Patient characteristics
A total of 81 patients diagnosed with MPE secondary to MPM in Tianjin Chest Hospital and Beijing Chaoyang Hospital were included in this study. The baseline characteristics of population in this study are shown in Table 1. The median age of the patients was 66 years (range 60 - 73 years), and there are 50 (61.7%) males and 31 (38.3%)females. A total of 18.5% of the patients had a clear history of asbestos exposure. The majority of patients present that ECOG PS is 0 - 1 (80.2%), were never smokers (60.5%), exhibited epithelioid histology (45.7%), received chemotherapy (72.8%), have no metastasis (86.4%) and weight loss (77.8%).
Association of clinicopathological factors and OS
Univariate associations between clinicopathologic factors and OS are shown in Table 2. Sarcomatoid type histology, low level of lymphocyte, MPV, and ALT, high level of FIB, CYFRA, and LDH in pleural fluid were significantly related to worse outcomes (all P < 0.1). As shown in Table 3, variables with P values < 0.1, along with variables that were found to be associated with OS including age, gender, ECOG PS, NLR, Hb, ALB and chemotherapy received were further fitted into a multivariate Cox’s proportional hazard model, LDH level in pleural fluid (HR 2.496; 95% CI 1.070 -5.823; P = 0.034), MPV level (HR 3.202; 95% CI 1.209 – 8.484; P = 0.019), lymphocyte count (HR 0.406; 95% CI 0.168 - 0.983; P = 0.046), and chemotherapy (HR 0.398; 95% CI 0.176 - 0.902; P = 0.027) were identified as independent indicators of OS in patients with MPE secondary to MPM.
Development and Assessment of LMLC Prognostic Score Model
In order to accurately distinguish patients with different risk levels, LDH level in pleural fluid, MPV level, lymphocyte count, and chemotherapy were employed to develop the LMLC prognostic score model. Table 4 describes the scoring system, with scores ranging from 0 - 4. For ease of interpretation, patients can be divided into low-risk (score 0 - 2), and high-risk (score 3 - 4) prognostic groups according to the LMLC score calculated at the time of presentation with MPE secondary to MPM. The patients with a low-risk LMLC score had a median survival of 42 months. Those with a high-risk LMLC score had a median survival of 19 months. The Kaplan–Meier survival curves are shown in Figure 1. In comparison with the low-risk group, the high-risk groups showed significantly poorer survival (HR 3.713; 95% CI 1.889 - 7.298; P <0.001).
Table 1 Baseline characteristics of patients in the study
Characteristic
|
All patients(n = 81)
|
OS (months) (95% CI)
|
30 (17, 42)
|
Age (years), Median (IQR)
|
66 (60, 73)
|
Gender, N (%)
|
|
Male
|
50(61.7)
|
Female
|
31 (38.3)
|
ECOG PS, N (%)
|
|
