Introduction
It is estimated that about 236 740 new cases of lung cancer will be diagnosed in the USA in 2022, with 130 180 cases of deaths. Lung cancer is the second most common cancer in both men and women, less than breast cancer (in female) or prostate cancer (in male), and is the leading cause of death of cancer patients, with low 5-year survival rate (Siegel et al., 2022 Fares et al., 2020 Achrol et al., 2019 Schouten et al., 2002 ; Lowery and Yu, 2017 Castrucci and Knisely, 2008
Despite the rapid development of multiple therapies, such as targeted therapy and immunotherapy, the prognosis of patients with advanced lung cancer remains poor (Achrol et al., 2019 Steeg et al., 2011 ; Bacha et al., 2018 ; Zhu et al., 2022 Bacha et al., 2018 Sanchez de Cos et al., 2009
Clinical characteristics including age, race, sex, Gleason score, smoking, histological type, T stage, N stage, insurance status, and marital status were found to correlate with survival of lung cancer patients with brain metastasis (Reddy et al., 2020 ; Shen et al., 2021 ; Sung et al., 2021 Aoyama et al., 2006 ; Sanchez de Cos et al., 2009 ; Yamamoto et al., 2013 Li et al., 2021 ; Zuo et al., 2021
Methods
Population
In this population-based study, lung cancer data were downloaded from the SEER database. SEER*Stat version 8.4.0 (https://seer.cancer.gov/seerstat/ Doll et al., 2018 Fig. 1 . A total of 76 483 patients diagnosed with lung cancer between 2010 and 2017 were used to investigate brain metastasis risk factors, and then prognostic factors were explored for 10 813 lung cancer patients with brain metastasis. Subgroup analysis was based on the pathology of lung cancer patients. Patient information with survival time was used to investigate the prognostic role of surgery for NSCLC patients with brain metastasis.
Fig. 1: Flowchart of the process of data selection. BM, brain metastasis.
Statistical analysis
This study included the following variables: age (<50, 50–59, 60–69, 70–79, ≥80); sex (male and female); race [white, black, other (American Indian/AK Native, Asian/Pacific Islander), unknown]; pathology (adenocarcinoma, non–small-cell carcinoma, small-cell carcinoma, large-cell carcinoma, squamous-cell carcinoma, other); site of primary tumor (left main bronchus, left upper lobe, left lower lobe, right main bronchus, right upper lobe, right middle lobe, right lower lobe, other); T stage (T1, T2, T3, T4, other); N stage (N0, N1, N2, N3, other); liver metastasis status (Yes, No, unknown); bone metastasis (Yes, No, unknown); brain metastasis (Yes, No, unknown); surgical treatment (Yes, No, unknown); radiotherapy (Yes, No, unknown); and chemotherapy (Yes, No, unknown). Univariate and multivariate logistic regression were used to identify the risk factors for brain metastasis. Kaplan–Meier method was conducted to investigate OS outcomes. Univariate and multivariate Cox regression analyses were used to identify potential prognostic factors. Propensity score matching (PSM) (ratio 1:1, caliper: 0.2 SD of propensity score) was conducted to eliminate baseline differences between the two groups using the ‘Matching’ R package (Huber et al., 2017 ; Zhao et al., 2021 P < 0.05 was considered to be statistically significant. All statistical analyses were conducted within R software (version 4.1.0).
Results
Patient characteristics
A total of 76 483 lung cancer patients were initially identified between 2010 and 2017. Of these patients, 10 818 (14.1%) patients were diagnosed with brain metastasis, and most patients were without brain metastasis (85.9%, N = 65 665). 13 960 (18.3%) patients were more than 80 years. A total of 39 642 (51.8%) patients were male. A total of 39.1% were diagnosed with lung adenocarcinoma (N = 29 878). Over half of the patients were white (76.7%, N = 155 877). As for the lesion site, the right upper lobe is the most common, about 28.6% (N = 21 842). Most patients were without bone metastases (N = 60 706, 79.4%), liver metastases (N = 66 410, 86.8%), or distant lymph node metastases (N = 17 880, 23.4%). 14.9 % of patients (N = 11 363) were T1 and 27.6% (N = 21 129) were N0. More details about patient clinical characteristics are shown in Table 1 .
Table 1 -
Clinical characteristics of lung cancer patients
Brain metastases
Overall
No
Yes
P
n
76 483
65 665
10 818
Age (%)
<0.001
<50
3040 (4.0)
2397 (3.7)
643 (5.9)
50–59
12 290 (16.1)
9781 (14.9)
2509 (23.2)
60–69
23 822 (31.1)
20 008 (30.5)
3814 (35.3)
70–79
23 371 (30.6)
20 611 (31.4)
2760 (25.5)
≥80
13 960 (18.3)
12 868 (19.6)
1092 (10.1)
Race (%)
<0.001
Black
6948 (9.1)
5902 (9.0)
1046 (9.7)
White
60 578 (79.2)
52 284 (79.6)
8294 (76.7)
Other
8802 (11.5)
7340 (11.2)
1462 (13.5)
Unknown
155 (0.2)
139 (0.2)
16 (0.1)
Sex (%)
Female
36 841 (48.2)
31 698 (48.3)
5143 (47.5)
0.162
Male
39 642 (51.8)
33 967 (51.7)
5675 (52.5)
Pathology (%)
<0.001
Squamous-cell carcinoma
14 957 (19.6)
14 058 (21.4)
899 (8.3)
Adenocarcinoma
29 878 (39.1)
24 393 (37.1)
5485 (50.7)
Non–small-cell carcinoma
4894 (6.4)
3976 (6.1)
918 (8.5)
Small-cell carcinoma
9544 (12.5)
7834 (11.9)
1710 (15.8)
Large-cell carcinoma
