 0.022 0.035 0.45 0.089 0.096

0.82 0.074 0.071 0.29 0.084 0.094

0.74 0.087 0.106 0.16 0.087 0.087

35.5

566

35.5

566

0.924 0.012 0.012 0.402 0.021 0.023

0.794 0.019 0.019 0.233 0.019 0.020

46

20

0.95 0.0487 0.0498

0.9 0.0671 0.0805

4 Years

5 Years

0.677 0.024 0.024 0.164 0.017 0.019

0.589 0.028 0.028 0.131 0.017 0.019

0.515 0.033 0.031 0.110 0.018 0.018

0.7597 0.1078 0.1095

0.6838 0.1209 0.1339

0.615 0.1301 0.1546

OS ¼ overall survival; PFS ¼ progression-free survival; SE ¼ standard error. *The study-reported standard errors of survival rates. † Standard errors of survival rates estimated by Weibull and exponential distribution model.

the quality of the included publications. We only assessed the most common AE with or without interventions. These included pneumothorax, pneumonia, and pleural effusion.

Statistical Analysis Pooled analysis was used to determine the weighted summary statistics for each treatment. The results are

presented as the pooled estimate with 95% CIs. As standard errors for the proportions of surviving patients were not reported consistently, we inferred them using the parametric bootstrap for survival data [5] (Table 1 and Table 2). The population survival progress for each study was modeled to the reported survival times (at 1, 2, 3, 4, and 5 years as reported). For studies with only one reported follow-up time, a one-parameter

Table 2. Pooled results of two methods RFA Outcomes OS 1 year 2 years 3 years 4 years 5 years PFS 1 year 2 years 3 years 4 years 5 years

MWA

Method 1*

Method 2†

Method 1

Method 2

89.2 (85.8-92.6) 68.3 (60.6-76.1) 56.0 (47.3-64.6) 45.5 (36.1-55.0) 41.3 (27.3-55.2)

89.1 (85.7-92.6) 68.3 (60.5-76.1) 55.9 (47.2-64.6) 45.4 (35.9-54.8) 41.2 (27.3-55.0)

79.3 (73.7-85.0) 51.9 (46.2-57.5) 34.6 (26.8-42.5) 30.9 (22.9-38.8) 16.0 (0-35.5)

79.3 (73.7-85.0) 51.9 (46.2-57.5) 34.6 (26.8-42.5) 30.9 (22.9-38.8) 16.0 (0-35.5)

62.4 (50.4-74.4) 31.7 (22.0-41.5) 33.1 (19.2-47.0) 22.8 (11.6-34.0) 31.3 (10.1-52.6)

62.5 (50.5-74.4) 31.8 (21.9-41.6) 33.1 (19.2-47.1) 22.8 (11.6-34.0) 31.3 (10.1-52.6)

64.8 (37.1-92.4) 43.1 (1.5-84.7) 56.0 (41.1-70.9) NA NA

64.8 (37.1-92.4) 43.1 (1.5-84.7) 56.0 (41.1-70.9) NA NA

MWA ¼ microwave ablation; NA ¼ not available; OS ¼ overall survival; PFS ¼ progression-free survival; RFA ¼ radiofrequency ablation. *The method used in our study. † The true SEs mentioned in Table 5 were replaced by the estimated SEs, and corresponding outcomes were reanalyzed.

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Table 3. Characteristics for studies included in the present meta-analysis First Author [Reference]

Year

Study Design

Treatment

Size

Male (%)

Median or Mean Age (range) (y)

Path (%)

Median (Range) F/U (Months)

Dupuy [7] Nour-Eldin [8]* Nour-Eldin [8]* Yang [9] Ko [10] Wei [11] Gianpaolo [12] Suzuki [13] Healey [14] Zheng [15] Sato [16] Liu [17] Vogl [18]* Vogl [18]* Gobara [19] Ferguson [20] Shen [21] de Baère [22] Li [23] Vogl [24] Schoellnast [25] Lanuti [26] Palussière [27] Kodama [28] Wei [29] Baba [30] Wang [31] Wang [32] Matsui [33] Iguchi [34] Higuchi [35] Garetto [36] Bonichon [37] Alexander [38] Petre [39] Simon [40] Carrafiello [41] Kim [42] Hiraki [43] Hiraki [44] Huang [45] Okuma [46] Hiraki [47] Kodama [48] Koizumi [49] Liu [50] Safi [51] Qiang [52] Vogl [53]