0 - 1
|
65 (80.2)
|
2 - 4
|
16 (19.8)
|
Smoking status, N (%)
|
|
Ever/current
|
32 (39.5)
|
Never
|
49 (60.5)
|
Weight loss
|
|
No
|
63 (77.8)
|
Yes
|
18 (22.2)
|
Asbestos exposure
|
|
No
|
66 (81.5)
|
Yes
|
15 (18.5)
|
Histology, N (%)
|
|
Epithelioid
|
37 (45.7)
|
Sarcomatoid
|
5 (6.1)
|
Biphasic
|
2 (2.5)
|
Unclassified
|
37 (45.7)
|
Metastasis, N (%)
|
|
Yes
|
11 (13.6)
|
No
|
70 (86.4)
|
Chemotherapy received
|
|
No
|
18 (22.2)
|
Yes
|
59 (72.8)
|
Abbreviations: OS overall survival, ECOG PS Eastern Cooperative Oncology Group performance status,
Table 2 Univariate analysis of potential associations between patient characteristics and OS
Variable
|
HR
|
95% CI
|
P value
|
Variable
|
HR
|
95% CI
|
P value
|
Age, years
|
|
|
|
ALB g/L
|
|
|
|
<66
|
1.00
|
|
|
<36.80
|
1.00
|
|
|
≥66
|
1.519
|
0.830, 2.779
|
0.175
|
≥36.80
|
0.802
|
0.443, 1.451
|
0.466
|
Gender
|
|
|
|
AST U/L
|
|
|
|
Female
|
1.00
|
|
|
<18.70
|
1.00
|
|
|
Male
|
1.288
|
0.700, 2.371
|
0.416
|
≥18.70
|
1.222
|
0.675, 2.210
|
0.508
|
ECOG PS
|
|
|
|
ALT U/L
|
|
|
|
0 – 1
|
1.00
|
|
|
<16.40
|
1.00
|
|
|
2 – 4
|
1.482
|
0.730, 3.009
|
0.293
|
≥16.40
|
0.556
|
0.307, 1.009
|
0.053
|
Smoking status
|
|
|
|
LDH U/L
|
|
|
|
Never
|
1.00
|
|
|
<179.00
|
1.00
|
|
|
Ever/current
|
1.507
|
0.824, 2.756
|
0.183
|
≥179.00
|
0.987
|
0.541, 1.802
|
0.967
|
Weight loss
|
|
|
|
ALP U/L
|
|
|
|
No
|
1.00
|
|
|
<75.00
|
1.00
|
|
|
Yes
|
0.955
|
0.454, 2.010
|
0.904
|
≥75.00
|
0.932
|
0.510, 1.704
|
0.820
|
Asbestos exposure
|
|
|
|
CRP mg/Dl
|
|
|
|
No
|
1.00
|
|
|
<2.20
|
1.00
|
|
|
Yes
|
1.495
|
0.769, 2.905
|
0.236
|
≥2.20
|
1.285
|
0.678, 2.436
|
0.443
|
Location
|
|
|
|
Cr μmol/L
|
|
|
|
One side
|
1.00
|
|
|
<66.30
|
1.00
|
|
|
Two sides
|
1.900
|
0.664, 5.433
|
0.231
|
≥66.30
|
0.999
|
0.553, 1.806
|
0.998
|
Histology
|
|
|
|
FIB g/L
|
|
|
|
Epithelioid
|
1.00
|
|
|
<3.88
|
1.00
|
|
|
Sarcomatoid vs
|
6.097
|
1.934, 19.224
|
0.002
|
≥3.88
|
1.713
|
0.946, 3.103
|
0.076
|
Biphasic vs
|
3.770
|
0.484, 29.385
|
0.205
|
D-D ng/ mL
|
|
|
|
Unclassified vs
|
0.839
|
0.442, 1.592
|
0.591
|
<0.91
|
1.00
|
|
|
Metastasis
|
|
|
|
≥0.91
|
1.114
|
0.607, 2.047
|
0.727
|
No
|
1.00
|
|
|
CEA ng/mL
|
|
|
|
Yes
|
1.487
|
0.714, 3.098
|
0.290
|
<1.56
|
1.00
|
|
|
WBC×109/L
|
|
|
|
≥1.56
|
0.930
|
0.513, 1.686
|
0.811
|
<6.24
|
1.00
|
|
|
NSE ng/mL
|
|
|
|
≥6.24
|
0.755
|
0.415, 1.375
|
0.358
|
<15.37
|
1.00
|
|
|
N×109/L
|
|
|
|
≥15.37
|
1.329
|
0.729, 2.421
|
0.353
|
<4.23
|
1.00
|
|
|
CYFRA ng/mL
|
|
|
|
≥4.23
|
0.965
|
0.533, 1.747
|
0.906
|
<4.38
|
1.00
|
|
|
L×109/L
|
|
|
|
≥4.38
|
1.738
|
0.942, 3.205
|
0.077
|
<1.47
|
1.00
|
|
|
PF WBCs/ mL
|
|
|
|
≥1.47
|
0.450
|
0.240, 0.843
|
0.013
|
<1096.00
|
1.00
|
|
|
NLR
|
|
|
|