1009 (1.3)
819 (1.2)
190 (1.8)
Other
16 201 (21.2)
14 585 (22.2)
1616 (14.9)
Location (%)
<0.001
Left lower
8995 (11.8)
7763 (11.8)
1232 (11.4)
Left upper
17 139 (22.4)
14 747 (22.5)
2392 (22.1)
Left main bronchus
1366 (1.8)
1163 (1.8)
203 (1.9)
Right lower
11 402 (14.9)
9993 (15.2)
1409 (13.0)
Right middle
3530 (4.6)
3094 (4.7)
436 (4.0)
Right upper
21 842 (28.6)
18 850 (28.7)
2992 (27.7)
Right main bronchus
1841 (2.4)
1539 (2.3)
302 (2.8)
Other
10 368 (13.6)
8516 (13.0)
1852 (17.1)
Bone metastasis (%)
<0.001
No
60 706 (79.4)
53 994 (82.2)
6712 (62.0)
Yes
15 094 (19.7)
11 275 (17.2)
3819 (35.3)
Unknown
683 (0.9)
396 (0.6)
287 (2.7)
Liver metastasis (%)
<0.001
No
66 410 (86.8)
58 173 (88.6)
8237 (76.1)
Yes
9274 (12.1)
7091 (10.8)
2183 (20.2)
Unknown
799 (1.0)
401 (0.6)
398 (3.7)
Distant lymph node metastasis (%)
<0.001
NO
17 880 (23.4)
15 616 (23.8)
2264 (20.9)
Yes
1730 (2.3)
1267 (1.9)
463 (4.3)
Unknown
56 873 (74.4)
48 782 (74.3)
8091 (74.8)
T (%)
<0.001
T1
11 363 (14.9)
10 550 (16.1)
813 (7.5)
T2
15 451 (20.2)
13 525 (20.6)
1926 (17.8)
T3
11 117 (14.5)
9386 (14.3)
1731 (16.0)
T4
12 184 (15.9)
9910 (15.1)
2274 (21.0)
Other
26 368 (34.5)
22 294 (34.0)
4074 (37.7)
N (%)
<0.001
N0
21 129 (27.6)
19 590 (29.8)
1539 (14.2)
N1
4930 (6.4)
4246 (6.5)
684 (6.3)
N2
19 457 (25.4)
15 985 (24.3)
3472 (32.1)
N3
8164 (10.7)
6439 (9.8)
1725 (15.9)
Other
22 803 (29.8)
19 405 (29.6)
3398 (31.4)
Risk factors for developing brain metastases
The univariate and multivariate logistic regression analyses were conducted to investigate the risk factors associated with brain metastases. Results showed that age, race, pathology, primary lesion site, bone metastases, liver metastases, distant lymph node metastases, T stage, N stage were all associated with the development of brain metastasis. The association between sex and brain metastasis was not significant. The multivariate logistic regression revealed that patients older than 60 were less likely to develop brain metastasis. Other races, non–squamous-cell carcinoma, bone metastases, liver metastases, distant lymph node metastases, higher T stage, and higher N stage were risk factors of brain metastasis. As for the primary site, compared with the left upper lobe, patients whose tumor were present in right middle lobe and right lower lobe had a lower risk of developing brain metastasis. The logistic regression analysis results are shown in Table 2 .
Table 2 -
The logistic regression analysis results
Univariate analysis
Multivariate analysis
OR (95% CI)
P value
OR (95% CI)
P value
Age
<50
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
50–59
0.96 (0.87–1.05)
0.368
1 (0.9–1.11)
0.971
60–69
0.71 (0.65–0.78)
<0.001
0.8 (0.72–0.88)
<0.001
70–79
0.5 (0.45–0.55)
<0.001
0.6 (0.54–0.66)
<0.001
≥80
0.32 (0.28–0.35)
<0.001
0.38 (0.34–0.43)
<0.001
Race
White
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Black
1.12 (1.04–1.2)
0.002
1 (0.93–1.08)
0.902
Other
1.26 (1.18–1.33)
<0.001
1.17 (1.09–1.24)
<0.001
Unknown
0.73 (0.43–1.22)
0.225
0.82 (0.48–1.39)
0.461
Sex
Female
1 (Reference)
1 (Reference)
Male
1.03 (0.99–1.07)
0.158
Pathology
Squamous-cell carcinoma
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Adenocarcinoma
3.52 (3.27–3.78)
<0.001
3.03 (2.81–3.27)
<0.001
Non–small-cell carcinoma
3.61 (3.27–3.98)
<0.001
3.04 (2.75–3.37)
<0.001
Small-cell carcinoma
3.41 (3.13–3.72)
<0.001
2.3 (2.1–2.51)
<0.001
Large-cell carcinoma
3.63 (3.06–4.31)
<0.001
2.92 (2.44–3.48)
<0.001
Other
1.73 (1.59–1.89)
<0.001
1.82 (1.67–1.99)
<0.001
Location
Left upper
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Left lower
0.98 (0.91–1.05)
0.563
1.02 (0.94–1.1)
0.684
left main bronchus
1.08 (0.92–1.26)
0.354
0.88 (0.75–1.04)
0.126
Right upper
0.98 (0.92–1.04)
0.464
0.95 (0.89–1.01)
0.098
Right middle
0.87 (0.78–0.97)
0.012
0.84 (0.75–0.95)
0.003
Right lower
0.87 (0.81–0.93)
<0.001
0.9 (0.84–0.97)
0.005
Right main bronchus
1.21 (1.06–1.38)
0.004
0.95 (0.83–1.09)
0.505
Other
1.34 (1.25–1.43)
<0.001
0.95 (0.88–1.02)
0.126
Bone metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
2.72 (2.61–2.85)
<0.001
1.79 (1.71–1.88)
<0.001
Unknown
5.83 (5–6.8)
<0.001
2.54 (2.12–3.05)
<0.001
Liver metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
2.17 (2.06–2.29)
<0.001
1.4 (1.31–1.48)
<0.001
Unknown
7.01 (6.09–8.07)
<0.001
3.76 (3.19–4.44)
<0.001
Distant lymph node metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
2.52 (2.25–2.83)
<0.001
1.7 (1.51–1.92)
<0.001
Unknown
1.14 (1.09–1.2)
<0.001
1.54 (1.37–1.72)
<0.001
T
T1
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
T2
1.85 (1.7–2.01)
<0.001
1.58 (1.44–1.73)
<0.001
T3
2.39 (2.19–2.61)
<0.001
1.73 (1.58–1.9)
<0.001
T4
2.98 (2.74–3.24)
<0.001
1.92 (1.76–2.11)
<0.001
Other
2.37 (2.19–2.57)
<0.001
1.93 (1.74–2.15)
<0.001
N
N0
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
N1
2.05 (1.86–2.26)
<0.001
1.65 (1.49–1.82)
<0.001
N2
2.76 (2.59–2.95)
<0.001
1.88 (1.75–2.01)
<0.001
N3
3.41 (3.17–3.67)
<0.001
1.98 (1.83–2.15)
<0.001
Other
2.23 (2.09–2.37)
<0.001
1.97 (1.76–2.2)
<0.001
CI, confidence interval; HR, hazard ratio; OR, odds ratio.
