Introduction
Methods
Study design
Inclusion criteria
Statistical analyses
Results
Patient selection and characteristics
Characteristics | Patients (n = 716) | Percentage (%) |
---|---|---|
Age (Mean ± SD) | 61.10 ± 10.55 | |
Sex | ||
Male | 611 | 85.3 |
Female | 105 | 14.8 |
Histological type | ||
LUAD | 390 | 54.5 |
LUSC | 280 | 39.1 |
Other NSCLC | 46 | 6.4 |
Clinical stage | ||
IIIB | 86 | 12 |
IIIC | 25 | 3.5 |
IV | 605 | 84.5 |
Smoking history | ||
Never smoker | 324 | 45.3 |
Smoker or ex-smoker | 392 | 54.7 |
PD-L1 expression | ||
< 1% | 154 | 21.5 |
1%-49% | 298 | 41.6 |
≥ 50% | 264 | 36.9 |
Treatment type | ||
Monotherapy | 284 | 39.7 |
Combination therapy | 432 | 60.3 |
ECOG PS | ||
0–1 | 645 | 90.1 |
2 | 71 | 9.9 |
Radiation history | ||
Yes | 452 | 63 |
No | 265 | 37 |
Metastasis sites | ||
Liver | 59 | 8.24 |
Lung | 179 | 25 |
Brain | 135 | 18.9 |
Bone | 213 | 29.7 |
Adrenal | 124 | 17.3 |
Drug | ||
Pembrolizumab | 451 | 63 |
Nivolumab | 108 | 15.1 |
Atezolizumab | 5 | 0.7 |
Sintilimab | 108 | 15.1 |
Camrelizumab | 31 | 4.3 |
Tislelizumab | 13 | 1.8 |
CEA (ng/ml) | ||
Mean ± SD | 57.29 ± 159.72 | |
Normal (≤ 5.0) | 307 | 42.9 |
High (> 5.0) | 409 | 57.1 |
NSE (ng/ml) | ||
Mean ± SD | 24.26 ± 18.19 | |
Normal (≤ 16.3) | 302 | 42.2 |
High (> 16.3) | 414 | 57.8 |
CYFRA21-1 (ng/ml) | ||
Mean ± SD | 15.69 ± 27.37 | |
Normal (≤ 3.3) | 98 | 13.7 |
High (> 3.3) | 618 | 86.3 |
CA19-9 (ng/ml) | ||
Mean ± SD | 45.99 ± 106.47 | |
Normal (≤ 27.0) | 448 | 62.6 |
High (> 27.0) | 268 | 37.4 |
CA125 (ng/ml) | ||
Mean ± SD | 69.04 ± 112.97 | |
Normal (≤ 35.0) | 300 | 41.9 |
High (> 35.0) | 416 | 58.1 |
Association between baseline serum tumor marker (STM) levels and survival
Analysis of the whole population
Covariate | Univariate analysis | Multivariate analysis (CEA) | Multivariate analysis (NSE) | Multivariate analysis (CYFRA21-1) | Multivariate analysis (CA19-9) | Multivariate analysis (CA125) | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | |
Progression-free survival | ||||||||||||
Age | 0.692 | 0.398 | 0.367 | 0.251 | 0.148 | 0.167 | ||||||
Old (≥ 65) | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Young (< 65) | 0.97(0.81–1.15) | 0.92(0.77–1.11) | 0.92(0.77–1.10) | 0.90(0.75–1.08) | 0.87(0.73–1.05) | 0.88(0.73–1.06) | ||||||
Sex | 0.732 | 0.33 | 0.025 | 0.226 | 0.109 | 0.137 | ||||||
Female | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Male | 1.05(0.81–1.34) | 1.15(0.87–1.52) | 1.38(1.04–1.82) | 1.19(0.90–1.57) | 1.25(0.95–1.65) | 1.23(0.94–1.62) | ||||||
ECOG PS | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | ||||||
0–1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
