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20
Table 1. Patient characteristics
Total
PY=0
0<PY<10
10≦PY<30
30<PY
(80,989)
(27,680)
(4,136)
(10,143)
(39,030)
Male
49,700 (61.4%)
4,901 (17.7%)
2,304 (55.7%)
7,346 (72.4%)
35,149 (90.1%)
Female
31,289 (38.6%)
22,779 (82.3%)
1,832 (44.3%)
2,797 (27.6%)
3,881 (9.9%)
-59
10,336 (12.8%)
3,759 (13.6%)
891 (21.5%)
2,103 (20.7%)
3,583 (9.2%)
60-64
10,002 (12.3%)
3,050 (11.0%)
600 (14.5%)
1,225 (12.1%)
5,127 (13.1%)
65-69
17,887 (22.1%)
5,747 (20.8%)
823 (19.9%)
2,063 (20.3%)
9,254 (23.7%)
70-74
19,103 (23.6%)
6,349 (22.9%)
740 (17.9%)
2,043 (20.1%)
9,971 (25.5%)
75-79
15,034 (18.6%)
5,483 (19.8%)
665 (16.1%)
1,691 (16.7%)
7,195 (18.4%)
80-
8,627 (10.7%)
3,292 (11.9%)
417 (10.1%)
1,018 (10.0%)
3,900 (10.0%)
0-1
78,494 (96.9%)
26,958 (97.4%)
4,031 (97.5%)
9,840 (97.0%)
37,665 (96.5%)
2,495 (3.1%)
722 (2.6%)
105 (2.5%)
303 (3.0%)
1,365 (3.5%)
100-
39,979 (49.4%)
15,674 (56.6%)
2,290 (55.4%)
5,188 (51.1%)
16,827 (43.1%)
90-99
20,245 (25.0%)
6,502 (23.5%)
969 (23.4%)
2,522 (24.9%)
10,252 (26.3%)
80-89
13,248 (16.4%)
3,744 (13.5%)
595 (14.4%)
1,612 (15.9%)
7,297 (18.7%)
70-79
5,335 (6.6%)
1,267 (4.6%)
202 (4.9%)
601 (5.9%)
3,265 (8.4%)
60-69
1,665 (2.1%)
393 (1.4%)
59 (1.4%)
166 (1.6%)
1,047 (2.7%)
50-59
408 (0.5%)
75 (0.3%)
17 (0.4%)
41 (0.4%)
275 (0.7%)
-49
109 (0.1%)
25 (0.1%)
4 (0.1%)
13 (0.1%)
67 (0.2%)
FEV1%
100-
29,522 (36.5%)
16,451 (59.4%)
1,933 (46.7%)
3,554 (35.0%)
7,584 (19.4%)
predicted
90-99
17,276 (21.3%)
5,603 (20.2%)
972 (23.5%)
2,457 (24.2%)
8,244 (21.1%)
80-89
15,511 (19.2%)
3,363 (12.1%)
693 (16.8%)
2,099 (20.7%)
9,356 (24.0%)
70-79
10,308 (12.7%)
1,487 (5.4%)
345 (8.3%)
1,198 (11.8%)
7,278 (18.6%)
60-69
5,216 (6.4%)
519 (1.9%)
130 (3.1%)
567 (5.6%)
4,000 (10.2%)
50-59
2,195 (2.7%)
191 (0.7%)
40 (1.0%)
20
188 (1.9%)
1,776 (4.6%)
Factor
Sex
Age
PS
%VC
p-value
<0.001
<0.001
<0.001
<0.001
<0.001
BMI
-49
961 (1.2%)
66 (0.2%)
23 (0.6%)
80 (0.8%)
792 (2.0%)
<18.5
6,890 (8.5%)
2,666 (9.6%)
338 (8.2%)
856 (8.4%)
3,030 (7.8%)
<0.001
>30
2,084 (2.6%)
814 (2.9%)
118 (2.9%)
230 (2.3%)
922 (2.4%)
<0.001
Values are presented as n (%). Pearson's chi-squared test was used for comparison.
