Background
Methods
Participants
Immunohistochemical staining of tissues
Statistical analysis
Results
Patient characteristics
With brain metastasis (n = 16) | No brain metastasis (n = 32) | p-value | |
---|---|---|---|
Sex | 0.759 | ||
Male | 7 (43.8%) | 12 (37.5%) | |
Female | 9 (56.3%) | 20 (62.5%) | |
Age (years) | 56.0 (52.0–65.5) | 60.8 (53.3–66.0) | 0.477 |
BMI (kg/m2) | 23.9 (21.8–25.2) | 23.3 (21.8–25.2) | 0.710 |
Smoking habits | 1.000 | ||
Never | 13 (81.3%) | 27 (84.4%) | |
Former/current | 3 (18.8%) | 5 (15.6%) | |
ECOG PS | 0.090 | ||
0 | 7 (43.8%) | 6 (18.8%) | |
≥ 1 | 9 (56.3%) | 26 (81.3%) | |
Comorbidities | |||
Hypertension Diabetes mellitus | 4 (25.0) 3 (18.8%) | 15 (46.9) 6 (18.8%) | 0.213 1.000 |
COPD | 1 (6.3%) | 3 (9.4%) | 1.000 |
Hyperlipidemia | 2 (12.5%) | 4 (12.5%) | 1.000 |
Chronic kidney disease | 3 (18.8%) | 9 (28.1%) | 0.725 |
Extrapulmonary metastasis | |||
Liver | 4 (25.0%) | 4 (12.5%) | 0.413 |
Bone | 7 (43.8%) | 16 (50.0%) | 0.765 |
EGFR mutation |
0.018
| ||
Exon 19 deletion | 9 (56.3%) | 11 (34.4%) | |
L858R mutation | 3 (18.8%) | 19 (59.4%) | |
Others | 4 (25.0%) | 2 (6.3%) | |
First-line TKI | 0.347 | ||
Gefitinib | 4 (25.0%) | 3 (9.4%) | |
Erlotinib | 3 (18.8%) | 8 (25.0%) | |
Afatinib | 9 (56.3%) | 21 (65.6%) | |
PFS (median, days) | 358.0 | 830.0 |
0.018
|
OS (median, days) | 930.0 | 1671.0 |
0.012
|
Lung tumor IHC stain | |||
PD-L1 | 0.894 | ||
< 1% | 9 (56.3%) | 17 (53.1%) | |
1–50% | 4 (25.0%) | 10 (31.3%) | |
> 50% | 3 (18.8%) | 5 (15.6%) | |
PD-L1 (median) | 1.0 (0-12.5) | 1.0 (1.0–35.0) | 0.503 |
CD8+ cell counts/HPF | 55.5 (8.5–97.5) | 52.5 (2.5-107.5) | 0.895 |
FOXP3+ cell counts/HPF | 37.5 (12.5–76.3) | 21.0 (2.8–88.8) | 0.375 |
E-cadherin score | 6.0 (6.0–9.0) | 6.0 (6.0–9.0) | 0.696 |
Vimentin score | 1.5 (1.0-3.5) | 1.0 (0.0-1.8) |
0.034
|
IHC staining results of paired lung and brain tumors from patients with brain metastasis at diagnosis
Lung tumor (n = 16) | Brain tumor (n = 16) | p-value | |
---|---|---|---|
PD-L1 | 0.856 | ||
<1% | 9 (56.3%) | 9 (56.3%) | |
1–50% | 4 (25.0%) | 5 (31.3%) | |
>50% | 3 (18.8%) | 2 (12.5%) | |
PD-L1 (median) | 1.0 (0.0-12.5) | 1.0 (1.0–16.3) | 0.590 |
CD8+ cell counts/HPF | 55.5 (8.5–97.5) | 108.5 (44.8–167.5) | 0.073 |
FOXP3+ cell counts/HPF | 37.5 (12.5–76.3) | 18.0 (12.3–56.0) | 0.381 |
E-cadherin score | 6.0 (6.0–9.0) | 9.0 (6.0–9.0) | 0.110 |
Vimentin score | 1.5 (1.0-3.5) | 1.5 (0.0–2.0) | 0.305 |
PD-L1 expression and association with prognosis
Parameters | PD-L1 < 1% (n = 26) | PD-L1 ≥ 1% (n = 22) | p-value |
---|---|---|---|
Sex | 0.771 | ||
Male | 11 | 8 | |
Female | 15 | 14 | |
Age (years) | 60.7 (54.0–66.0) | 57.6 (48.7–67.7) | 0.535 |
BMI (kg/m2) | 23.3 (20.9–25.4) | 23.6 (22.2–25.0) | 0.772 |
Smoking habits | 0.260 | ||
Never | 20 (76.9%) | 20 (90.9%) | |
Former/current | 6 (23.1%) | 2 (9.1%) | |
ECOG PS | 0.532 | ||
0 | 6 (23.1%) | 7 (31.8%) | |
≥ 1 | 20 (76.9%) | 15 (68.2%) | |
Extrapulmonary metastasis | |||