Considering that there are significant differences in tissue behavior between SCLC and NSCLC, we divided the patients in the cohort into two groups according to the pathological type: NSCLC group and SCLC group, and carried out logistic regression in two subgroups. The results showed that there were significant differences between NSCLC and SCLC in the factors related to brain metastasis. In NSCLC, the results of univariate logistic regression suggested that age, race, location of primary lesion, presence of bone metastasis, liver metastasis, distant lymph node metastasis, T stage and N stage were related to the occurrence of brain metastasis. While in multivariate analysis, lesion in middle and lower lobe of the right lung were related to the lower risk of brain metastasis. The risk of synchronous brain metastasis is increased in patients with other races, synchronous distant metastasis (liver, bone, distant lymph node metastasis), higher T stage, and higher N stage. More details are shown in Table 3 .
Table 3 -
The logistic regression analysis results of brain metastasis in non–small-cell lung cancer patients
Univariate analysis
Multivariate analysis
OR (95% CI)
P
OR (95%CI)
P
Age
<50
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
50–59
0.94 (0.85–1.04)
0.229
0.98 (0.88–1.09)
0.704
60–69
0.67 (0.61–0.74)
<0.001
0.74 (0.67–0.82)
<0.001
70–79
0.48 (0.43–0.53)
<0.001
0.54 (0.49–0.6)
<0.001
≥80
0.3 (0.27–0.33)
<0.001
0.34 (0.3–0.38)
<0.001
Race
White
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Black
1.12 (1.04–1.2)
0.004
0.99 (0.91–1.07)
0.755
Other
1.3 (1.22–1.39)
<0.001
1.23 (1.15–1.31)
<0.001
Unknown
0.64 (0.35–1.15)
0.136
0.76 (0.41–1.39)
0.368
Sex
Female
1 (Reference)
1 (Reference)
Male
1.01 (0.97–1.06)
0.530
Location
Left upper
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Left lower
0.98 (0.9–1.06)
0.602
1.01 (0.93–1.1)
0.813
left main bronchus
1.1 (0.91–1.32)
0.319
0.83 (0.69–1.01)
0.063
Right upper
0.98 (0.92–1.04)
0.530
0.99 (0.92–1.05)
0.656
Right middle
0.87 (0.77–0.98)
0.017
0.86 (0.76–0.98)
0.019
Right lower
0.88 (0.81–0.95)
0.001
0.9 (0.83–0.98)
0.010
Right main bronchus
1.26 (1.08–1.47)
0.003
0.92 (0.78–1.08)
0.304
Other
1.41 (1.32–1.52)
<0.001
1.01 (0.93–1.1)
0.775
Bone metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
3.03 (2.89–3.18)
<0.001
2.08 (1.97–2.19)
<0.001
Unknown
6.68 (5.63–7.93)
<0.001
2.75 (2.24–3.37)
<0.001
Liver metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
2.66 (2.51–2.83)
<0.001
1.62 (1.51–1.73)
<0.001
Unknown
7.92 (6.79–9.24)
<0.001
4.03 (3.36–4.82)
<0.001
Distant lymph node metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
2.66 (2.34–3.02)
<0.001
1.75 (1.53–2)
<0.001
Unknown
1.14 (1.08–1.2)
<0.001
1.53 (1.36–1.73)
<0.001
T
T1
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
T2
1.92 (1.75–2.1)
<0.001
1.53 (1.39–1.68)
<0.001
T3
2.53 (2.3–2.78)
<0.001
1.62 (1.47–1.8)
<0.001
T4
3.19 (2.91–3.5)
<0.001
1.85 (1.67–2.04)
<0.001
Other
2.49 (2.29–2.71)
<0.001
1.94 (1.72–2.17)
<0.001
N
N0
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
N1
2.08 (1.87–2.3)
<0.001
1.64 (1.47–1.82)
<0.001
N2
2.97 (2.77–3.17)
<0.001
2.05 (1.9–2.2)
<0.001
N3
3.77 (3.48–4.09)
<0.001
2.23 (2.05–2.43)
<0.001
Other
2.29 (2.14–2.45)
<0.001
1.96 (1.73–2.21)
<0.001
CI, confidence interval; HR, hazard ratio; OR, odds ratio.
In the SCLC group, we got different results. First of all, in the univariate logistic regression, the site of the primary lesion and N stage were not related to the occurrence of brain metastasis. In multivariate logistic regression, compared with patients younger than 50 years old, patients older than 70 years old have a lower risk of synchronous brain metastasis. Compared with white race, black race patients with SCLC have a higher risk of brain metastasis. There was no significant correlation between sex and brain metastasis. Patients with bone metastasis and distant lymph node metastasis were associated with a higher risk of brain metastasis, but not synchronous liver metastasis. It is worth noting that compared with T1, only T4 has significant correlation with the risk of synchronous brain metastasis, while T2 and T3 have no difference compared with T1. See Table 4 for more details of logistic regression analysis.