PY: pack-years, PS: Eastern Cooperative Oncology Group performance status, VC: vital capacity, FEV1: forced expiratory volume in 1 second,
BMI: body mass index
21
Table 2. Detailed information of lung cancer and treatment
Total
PY=0
0<PY<10
10≦PY<30
30<PY
(80,989)
(27,680)
(4,136)
(10,143)
(39,030)
Tis-1
48,663 (60.1%)
18,574 (67.1%)
2,647 (64.0%)
6,121 (60.3%)
21,321 (54.6%)
T2
27,381 (33.8%)
8,252 (29.8%)
1,299 (31.4%)
3,389 (33.4%)
14,441 (37.0%)
T3-4
4,945 (6.1%)
854 (3.1%)
190 (4.6%)
633 (6.2%)
3,268 (8.4%)
N0
70,291 (86.8%)
25,734 (93.0%)
3,762 (91.0%)
8,854 (87.3%)
31,941 (81.8%)
N1
6,787 (8.4%)
1,239 (4.5%)
223 (5.4%)
809 (8.0%)
4,516 (11.6%)
N2
3,911 (4.8%)
707 (2.6%)
151 (3.7%)
480 (4.7%)
2,573 (6.6%)
Histology
AD
57,124 (70.5%)
25,142 (90.8%)
3,545 (85.7%)
7,472 (73.7%)
20,965 (53.7%)
<0.001
Preoperative
CT
1,725 (2.1%)
292 (1.1%)
62 (1.5%)
211 (2.1%)
1,160 (3.0%)
<0.001
treatment
RT
853 (1.1%)
130 (0.5%)
36 (0.9%)
94 (0.9%)
593 (1.5%)
<0.001
Procedure
Thoracotomy
10,400 (12.8%)
2,565 (9.3%)
421 (10.2%)
1,290 (12.7%)
6,124 (15.7%)
<0.001
Mini-thoracotomy
37,604 (46.4%)
12,602 (45.5%)
1,851 (44.8%)
4,712 (46.5%)
18,439 (47.2%)
cVATS
32,985 (40.7%)
12,513 (45.2%)
1,864 (45.1%)
4,141 (40.8%)
14,467 (37.1%)
1,411 (1.7%)
240 (0.9%)
43 (1.0%)
158 (1.6%)
970 (2.5%)
Factor
cT factor
cN factor
Bronchoplasty
Values are presented as n (%).
Pearson's chi-squared test was used for comparison.
PY: pack-years, cT: clinical T, cN: clinical N, AD: adenocarcinoma, CT: chemotherapy,
RT: radiation therapy, cVATS: complete video assisted thoracic surgery
22
p-value
<0.001
<0.001
<0.001
Table 3. Preoperative comorbidities
Total
PY=0
0<PY<10
10≦PY<30
30<PY
(80,989)
(27,680)
(4,136)
(10,143)
(39,030)
3,480 (4.3%)
212 (0.8%)
70 (1.7%)
403 (4.0%)
2,795 (7.2%)
<0.001
498 (0.6%)
118 (0.4%)
24 (0.6%)
78 (0.8%)
278 (0.7%)
<0.001
12,414 (15.3%)
2,760 (10.0%)
437 (10.6%)
1,399 (13.8%)
7,818 (20.0%)
<0.001
Ischemic heart disease
4,490 (5.5%)
691 (2.5%)
150 (3.6%)
518 (5.1%)
3,131 (8.0%)
<0.001
Cerebral stroke
4,944 (6.1%)
1,105 (4.0%)
201 (4.9%)
589 (5.8%)
3,049 (7.8%)
<0.001
Autoimmune disease
1,705 (2.1%)
619 (2.2%)
80 (1.9%)
244 (2.4%)
762 (2.0%)
0.008
Arrhythmia
3,120 (3.9%)
795 (2.9%)
158 (3.8%)
445 (4.4%)
1,722 (4.4%)
<0.001
349 (0.4%)
65 (0.2%)
15 (0.4%)
53 (0.5%)
216 (0.6%)
<0.001
Comorbidity
Interstitial pneumonia
Hemodialysis
Diabetes mellitus
Hepatic dysfunction
Values are presented as n (%).
Pearson's chi-squared test was used for comparison.
PY: pack-years
23
p-value
Table 4. Postoperative outcomes
Total
PY=0
0<PY<10
10≦PY<30
30<PY
(80,989)
(27,680)
(4,136)
(10,143)
(39,030)
Mortality (30 day)
600 (0.7%)
45 (0.2%)
20 (0.5%)
69 (0.7%)
466 (1.2%)
<0.001
Complication (Lung)
6,420 (7.9%)
947 (3.4%)
223 (5.4%)
767 (7.6%)
4,483 (11.5%)
<0.001
Complication (CVD)
2,013 (2.5%)
500 (1.8%)
92 (2.2%)
234 (2.3%)
1,187 (3.0%)
<0.001
Complication (Infection)
848 (1.0%)
144 (0.5%)
33 (0.8%)
95 (0.9%)
576 (1.5%)
<0.001
Operation time
200 (158-253)
185 (147-233)
195 (153-243)
200 (158-252)
213 (168-269)
<0.001
Blood loss
52 (18-130)
42 (10-100)
50 (12.5-110)
50 (19-128)
75 (25-165)
<0.001
Hospital LOS
9 (7-13)
8 (7-11)
8 (7-12)
9 (7-12)
10 (7-14)
<0.001
Outcome
Values are presented as median (25th–75th percentile interval) or n (%).