Brain | 9 (34.6%) | 7 (31.8%) | 1.000 |
Liver | 5 (19.2%) | 3 (13.6%) | 0.710 |
Bone | 9 (34.6%) | 14 (63.6%) | 0.081 |
EGFR mutation | 0.516 | ||
Exon 19 deletion | 12 (46.2%) | 8 (36.4%) | |
L858R mutation | 12 (46.2%) | 10 (45.5%) | |
Others | 2 (7.7%) | 4 (18.2%) | |
First-line TKI | 0.109 | ||
Gefitinib | 3 (11.5%) | 4 (18.2%) | |
Erlotinib | 9 (34.6%) | 2 (9.1%) | |
Afatinib | 14 (53.8%) | 16 (72.7%) | |
PFS (median, days) | 972.0 | 500.0 |
0.013
|
OS (median, days) | 2077.0 | 1222.0 |
0.044
|
IHC stain | |||
CD8+ cell counts/HPF | 53.0 (6.0–92.5) | 55.0 (11.3–145.3) | 0.755 |
FOXP3+ cell counts/HPF | 16.5 (0.0–64.3) | 45.0 (13.3–89.8) | 0.054 |
E-cadherin score | 6.0 (6.0–6.0) | 6.0 (6.0–9.0) | 0.137 |
Vimentin score | 1.0 (0.0–2.0) | 1.0 (0.8–2.0) | 0.469 |
Independent factors affecting PFS and OS
Parameters | Univariate analysis | Multivariate analysis |
---|---|---|
HR (95% CI) p-value | HR (95% CI) p-value | |
Age (years) | 0.953 (0.913–0.994) 0.024 | 0.140 |
Sex (male vs. female) | 0.822 (0.386–1.750) 0.611 | |
BMI (kg/m2) | 1.092 (0.991–1.204) 0.076 | 1.165 (1.040–1.305) 0.008 |
Never vs. Former/current | 1.172 (0.468–2.937) 0.735 | |
ECOG PS (≥ 1 vs. 0) | 1.422 (0.582–3.476) 0.440 | |
Extrapulmonary metastasis | ||
Brain | 2.405 (1.136–5.088) 0.022 | 3.994 (1.695–9.410) 0.002 |
Liver | 1.829 (0.745–4.489) 0.187 | |
Bone | 2.435 (1.144–5.182) 0.021 | 3.188 (1.465–6.939) 0.003 |
EGFR mutation | ||
Exon 19 deletion, L858R | 0.248 (0.091–0.679) 0.007 | 0.229 (0.080–0.654) 0.006 |
Others | 1 | |
1st -line TKI | ||
Afatinib | 0.612 (0.298–1.259) 0.182 | |
Erlotinib, Gefitinib | 1 | |
IHC stain | ||
PD-L1 (≥ 1% vs. < 1%) | 2.446 (1.177–5.082) 0.017 | 0.090 |
CD8+ cell counts/HPF | 1.001 (0.997–1.004) 0.737 | |
FOXP3+ cell counts/HPF | 0.997 (0.990–1.004) 0.384 | |
E-cadherin score | ||
= 9 | 2.249 (0.958–5.281) 0.063 | 0.536 |
< 9 | 1 | |
Vimentin score | ||
≥ 2 | 1.108 (0.518–2.373) 0.791 | |
< 2 | 1 |
Parameters | Univariate analysis | Multivariate analysis |
---|---|---|
HR (95% CI) p-value | HR (95% CI) p-value | |
Age (years) | 0.955 (0.902–1.012) 0.118 | |
Sex (male vs. female) | 1.270 (0.480–3.359) 0.630 | |
BMI (kg/m2) | 1.094 (0.953–1.255) 0.201 | |
Never vs. Former/current | 3.003 (0.662–13.611) 0.154 | |
ECOG PS (≥ 1 vs. 0) | 0.954 (0.270–3.368) 0.942 | |
Extrapulmonary metastasis | ||
Brain | 3.401 (1.237–9.345) 0.018 | 3.704 (1.334–10.285) 0.012 |
Liver | 1.541 (0.343–6.931) 0.573 | |
Bone | 1.993 (0.770–5.157) 0.155 | |
EGFR mutation | ||
Exon 19 deletion, L858R | 0.209 (0.040–1.090) 0.063 | 0.268 |
Others | 1 | |
`1st line TKI | ||
Afatinib | 1.285 (0.460–3.592) 0.632 | |
Erlotinib, Gefitinib | 1 | |
IHC stain | ||
PD-L1 (≥ 1% vs. < 1%) | 2.657 (0.989–7.133) 0.053 | 0.408 |
CD8 | 0.998 (0.992–1.005) 0.585 | |
FOXP3 | 0.995 (0.984–1.006) 0.360 | |
E-cadherin score | ||
= 9 | 9.487 (2.631–34.207) 0.001 | 10.281 (2.795–37.815) <0.001 |
< 9 | 1 | |
Vimentin score | ||
≥ 2 | 0.709 (0.253–1.987) 0.513 | |
< 2 | 1 |