Table 1
Baseline characteristics of patients with lung cancer
Variables
|
Total
(N=20689),
n (%)
|
With cardiovascular disease (N=6436),
n (%)
|
Without cardiovascular disease (N=14253),
n (%)
|
P-value
|
Age, in years
|
|
|
|
<.0001
|
Mean (+STD)
|
69.5 (+11)
|
73.7 (+9.7)
|
67.6 (+11.1)
|
|
Median (IQR)
|
70 (62 - 78)
|
75 (67 - 81)
|
68 (60 - 76)
|
|
Age group
|
|
|
|
<.0001
|
<=60
|
4443 (21.5 %)
|
658 (10.2 %)
|
3785 (26.6 %)
|
|
61-70
|
6112 (29.5 %)
|
1549 (24.1 %)
|
4563 (32 %)
|
|
71-80
|
6717 (32.5 %)
|
2590 (40.2 %)
|
4127 (29 %)
|
|
>80
|
3417 (16.5 %)
|
1639 (25.5 %)
|
1778 (12.5 %)
|
|
Sex
|
|
|
|
<.0001
|
Female
|
10156 (49.1 %)
|
2874 (44.7 %)
|
7282 (51.1 %)
|
|
Male
|
10533 (50.9 %)
|
3562 (55.3 %)
|
6971 (48.9 %)
|
|
Year of diagnosis
|
|
|
|
0.0337
|
2004-2009
|
9993 (48.3 %)
|
3038 (47.2 %)
|
6955 (48.8 %)
|
|
2010-2015
|
10696 (51.7 %)
|
3398 (52.8 %)
|
7298 (51.2 %)
|
|
CCI score
|
|
|
|
<.0001
|
0
|
2566 (12.4 %)
|
310 (4.8 %)
|
2256 (15.8 %)
|
|
1
|
2614 (12.6 %)
|
627 (9.7 %)
|
1987 (13.9 %)
|
|
>1
|
15509 (75 %)
|
5499 (85.4 %)
|
10010 (70.2 %)
|
|
Histology
|
|
|
|
<.0001
|
Adenocarcinoma
|
7727 (37.3 %)
|
2024 (31.4 %)
|
5703 (40 %)
|
|
SCC
|
3680 (17.8 %)
|
1184 (18.4 %)
|
2496 (17.5 %)
|
|
SCLC
|
2571 (12.4 %)
|
799 (12.4 %)
|
1772 (12.4 %)
|
|
Carcinoid/LCNE
|
520 (2.5 %)
|
117 (1.8 %)
|
403 (2.8 %)
|
|
Large cell cancer
|
260 (1.3 %)
|
59 (0.9 %)
|
201 (1.4 %)
|
|
Others
|
5931 (28.7 %)
|
2253 (35 %)
|
3678 (25.8 %)
|
|
Stage
|
|
|
|
|
I
|
3636 (17.6 %)
|
1127 (17.5 %)
|
2509 (17.6 %)
|
<.0001
|
II
|
880 (4.3 %)
|
250 (3.9 %)
|
630 (4.4 %)
|
|
III
|
5168 (25 %)
|
1591 (24.7 %)
|
3577 (25.1 %)
|
|
IV
|
10409 (50.3 %)
|
3207 (49.8 %)
|
7202 (50.5 %)
|
|
Unknown
|
596 (2.9 %)
|
261 (4.1 %)
|
335 (2.4 %)
|
|
T stage
|
|
|
|
|
T0
|
110 (0.5 %)
|
44 (0.7 %)
|
66 (0.5 %)
|
<.0001
|
T1
|
3095 (15 %)
|
985 (15.3 %)
|
2110 (14.8 %)
|
|
T2
|
6581 (31.8 %)
|
2001 (31.1 %)
|
4580 (32.1 %)
|
|
T3
|
788 (3.8 %)
|
188 (2.9 %)
|
600 (4.2 %)
|
|
T4
|
9378 (45.3 %)
|
2966 (46.1 %)
|
6412 (45 %)
|
|
Unknown
|
737 (3.6 %)
|
252 (3.9 %)
|
485 (3.4 %)
|
|
N stage
|
|
|
|
|
N0
|
6540 (31.6 %)
|
2126 (33 %)
|
4414 (31 %)
|
<.0001
|
N1
|
1729 (8.4 %)
|
494 (7.7 %)
|
1235 (8.7 %)
|
|
N2
|
7453 (36 %)
|
2302 (35.8 %)
|
5151 (36.1 %)
|
|
N3
|
3803 (18.4 %)
|
1073 (16.7 %)
|
2730 (19.2 %)
|
|
Unknown
|
1164 (5.6 %)
|
441 (6.9 %)
|
723 (5.1 %)
|
|
M stage
|
|
|
|
|
M0
|
9877 (47.7 %)
|
3069 (47.7 %)
|
6808 (47.8 %)
|
0.0008
|
M1
|
10409 (50.3 %)
|
3207 (49.8 %)
|
7202 (50.5 %)
|
|
Unknown