Pearson's chi-squared test for mortality and complications.
Kruskal-Wallis test for operation time, blood loss and hospital LOS.
PY: pack-years, CVD: cardiovascular disease, LOS: length of stay
24
p-value
Table 5. Postoperative complications
Total
PY=0
0<PY<10
10≦PY<30
30<PY
(80,989)
(27,680)
(4,136)
(10,143)
(39,030)
Prolonged air leakage
3,927 (4.8%)
638 (2.3%)
160 (3.9%)
471 (4.6%)
2,658 (6.8%)
<0.001
Bronchopleural fistula
282 (0.3%)
25 (0.1%)
12 (0.3%)
32 (0.3%)
213 (0.5%)
<0.001
Pneumonia
1,621 (2.0%)
184 (0.7%)
41 (1.0%)
179 (1.8%)
1,217 (3.1%)
<0.001
Interstitial pneumonia
504 (0.6%)
22 (0.1%)
5 (0.1%)
56 (0.6%)
421 (1.1%)
<0.001
Atelectasis
557 (0.7%)
90 (0.3%)
10 (0.2%)
58 (0.6%)
399 (1.0%)
<0.001
Respiratory insufficiency
408 (0.5%)
35 (0.1%)
8 (0.2%)
39 (0.4%)
326 (0.8%)
<0.001
Cardiac infarction
37 (0.0%)
1 (0.0%)
1 (0.0%)
4 (0.0%)
31 (0.1%)
<0.001
Cerebral stroke
296 (0.4%)
66 (0.2%)
17 (0.4%)
39 (0.4%)
174 (0.4%)
<0.001
Pulmonary embolism
111 (0.1%)
31 (0.1%)
6 (0.1%)
8 (0.1%)
66 (0.2%)
0.080
Arrhythmia
1,601 (2.0%)
408 (1.5%)
68 (1.6%)
186 (1.8%)
939 (2.4%)
<0.001
Wound infection
233 (0.3%)
48 (0.2%)
9 (0.2%)
26 (0.3%)
150 (0.4%)
<0.001
Empyema
648 (0.8%)
104 (0.4%)
27 (0.7%)
75 (0.7%)
442 (1.1%)
<0.001
Complication
Lung
Cardiovascular
Infection
Values are presented as n (%).
Pearson's chi-squared test for prolonged air leakage, pneumonia, empyema and arrhythmia.
Fisher's exact test for other complications.
PY: pack-years
25
p-value
Table 6. Multivariable analysis for postoperative mortality and complications (Cumulative smoking dose)
Mortality
Variable
OR
95%CI
Complication (Lung)
p-value
OR
95%CI
p-value
Complication (CVD)
OR
95%CI
p-value
Complication (Infection)
OR
95%CI
p-value
PY=0
Ref.
Cumulative
0<PY<10
1.76
1.02-3.04
0.044
1.20
1.03-1.40
0.022
1.15
0.91-1.45
0.232
1.16
0.79-1.72
0.446
smoking dose
10≤PY<30
1.60
1.06-2.43
0.026
1.40
1.25-1.56
<0.001
1.09
0.91-1.30
0.334
1.12
0.84-1.49
0.458
30≤PY
1.73
1.20-2.50
0.003
1.72
1.57-1.89
<0.001
1.26
1.09-1.46
0.002
1.39
1.09-1.77
0.007
Ref.
Ref.
Ref.
This result was assessed after adjusting for the following covariates: sex; age; smoking status; surgical procedure; Eastern Cooperative Oncology Group
performance status; respiratory function; body mass index; preoperative comorbidities (interstitial pneumonia, hemodialysis, diabetes mellitus,
ischemic heart disease, cerebral stroke, autoimmune disease, arrhythmia, hepatic dysfunction); preoperative treatment (chemotherapy, radiotherapy);
histology, and clinical T and clinical N factor.