2015 2017 2017 2014 2016 2015 2013 2010 2017 2016 2016 2016 2016 2016 2016 2015 2013 2015 2013 2013 2012 2012 2011 2012 2016 2014 2015 2015 2014 2014 2014 2014 2013 2013 2013 2012 2012 2010 2011 2011 2011 2010 2010 2015 2015 2014 2015 2012 2011

P R R R R R R R R R R R R R P R R P R R R R R R R R P P R R P R P R R R R R R R R R R P P R P R P

RFA RFA MWA MWA MWA MWA MWA RFA MWA MWA RFA RFA RFA MWA RFA RFA RFA RFA RFA MWA RFA RFA RFA RFA MWA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA RFA MWA MWA

51 29 63 47 15 46 24 14 108 183 46 20 41 47 33 157 21 566 49 57 33 45 27 44 61 10 35 67 21 16 20 81 89 56 45 82 32 8 50 32 329 72 105 33 20 29 25 69 80

23 10 23 30 7 27 15 9 66 116 11 8 28 29 26 85 12 290 40 27 12 18 NA 26 30 10 0 38 21 5 NA 61 42 24 29 34 25 7 29 24 208 56 73 26 9 18 18 45 30

76(60-89) 57 (40-71) 60 (39-74) 69 (56-82) 58 (43-82) NA 72 (46-83) 63 (29-77) 73 (42-89) 62 (19-85) 55 (24-79) 65 (44-81) 71 (50-90) 65 (34-86) 72 (48-85) 64 (28-86) 62 63 (17-92) 60 (24-82) 58 (25-81) 75 (61-86) 70 (51-89) 62 (30-82) 70 (48-84) NA 67 (47-81) NA NA 66 (44-85) 73 (58-88) NA 62 (17-88) 65 78 63 (43-81) 76 (59-91) 68 (49-84) 72 75 (52-88) 62 (35-82) 62 (20-82) 70 (31-94) 67 71 (46-87) 76 (58-87) 76 (56-85) 71 (55-80) 65 60 (48-68)

51 29 63 47 NA 46 24 14 NA 183 3 20 NA NA 33 NA 21 NA 49 NA 29 45 NA 44 61 NA 35 67 9 16 NA NA NA 56 5 82 NA 8 50 NA NA NA NA NA 20 29 25 NA 80

NA NA NA 30 (7-70) 6.5-30.1 5.1-39.2 9.9 (3-26) NA 14.1 (0-74.7) 34.5 (24.7-51.8) 16.7 (2.1-103.3) 13 (3-56) NA NA 37 (1-55) NA NA 35.5 19 (6-34) 6.0-29.2 24 32 (2-75.2) 21.3 1-98 16.9 (2.5-36.5) NA 25 24 (3-39) 22.4 (6.2-76.1) 65.6 (6.1-96.6) 35.9 (1-62) NA 26.7 NA 18 16.1 NA 9y 37 (2-88) 20.5 (3.8-97.9) 24 14 (3-60) NA 22 46 19 13 18 NA (continued)

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Table 3. Continued First Author [Reference] Hess [54] Chua [55] Kodama [56] Ridge [57] Sakurai [58] Viti [59]

Year

Study Design

Treatment

Size

Male (%)

Median or Mean Age (range) (y)

Path (%)

Median (Range) F/U (Months)

2011 2012 2014 2014 2010 2014

R R R R R R

RFA RFA RFA RFA RFA RFA

15 64 33 29 36 22

9 31 14 12 20 17

64 (42-82) 66 (35-83) 71 (46-84) 73 (55-86) 57 (35-80) 77 (70-84)