|
403 (1.9 %)
|
160 (2.5 %)
|
243 (1.7 %)
|
|
Laterality
|
|
|
|
|
Bilateral
|
211 (1 %)
|
74 (1.1 %)
|
137 (1 %)
|
0.0003
|
Left
|
8477 (41 %)
|
2677 (41.6 %)
|
5800 (40.7 %)
|
|
Right
|
11568 (55.9 %)
|
3515 (54.6 %)
|
8053 (56.5 %)
|
|
Unknown
|
433 (2.1 %)
|
170 (2.6 %)
|
263 (1.8 %)
|
|
Surgery
|
|
|
|
|
No
|
17274 (83.5 %)
|
5721 (88.9 %)
|
11553 (81.1 %)
|
<.0001
|
Lobectomy or segmental
|
3168 (15.3 %)
|
686 (10.7 %)
|
2482 (17.4 %)
|
|
Pneumonectomy
|
247 (1.2 %)
|
29 (0.5 %)
|
218 (1.5 %)
|
|
Chemotherapy
|
|
|
|
|
No
|
15029 (72.6 %)
|
5378 (83.6 %)
|
9651 (67.7 %)
|
<.0001
|
Yes
|
5660 (27.4 %)
|
1058 (16.4 %)
|
4602 (32.3 %)
|
|
Immunotherapy
|
|
|
|
|
No
|
20669 (99.9 %)
|
6433 (100 %)
|
14236 (99.9 %)
|
0.1195
|
Yes
|
20 (0.1 %)
|
3 (0 %)
|
17 (0.1 %)
|
|
Radiation
|
|
|
|
|
No
|
14418 (69.7 %)
|
4743 (73.7 %)
|
9675 (67.9 %)
|
<.0001
|
Yes
|
6271 (30.3 %)
|
1693 (26.3 %)
|
4578 (32.1 %)
|
|
Institution type
|
|
|
|
|
Academic
|
10713 (51.8 %)
|
3119 (48.5 %)
|
7594 (53.3 %)
|
<.0001
|
Community
|
9976 (48.2 %)
|
3317 (51.5 %)
|
6659 (46.7 %)
|
|
Driving time (hours)
|
|
|
|
|
1
|
15419 (74.5 %)
|
4704 (73.1 %)
|
10715 (75.2 %)
|
<.0001
|
2
|
2885 (13.9 %)
|
1010 (15.7 %)
|
1875 (13.2 %)
|
|
>2
|
2385 (11.5 %)
|
722 (11.2 %)
|
1663 (11.7 %)
|
|
Health Zone
|
|
|
|
|
Calgary
|
6192 (29.9 %)
|
1781 (27.7 %)
|
4411 (30.9 %)
|
<.0001
|
Central
|
3125 (15.1 %)
|
1045 (16.2 %)
|
2080 (14.6 %)
|
|
Edmonton
|
7159 (34.6 %)
|
2239 (34.8 %)
|
4920 (34.5 %)
|
|
North
|
2459 (11.9 %)
|
755 (11.7 %)
|
1704 (12 %)
|
|
South
|
1754 (8.5 %)
|
616 (9.6 %)
|
1138 (8 %)
|
|
Educational level*
|
|
|
|
|
<= 80%
|
10133 (49 %)
|
3281 (51 %)
|
6852 (48.1 %)
|
0.0005
|
> 80%
|
10527 (50.9 %)
|
3147 (48.9 %)
|
7380 (51.8 %)
|
|
Unknown
|
29 (0.1 %)
|
8 (0.1 %)
|
21 (0.1 %)
|
|
Income level
|
|
|
|
|
<= 46k
|
12849 (62.1 %)
|
4085 (63.5 %)
|
8764 (61.5 %)
|
0.0237
|
> 46k
|
7811 (37.8 %)
|
2343 (36.4 %)
|
5468 (38.4 %)
|
|
Unknown
|
29 (0.1 %)
|
8 (0.1 %)
|
21 (0.1 %)
|
|
cardiovascular disease: cardiovascular disease. *80% of residents have high school and above level of education in the neighborhood. |
Pre-existing cardiovascular diseases
Of all patients with lung cancer, 6436 (31.1%) had at least one pre-existing cardiovascular disease. The most common pre-existing cardiovascular disease at the diagnosis of lung cancer included congestive heart failure (47.4%), followed by previous cerebrovascular accident (40.3%), myocardial infarction (33.0%), and chronic arrythmias (30.4%), respectively (Table 2).