2 | 3.06(2.36–3.97) | 2.75(2.10–3.60) | 2.96(2.26–3.88) | 2.98(2.27–3.91) | 2.94(2.24–3.86) | 3.19(2.43–4.19) | ||||||
Smoke history | 0.191 | 0.01 | 0.214 | 0.154 | 0.106 | 0.039 | ||||||
No | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Yes | 0.89(0.75–1.06) | 0.77(0.63–0.94) | 0.88(0.72–1.07) | 0.87(0.71–1.06) | 0.85(0.70–1.04) | 0.81( 0.67–0.99) | ||||||
Histological type | < 0.001 | < 0.001 | < 0.001 | 0.007 | 0.001 | < 0.001 | ||||||
LUAD | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
LUSC | < 0.001 | 1.37(1.14–1.63) | < 0.001 | 1.57(1.29–1.90) | < 0.001 | 1.37(1.14–1.65) | 0.018 | 1.26(1.04–1.53) | 0.001 | 1.35(1.12–1.63) | < 0.001 | 1.43(1.18–1.72) |
Other_NSCLC | 0.003 | 0.50(0.32–0.79) | 0.006 | 0.53(0.33–0.84) | < 0.001 | 0.45(0.29–0.71) | 0.005 | 0.52(0.33–0.82) | 0.001 | 0.47(0.30–0.74) | 0.004 | 0.51(0.32–0.80) |
Stage | 0.002 | < 0.001 | 0.005 | 0.008 | 0.01 | 0.002 | ||||||
IIIB | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
IIIC | < 0.001 | 2.67(1.63–4.37) | < 0.001 | 2.52(1.51–4.23) | 0.003 | 2.20(1.31–3.70) | 0.005 | 2.24(1.33–3.76) | 0.003 | 2.21(1.32–3.72) | 0.001 | 2.32(1.38–3.91) |
IV | 0.134 | 1.24(0.94–1.64) | 0.079 | 1.30(0.97–1.74) | 0.07 | 1.31(0.98–1.76) | 0.042 | 1.09(0.82–1.47) | 0.07 | 1.31(0.98–1.76) | 0.065 | 1.32(0.98–1.77) |
PD-L1 expression | 0.048 | 0.316 | 0.481 | 0.376 | 0.208 | 0.19 | ||||||
< 1% | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
≥ 1% | 0.81(0.66–1.00) | 0.89(0.71–1.11) | 0.92(0.74–1.15) | 0.90(0.72–1.13) | 0.87(0.70–1.08) | 0.86(0.69–1.08) | ||||||
Treatment | 0.133 | 0.022 | 0.038 | 0.024 | 0.133 | 0.03 | ||||||
Monotherapy | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Combination therapy | 0.87(0.73–1.04) | 0.80(0.66–0.97) | 0.82(0.67–0.99) | 0.80(0.66–0.97) | 0.86(0.71–1.05) | 0.81(0.67–0.98) | ||||||
CEA | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 15) | 1 | 1 | ||||||||||
Normal to 3-Fold (5–15) | 0.163 | 0.86(0.69–1.07) | 0.043 | 0.79(0.63–0.99) | ||||||||
Normal (≤ 5.0) | < 0.001 | 0.53(0.44–0.66) | < 0.001 | 0.45(0.36–0.56) | ||||||||
NSE | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 48.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (16.3–48.9) | < 0.001 | 0.40(0.29–0.55) | < 0.001 | 0.39(0.28–0.54) | ||||||||
Normal (≤ 16.3) | < 0.001 | 0.27(0.19–0.38) | < 0.001 | 0.26(0.18–0.36) | ||||||||
CYFRA21-1 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 9.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (3.3–9.9) | < 0.001 | 0.72(0.60–0.86) | 0.014 | 0.79(0.65–0.95) | ||||||||
Normal (≤ 3.3) | < 0.001 | 0.49(0.36–0.66) | < 0.001 | 0.56(0.42–0.77) | ||||||||
CA19-9 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 81) | 1 | 1 | ||||||||||