0 0 23 29 NA 22

17.6 32 NA 30 13.2 NA

F/U ¼ follow-up period; MWA ¼ microwave ablation; NA ¼ not reported or not specified; P ¼ prospective; Path ¼ percentage of disease with pathologic confirmation; R ¼ retrospective; RFA ¼ radiofrequency ablation. *Studies included RFA and MWA.

exponential model was used; a two-parameter Weibull model was used for studies with 2 or more reported follow-up times. The censoring process was modeled as an exponential distribution, with the median equal to the reported median follow-up time. Simulation was then used to estimate the standard errors for estimating the surviving patient proportions based on data sets of the reported sample size from the estimated survival and censoring processes [6]. Interstudy heterogeneity was evaluated using the I2 statistic. If I2 > 50%, implying significant statistical interstudy heterogeneity, the random-effects model was adopted; in the presence of no observable interstudy heterogeneity (I2 < 50%), the fixed-effects model was applied. Two-sided P < .05 was considered statistically significant. Evidence of publication bias was evaluated using Egger’s test. Subgroup analyses based on tumor type were performed only for the primary endpoint. All analyses were performed using Stata version 14.0 (Stata Corp, College Station, Texas) and SAS version 9.4 (SAS Institute Inc, Cary, North Carolina).

RESULTS Baseline Characteristics The search strategy initially identified 1,456 potential papers, of which 53 studies (Appendix 2) met the inclusion criteria. Table 3 summarizes the detailed information of the included studies. The NewcastleOttawa Scale (Supplemental Table S1) and Quality Appraisal Tool (Supplemental Table S2) showed that the included studies were considered high quality. CA and Local Tumor Progression Figure 2 shows the CA rates of RFA and MWA groups. The CA rates were 86.1% (95% CI: 78.5%-92.4%) in RFA-treated patients and 81.1% (95% CI: 75.8%86.0%) in MWA-treated patients.

Figure 3 and Table 4 show the median LTPFS and estimated LTPFS rates in the RFA group and the MWA group. The median LTPFS was 22.0 months (95% CI: 11.8-32.2 months) for RFA-treated tumors and 31.5 months (95% CI: 19.0-44.0 months) for MWA-treated tumors (P ¼ .249). No significant differences were observed in the 1-, 2-, 3-, 4-, and 5-year LTPFS rates between the RFA and MWA groups (P ¼ .294 to .665).

Survival and Subgroup Analysis Figure 4 shows the median OS between the RFA group and the MWA group. The random-effects model revealed no significant difference in the median survival time between the RFA group (pooled estimate: 30.9 months; 95% CI: 26.4-35.5 months) and MWA group (pooled estimate: 25.6 months, 95% CI: 19.4-31.8 months). Table 4 shows the estimated OS rates of RFA and MWA. The rates were higher for RFA-treated patients compared with those treated by MWA (all P < .05). Figure 5 shows the median OS of subgroup analysis based on tumor type. For pulmonary metastases, the RFA group had an estimated median OS of 34.8 months (95% CI: 27.6-42.1 months; I2 ¼ 57.9%, P ¼ .027), which was significantly different (P ¼ .001) compared with the MWA group (estimate, 18.7 months; 95% CI: 12.1-25.3 months; I2 ¼ NA). For patients with primary lung cancer, the estimated median OS in the RFA and MWA groups was 28.4 months (95% CI: 20.9-35.8 months; eight studies; I2 ¼ 91.8%, P < .01) and 24.4 months (95% CI: 16.9-31.8 months; six studies; I2 ¼ 93.5%, P < .01), respectively (Fig. 5). Figure 6 and Table 4 show the median PFS and estimated PFS rates in the RFA group and the MWA

Journal of the American College of Radiology Clinical Practice Management n Yuan et al n Clinical Outcomes After RFA and MWA

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Fig 2. Overview of complete ablation and 95% confidence intervals (CIs) for all studies and pooled estimates. MWA ¼ microwave ablation; RFA ¼ radiofrequency ablation.

group. The median PFS was 14.6 months (95% CI: 10.219.0 months) in the RFA group (I2 ¼ 94.5%, P < .001) and 8.4 months (95% CI: 3.6-13.2 months) in the MWA group (I2 ¼ 51.4%, P ¼ .128). Remarkably, there was a

significant difference (P ¼ .028) in the 3-year PFS rate between the RFA (33.1%, 95% CI: 19.2%-47.0%; I2 ¼ 87.9%, P < .001) and MWA groups (56.0%, 95% CI: 41.1%-70.9%; I2 ¼ NA).

