Study characteristics
Initially, we explored a total of 1783 studies that were potentially relevant to the present analysis. Thereafter, 282 duplicate studies were excluded from analysis. Based on the selection criteria, 15 articles were assessed for eligibility. Among these 15 articles, 3 studies were excluded because of lack of the data about endpoints (n = 2) and insufficient information about the needle types used (n = 1). Finally, 12 articles were included in this meta-analysis (Table 1, Fig. 1).
Table 1
Characteristics of studies included in meta-analysis.
Studies
|
Year
|
Country
|
All patients number
|
Gender (male/female)
|
Patients with molecular test
|
Mean age (y)
|
Size of lesion (cm)
|
NOS
|
Zhuang [10]
|
2011
|
China
|
43
|
16/27
|
43
|
62
|
4
|
8
|
Cheung [11]
|
2010
|
Taiwan
|
47
|
24/23
|
47
|
64.6
|
4
|
8
|
Hou [12]
|
2013
|
China
|
40
|
29/11
|
40
|
32–81
|
3.3
|
8
|
Hsiao [13]
|
2013
|
Taiwan
|
332
|
199/153
|
134
|
65.3
|
4.9
|
8
|
Wang[14]
|
2013
|
China
|
228
|
93/135
|
228
|
62.1
|
3.4
|
8
|
Chen [15]
|
2014
|
China
|
353
|
228/125
|
236
|
59
|
4
|
8
|
Coley [16]
|
2015
|
USA
|
210
|
Not given
|
115
|
Not given
|
Not given
|
6
|
Florentine [17]
|
2015
|
USA
|
216
|
103/113
|
22
|
70
|
Not given
|
7
|
Lian [18]
|
2017
|
China
|
250
|
156/94
|
250
|
63
|
Not given
|
7
|
Tian [19]
|
2017
|
China
|
560
|
323/237
|
176
|
51.8
|
1.8
|
8
|
Beck [20]
|
2017
|
Korea
|
196
|
72/124
|
100
|
67.7
|
4.1
|
8
|
Porrello [21]
|
2019
|
Italy
|
42
|
Not given
|
23
|
Not given
|
Not given
|
6
|
NOS: Newcastle–Ottawa score. |
All articles included were retrospective studies. Moreover, 10 articles could be considered as of high quality [10–15, 17–20], while 2 articles were regarded belonging to moderate quality [16, 21. A total of 2559 patients underwent CT-guided lung biopsy and 1414 of them received molecular testing.
Moreover, among the 12 articles, 9 articles were from Asia and 3 articles were from Western countries. Two articles used fine needles [10, 14], 7 articles used core needles [11–13, 15, 19–21], and 3 articles employed both fine and core needles [16–18]. The sizes of the needles ranged from 16G to 20G. Five articles only tested the EGFR mutations [10–14], 5 articles tested EGFR mutations and ALK translocation [15, 17–19, 21], and 2 articles tested EGFR mutations, ALK translocation, and KRAS mutations [16, 20] (Table 2).
Table 2
Characteristics of CT-guided biopsy.
Studies
|
Types of needles
|
Size of needles
|
Contents of molecular tests
|
Adequacy for molecular test
|
Positive EGFR mutation
|
Positive ALK translocation
|
Positive KRAS mutation
|
Zhuang [10]
|
Fine
|
18 and 20G
|
EGFR
|
Not given
|
53%
|
-
|
-
|
Cheung [11]
|
Core
|
18 and 20G
|
EGFR
|
Not given
|
72%
|
-
|
-
|
Hou [12]
|
Core
|
18 and 20G
|
EGFR
|
Not given
|
38%
|
-
|
-
|
Hsiao [13]
|
Core
|
18 and 20G
|
EGFR
|
99%
|
60%
|
-
|
-
|
Wang[14]
|
Fine
|
18 and 20G
|
EGFR
|
96%
|
43%
|
-
|
-
|
Chen [15]
|
Core
|
16G
|
EGFR, ALK
|
99%
|
Not given
|
Not given
|
-
|
Coley [16]
|
Core, Fine
|
20 and 22G
|
EGFR, ALK, KRAS
|
96%
|
Not given
|
Not given
|
Not given
|
Florentine [17]
|
Core, Fine
|
20G
|
EGFR, ALK
|
95%
|
Not given
|
Not given
|
-
|
Lian [18]
|
Core, Fine
|
16-20G
|
EGFR, ALK
|
83%
|
50%
|
7%
|
-
|
Tian [19]
|
Core
|
18G
|
EGFR, ALK
|
95%
|
43%
|
8%
|
-
|
Beck [20]
|
Core
|
20G
|
EGFR, ALK, KRAS
|
96%
|
34%
|
5%
|
6%
|
Porrello [21]
|
Core
|
16-18G
|
EGFR, ALK
|
Not given
|
44%
|
9%
|
-
|
CT: computed tomography; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma receptor tyrosine kinase; KRAS: kirsten rat sarcoma viral oncogene homolog. |
Adequacy rate for molecular tests
It was found that eight articles with 1261 patients reported the adequacy rates for molecular test [13–20]. The pooled adequacy rate for molecular test was 95% (95% CI: 93%-98%, Fig. 2). A significant heterogeneity was detected among these studies (I2 = 86.2%, P < 0.001). A high risk of publication bias was also found (Egger test: P = 0.043).