Table 4 -
The logistic regression analysis results of brain metastasis in small-cell lung cancer patients
Univariate analysis
Multivariate analysis
OR (95% CI)
P
OR (95% CI)
P
Age
<50
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
50–59
1.08 (0.79–1.46)
0.634
1.11 (0.82–1.51)
0.493
60–69
0.97 (0.72–1.3)
0.843
0.99 (0.73–1.33)
0.930
70–79
0.69 (0.51–0.93)
0.016
0.71 (0.53–0.97)
0.031
≥80
0.54 (0.39–0.76)
<0.001
0.57 (0.41–0.8)
0.001
Race
White
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Black
1.27 (1.05–1.54)
0.015
1.24 (1.02–1.51)
0.032
Other
1.09 (0.9–1.32)
0.385
1.11 (0.92–1.35)
0.281
Unknown
1.34 (0.44–4.09)
0.604
1.31 (0.43–4.02)
0.636
Sex
Female
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Male
1.14 (1.02–1.26)
0.017
1.08 (0.97–1.21)
0.141
Location
Left upper
1 (Reference)
1 (Reference)
Left lower
1.01 (0.83–1.24)
0.892
left main bronchus
0.82 (0.61–1.1)
0.186
Right upper
1 (0.86–1.17)
0.981
Right middle
0.9 (0.67–1.2)
0.481
Right lower
0.87 (0.71–1.05)
0.146
Right main bronchus
0.88 (0.68–1.14)
0.341
Other
0.94 (0.8–1.11)
0.480
Bone metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.42 (1.27–1.6)
<0.001
1.4 (1.23–1.58)
<0.001
Unknown
2.86 (2–4.08)
<0.001
2.11 (1.41–3.14)
<0.001
Liver metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.01 (0.9–1.13)
0.847
0.89 (0.79–1.01)
0.063
Unknown
3.27 (2.31–4.65)
<0.001
2.36 (1.6–3.49)
<0.001
Distant lymph node metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.81 (1.39–2.36)
<0.001
1.7 (1.3–2.23)
<0.001
Unknown
1.15 (1.01–1.32)
0.038
1.19 (0.98–1.44)
0.076
T
T1
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
T2
1.21 (0.95–1.53)
0.125
1.16 (0.91–1.47)
0.231
T3
1.33 (1.04–1.69)
0.023
1.27 (0.99–1.62)
0.057
T4
1.46 (1.16–1.83)
0.001
1.33 (1.06–1.68)
0.014
Other
1.34 (1.08–1.67)
0.008
1.32 (1.03–1.7)
0.029
N
N0
1 (Reference)
1 (Reference)
N1
1.18 (0.9–1.54)
0.223
N2
1.12 (0.92–1.35)
0.250
N3
1.21 (0.98–1.49)
0.083
Other
1.18 (0.97–1.43)
0.099
CI, confidence interval; HR, hazard ratio; OR, odds ratio.
Prognostic factors for lung cancer patients with brain metastasis
A total of 10 813 lung cancer patients with brain metastasis and follow-up information between 2010 and 2017 were included to conduct Cox regression analysis and investigate potential prognostic factors. Treatment information was also collected, including surgery , radiotherapy and chemotherapy. Two hundred sixty-one patients (2.4%) received surgical treatment of primary lesions, 7861 patients (72.7%) received radiotherapy, and 6036 patients (55.8%) received chemotherapy. SEER database also provides the type of radiotherapy, as shown in Supplementary Table 1 and 2, Supplemental Digital Content 1, https://links.lww.com/EJCP/A378 surgery , no radiotherapy, no chemotherapy were risk factors of brain metastasis patient prognosis. Multivariable Cox regression analysis showed that older age, male, white race, SCC, liver metastases, bone metastases, distant lymph node metastases, T2-4, N1-3, no surgery , no chemotherapy were associated with worse prognosis. Compared with SCC, brain metastasis patients whose pathology was adenocarcinoma had a better prognosis. Brain metastasis patients with tumors that originated in the left upper lobe of lung had longer survival time than those in the right main bronchus. Cox analysis results are shown in Table 5 .
Table 5 -
Univariate and multivariate Cox regression analysis results.
P < 0.05 was considered statistically significant
Univariate Cox regression
Multivariate Cox regression
HR (95% CI)
P value
HR (95% CI)
P value
Age
<50
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
50–59
1.42 (1.30–1.56)
<0.001
1.38 (1.26–1.52)
<0.001
60–69
1.66 (1.51–1.81)
<0.001
1.55 (1.42–1.70)
<0.001
70–79
2.12 (1.93–2.32)
<0.001
1.81 (1.65–1.99)
<0.001
≥80
3.16 (2.84–3.50)
<0.001
2.31 (2.07–2.57)
<0.001
Sex
Female
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Male
1.22 (1.18–1.27)
<0.001
1.18 (1.14–1.23)
<0.001
Race
Wihte
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Black
0.95 (0.89–1.01)
0.114
0.92 (0.86–0.99)
0.018
Other
0.73 (0.69–0.78)
<0.001
0.73 (0.69–0.77)
<0.001
Unknown
0.76 (0.44–1.30)
0.312
0.94 (0.54–1.62)
0.817
Pathology
Squamous-cell carcinoma
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Adenocarcinoma
0.61 (0.57–0.66)
<0.001
0.71 (0.66–0.76)
<0.001
Non–small-cell carcinoma
0.88 (0.80–0.96)
0.005
0.88 (0.80–0.97)
0.011
Small-cell carcinoma
0.81 (0.75–0.88)
<0.001
0.94 (0.86–1.02)
0.132
Large-cell carcinoma
0.82 (0.70–0.96)
0.014
1.03 (0.88–1.21)
0.736
Other
0.98 (0.90–1.07)
0.686
0.85 (0.78–0.92)
<0.001
Primary lesion site
Left upper
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Left lower
1.02 (0.95–1.09)
0.682
1.01 (0.94–1.09)
0.768
Left main bronchus
1.22 (1.06–1.42)
0.007
1.16 (1.00–1.34)
0.055
Right upper
1.03 (0.98–1.09)
0.236
1.02 (0.96–1.07)
0.589
Right middle
0.99 (0.89–1.10)
0.860
0.95 (0.85–1.05)
0.316
Right lower
1.05 (0.98–1.13)
0.154
1.04 (0.97–1.11)
0.273
Right main bronchus
1.27 (1.13–1.44)
<0.001
1.14 (1.01–1.29)
0.040
Other
1.26 (1.18–1.34)
<0.001
1.07 (1.00–1.14)
0.053
Bone metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.17 (1.12–1.22)
<0.001
1.23 (1.18–1.29)
<0.001
Unknown
1.38 (1.22–1.55)
<0.001
1.00 (0.86–1.18)
0.973
Liver metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.51 (1.44–1.58)
<0.001
1.47 (1.40–1.55)
<0.001
Unknown
1.29 (1.16–1.43)
<0.001
0.94 (0.82–1.08)
0.369
Distant lymph node metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.18 (1.06–1.31)
0.002
1.16 (1.04–1.30)
0.006
Unknown
1.24 (1.18–1.30)
<0.001
1.08 (0.97–1.20)
0.144
T
T1