Table 2
Type of cardiovascular disease
Cardiovascular disease | Number (percentage of those with cardiovascular disease ) (n = 6436) | Percentage of overall population (n = 20689) |
Previous myocardial infarction | 2127 (33%) | 10.3% |
Congestive heart failure | 3049 (47.4%) | 14.7% |
Cerebrovascular accident | 2596 (40.3%) | 12.5% |
Chronic arrhythmias | 1954 (30.4%) | 9.4% |
Patients with pre-existing cardiovascular disease were more likely to be older (mean age 73.7 vs. 67.6 years, P < 0.0001), male (55.3% vs. 48.9%, P < 0.0001), have a higher burden of comorbid conditions (Charlson’s comorbidity index score > 1, 85.4% vs. 70.2%, P < 0.0001), and advanced stages of lung cancer at diagnosis (stage III and IV, 74.5% vs. 75.6%, P < 0.0001). Similarly, they were more likely to have lower neighborhood-level income (< 46K per year, 36.4% vs. 38.4%, P = 0.0237) and education levels (> 80% population attained high-school or greater, 48.9% vs. 51.8%, P = 0.0005), and also tended to reside rurally (37.5% vs. 34.6%, P < 0.0001). The driving time from place of residence to cancer center (> 2 hours, 11.2% vs 11.7%, P < 0.0001) was also longer in this subpopulation.
Patients with lung cancer and pre-existing cardiovascular disease were less likely to be treated with surgery (11.2% vs. 18.9%, P < 0.0001), chemotherapy (16.4% vs. 32.3%, P < 0.0001), or radiotherapy (26.3% vs. 32.1%, P < 0.0001). Moreover, such patients were more likely to be treated in community centers rather than academic institutions (51.5% vs. 46.7%, P < 0.0001).
Pre-existing cardiovascular disease and treatment patterns
We used multivariable logistic regression analysis to assess the impact of pre-existing cardiovascular disease on lung cancer treatment, including chemotherapy, radiation therapy, and surgery (Table 3). Adjusting for baseline variables including age, sex, year of diagnosis, Charlson’s comorbidity index, histological subtype, stage (T, N, and M), laterality, other treatments, management at either academic or community center, zone of residence, driving distance from residence to nearest cancer center, education and income levels, the presence of pre-existing cardiovascular disease was associated with lower likelihood of chemotherapy (odds ratio, 0.53; 95% confidence interval [CI], 0.48 to 0.58; P < 0.0001), radiation therapy (odds ratio, 0.76; 95% CI 0.7 to 0.82, P < 0.0001) or surgery (odds ratio, 0.56; 95% CI, 0.44 to 0.7; P < 0.0001), respectively.