Fig 3. Overview of median time to local tumor progression (LTPF) and 95% confidence intervals (CIs) for all studies and pooled estimates. MWA ¼ microwave ablation; RFA ¼ radiofrequency ablation.

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Table 4. Results of meta-analysis for OS rate, PFS rate, and LTPF rate RFA Number of Outcome Study

MWA

Heterogeneity

Estimate (95%CI)

Number of Study

Heterogeneity

25

I2 ¼ 75.0%, P < .001

89.2 (85.8-92.6)

6

I2 ¼ 37.7%, P ¼ .155

2 years 3 years

24 24

I2 ¼ 87.0%, P < .001 I2 ¼ 82.5%, P < .001

68.3 (60.6-76.1) 56.0 (47.3-64.6)

6 3

4 years 5 years PFS 1 year 2 years 3 years 4 years 5 years LTPF 1 years

13 16

I2 ¼ 64.9%, P ¼ .001 I2 ¼ 91.0%, P < .001

45.5 (36.1-55.0) 41.3 (27.3-55.2)

2 1

79.3 (73.785.0) I2 ¼ 0.0%, P ¼ .691 51.9 (46.2-57.5) I2 ¼ 7.6%, P ¼ .339 34.6 (26.842.5) I2 ¼ 0.0%, P ¼ .458 30.9 (22.9-38.8) NA 16.0 (0-35.5)

12 10 9 6 5

I2 ¼ 89.7%, P < .001 I2 ¼ 76.3%, P < .001 I2 ¼ 87.9%, P < .001 I2 ¼ 70.1%, P ¼ .005 I2 ¼ 92.5%, P < .001

62.4 (50.4-74.4) 31.7 (22.0-41.5) 33.1 (19.2-47.0) 22.8 (11.6-34.0) 31.3 (10.1-52.6)

2 2 1 NA NA

I2 ¼ 88.4%, P ¼ .003 64.8 (37.1-92.4) I2 ¼ 94.3%, P < .001 43.1 (1.5-84.7) NA 56.0 (41.1-70.9) NA NA NA NA

11

I2 ¼ 99.2%, P < .001

3

I2 ¼ 87.9%, P < .001 84.6 (72.9-96.3) .451

10 9 4 4

I2 ¼ 97.8%, P < .001 I2 ¼ 97.9%, P < .001 I2 ¼ 97.1%, P < .001 2 I ¼ 78.8%, P ¼ .003

73.0 (45.2100.8) 62.1 (38.4-85.8) 62.2 (37.2-87.2) 53.4 (15.4-91.4) 64.2 (42.3-86.1)

2 2 1 1

I2 ¼ 81.9%, P ¼ .019 68.5 (51.8-85.1) .665 I2 ¼ 15.1%, P ¼ .278 72.2 (64.5-79.9) .454 NA 74.1 (67.0-81.2) .294 NA 48.0 (23.8-72.2) .331

OS 1 year

2 years 3 years 4 years 5 years

Estimate (95% CI)

P .003 .001 <.001 .020 .039 .876 .601 .028 NA NA

CI ¼ confidence interval; LTPF ¼ local tumor progression-free; MWA ¼ microwave ablation; NA ¼ not reported; OS ¼ overall survival; PFS ¼ progression-free survival; RFA ¼ radiofrequency ablation.