Ref: reference, CVD: cardiovascular disease, OR: odds ratio, CI: confidence interval, PY: pack-years
26
Figure legends
Figure 1
Flowchart of inclusion criteria in this study.
23
Supplemental Table 1. Surgical mortality according to age and PY
Age, range
Total
PY=0
0<PY<10
10≦PY<30
30<PY
(n)
(80,989)
(27,680)
(4,136)
(10,143)
(39,030)
-59
19/10,366
3/3,759
0/891
3/2,103
13/3,583
(10,336)
(0.18%)
(0.08%)
(0.00%)
(0.14%)
(0.36%)
60-64
32/10,002
1/3,050
1/600
5/1,225
25/5,127
(10,002)
(0.32%)
(0.03%)
(0.17%)
(0.41%)
(0.49%)
65-69
79/17,887
2/5,747
2/823
4/2,063
71/9,254
(17,887)
(0.44%)
(0.03%)
(0.24%)
(0.19%)
(0.77%)
70-74
154/19,103
8/6,349
4/740
15/2,043
127/9,971
(19,103)
(0.81%)
(0.13%)
(0.54%)
(0.73%)
(1.27%)
75-79
178/15,034
15/5,483
6/665
18/1,691
139/7,195
(15,034)
(1.18%)
(0.27%)
(0.90%)
(1.06%)
(1.93%)
80-
138/8,627
16/3,292
7/417
24/1,018
91/3,900
(8,627)
(1.60%)
(0.49%)
(1.68%)
(2.36%)
(2.33%)
Total
600/80,989
45/27,680
20/4,136
69/10,143
466/39,030
(80,989)
(0.74%)
(0.16%)
(0.48%)
(0.68%)
(1.19%)
PY: pack-years
Supplemental Table 2 Multivariable analysis for postoperative mortality and complications (Other covariates)
Mortality
Gender
Age
PS
%VC
Complication (CVD)
Complication (Infection)
OR
95%CI
p-value
OR
95%CI
p-value
OR
95%CI
p-value
OR
95%CI
p-value
Male
2.84
2.02-3.99
<0.001
2.14
1.97-2.34
<0.001
1.22
1.07-1.39
0.004
1.91
1.53-2.39
<0.001
Female
Ref.
Ref.
Ref.
Ref.
< 60 years
Ref.
Ref.
Ref.
Ref.
1.07 1.02-1.12
0.005
5 year increase
(60-80 years)
Procedure
Complication (Lung)
1.48
1.38-1.58
<0.001
1.14
1.12-1.16
<0.001
Ref.
1.21
1.17-1.25
<0.001
Ref.
Ref.
Thoracotomy
Ref.
Mini-thoracotomy
0.86
0.70-1.06
0.168
0.92
0.85-0.99
0.036
0.92
0.81-1.05
0.231
0.88
0.73-1.06
0.188
Complete VATS
0.61
0.47-0.78
<0.001
0.90
0.83-0.98
0.012
0.85
0.74-0.98
0.024
0.71
0.58-0.87
<0.001
0-1
Ref.
>2
1.87
0.92-1.76
0.144
> 100%
Ref.
10% decrease
Ref.
1.39-2.51
<0.001
1.11
Ref.
0.97-1.27
0.119
Ref.
0.74
Ref.
0.56-0.96
0.025
Ref.
1.27
Ref.
1.44
1.35-1.52
<0.001
1.09
1.06-1.11
<0.001
1.03
0.99-1.07
0.118
1.06
1.00-1.13
0.033
<18.5
1.55
1.20-1.99
0.001
1.94
1.79-2.11
<0.001
1.08
0.92-1.27
0.351
1.39
1.11-1.73
0.004
≥18.5
Ref.
Ref.
Ref.
Ref.
≤30
Ref.
Ref.
Ref.
Ref.
>30
0.86
0.47-1.58
0.618
0.90
0.75-1.09
0.281
0.88
0.64-1.20
0.414
1.63
1.13-2.34
0.008
Interstitial
4.57
3.76-5.54
<0.001
1.96
1.79-2.15
<0.001
1.16
0.96-1.40
0.122
1.14
0.87-1.49
0.33
pneumonia
Ref.
2.90
0.55-2.47
0.696
Ref.
Diabetes
0.86
1.02-1.42
0.032
mellitus
Ref.
(50-100%)
BMI
BMI
Hemodialysis
Ref.
1.63-5.14
<0.001
1.19
Ref.
0.89-1.59
0.237
Ref.
0.70-1.05
0.139
0.97
Ref.
1.59
Ref.
1.02-2.48
0.04
Ref.