Table 3
Multivariable Logistic regression for factors associated with surgery, chemotherapy, and radiation therapy in patients with lung cancer
Variable | Chemotherapy | Radiation | Surgery |
Odds Ratio (95% Confidence Limit) | P value | Odds Ratio (95% Confidence Limit) | P value | Odds Ratio (95% Confidence Limit) | P value |
Age group | | | | | | |
<=60 | Reference | | Reference | | Reference | |
61–70 | 0.68 (0.62 to 0.75) | < .0001 | 0.82 (0.74 to 0.9) | < .0001 | 0.57 (0.44 to 0.75) | < .0001 |
71–80 | 0.34 (0.3 to 0.37) | < .0001 | 0.61 (0.55 to 0.67) | < .0001 | 0.35 (0.27 to 0.46) | < .0001 |
> 80 | 0.09 (0.08 to 0.11) | < .0001 | 0.38 (0.34 to 0.43) | < .0001 | 0.12 (0.08 to 0.18) | < .0001 |
Sex | | | | | | |
Female | Reference | | Reference | | Reference | |
Male | 0.92 (0.85 to 0.99) | 0.0225 | 1.11 (1.04 to 1.18) | 0.0029 | 0.99 (0.82 to 1.21) | 0.9448 |
Year of diagnosis | 1.01 (1 to 1.02) | 0.0337 | 1 (0.99 to 1.01) | 0.6327 | 0.99 (0.96 to 1.02) | 0.4833 |
CCI score | | | | | | |
0 | Reference | | Reference | | Reference | |
1 | 0.77 (0.67 to 0.89) | 0.0002 | 1.02 (0.89 to 1.17) | 0.7471 | 0.79 (0.55 to 1.13) | 0.1945 |
> 1 | 0.68 (0.61 to 0.75) | < .0001 | 1.16 (1.04 to 1.29) | 0.0058 | 0.68 (0.52 to 0.9) | 0.0078 |
cardiovascular disease | | | | | | |
No | Reference | | Reference | | Reference | |
Yes | 0.53 (0.48 to 0.58) | < .0001 | 0.76 (0.7 to 0.82) | < .0001 | 0.56 (0.44 to 0.7) | < .0001 |
Histology | | | | | | |
Adenocarcinoma | Reference | | Reference | | Reference | |
SCC | 0.61 (0.55 to 0.68) | < .0001 | 0.77 (0.71 to 0.85) | < .0001 | 0.12 (0.08 to 0.16) | < .0001 |
SCLC | 6.64 (5.93 to 7.45) | < .0001 | 2.17 (1.96 to 2.39) | < .0001 | 0.47 (0.37 to 0.61) | < .0001 |
Carcinoid/LCNE | 1.05 (0.84 to 1.31) | 0.6779 | 0.82 (0.62 to 1.08) | 0.148 | 3.46 (2.16 to 5.54) | < .0001 |
Large cell ca | 0.79 (0.58 to 1.08) | 0.1382 | 1.98 (1.45 to 2.71) | < .0001 | 9.65 (4.74 to 19.6) | < .0001 |
Others | 6.64 (5.93 to 7.45) | < .0001 | 0.71 (0.63 to 0.79) | < .0001 | 0.48 (0.32 to 0.73) | 0.0005 |
T stage | | | | | | |
T0 | Reference | | Reference | | | |
T1 | 0.63 (0.37 to 1.09) | 0.1007 | 1.39 (0.78 to 2.48) | 0.2709 | Reference | |
T2 | 1.02 (0.59 to 1.75) | 0.9435 | 1.74 (0.98 to 3.09) | 0.0588 | 0.78 (0.61 to 1) | 0.0517 |
T3 | 1.28 (0.73 to 2.24) | 0.391 | 3.52 (1.94 to 6.39) | < .0001 | 0.75 (0.48 to 1.17) | 0.204 |
T4 | 1 (0.58 to 1.7) | 0.9861 | 1.65 (0.93 to 2.93) | 0.0862 | 0.2 (0.15 to 0.27) | < .0001 |
Unknown | 0.74 (0.42 to 1.29) | 0.2909 | 1.06 (0.58 to 1.92) | 0.8544 | 0.97 (0.46 to 2.03) | 0.9319 |
N stage | | | | | | |
N0 | Reference | | Reference | | Reference | |
N1 | 2.72 (2.37 to 3.12) | < .0001 | 1.07 (0.93 to 1.24) | 0.34 | 0.97 (0.72 to 1.3) | 0.8284 |
N2 | 2.22 (1.99 to 2.48) | < .0001 | 1.66 (1.51 to 1.82) | < .0001 | 0.13 (0.1 to 0.17) | < .0001 |
N3 | 2.36 (2.08 to 2.67) | < .0001 | 1.73 (1.55 to 1.92) | < .0001 | 0.02 (0.01 to 0.03) | < .0001 |
Unknown | 1.05 (0.84 to 1.32) | 0.6623 | 0.68 (0.56 to 0.82) | < .0001 | 0.28 (0.15 to 0.51) | < .0001 |
M stage | | | | | | |
M0 | Reference | | Reference | | Reference | |
