Table 2 Stratified analysis of pooled hazard ratios of lactate dehydrogenase on overall survival

Study location

0.581

 Asia

4

580

1.66 [1.29, 2.14]

1.82 [1.14, 2.9]

67.9

0.025

 Europe

19

5276

1.66 [1.53, 1.80]

1.67 [1.40, 2.0]

69.5

<0.001

 Other regions

5

1065

1.85 [1.52, 2.25]

2.07 [1.45, 2.94]

64.1

0.025

Age

0.563

  ≤ 50

2

191

1.98 [1.33, 2.94]

2.31 [1.04, 5.13]

63.1

0.1

 No limitation

22

5623

1.70 [1.57, 1.84]

1.77 [1.51, 2.08]

68.5

<0.001

Number of patients

0.68

  ≥ 100

22

6428

1.68 [1.56, 1.81]

1.73 [1.49, 2.01]

69

<0.001

  < 100

6

439

1.84 [1.66, 2.04]

1.96 [1.11, 3.43]

60.3

0.28

Metastasis

0.059

 Yes

16

5044

1.84 [1.66, 2.04]

1.96 [1.61, 2.37]

64.4

<0.001

 No

5

883

1.53 [1.29, 1.82]

1.21 [0.79, 1.86]

74.4

0.028

LDH cutoff

0.309

  > 300 U/L

7

764

1.93 [1.50, 2.49]

1.98 [1.41, 2.77]

29.1

0.206

 250–300 U/L

5

1028

1.61 [1.38, 1.88]

1.84 [1.08, 3.13]

88.6

<0.001

  < 250 U/L

6

1174

1.58 [1.31, 1.90]

1.44 [0.94, 2.21]

75.4

0.001

Chemotherapy with anti-angiogenesis drugs

0.64

 Yes

5

1675

1.75 [1.51, 2.02]

1.78 [1.41, 2.23]

57.3

0.053

 No

16

4166

1.60 [1.46, 1.75]

1.65 [1.40, 1.94]

54.8

0.003

Study type

0.863

 non-RCT^a

22

3683

1.66 [1.51, 2.02]

2.03 [1.31, 3.13]

71.5

<0.001

 RCT

5

3238

1.73 [1.54, 1.94]

1.73 [1.54, 1.94]

<0.01

0.535

Risk of bias

0.31

 High

16

3142

1.52 [1.36, 1.68]

1.63 [1.28, 2.09]

76.5

<0.001

 Low

11

3799

1.87 [1.69, 2.07]

1.65 [1.28, 2.12]

<0.01

0.655