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
T2
1.17 (1.07–1.27)
<0.001
1.16 (1.07–1.27)
<0.001
T3
1.34 (1.23–1.46)
<0.001
1.30 (1.19–1.42)
<0.001
T4
1.38 (1.27–1.50)
<0.001
1.32 (1.22–1.44)
<0.001
Other
1.17 (1.08–1.27)
<0.001
1.09 (0.99–1.20)
0.096
N
N0
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
N1
1.05 (0.96–1.15)
0.301
1.12 (1.02–1.23)
0.015
N2
1.15 (1.08–1.22)
<0.001
1.24 (1.17–1.32)
<0.001
N3
1.17 (1.10–1.26)
<0.001
1.31 (1.22–1.41)
<0.001
Other
1.01 (0.95–1.08)
0.762
1.08 (0.98–1.20)
0.126
Surgery
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.43 (0.38–0.50)
<0.001
0.53 (0.46–0.61)
<0.001
Unknown
1.59 (0.99–2.56)
0.056
1.07 (0.66–1.74)
0.788
Radiotherapy
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.39 (0.32–0.46)
<0.001
0.99 (0.82–1.19)
0.896
None/unknown
0.73 (0.61–0.87)
<0.001
1.15 (0.96–1.38)
0.137
Chemotherapy
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.35 (0.34–0.37)
<0.001
0.38 (0.36–0.39)
<0.001
CI, confidence interval; HR, hazard ratio.
Supplementary Table 1, Supplemental Digital Content 1, https://links.lww.com/EJCP/A378
Since our previous analysis results suggest that there is significant heterogeneity between SCLC group and NSCLC group, here we conducted subgroup analysis again, and compared the prognostic factors of patients with brain metastasis in SCLC and NSCLC groups through univariate and multivariate cox analysis. In NSCLC group, the prognosis of patients with brain metastasis was worse with older age, and the prognosis of female patients was better than that of male patients. Compared with white race, patients of black race and other races have better prognosis. As for the primary lesion, compared with the left upper lobe, the prognosis of patients with primary lesions in the left and right main bronchi was worse. Based on the existence of brain metastasis, synchronous liver metastasis, bone metastasis, distant lymph node metastasis, and higher T and N staging led to poor prognosis. Surgical treatment, radiotherapy and chemotherapy of primary lesions could prolong the survival of patients (Table 6 ).
Table 6 -
Univariate and multivariate Cox regression analysis results of non–small-cell lung carcinoma-brain metastasis patients
Univariate cox
Multivariate cox
HR (95% CI)
P
HR (95% CI)
P
Age
<50
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
50–59
1.43 (1.29–1.58)
<0.001
1.4 (1.27–1.55)
<0.001
60–69
1.7 (1.54–1.87)
<0.001
1.6 (1.45–1.77)
<0.001
70–79
2.13 (1.93–2.35)
<0.001
1.82 (1.64–2.01)
<0.001
≥80
3.14 (2.81–3.5)
<0.001
2.32 (2.07–2.6)
<0.001
Sex
Female
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Male
1.25 (1.2–1.3)
<0.001
1.2 (1.15–1.26)
<0.001
Race
White
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Black
0.97 (0.9–1.04)
0.361
0.92 (0.86–0.99)
0.035
Other
0.73 (0.69–0.78)
<0.001
0.7 (0.66–0.74)
<0.001
Unknown
0.9 (0.48–1.67)
0.728
1.15 (0.62–2.14)
0.661
Location
Left upper
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Left lower
1.02 (0.94–1.1)
0.677
1.01 (0.94–1.1)
0.714
left main bronchus
1.35 (1.13–1.61)
0.001
1.31 (1.09–1.56)
0.003
Right upper
1.06 (0.99–1.12)
0.074
1.03 (0.97–1.09)
0.381
Right middle
0.98 (0.88–1.11)
0.785
0.94 (0.84–1.06)
0.298
Right lower
1.05 (0.98–1.13)
0.173
1.05 (0.98–1.13)
0.181
Right main bronchus
1.32 (1.14–1.52)
<0.001
1.21 (1.05–1.4)
0.010
Other
1.29 (1.21–1.39)
<0.001
1.11 (1.03–1.19)
0.006
Bone metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.16 (1.11–1.22)
<0.001
1.22 (1.17–1.28)
<0.001
Unknown
1.38 (1.2–1.57)
<0.001
1.04 (0.87–1.24)
0.648
Liver metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.49 (1.41–1.57)
<0.001
1.48 (1.4–1.57)
<0.001
Unknown
1.3 (1.16–1.45)
<0.001
0.93 (0.8–1.08)
0.350
Distant lymph node metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.16 (1.03–1.3)
0.017
1.15 (1.02–1.3)
0.020
Unknown
1.24 (1.18–1.31)
<0.001
1.21 (1.08–1.35)
0.001
T
T1
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
T2
1.19 (1.09–1.3)
<0.001
1.19 (1.08–1.3)
<0.001
T3
1.39 (1.26–1.52)
<0.001
1.34 (1.22–1.48)
<0.001
T4
1.42 (1.3–1.56)
<0.001
1.37 (1.25–1.51)
<0.001
Other
1.21 (1.11–1.32)
<0.001
1.17 (1.05–1.3)
0.004
N
N0
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
N1
1.07 (0.97–1.19)
0.165
1.18 (1.06–1.3)
0.002
N2
1.14 (1.07–1.22)
<0.001
1.24 (1.16–1.33)
<0.001
N3
1.16 (1.08–1.25)
<0.001
1.32 (1.22–1.43)
<0.001
Other
1.01 (0.94–1.08)
0.851
1.12 (1–1.25)
0.045
Surgery
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.44 (0.38–0.51)
<0.001
0.51 (0.44–0.59)
<0.001
Unknown
1.62 (0.92–2.85)
0.097
1.22 (0.69–2.16)
0.500
Radiotherapy
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.4 (0.33–0.49)
<0.001
0.77 (0.63–0.93)
0.008
None/unknown
0.76 (0.63–0.93)
0.006
1.08 (0.89–1.32)
0.419
Chemotherapy
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.35 (0.33–0.36)
<0.001
0.35 (0.34–0.37)
<0.001
In SCLC, gender and the site of the primary lesion did not affect the survival of patients with brain metastasis (Table 7 ). Patients older than 80 years old, with liver metastasis and bone metastasis had a worse prognosis, while patients of other race groups had a better prognosis. It should be noted that the T and N stages of the primary lesion and the metastatic status of distant lymph node were not related to the survival time of SCLC patients with brain metastasis. Primary lesion surgery cannot prolong the survival time of patients, while radiotherapy and chemotherapy were associated with a better prognosis for patients. This is different from the cox analysis results of NSCLC patients with brain metastasis, suggesting that there is heterogeneity between SCLC and NSCLC.