Adverse Events Table 5 lists the proportion of AEs and 95% CI for RFA and MWA, which were pooled by meta-analysis. Pneumothorax was reported in 34.3% (95% CI: 25.9%43.1%; n ¼ 1,117; at risk ¼ 2,614) of the RFA group and in 33.9% (95% CI: 23.8%-44.8%; n ¼ 217; at risk ¼ 760) of the MWA group, and no statistical difference between the RFA and MWA groups was detected (P ¼ .957). Severe pneumothorax that required intervention (grade 3 or grade 4) occurred in 12.3% of patients (95% CI: 6.8%-19.1%; n ¼ 535; at risk ¼ 2,735) in the RFA group and in 11.0% of patients (95% CI: 4.5%-19.7%; n ¼ 73; at risk ¼ 587) in the MWA group (P ¼ .797). Pleural effusion occurred in 9.6% of patients (95% CI: 1.5%-22.4%; n ¼ 103; at risk ¼ 760) in the MWA group and in 5.2% of patients (95% CI: 2.5%8.5%; n ¼ 163; at risk ¼ 2,558) in the RFA group, which was not significantly different between the two groups (P ¼ .428). Grade 3 or 4 pleural effusion occurred in 0.3% in the MWA group (95% CI: 0%-1.4%; n ¼ 9; at risk ¼ 682) and in 0.6% in the RFA group (95% CI: 0%-1.7%; n ¼ 31; at risk ¼ 2,297) (P ¼ .517). Notably, two deaths were recorded among the MWA-treated

patients [14], and no treatment-related death occurred in the RFA group.

Publication Bias Supplemental Figure S1 and Supplemental Figure S2 present the publication bias by Egger’s test. Publication bias was assessed using Egger’s test, which indicated certain evidence of publication bias in the RFA group (P ¼ .015) but not in the MWA group (P ¼ .361). DISCUSSION We demonstrate conclusively that RFA is superior to MWA with regard to the 1-, 2-, 3-, 4-, and 5-year OS rates for treating lung malignancy. However, the analysis of the 4- and 5-year OS rates between the two modalities only included small-sample studies (RFA group: Yang [9], Zheng [15]; MWA: Yang [9]), which restricted further interpretation of this outcome. The subgroup analysis evaluating the median OS of different tumor types revealed no significant difference between RFA and MWA for primary lung cancer. For pulmonary metastasis, RFA led to better median OS compared

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Fig 4. Overview of median survival time and 95% confidence intervals (CIs) for all studies and pooled estimates. MWA ¼ microwave ablation; RFA ¼ radiofrequency ablation.

with MWA. This may indicate that RFA seems more efficacious than MWA for treating pulmonary metastasis. However, this result should be interpreted with caution, as only seven and one retrospective studies were included in RFA and MWA groups, respectively. Moreover, the largest sample size in the RFA group was 64 patients, and the smallest was 21, which may decrease the statistical power and yield immature survival data. Hence, we could not definitively conclude that RFA is superior to MWA for treating lung metastasis. In contrast, several studies maintained that MWA is a superior therapy to RFA for pulmonary metastasis [60,61]. The possible cause may be that metastatic lesions often have irregular margins [62], and MWA, with higher temperatures and effectiveness on lesions near vascular structures with reduced heat sink effect, seems to have a greater capacity for achieving a CA margin. Our findings are 8

contrary to these views, but there is no consensus in terms of the difference in treatment efficacy between MWA and RFA. Further long-term RCTs monitoring for these factors are necessary for clarifying the comparative effectiveness of MWA and RFA. Recently, Li et al [63] published a pooled analysis investigating the efficacy of RFA for lung cancer. They indicated a local tumor progression rate of 26% without a timeframe. Furthermore, Bi et al [6] investigated the local control rate of RFA for stage I non–small-cell lung cancer, and the 1-, 2-, 3-, and 5year local control rates of RFA were 77%, 48%, 55%, and 42%, respectively. These findings reported previously and the outcomes presented in our study both indicate the efficacy of RFA for lung cancer. Compared with RFA, MWA showed a similar CA rate, LTPFS rate, and median PFS. Although the 3-year PFS rates of RFA and MWA differed in the current study, the limited number Journal of the American College of Radiology Volume - n Number - n Month 2018

Fig 5. Subgroup analyses based on tumor types and 95% confidence intervals (CIs) for all studies and pooled estimates. MWA ¼ microwave ablation; RFA ¼ radiofrequency ablation.