Normal to 3-Fold (27–81) | 0.07 | 0.74(0.53–1.03) | 0.063 | 0.73(0.52–1.02) | ||||||||
Normal (≤ 27.0) | < 0.001 | 0.56(0.41–0.77) | < 0.001 | 0.56(0.41–0.76) | ||||||||
CA125 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 105) | 1 | 1 | ||||||||||
Normal to 3-Fold (35–105) | < 0.001 | 0.59(0.46–0.77) | < 0.001 | 0.49(0.37–0.64) | ||||||||
Normal (≤ 35.0) | < 0.001 | 0.48(0.37–0.63) | < 0.001 | 0.39(0.30–0.53) | ||||||||
Overall survival | ||||||||||||
Age | 0.023 | 0.013 | 0.018 | 0.005 | 0.001 | 0.002 | ||||||
Old (≥ 65) | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Young (< 65) | 0.80(0.66–0.97) | 0.77(0.63–0.95) | 0.78(0.64–0.96) | 0.75(0.61–0.92) | 0.72(0.59–0.89) | 0.73(0.59–0.89) | ||||||
Sex | 0.092 | 0.115 | 0.041 | 0.078 | 0.035 | 0.06 | ||||||
Female | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Male | 1.28(0.96–1.70) | 1.29(0.94–1.78) | 1.39(1.01–1.92) | 1.33(0.97–1.83) | 1.41(1.02–1.93) | 1.36(0.99–1.86) | ||||||
ECOG PS | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | ||||||
0–1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
2 | 3.22(2.46–4.21) | 3.09(2.33–4.08) | 3.25(2.45–4.31) | 3.31(2.50–4.40) | 3.28(2.47–4.35) | 3.49(2.62–4.63) | ||||||
Smoke history | 0.384 | 0.484 | 0.404 | 0.984 | 0.767 | 0.806 | ||||||
No | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Yes | 1.09(0.90–1.32) | 0.93(0.75–1.15) | 1.10(0.88–1.36) | 1.00(0.81–1.24) | 0.97(0.78–1.20) | 0.97(0.78–1.21) | ||||||
Histological type | < 0.001 | < 0.001 | 0.005 | 0.041 | 0.001 | < 0.001 | ||||||
LUAD | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
LUSC | 0.002 | 1.36(1.12–1.66) | < 0.001 | 1.70(1.37–2.11) | 0.001 | 1.40(1.14–1.72) | 0.034 | 1.26(1.02–1.55) | 0.001 | 1.41(1.14–1.73) | < 0.001 | 1.49(1.21–1.83) |
Other_NSCLC | 0.042 | 0.59(0.36–0.98) | 0.073 | 0.62(0.37–1.04) | 0.019 | 0.54(0.32–0.90) | 0.085 | 0.64(0.38–1.06) | 0.002 | 0.55(0.33–0.92) | 0.054 | 0.60(0.36–1.01) |
Stage | 0.034 | 0.042 | 0.234 | 0.159 | 0.162 | 0.068 | ||||||
IIIB | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
IIIC | 0.006 | 2.10(1.23–3.57) | 0.014 | 2.00(1.15–3.46) | 0.187 | 1.45(0.83–2.53) | 0.121 | 1.55(0.89–2.71) | 0.075 | 1.66(0.95–2.90) | 0.043 | 1.78(1.02–3.10) |
IV | 0.3 | 1.18(0.86–1.62) | 0.252 | 062(0.37–1.04) | 0.276 | 1.20(0.86–1.67) | 0.187 | 1.25(0.90–1.74) | 0.265 | 1.21(0.87–1.68) | 0.235 | 1.22(0.88–3.10) |
PD-L1 expression | 0.001 | 0.265 | 0.209 | 0.172 | 0.087 | 0.044 | ||||||
< 1% | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
≥ 1% | 0.69(0.55–0.87) | 0.87(0.69–1.11) | 0.86(0.67–1.09) | 0.85(0.67–1.07) | 0.81(0.64–1.03) | 0.78(0.62–0.99) | ||||||
Treatment | 0.103 | 0.013 | 0.044 | 0.012 | 0.107 | 0.023 | ||||||