Table 7 -
Univariate and multivariate Cox regression analysis results of small-cell lung cancer-brain metastasis patients
Univariate cox regression
Multivariate cox regression
HR (95% CI)
P
HR (95% CI)
P
Age
<50
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
50–59
1.16 (0.88–1.53)
0.303
1.03 (0.78–1.37)
0.812
60–69
1.2 (0.91–1.57)
0.198
1.03 (0.78–1.36)
0.825
70–79
1.73 (1.31–2.28)
<0.001
1.29 (0.98–1.71)
0.074
≥80
2.94 (2.16–4.01)
<0.001
1.61 (1.17–2.21)
0.004
Sex
Female
1 (Reference)
1 (Reference)
Male
1.08 (0.98–1.19)
0.111
Race
White
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Black
0.85 (0.71–1.01)
0.063
0.87 (0.73–1.04)
0.115
Other
0.83 (0.7–0.99)
0.037
0.78 (0.65–0.93)
0.006
Unknown
0.45 (0.14–1.39)
0.163
0.7 (0.22–2.21)
0.549
Location
Left upper
1 (Reference)
1 (Reference)
Left lower
1.03 (0.86–1.23)
0.779
left main bronchus
0.88 (0.67–1.16)
0.374
Right upper
0.89 (0.78–1.03)
0.125
Right middle
1.04 (0.79–1.37)
0.758
Right lower
1.07 (0.89–1.28)
0.479
Right main bronchus
1.05 (0.83–1.33)
0.693
Other
1.03 (0.89–1.2)
0.701
Bone metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.3 (1.17–1.45)
<0.001
1.13 (1–1.27)
0.042
Unknown
1.4 (1.05–1.86)
0.022
1.02 (0.7–1.5)
0.909
Liver metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.59 (1.43–1.77)
<0.001
1.59 (1.42–1.79)
<0.001
Unknown
1.23 (0.94–1.62)
0.136
0.93 (0.65–1.34)
0.699
Distant lymph node metastases
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
1.25 (0.98–1.59)
0.070
1.03 (0.81–1.32)
0.796
Unknown
1.19 (1.05–1.35)
0.008
1.14 (1–1.29)
0.053
T
T1
1 (Reference)
1 (Reference)
T2
0.99 (0.79–1.24)
0.941
T3
1.04 (0.83–1.31)
0.713
T4
1.1 (0.89–1.36)
0.370
Other
0.91 (0.74–1.11)
0.360
N
N0
1 (Reference)
1 (Reference)
N1
0.86 (0.67–1.1)
0.228
N2
1.15 (0.96–1.37)
0.128
N3
1.21 (1–1.47)
0.056
Other
1 (0.83–1.2)
0.978
Surgery
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.39 (0.21–0.74)
0.003
0.54 (0.29–1.01)
0.054
Unknown
1.51 (0.63–3.64)
0.356
0.93 (0.37–2.34)
0.880
Radiotherapy
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.23 (0.14–0.39)
<0.001
0.58 (0.34–0.99)
0.047
None/unknown
0.44 (0.26–0.75)
0.003
0.86 (0.5–1.47)
0.571
Chemotherapy
No
1 (Reference)
1 (Reference)
1 (Reference)
1 (Reference)
Yes
0.26 (0.23–0.29)
<0.001
0.29 (0.26–0.33)
<0.001
CI, confidence interval; HR, hazard ratio.
Effects of surgery on survival of non–small-cell lung carcinoma patients with brain metastasis
Since the cox results showed that surgery on primary tumor was associated with longer survival of NSCLC-brain metastasis patients, we then explored whether it still benefited patients after adjusting for other clinical factors. Among 10 813 patients with survival time, 10 795 patients were confirmed with or without surgery , and 9090 patients were NSCLC. Therefore, these patients were included in Kaplan–Meier survival analysis to explore the significance of surgery for primary lesion. In order to explore whether there were confounding bias, we analyzed the differences in clinical information between surgery and non-surgery groups. Results showed that all clinical characteristics, except sex, race, and distant lymph node metastases were unevenly distributed between two groups. Therefore, 1:1 PSM (caliper: 0.2 SD of propensity score) was then conducted using the ‘Matching’ package in R software. All the clinical factors including age, race, sex, location, bone metastasis, liver metastasis, Distant lymph node metastasis, T, N, radiotherapy, chemotherapy were included to calculate propensity score. Clinical characteristics between surgery and non-surgery groups are shown in Table 8 . After PSM, 498 patients were selected and the baseline differences between two groups were balanced.