0.90-1.04
0.34
0.97
Ref.
1.16
Ref.
0.86-1.10
0.656
1.20
Ref.
Ischemic
1.29
heart disease
Ref.
Cerebral
1.28
stroke
Ref.
Autoimmune
1.10
disease
Ref.
1.51
Ref.
Hepatic
4.76
dysfunction
Ref.
Preoperative
1.38
CT
Ref.
Preoperative
1.04
RT
Ref.
Ref.
Ref.
Ref.
Tis-1
Ref.
Ref.
Ref.
Ref.
T2
1.07
0.89-1.29
0.453
1.12
1.06-1.19
<0.001
1.16
1.05-1.28
0.003
1.19
1.02-1.38
0.023
T3-4
1.41
1.08-1.84
0.012
1.23
1.11-1.36
<0.001
1.20
1.01-1.43
0.043
1.37
1.08-1.74
0.01
N0
Ref.
N1
1.44
1.15-1.81
0.002
1.21
1.11-1.31
<0.001
1.11
0.96-1.30
0.159
1.5
1.23-1.83
<0.001
N2
1.39
1.03-1.87
0.029
1.03
0.92-1.16
0.620
1.5
1.25-1.80
<0.001
1.5
1.16-1.94
0.002
AD
0.55
0.45-0.66
<0.001
0.78
0.73-0.82
<0.001
0.93
0.84-1.03
0.148
0.81
0.70-0.94
0.006
Non AD
Ref.
1.77
1.19-2.31
0.003
Ref.
Arrhythmia
T factor
N factor
Histology
Bronchoplasty
0.99-1.66
0.056
1.17
1.06-1.29
0.002
Ref.
0.99-1.66
0.058
1.20
0.698
1.39
1.09-1.32
<0.001
0.007
1.26
1.18-1.64
<0.001
<0.001
1.37
1.12-1.42
<0.001
0.256
1.14
0.99-1.91
0.057
0.926
1.12
0.92-1.40
0.222
0.84-1.48
0.439
1.33
Ref.
0.71-1.35
2.75
0.95
0.49
2.19
2.38-3.18
<0.001
<0.001
1.68
0.95-1.54
0.13
1.18-2.55
0.005
0.99-1.78
0.057
1.58-5.10
<0.001
1.20 0.75-1.93
0.439
1.21
1.73
1.33
Ref.
0.49-1.84
0.87
2.84
Ref.
0.30-0.78
0.003
Ref.
1.27-3.78
0.005
1.05 0.56-1.96
0.884
Ref.
Ref.
1.13-1.56
0.349
Ref.
Ref.
1.30-2.18
Ref.
Ref: reference, CVD: cardiovascular disease, OR: odds ratio, CI: confidence interval, VATS: video assisted thoracic surgery,
PS: Eastern Cooperative Oncology Group performance status, VC: vital capacity, BMI: body mass index, AD: adenocarcinoma,
CT: chemotherapy, RT: radiation therapy
0.89
Ref.
Ref.
0.003
0.98
0.66-1.16
Ref.
Ref.
Ref.
1.22-2.58
<0.001
Ref.
Ref.
0.48-2.26
1.18-1.59
Ref.
Ref.
0.79-2.42
1.37
0.88
Ref.
Ref.
Ref.
2.65-8.54
0.005
Ref.
Ref.
1.12-2.04
1.07-1.48
Ref.
Ref.
0.67-1.82
1.26
<0.001
1.66
Ref.
Figure legends
Supplemental Figure 1
Relationship between postoperative outcomes and preoperative cumulative smoking dose.
Preoperative cumulative smoking dose was categorized by pack-years (PY): Non-smokers, PY =
0; light smokers, 0 < PY < 10; moderate smokers, 10 ≤ PY < 30; and heavy smokers, 30 ≤ PY. A)
Surgical mortality; B) Postoperative pulmonary complications; C) Postoperative cardiovascular
complications; and D) Postoperative infectious complications.
Supplemental Figure 2
Risk of short-term outcomes was assessed according to cumulative smoking dose using
multivariable analysis. The odds were adjusted for covariates. Preoperative cumulative smoking
dose was categorized by pack-years (PY): Non-smokers, PY = 0; light smokers, 0 < PY < 10;
moderate smokers, 10 ≤ PY < 30; and heavy smokers, 30 ≤ PY. A) Surgical mortality; B)
Postoperative pulmonary complications; C) Postoperative cardiovascular complications; and D)
Postoperative infectious complications.
...
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