M1 | 0.65 (0.6 to 0.71) | < .0001 | 0.35 (0.32 to 0.37) | < .0001 | 0.03 (0.02 to 0.04) | < .0001 |
Unknown | 0.29 (0.18 to 0.45) | < .0001 | 0.28 (0.2 to 0.39) | < .0001 | 1.34 (0.61 to 2.92) | 0.4665 |
Laterality | | | | | | |
Bilateral | Reference | | Reference | | Reference | |
Left | 0.62 (0.43 to 0.88) | 0.0071 | 3.46 (2.13 to 5.63) | < .0001 | 5.62 (0.69 to 45.6) | 0.1063 |
Right | 0.56 (0.39 to 0.79) | 0.0012 | 3.59 (2.21 to 5.83) | < .0001 | 5.63 (0.69 to 45.6) | 0.1058 |
Unknown | 0.47 (0.3 to 0.74) | 0.0012 | 1.82 (1.03 to 3.22) | 0.0397 | | |
Chemotherapy | | | | | | |
0 | | | Reference | | Reference | |
1 | | | 1.21 (1.11 to 1.31) | < .0001 | 1.85 (1.45 to 2.35) | < .0001 |
Surgery type | | | | | | |
Segmental | Reference | | Reference | | | |
Non-surgery | 1.32 (1.13 to 1.55) | 0.0006 | 36.5(29.3 to 45.48) | < .0001 | | |
Pneumonectomy | 1.8 (1.34 to 2.41) | < .0001 | 0.43 (0.2 to 0.95) | 0.0363 | | |
Radiation | | | | | | |
0 | Reference | | | | Reference | |
1 | 1.18 (1.08 to 1.28) | 0.0001 | | | 0.05 (0.04 to 0.07) | < .0001 |
Immunotherapy | | | | | | |
0 | Reference | | Reference | | Reference | |
1 | 4.06 (1.53 to 10.8) | 0.005 | 0.79 (0.29 to 2.1) | 0.6303 | 0.02 (0 to 0.31) | 0.0045 |
Institution type | | | | | | |
Academic | Reference | | Reference | | Reference | |
Community | 0.81 (0.74 to 0.89) | < .0001 | 0.9 (0.83 to 0.98) | 0.0097 | 0 (0 to 0.01) | < .0001 |
Driving time (hours) | | | | | | |
1 | Reference | | Reference | | Reference | |
2 | 0.88 (0.77 to 1) | 0.0563 | 0.97 (0.86 to 1.1) | 0.6531 | 1.93 (1.17 to 3.19) | 0.0097 |
> 2 | 0.92 (0.75 to 1.12) | 0.4131 | 0.9 (0.74 to 1.08) | 0.2578 | 1.05 (0.53 to 2.08) | 0.8908 |
Health Zone | | | | | | |
Calgary | Reference | | Reference | | Reference | |
Central | 1.36 (1.19 to 1.56) | < .0001 | 0.75 (0.66 to 0.85) | < .0001 | 5.21 (3.26 to 8.34) | < .0001 |
Edmonton | 0.97 (0.89 to 1.06) | 0.5263 | 0.99 (0.91 to 1.08) | 0.8189 | 1.9 (1.52 to 2.36) | < .0001 |
North | 1.17 (0.95 to 1.44) | 0.1448 | 0.94 (0.77 to 1.15) | 0.5443 | 6.86 (3.4 to 13.85) | < .0001 |
South | 1.29 (1.1 to 1.52) | 0.0019 | 0.92 (0.79 to 1.06) | 0.2432 | 2.66 (1.38 to 5.16) | 0.0036 |
Education level* | | | | | | |
<= 80% | Reference | | Reference | | Reference | |
> 80% | 1.06 (0.98 to 1.15) | 0.1557 | 1 (0.92 to 1.08) | 0.948 | 0.94 (0.75 to 1.18) | 0.6046 |
Income level | | | | | | |
<= 46 k | Reference | | Reference | | Reference | |
> 46 k | 1.21 (1.12 to 1.32) | < .0001 | 1.03 (0.95 to 1.11) | 0.4565 | 1.35 (1.09 to 1.67) | 0.0069 |
cardiovascular disease: cardiovascular disease. *80% of residents have high school and above level of education in the neighborhood. |
Impact of pre-existing cardiovascular disease on survival outcomes
The median overall survival (OS) of patients with lung cancer and pre-existing cardiovascular disease was significantly shorter (13.5 [95% CI, 12.8–14.2] years) compared with those without any baseline cardiovascular disease (23.5 [95% CI, 22.8–24.2] years, P < 0.0001) (Fig. 1). Likewise, cancer specific survival (CSS) was significantly shorter for those with pre-existing cardiovascular disease (15.2 vs 24.8 years, P < 0.0001).