Table 8 -
The clinical characters of
surgery and non-
surgery groups, before Propensity score matching and after Propensity score matching
Before PSM
After PSM
Overall
Surgery – NoSurgery – Yes
P
Overall
Surgery – NoSurgery – Yes
P
9090
8841
249
498
249
249
Age
<0.001
Age
0.62
<50
583 (6.4)
553 (6.3)
30 (12.0)
<50
54 (10.8)
24 (9.6)
30 (12.0)
50–59
2101 (23.1)
2031 (23.0)
70 (28.1)
50–59
147 (29.5)
77 (30.9)
70 (28.1)
60–69
3141 (34.6)
3041 (34.4)
100 (40.2)
60–69
199 (40.0)
99 (39.8)
100 (40.2)
70–79
2316 (25.5)
2274 (25.7)
42 (16.9)
70–79
79 (15.9)
37 (14.9)
42 (16.9)
≥80
949 (10.4)
942 (10.7)
7 (2.8)
≥80
19 (3.8)
12 (4.8)
7 (2.8)
Sex
0.058
Sex
1
Female
4336 (47.7)
4202 (47.5)
134 (53.8)
Female
267 (53.6)
133 (53.4)
134 (53.8)
Male
4754 (52.3)
4639 (52.5)
115 (46.2)
Male
231 (46.4)
116 (46.6)
115 (46.2)
Race
0.087
Race
0.704
White
904 (9.9)
881 (10.0)
23 (9.2)
White
42 (8.4)
19 (7.6)
23 (9.2)
Black
6859 (75.5)
6656 (75.3)
203 (81.5)
Black
406 (81.5)
203 (81.5)
203 (81.5)
Other
1315 (14.5)
1292 (14.6)
23 (9.2)
Other
50 (10.0)
27 (10.8)
23 (9.2)
Unknown
12 (0.1)
12 (0.1)
0 (0.0)
Unknown
Location
0.008
Location
0.808
Left upper
2022 (22.2)
1955 (22.1)
67 (26.9)
Left upper
134 (26.9)
67 (26.9)
67 (26.9)
Left lower
1057 (11.6)
1028 (11.6)
29 (11.6)
Left lower
58 (11.6)
29 (11.6)
29 (11.6)
left main bronchus
140 (1.5)
138 (1.6)
2 (0.8)
Left main bronchus
2 (0.4)
0 (0.0)
2 (0.8)
Right upper
2564 (28.2)
2491 (28.2)
73 (29.3)
Right upper
151 (30.3)
78 (31.3)
73 (29.3)
Right middle
371 (4.1)
358 (4.0)
13 (5.2)
Right middle
28 (5.6)
15 (6.0)
13 (5.2)
Right lower
1220 (13.4)
1178 (13.3)
42 (16.9)
Right lower
75 (15.1)
33 (13.3)
42 (16.9)
Right main bronchus
216 (2.4)
213 (2.4)
3 (1.2)
Right main bronchus
6 (1.2)
3 (1.2)
3 (1.2)
Other
1500 (16.5)
1480 (16.7)
20 (8.0)
Other
44 (8.8)
24 (9.6)
20 (8.0)
Bone metastases
<0.001
Bone metastases
0.801
No
5557 (61.1)
5347 (60.5)
210 (84.3)
No
425 (85.3)
215 (86.3)
210 (84.3)
Yes
3303 (36.3)
3268 (37.0)
35 (14.1)
Yes
66 (13.3)
31 (12.4)
35 (14.1)
Unknown
230 (2.5)
226 (2.6)
4 (1.6)
Unknown
7 (1.4)
3 (1.2)
4 (1.6)
Liver metastases
<0.001
Liver metastases
0.721
No
7112 (78.2)
6880 (77.8)
232 (93.2)
No
464 (93.2)
232 (93.2)
232 (93.2)
Yes
1642 (18.1)
1630 (18.4)
12 (4.8)
Yes
26 (5.2)
14 (5.6)
12 (4.8)
Unknown
336 (3.7)
331 (3.7)
5 (2.0)
Unknown
8 (1.6)
3 (1.2)
5 (2.0)
Distant lymph node metastases
0.215
Distant lymph node metastases
0.886
No
1944 (21.4)
1893 (21.4)
51 (20.5)
No
99 (19.9)
48 (19.3)
51 (20.5)
Yes
370 (4.1)
365 (4.1)
5 (2.0)
Yes
9 (1.8)
4 (1.6)
5 (2.0)
Unknown
6776 (74.5)
6583 (74.5)
193 (77.5)
Unknown
390 (78.3)
197 (79.1)
193 (77.5)
T
<0.001
T
0.883
T1
700 (7.7)
668 (7.6)
32 (12.9)
T1
67 (13.5)
35 (14.1)
32 (12.9)
T2
1655 (18.2)
1585 (17.9)
70 (28.1)
T2
131 (26.3)
61 (24.5)
70 (28.1)
T3
1490 (16.4)
1446 (16.4)
44 (17.7)
T3
93 (18.7)
49 (19.7)
44 (17.7)
T4
1838 (20.2)
1802 (20.4)
36 (14.5)
T4
75 (15.1)
39 (15.7)
36 (14.5)
Other
3407 (37.5)
3340 (37.8)
67 (26.9)
Other
132 (26.5)
65 (26.1)
67 (26.9)
N
<0.001
N
0.896
N0
1376 (15.1)
1283 (14.5)
93 (37.3)
N0
189 (38.0)
96 (38.6)
93 (37.3)
N1
575 (6.3)
546 (6.2)
29 (11.6)
N1
60 (12.0)
31 (12.4)
29 (11.6)
N2
2827 (31.1)
2771 (31.3)
56 (22.5)
N2
116 (23.3)
60 (24.1)
56 (22.5)
N3
1429 (15.7)
1419 (16.1)
10 (4.0)
N3
17 (3.4)
7 (2.8)
10 (4.0)
Other
2883 (31.7)
2822 (31.9)
61 (24.5)
Other
116 (23.3)
55 (22.1)
61 (24.5)
Radiotherapy
0.006
Radiotherapy
0.179
No
109 (1.2)
109 (1.2)
0 (0.0)
No
80 (16.1)
34 (13.7)
46 (18.5)
Yes
6663 (73.3)
6460 (73.1)
203 (81.5)
Yes
418 (83.9)
215 (86.3)
203 (81.5)
None/unknown
2318 (25.5)
2272 (25.7)
46 (18.5)
Chemotherapy
<0.001
Chemotherapy
0.499
No
4281 (47.1)
4199 (47.5)
82 (32.9)
No
156 (31.3)
74 (29.7)
82 (32.9)
Yes
4809 (52.9)
4642 (52.5)
167 (67.1)
Yes
342 (68.7)
175 (70.3)
167 (67.1)
PSM, Propensity score matching.