Monotherapy | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Combination therapy | 0.85(0.70–1.03) | 0.76(0.62–0.94) | 0.80(0.65–0.99) | 0.76(0.62–0.94) | 0.84(0.68–1.04) | 0.78(0.63–0.97) | ||||||
CEA | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 15) | 1 | 1 | ||||||||||
Normal to 3-Fold (5–15) | 0.539 | 0.93(0.73–1.18) | 0.139 | 0.83(0.65–1.06) | ||||||||
Normal (≤ 5.0) | < 0.001 | 0.50(0.40–0.63) | < 0.001 | 0.42(0.32–0.54) | ||||||||
NSE | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 48.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (16.3–48.9) | < 0.001 | 0.38(0.27–0.53) | < 0.001 | 0.40(0.29–0.56) | ||||||||
Normal (≤ 16.3) | < 0.001 | 0.25(0.17–0.35) | < 0.001 | 0.26(0.18–0.37) | ||||||||
CYFRA21-1 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 9.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (3.3–9.9) | < 0.001 | 0.66(0.54–0.80) | < 0.001 | 0.69(0.56–0.85) | ||||||||
Normal (≤ 3.3) | < 0.001 | 0.39(0.27–0.55) | < 0.001 | 0.45(0.31–0.64) | ||||||||
CA19-9 | < 0.001 | < 0.001 | ||||||||||
3-Flod(> 81) | 1 | 1 | ||||||||||
Normal to 3-Fold (27–81) | 0.007 | 0.62(0.44–0.88) | 0.001 | 0.55(0.38–0.79) | ||||||||
Normal (≤ 27.0) | < 0.001 | 0.45(0.32–0.62) | < 0.001 | 0.41(0.30–0.58) | ||||||||
CA125 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 105) | 1 | 1 | ||||||||||
Normal to 3-Fold (35–105) | < 0.001 | 0.56(0.42–0.74) | < 0.001 | 0.44(0.33–0.59) | ||||||||
Normal (≤ 35.0) | < 0.001 | 0.44(0.33–0.59) | < 0.001 | 0.35(0.26–0.48) |
Analysis of patients with lung adenocarcinoma
Covariate | Univariate analysis | Multivariate analysis (CEA) | Multivariate analysis (NSE) | Multivariate analysis (CYFRA21-1) | Multivariate analysis (CA19-9) | Multivariate analysis (CA125) | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | |
Progression-free survival | ||||||||||||
Age | 0.458 | 0.415 | 0.251 | 0.277 | 0.057 | 0.106 | ||||||
Old (≥ 65) | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Young (< 65) | 0.91(0.72–1.16) | 0.90(0.70–1.16) | 0.86(0.67–1.11) | 0.87(0.68–1.12) | 0.78(0.61–1.01) | 0.81(0.63–1.05) | ||||||
Sex | 0.238 | 0.736 | 0.463 | 0.655 | 0.967 | 0.808 | ||||||
Female | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Male | 0.81(0.56–1.15) | 1.08(0.72–1.60) | 1.16(0.78–1.75) | 1.10(0.73–1.64) | 0.99(0.67–1.47) | 105(0.71–1.56) | ||||||
ECOG PS | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | ||||||
0–1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
2 | 3.86(2.71–5.50) | 3.34(2.31–4.84) | 3.41(2.34–4.97) | 3.96(2.72–5.76) | 3.77(2.60–5.45) | 4.29(2.94–6.26) | ||||||
Smoke history | < 0.001 | < 0.001 | 0.016 | 0.005 | 0.008 | < 0.001 | ||||||
No | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Yes | 0.65(0.51–0.83) | 0.62(0.48–0.81) | 0.72(0.55–0.94) | 0.69(0.53–0.90) | 0.70(0.54–0.91) | 0.62(0.48–0.81) | ||||||
Stage | 0.193 | 0.043 | 0.512 | 0.482 | 0.565 | 0.351 | ||||||
IIIB | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
IIIC | 0.167 | 1.77(0.79–3.99) | 0.029 | 2.77(1.11–6.89) | 0.708 | 1.18(0.49–2.85) | 0.562 | 1.30(0.53–3.18) | 0.565 | 1.29(0.54–3.10) | 0.368 | 1.50(0.62–3.62) |
IV | 0.573 | 0.88(0.57–1.37) | 0.868 | 0.96(0.61–1.52) | 0.358 | 0.75(0.58–0.97) | 0.432 | 0.83(0.53–1.31) | 0.4 | 0.82(0.52–1.30) | 0.333 | 0.80(0.51–1.26) |
PD-L1 expression | 0.032 | 0.413 | 0.448 | 0.246 | 0.439 | 0.624 | ||||||
< 1% | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
≥ 1% | 0.72(0.53–0.97) | 0.88(0.64–1.22) | 0.88(0.63–1.22) | 0.83(0.60–1.14) | 0.88(0.64–1.21) | 0.92(0.67–1.27) | ||||||
Treatment | 0.02 | 0.002 | 0.032 | 0.006 | 0.044 | 0.017 | ||||||
Monotherapy | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Combination therapy | 0.75(0.59–0.95) | 0.67(0.5–0.87) | 0.75(0.58–0.97) | 0.69(0.53–0.90) | 0.76(0.59–0.99) | 0.72(0.55–0.94) | ||||||
CEA | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 15) | 1 | 1 | ||||||||||
Normal to 3-Fold (5–15) | 0.246 | 0.85(0.64–1.12) | 0.137 | 0.81(0.61–1.07) | ||||||||
Normal (≤ 5.0) | < 0.001 | 0.38(0.28–0.52) | < 0.001 | 0.33(0.23–0.46) | ||||||||
NSE | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 48.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (16.3–48.9) | < 0.001 | 0.37(0.24–0.58) | < 0.001 | 0.41(0.26–0.66) | ||||||||
Normal (≤ 16.3) | < 0.001 | 0.24(0.15–0.39) | < 0.001 | 0.29(0.18–0.47) | ||||||||
CYFRA21-1 | 0.011 | 0.004 | ||||||||||
3-Fold(> 9.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (3.3–9.9) | 0.033 | 0.75(0.58–0.98) | 0.006 | 0.69(0.53–0.90) | ||||||||
Normal (≤ 3.3) | 0.007 | 0.57(0.37–0.86) | 0.003 | 0.53(0.35–0.80) | ||||||||
CA19-9 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 81) | 1 | 1 | ||||||||||
Normal to 3-Fold (27–81) | 0.042 | 0.67(0.44–0.99) | 0.063 | 0.68(0.45–1.02) | ||||||||
Normal (≤ 27.0) | < 0.001 | 0.43(0.30–0.64) | < 0.001 | 0.45(0.31–0.67) | ||||||||
CA125 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 105) | 1 | 1 | ||||||||||
Normal to 3-Fold (35–105) | 0.026 | 0.70(0.51–0.96) | < 0.001 | 0.54(0.39–0.76) | ||||||||
Normal (≤ 35.0) | < 0.001 | 0.41(0.29–0.59) | < 0.001 | 0.31(0.21–0.44) | ||||||||
Overall survival | ||||||||||||
Age | 0.132 | 0.057 | 0.102 | 0.085 | 0.008 | 0.017 | ||||||
Old (≥ 65) | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Young (< 65) | 0.81(0.62–1.07) | 0.76(0.57–1.01) | 0.79(0.59–1.05) | 0.78(0.59–1.03) | 0.68(0.51–0.90) | 0.71(0.53–0.94) | ||||||