Multivariable Cox regression model was constructed to analyze the factors that impacted OS and CSS (Table 4). Adjusting for baseline factors, pre-existing cardiovascular disease was predictive of inferior OS (hazard ratio, 1.1; 95% CI, 1.1 to 1.2; P < 0.0001), as well as shorter CSS (hazard ratio, 1.1; 95% CI, 1.1 to 1.1; P < 0.0001), respectively. Other factors predictive of shorter OS and CSS included older age, male sex, Charlson’s comorbidity index > 1, histologies other than carcinoid and adenocarcinoma, advanced TNM stage, and > 2 hours drive from residence to the nearest cancer center. Conversely, treatment with surgery, chemotherapy, or radiotherapy predicted longer OS and CSS. Notably, treatment setting (academic vs community treatment center), education, and income did not influence survival outcomes.
Table 4
Multivariable Cox regression model for factors associated with overall survival and cancer-specific survival in patients with lung cancer
Variable | Overall survival | Cancer specific survival |
Hazard Ratio (95% Confidence Limit) | P value | Hazard Ratio (95% Confidence Limit) | P value |
Age group | | | | |
<=60 | Reference | | Reference | |
61–70 | 1.1 (1 to 1.1) | 0.0005 | 1.1 (1 to 1.1) | 0.0061 |
71–80 | 1.1 (1 to 1.1) | 0.0012 | 1 (1 to 1.1) | 0.2039 |
> 80 | 1.1 (1.1 to 1.2) | < .0001 | 1.1 (1 to 1.1) | 0.0037 |
Sex | | | | |
Female | Reference | | Reference | |
Male | 1.2 (1.2 to 1.2) | < .0001 | 1.2 (1.2 to 1.2) | < .0001 |
Year of diagnosis | 1 (1 to 1) | 0.0012 | 1 (1 to 1) | 0.1635 |
CCI score | | | | |
0 | Reference | | Reference | |
1 | 1 (0.9 to 1) | 0.2999 | 1 (0.9 to 1) | 0.145 |
> 1 | 1.2 (1.1 to 1.2) | < .0001 | 1.2 (1.1 to 1.2) | < .0001 |
cardiovascular disease | | | | |
Yes | Reference | | Reference | |
No | 1.1 (1.1 to 1.2) | < .0001 | 1.1 (1.1 to 1.1) | < .0001 |
Histology | | | | |
Adenocarcinoma | Reference | | Reference | |
SCC | 1.1 (1 to 1.1) | 0.0182 | 1 (1 to 1.1) | 0.2506 |
SCLC | 1.6 (1.5 to 1.7) | < .0001 | 1.6 (1.5 to 1.7) | < .0001 |
Carcinoid/LCNE | 0.7 (0.7 to 0.8) | < .0001 | 0.8 (0.7 to 0.9) | < .0001 |
Large cell ca | 1.3 (1.1 to 1.4) | 0.0011 | 1.3 (1.1 to 1.5) | 0.0005 |
Others | 1.2 (1.2 to 1.3) | < .0001 | 1.2 (1.2 to 1.3) | < .0001 |
T stage | | | | |
T0 | Reference | | Reference | |
T1 | 1.3 (1 to 1.6) | 0.0394 | 1.1 (0.9 to 1.4) | 0.2457 |
T2 | 1.8 (1.5 to 2.3) | < .0001 | 1.8 (1.4 to 2.2) | < .0001 |
T3 | 2.5 (2 to 3.1) | < .0001 | 2.4 (1.9 to 3) | < .0001 |
T4 | 2.6 (2.1 to 3.2) | < .0001 | 2.5 (2 to 3.1) | < .0001 |
Unknown | 1.8 (1.4 to 2.2) | < .0001 | 1.7 (1.4 to 2.2) | < .0001 |
N stage | | | | |
N0 | Reference | | Reference | |
N1 | 1.4 (1.3 to 1.5) | < .0001 | 1.5 (1.4 to 1.6) | < .0001 |