The meta-regression analysis indicated that the adequacy rate for molecular test was not directly associated to the needle types used (P = 0.338, 95% CI: -0.25-0.11), lesion sizes (P = 0.729, 95% CI: -0.12-0.15), and counties (P = 0.452, 95% CI: -0.10-0.19).
The subgroup analyses have been shown in Table 3. The pooled adequacy rates for molecular test were 98%, 96%, and 91% based on the use of core needle, fine needle, or both types, retrospectively. A significant heterogeneity was only detected in the subgroup in which both types of needles were used (I2 = 94.7%, P < 0.001). The pooled adequacy rates for molecular test were 99%, 96%, and 91% based on the different mean lesion sizes (≥ 4 cm, < 4 cm, and unknown), retrospectively. A significant heterogeneity was only detected in the subgroup of unknown (I2 = 94.7%, P < 0.001). The pooled adequacy rates for molecular test were 96% and 96% based on patients belonging to Asian and Western countries, retrospectively, however a significant heterogeneity was only detected in the subgroup of patients in Asian countries (I2 = 90%, P < 0.001).
Table 3
Subgroup analysis in adequacy for molecular test.
|
Studies (n)
|
Pooled rates
|
95% confidential interval
|
Heterogeneity
|
Needle types
|
|
|
|
|
Core
|
5
|
98%
|
0.98–0.99
|
I2 = 47.7%
|
Fine
|
1
|
96%
|
0.93–0.99
|
-
|
Both
|
2
|
91%
|
0.88–0.94
|
I2 = 94.7%
|
Mean lesion size
|
|
|
|
|
≥ 4 cm
|
3
|
99%
|
0.98-1.00
|
I2 = 8.7%
|
< 4 cm
|
3
|
96%
|
0.94–0.98
|
I2 = 0.0%
|
Unknown
|
2
|
91%
|
0.88–0.94
|
I2 = 94.7%
|
Countries
|
|
|
|
|
Asian
|
6
|
96%
|
0.97–0.99
|
I2 = 90.0%
|
Western
|
2
|
96%
|
0.93–0.99
|
I2 = 0.0%
|
The sensitivity analysis data showed that the significant heterogeneity disappeared (I2 = 50%, P = 0.060) when Lian et al. study [18] was removed.
Positive rates of EGFR mutations
Nine articles with 971 patients reported positive rates of EGFR mutations [10–14, 18–21]. The pooled positive rate of EGFR mutation was 49% (95% CI: 42%-55%, Fig. 3) and a significant publication bias was found (Egger test: P = 0.727).
The meta-regression analysis found that the positive rates of EGFR mutations were not associated with the needle types used (P = 0.655, 95% CI: -0.29-0.20), lesion size (P = 0.349, 95% CI: -0.13-0.31), and the countries (P = 0.590, 95% CI: -0.60-0.38).
The subgroup analyses have been shown in Table 4. The pooled positive rates of EGFR mutations were 49%, 47%, and 44% based on the application of core needle, fine needle, and both of them, retrospectively. A significant heterogeneity was only detected in the subgroup of core needle (I2 = 87.8%, P < 0.001). The pooled positive rates of EGFR mutation were 53%, 43%, and 49% based on the different mean lesion sizes (≥ 4 cm, < 4 cm, and unknown), retrospectively. A significant heterogeneity was only detected in the subgroup of lesion size ≥ 4 cm (I2 = 88.4%, P < 0.001). The pooled positive rates of EGFR mutations were 48% and 44% based on patients in Asian and Western countries, retrospectively. A significant heterogeneity was only detected in the subgroup of Asian countries (I2 = 80.4%, P < 0.001).
Table 4
Subgroup analysis in positive rate of EGFR mutation.
|
Studies (n)
|
Pooled rates
|
95% confidential interval
|
Heterogeneity
|
Needle types
|
|
|
|
|
Core
|
5
|
49%
|
0.44–0.53
|
I2 = 87.8%
|
Fine
|
3
|
47%
|
0.42–0.51
|
I2 = 28.4%
|
Both
|
1
|
44%
|
0.24–0.64
|
-
|
Mean lesion size
|
|
|
|
|
≥ 4 cm
|
4
|
53%
|
0.48–0.59
|
I2 = 88.4%
|
< 4 cm
|
3
|
43%
|
0.38–0.47
|
I2 = 0.0%
|
Unknown
|
2
|
49%
|
0.43–0.56
|
I2 = 0.0%
|
Countries
|
|
|
|
|
Asian
|
8
|
48%
|
0.45–0.51
|
I2 = 80.4%
|
Western
|
1
|
44%
|
0.24–0.64
|
-
|
EGFR: epidermal growth factor receptor. |
The sensitivity analysis showed that a significant heterogeneity always existed after removing any of these included studies.
Positive rates of ALK translocation
Four articles with 383 patients reported the positive rates of ALK translocation [18–21]. The pooled positive rate of ALK translocation was 7% (95% CI: 42%-55%, Fig. 4). However, no significant heterogeneity was detected among these studies (I2 = 0%, P = 0.837). A low risk of publication bias was found (Egger test: P = 0.576) among the analyzed reports.
Positive rates of KRAS mutation
Only 1 article reported the positive rate of KRAS mutation at 6% [20].