Kaplan–Meier survival analysis suggested that for NSCLC patients with brain metastasis, surgical treatment of the primary lesion could prolong patients’ survival. A similar result was obtained after removing the influence of other clinical factors (Fig. 2 ). NSCLC patients with brain metastasis who received surgery for primary lesion had longer median survival time than those who did not have surgery (16.0 months vs. 4.0 months P < 0.001 and 16.0 months vs. 8.0 months P < 0.001 after PSM). This result suggests that surgery on primary site could bring survival benefits to NSCLC-brain metastasis patients. Further clinical trials are required to explore its therapeutic value and side effects in the future.
Fig. 2: Result of Kaplan–Meier analysis. (a) Kaplan–Meier analysis including 9090 patients. (b) After PSM, a similar result was obtained. PSM, Propensity score matching.
Considering that the T and N stage of tumor, liver metastasis and bone metastasis status all affected the survival time of patients with brain metastasis, we divided the patients cohort after PSM into T1-2 or T3-4 groups, N0-1 or N2-3 groups, with or without liver metastasis groups, with or without bone metastasis groups, and further explored the impact of primary lesion surgery on the prognosis in subgroups. The results showed that for NSCLC-brain metastasis patients with different T and N groups, the resection of the primary lesion could prolong the survival time of patients (Fig. 3 ).
Fig. 3: Kaplan–Meier analysis of the effect of primary lesion surgery in T1-2 patients (a), T3-4 patients (b), N0-1 patients (c), and N2-3 patients (d).
The metastasis of other organs affected the prognosis of patients. For NSCLC-brain metastasis patients with no liver metastasis or bone metastasis, surgical treatment of the primary focus could significantly prolong the survival of patients. However, for patients with liver metastasis and bone metastasis, there was no significant difference in survival time between surgery and non-surgery groups (Fig. 4 ). These results suggested that for NSCLC patients with brain metastasis, if there is no other organ metastasis, the operation of the primary focus can benefit the patient’s survival, while if there is other organ metastasis, the surgical treatment is meaningless.
Fig. 4: Kaplan–Meier analysis of the effect of primary lesion surgery in patients without liver metastasis (a), with liver metastasis (b), without bone metastasis (c), and with bone metastasis (d).
Discussion
Our results showed that brain metastases occurred in 14.1% of patients with lung cancer. Adenocarcinoma is the most common pathological type of lung cancer (Yang et al., 2018 Barnholtz-Sloan et al., 2004 ; Reddy et al., 2020 Cheng et al., 2021
Few articles focused on the site of primary lesion. In our study, primary site is associated with the risk of developing brain metastasis. NSCLC patients whose tumor was present at right middle/lower lobe had a lower risk of developing brain metastasis than at left upper lobe. However, for NSCLC-brain metastasis patients, primary lesion at main bronchus was associated with worse survival. For SCLC, primary lesion site was not related to brain metastasis risk or survival time. Further studies are required to reveal the molecular mechanism of this result.
Surgery , chemotherapy, and radiotherapy are common therapies for cancers. Providing individualized treatment for different patients so as to maximize the personal survival benefits is a research direction (Kang et al., 2020 surgery could improve the prognosis of IV cancer patients with distant metastases. Mastectomy is associated with better OS among patients with stage IV breast cancer, compared with those who do not undergo surgery (Bilani et al., 2021 surgery improved OS and cancer-specific survival (Tsilimigras et al., 2021 Wang et al., 2017 surgery cannot prolong the survival time of SCLC-brain metastasis patients, but could improve the survival of NSCLC-brain metastasis patients with different T and N stages. Radiotherapy and chemotherapy were associated with a better prognosis for patients. We also performed a subgroup analysis of NSCLC-brain metastasis patients to investigate the role of primary lesion surgery . The results suggested that surgery could improve the prognosis of patients with brain metastasis only. However, for NSCLC-brain metastasis patients with liver and bone metastases, there was no significant difference in survival between the surgical and non-surgical groups. Further multicenter prospective studies are still required to validate these outcomes.
This study has some limitations. The accuracy of identifying brain metastasis depends on brain imaging type (including CT and MRI) (Lamba et al., 2021 surgery , lymph node metastasis, T stage, N stage, radiotherapy, and chemotherapy were unknown, which reduced the number of patients included in the study cohort. In addition, we do not have specific treatment information such as chemotherapy protocol and radiation planning technique, which may influence the prognosis of brain metastasis patients.
Conclusion
In this study, we found that the incidence of brain metastasis in lung cancer patients was about 14.1%, and the median survival of lung cancer patients with brain metastasis was 5 months. Our study also suggested several homogeneous and heterogeneous risk/prognostic factors associated with brain metastasis, which need to be paid more attention in clinical practice. Using PSM approach, we found that surgery on primary lesion could improve survival in NSCLC patients with brain metastasis, but not SCLC patients with brain metastasis. These results are helpful for clinicians to conduct clinical evaluations and make individualized therapeutic strategies.
Acknowledgements
Y.H.: research design, data collection, interpretation and analysis, article drafting. GL: Research design, critical article revision.
The data used in this study are available from publicly available SEER database. SEER*Stat version 8.4.0 (https://seer.cancer.gov/seerstat/
SEER database is publicly accessible worldwide. The authors signed the SEER database agreement and got the license to access SEER data.
Conflicts of interest
There are no conflicts of interest.
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