N2 | 1.8 (1.7 to 1.8) | < .0001 | 1.9 (1.8 to 1.9) | < .0001 |
N3 | 1.8 (1.7 to 1.9) | < .0001 | 1.9 (1.8 to 2) | < .0001 |
Unknown | 1.6 (1.5 to 1.7) | < .0001 | 1.7 (1.5 to 1.8) | < .0001 |
M stage | | | | |
M0 | Reference | | Reference | |
M1 | 1.9 (1.8 to 1.9) | < .0001 | 2 (1.9 to 2.1) | < .0001 |
Unknown | 0.9 (0.8 to 1) | 0.2007 | 0.9 (0.8 to 1.1) | 0.2776 |
Lateral | | | | |
Bilateral | Reference | | Reference | |
Left | 1.3 (1.1 to 1.5) | 0.0001 | 1.3 (1.1 to 1.5) | 0.0014 |
Right | 1.3 (1.2 to 1.5) | < .0001 | 1.3 (1.1 to 1.5) | 0.0005 |
Unknown | 2 (1.7 to 2.4) | < .0001 | 1.9 (1.6 to 2.3) | < .0001 |
Surgery type | | | | |
Pneumonectomy | Reference | | Reference | |
Lobectomy or segmental | 0.7 (0.6 to 0.9) | 0.0002 | 0.6 (0.5 to 0.8) | < .0001 |
Non-surgery | 2.8 (2.4 to 3.3) | < .0001 | 2.7 (2.3 to 3.3) | < .0001 |
Chemotherapy | | | | |
No | Reference | | Reference | |
Yes | 0.4 (0.4 to 0.4) | < .0001 | 0.4 (0.4 to 0.4) | < .0001 |
Radiation | | | | |
No | Reference | | Reference | |
Yes | 0.6 (0.6 to 0.7) | < .0001 | 0.6 (0.6 to 0.7) | < .0001 |
Surgery institution type | | | | |
Academic | Reference | | Reference | |
Community | 1 (1 to 1.1) | 0.44 | 1 (1 to 1.1) | 0.069 |
Driving time (hours) | | | | |
1 | Reference | | Reference | |
2 | 1 (1 to 1.1) | 0.5613 | 1 (1 to 1.1) | 0.4693 |
3 | 0.9 (0.8 to 1) | 0.0215 | 0.9 (0.8 to 1) | 0.0073 |
Zone name | | | | |
Calgary | Reference | | Reference | |
Central | 1.1 (1 to 1.1) | 0.004 | 1.1 (1 to 1.1) | 0.03 |
Edmonton | 1.1 (1 to 1.1) | < .0001 | 1.1 (1.1 to 1.1) | < .0001 |
North | 1.2 (1.1 to 1.3) | < .0001 | 1.2 (1.1 to 1.3) | < .0001 |
South | 1.2 (1.1 to 1.3) | < .0001 | 1.2 (1.1 to 1.3) | < .0001 |
Education level | | | | |
<= 80% | Reference | | Reference | |
> 80% | 1 (1 to 1) | 0.3769 | 1 (1 to 1) | 0.5999 |
Income level | | | | |
<= 46 k | Reference | | Reference | |
> 46 k | 1 (1 to 1) | 0.9992 | 1 (1 to 1) | 0.8051 |
cardiovascular disease: cardiovascular disease. *80% of residents have high school and above level of education in the neighborhood. |
The presence of pre-existing cardiovascular disease can alter the effect of various treatments on the outcomes of patients with lung cancer. Therefore, we assessed for any effect modification by examining interactions in the statistical models. The effect of baseline cardiovascular disease on OS varied for chemotherapy (P = 0.026), surgery (P < .0001), and radiotherapy (P = 0.001). Likewise for CSS, the interactions were significant for radiotherapy and surgery (P = 0.05, and P = 0.001, respectively). However, the interaction of chemotherapy on CSS showed only a trend towards significance (P = 0.06).