of MWA trials may have affected further interpretation of this finding. Equivalent frequencies were observed between RFA and MWA with respect to the occurrence rates of pneumothorax and pleural effusion. Pneumothorax is one of the most common complications after ablation. Several risk factors are relevant to pneumothorax, such as tumor number, electrode position, and electrode trajectory through the aerated lung [64]. The reported incidence of RFA-related pneumothorax was between 8.5% and 50% [65-68]. Approximately 1.6% to 21% [64-69] of pneumothorax requires chest tube placement. Kennedy et al [70] reported a pneumothorax occurrence rate of

37% in patients with pulmonary malignancy treated with RFA. Our outcomes are comparable to that of the previous studies. Pleural effusion might develop as a major complication requiring intervention, with an occurrence rate ranging from 1% to 7% [64,67]. In the present study, the rates of pleural effusion and pleural effusion requiring intervention after RFA were 5.2% and 0.6%, respectively. The outcomes of both illustrate that RFA is a safe approach for preventing tumor progression. Our findings also demonstrate that RFA and MWA are both safe for treating lung cancer, with no significant difference. Notably, because MWA does not require grounding pads, and there is no energy

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Fig 6. Overview of median time to progression-free survival (PFS) and 95% confidence intervals (CIs) for all studies and pooled estimates. MWA ¼ microwave ablation; RFA ¼ radiofrequency ablation.

conduction through the body [60,61], it is expected that MWA is associated with a lower rate of skin burns and postoperative pain. However, the present meta-analysis and other previous studies did not identify skin burns and postoperative pain reported after MWA compared with RFA. Therefore, based on the similar AE risk, further high-quality RCTs could investigate skin burns and postoperative pain. Several factors limited the conclusions of this metaanalysis. Of the analyses performed, publication bias, which was found in the RFA group, and heterogeneity were important limitations. The heterogeneity of design and the clinical outcome and populations introduced by a retrospective study may have affected the pooled estimates. However, we used the random-effects model

to correct some of the heterogeneity. The sample size of the included studies reporting on MWA was limited, which can lead to false-positive or falsenegative conclusions (risk of random errors). Furthermore, the studies used different patient inclusion eligibility criteria (eg, tumor size, lesion number, age, follow-up). This might have influenced the consistency of effects across the included studies and led to interstudy heterogeneity. Moreover, subgroup analyses by tumor size or tumor number were not possible because the relative data extracted from the eligible studies were inadequate. In summary, the present meta-analysis demonstrates that RFA and MWA are both effective and safe approaches for treating lung cancer and that RFA confers

Table 5. Adverse Events for RFA and MWA

Adverse Events Pneumothorax Pneumothorax needs intervention Pleural effusion Pleural effusion needs intervention

No. of Events

No. at Risk

RFA Proportion (%)*

95% CI (%)*

No. of Events

No. at Risk

MWA Proportion (%)*

95% CI (%)*

P

1,117 535

2,614 2,735

34.3 12.3

25.9-43.1 6.8-19.1

217 73

760 587

33.9 11.0

23.8-44.8 4.5-19.7

.957 .797

163 31

2,558 2,297

5.2 0.6

2.5-8.5 0.0-1.7

103 9

68,760 682

9.6 0.3

1.5-22.4 0.0-1.4

.428 .517

CI ¼ confidence interval; MWA ¼ microwave ablation; RFA ¼ radiofrequency ablation. *The proportions of adverse events and 95% CIs were pooled by meta-analysis.

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Journal of the American College of Radiology Volume - n Number - n Month 2018

superior OS rates over MWA. Likewise, in treating pulmonary metastases, RFA efficacy seems favorable compared with MWA. Future long-term, large-sample RCTs are necessary to compare the clinical outcomes between MWA and RFA.

TAKE-HOME POINTS -

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Results from 53 studies (11 prospective and 42 retrospective) with 3,432 patients were pooled, and meta-analysis indicate that percutaneous RFA and MWA were both effective for treatment of lung malignancy with a high safety profile. The 1-, 2-, 3-, 4-, and 5-year OS rates were higher in RFA-treated patients compared with those treated by MWA (P  .001). RFA correlates with a more favorable median OS in patients with pulmonary metastases than MWA.

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