Sex | 0.673 | 0.728 | 0.527 | 0.351 | 0.87 | 0.675 | ||||||
Female | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Male | 0.92(0.62–1.36) | 1.08(0.69–1.69) | 1.15(0.74–1.82) | 1.24(0.79–1.94) | 1.04(0.67–1.61) | 1.11(0.71–1.72) | ||||||
ECOG PS | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | ||||||
0–1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
2 | 4.11(2.87–5.87) | 3.61(2.45–5.33) | 3.69(2.49–5.46) | 4.43(2.99–6.56) | 4.31(2.93–6.35) | 4.76(3.20–7.08) | ||||||
Smoke history | 0.089 | 0.117 | 0.653 | 0.166 | 0.219 | 0.102 | ||||||
No | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Yes | 0.79(0.60–1.04) | 0.79(0.59–1.06) | 1.45(0.55–3.80) | 0.81(0.61–1.09) | 0.83(0.62–1.12) | 0.78(0.58–1.05) | ||||||
Stage | 0.169 | 0.034 | 0.45 | 0.674 | 0.657 | 0.275 | ||||||
IIIB | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
IIIC | 0.059 | 2.34(0.97–5.65) | 0.007 | 4.01(1.17–10.94) | 0.884 | 0.93(0.69–1.26) | 0.261 | 1.75(0.66–4.64) | 0.321 | 1.62(0.62–4.22) | 0.902 | 1.71(0.65–4.48) |
IV | 0.682 | 1.13(0.64–1.98) | 0.519 | 1.21(0.68–2.17) | 0.922 | 1.03(0.57–1.85) | 0.832 | 1.07(0.60–1.91) | 0.869 | 1.06(0.59–1.88) | 0.831 | 0.94(0.53–1.68) |
PD-L1 expression | 0.037 | 0.756 | 0.867 | 0.831 | 0.759 | 0.935 | ||||||
< 1% | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
≥ 1% | 0.71(0.51–0.98) | 1.06(0.74–1.51) | 1.10(0.77–1.58) | 0.96(0.68–1.36) | 1.05(0.74–1.51) | 1.02(0.71–1.45) | ||||||
Treatment | 0.122 | 0.001 | 0.019 | 0.003 | 0.036 | 0.009 | ||||||
Monotherapy | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Combination therapy | 0.81(0.61–1.06) | 0.62(0.46–0.82) | 0.70(0.52–0.94) | 0.65(0.48–0.77) | 0.73(0.55–0.98) | 0.67(0.50–0.91) | ||||||
CEA | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 15) | 1 | 1 | ||||||||||
Normal to 3-Fold (5–15) | 0.523 | 0.90(0.66–1.23) | 0.309 | 0.85(0.62–1.16) | ||||||||
Normal (≤ 5.0) | < 0.001 | 0.33(0.23–0.48) | < 0.001 | 0.28(0.18–0.42) | ||||||||
NSE | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 48.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (16.3–48.9) | < 0.001 | 0.37(0.24–0.59) | < 0.001 | 0.42(0.26–0.68) | ||||||||
Normal (≤ 16.3) | < 0.001 | 0.22(0.14–0.36) | < 0.001 | 0.27(0.16–0.46) | ||||||||
CYFRA21-1 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 9.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (3.3–9.9) | 0.012 | 0.69(0.52–0.92) | < 0.001 | 0.58(0.43–0.77) | ||||||||
Normal (≤ 3.3) | < 0.001 | 0.38(0.23–0.64) | < 0.001 | 0.37(0.22–0.62) | ||||||||
CA19-9 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 81) | 1 | 1 | ||||||||||
Normal to 3-Fold (27–81) | 0.004 | 0.54(0.35–0.82) | < 0.001 | 0.48(0.31–0.73) | ||||||||