≥1096.00
|
0.789
|
0.436, 1.428
|
0.434
|
<2.94
|
1.00
|
|
|
PF LDH U/L
|
|
|
|
≥2.94
|
1.480
|
0.821, 2.669
|
0.193
|
<359.00
|
1.00
|
|
|
M×109/L
|
|
|
|
≥359.00
|
1.890
|
1.022, 3.493
|
0.042
|
<0.39
|
1.00
|
|
|
PF ADA U/L
|
|
|
|
≥0.39
|
1.327
|
0.737, 2.390
|
0.346
|
<15.00
|
1.00
|
|
|
Hb g/L
|
|
|
|
≥15.00
|
1.398
|
0.759, 2.573
|
0.282
|
<133.00
|
1.00
|
|
|
PF TP g/L
|
|
|
|
≥133.00
|
0.916
|
0.506, 1.658
|
0.771
|
<41.40
|
1.00
|
|
|
PLT×109/L
|
|
|
|
≥41.40
|
1.337
|
0.707, 2.527
|
0.372
|
<241.00
|
1.00
|
|
|
PF Glu mmol/L
|
|
|
|
≥241.00
|
1.339
|
0.743, 2.413
|
0.332
|
<5.32
|
1.00
|
|
|
MPV fl
|
|
|
|
≥5.32
|
0.769
|
0.418, 1.382
|
0.369
|
<11.90
|
1.00
|
|
|
PF CEA ng/ mL
|
|
|
|
≥11.90
|
1.820
|
0.929, 3.564
|
0.081
|
<0.94
|
1.00
|
|
|
TP g/L
|
|
|
|
≥0.94
|
0.860
|
0.468, 1.579
|
0.626
|
<64.30
|
1.00
|
|
|
Chemotherapy received
|
|
|
|
≥64.30
|
0.738
|
0.404,1.349
|
0.323
|
No/unknown
|
1.00
|
|
|
|
|
|
|
Yes
|
0.711
|
0.377, 1.342
|
0.292
|
Abbreviations: OS overall survival, ECOG PS Eastern Cooperative Oncology Group performance status, WBC white blood cell, N neutrophil, L lymphocyte, NLR neutrophil to lymphocyte ratio, M monocyte, Hb hemoglobin, PLT platelet, MPV mean palate volume, TP total protein, ALB albumin, AST aspartate aminotransferase, ALT alanine aminotransferase, LDH lactic dehydrogenase, ALP alkaline phosphatase, γ-GT gamma-glutamyltransferase, CRP C-reaction protein, Cr creatinine, FIB fibrinogen, D-D D-dimer, CEA carcino-embryonic antigen, NSE neuron specific enolase, CYFRA Cytokeratin 19 fragment, PF pleural fluid, ADA adenosine deaminase, Glu glucose
Table 3 Multivariate analysis of potential associations between patient characteristics and OS
Variable
|
HR
|
95%CI
|
P value
|
PF LDH U/L
|
|
|
|
<359.00
|
1.00
|
|
|
≥359.00
|
2.496
|
1.070, 5.823
|
0.034
|
MPV fl
|
|
|
|
<11.90
|
1.00
|
|
|
≥11.90
|
3.202
|
1.209, 8.484
|
0.019
|
L×109/L
|
|
|
|
<1.47
|
1.00
|
|
|
≥1.47
|
0.406
|
0.168, 0.983
|
0.046
|
Chemotherapy received
|
|
|
|
No/unknown
|
1.00
|
|
|
Yes
|
0.398
|
0.176, 0.902
|
0.027
|
LMLC score
|
|
|
|
Low risk
|
1.00
|
|
|
High risk
|
3.713
|
1.889, 7.298
|
<0.001
|
Abbreviations: OS overall survival, L lymphocyte, MPV mean palate volume, PF pleural fluid, LDH lactic dehydrogenase
Table 4 The LMLC score calculation
|
Variable
|
Score
|
L
|
PF LDH U/L
|
|
|
< 359.00
|
0
|
|
≥ 359.00
|
1
|
M
|
MPV
|
|
|
< 11.9 fl
|
0
|
|
≥ 11.9 fl
|
1
|
L
|
Lymphocyte count
|
|
|
≥ 1.47×109/L
|
0
|
|
< 1.47×109/L
|
1
|
C
|
Chemotherapy received
|
|
|
Yes
|
0
|
|
No/unknown
|
1
|
Risk categories
|
Total score
|
|
Low risk
|
0-2
|
|
High risk
|
3-4
|
|
Abbreviations: LDH lactic dehydrogenase, MPV mean palate volume, PF pleural fluid, L lymphocyte