Normal (≤ 27.0) | < 0.001 | 0.33(0.22–0.49) | < 0.001 | 0.29(0.19–0.44) | ||||||||
CA125 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 105) | 1 | 1 | ||||||||||
Normal to 3-Fold (35–105) | 0.007 | 0.62(0.43–0.88) | < 0.001 | 0.47(0.33–0.68) | ||||||||
Normal (≤ 35.0) | < 0.001 | 0.38(0.25–0.56) | < 0.001 | 0.28(0.19–0.42) |
Analysis of patients with lung squamous carcinoma
Covariate | Univariate analysis | Multivariate analysis (CEA) | Multivariate analysis (NSE) | Multivariate analysis (CYFRA21-1) | Multivariate analysis (CA19-9) | Multivariate analysis (CA125) | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | |
Progression-free survival | ||||||||||||
Age | 0.625 | 0.8 | 0.336 | 0.782 | 0.642 | 0.682 | ||||||
Old (≥ 65) | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Young (< 65) | 0.93(0.72–1.22) | 1.04(0.77–1.39) | 1.16(0.86–1.57) | 1.04(0.78–1.40) | 1.07(0.80–1.44) | 1.06(0.79–1.43) | ||||||
Sex | 0.02 | 0.186 | 0.041 | 0.314 | 0.102 | 0.158 | ||||||
Female | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Male | 1.52(1.06–2.17) | 1.32(0.87–2.01) | 1.55(1.02–2.35) | 1.24(0.81–1.89) | 1.41(0.93–2.14) | 1.35(0.89–2.04) | ||||||
ECOG PS | < 0.001 | 0.005 | < 0.001 | 0.004 | 0.003 | 0.001 | ||||||
0–1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
2 | 2.30(1.52–3.48) | 0.90(1.22–2.96) | 2.19(1.40–3.43) | 1.92(1.22–2.99) | 1.96(1.26–3.07) | 2.05(1.32–3.19) | ||||||
Smoke history | 0.006 | 0.372 | 0.119 | 0.108 | 0.147 | 0.179 | ||||||
No | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Yes | 1.45(1.11–1.88) | 1.17(0.83–1.63) | 1.30(0.94–1.80) | 1.31(0.94–1.81) | 1.28(0.92–1.78) | 1.25(0.90–1.77) | ||||||
Stage | < 0.001 | 0.007 | 0.008 | 0.006 | 0.002 | < 0.001 | ||||||
IIIB | 1 | 1 | 1 | 1 | ||||||||
IIIC | < 0.001 | 3.20(1.71–5.99) | 0.002 | 2.82(1.46–5.47) | 0.001 | 3.00(1.55–5.82) | 0.005 | 2.61(1.33–5.10) | 0.002 | 2.87(1.48–5.58) | < 0.001 | 3.29(1.69–6.38) |
IV | 0.005 | 1.70(1.17–2.45) | 0.017 | 1.59(1.08–2.34) | 0.011 | 1.64(1.12–2.40) | 0.006 | 1.70(1.16–2.48) | 0.006 | 1.70(1.16–2.50) | 0.005 | 1.72(1.18–2.52) |
PD-L1 expression | 0.774 | 0.658 | 0.485 | 0.383 | 0.665 | 0.846 | ||||||
< 1% | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
≥ 1% | 0.97(1.05–1.30) | 1.08(0.77–1.51) | 1.13(0.80–1.59) | 1.16(0.83–1.64) | 1.08(0.77–1.51) | 0.97(0.69–1.36) | ||||||
Treatment | 0.553 | 0.628 | 363 | 0.489 | 0.708 | 0.562 | ||||||
Monotherapy | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Combination therapy | 1.09(0.82–1.44) | 0.93(0.68–1.27) | 0.87(0.63–1.18) | 0.90(0.65–1.23) | 0.94(0.69–1.29) | 0.91(0.67–1.24) | ||||||
CEA | < 0.001 | 0.041 | ||||||||||
3-Fold(> 15) | 1 | 1 | ||||||||||
Normal to 3-Fold (5–15) | 0.058 | 0.68(0.46–1.01) | 0.233 | 0.78(0.51–1.18) | ||||||||
Normal (≤ 5.0) | < 0.001 | 0.49(0.35–0.70) | 0.023 | 0.64(0.44–0.94) | ||||||||
NSE | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 48.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (16.3–48.9) | < 0.001 | 0.36(0.22–0.58) | < 0.001 | 0.31(0.19–0.52) | ||||||||
Normal (≤ 16.3) | < 0.001 | 0.21(0.13–0.36) | < 0.001 | 0.18(0.11–0.31) | ||||||||
CYFRA21-1 | 0.013 | 0.036 | ||||||||||
3-Fold(> 9.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (3.3–9.9) | 0.035 | 0.74(0.56–0.98) | 0.303 | 0.86(0.64–1.15) | ||||||||
Normal (≤ 3.3) | 0.001 | 0.44(0.26–0.73) | 0.013 | 0.51(0.30–0.87) | ||||||||
CA19-9 | 0.754 | 0.857 | ||||||||||
3-Fold(> 81) | 1 | 1 | ||||||||||
Normal to 3-Fold (27–81) | 0.911 | 1.03(0.57–1.89) | 0.715 | 1.12(0.61–2.07) | ||||||||
Normal (≤ 27.0) | 0.553 | 0.84(0.48–1.49) | 0.952 | 1.02(0.57–1.83) | ||||||||
CA125 | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 105) | 1 | 1 | ||||||||||
Normal to 3-Fold (35–105) | < 0.001 | 0.44(0.27–0.71) | < 0.001 | 0.41(0.25–0.69) | ||||||||
Normal (≤ 35.0) | < 0.001 | 0.45(0.28–0.72) | 0.004 | 0.48(0.29–0.79) | ||||||||
Overall survival | ||||||||||||
Age | 0.006 | 0.057 | 0.107 | 0.054 | 0.055 | 0.062 | ||||||
Old (≥ 65) | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Young (< 65) | 0.67(0.50–0.89) | 0.73(0.53–1.01) | 0.76(0.55–1.06) | 0.73(0.52–1.01) | 0.73(0.53–1.01) | 0.73(0.53–1.02) | ||||||
Sex | 0.003 | 0.068 | 0.041 | 0.147 | 0.033 | 0.053 | ||||||
Female | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Male | 1.88(1.24–2.85) | 1.56(0.97–2.52) | 1.65(1.02–2.66) | 1.43(0.88–2.32) | 1.56(0.95–2.56) | 1.60(0.99–2.58) | ||||||
ECOG PS | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 | ||||||
0–1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
2 | 2.30(1.50–3.55) | 2.36(1.49–3.73) | 2.71(1.70–4.34) | 2.24(1.40–3.60) | 2.34(1.46–3.73) | 2.46(1.55–3.90) | ||||||
Smoke history | < 0.001 | 0.542 | 0.126 | 0.104 | 0.271 | 0.244 | ||||||
No | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Yes | 1.77(1.33–2.36) | 1.12(0.78–1.60) | 1.33(0.92–1.91) | 1.34(0.94–1.92) | 1.22(0.85–1.76) | 1.23(0.86–1.77) | ||||||
Stage | 0.062 | 0.215 | 0.313 | 0.268 | 0.172 | 0.115 | ||||||
IIIB | 1 | 1 | 1 | 1 | ||||||||
IIIC | 0.078 | 1.83(0.93–3.57) | 0.136 | 1.70(0.85–3.39) | 0.338 | 1.42(0.70–2.88) | 0.333 | 1.42(0.69–2.90) | 0.151 | 1.68(0.83–3.40) | 0.086 | 1.85(0.92–3.74) |
IV | 0.14 | 1.35(0.91–1.99) | 0.291 | 1.24(0.83–1.86) | 0.228 | 1.28(0.86–1.92) | 0.217 | 1.29(0.86–1.93) | 0.191 | 1.31(0.87–1.96) | 0.173 | 1.32(0.88–1.97) |
PD-L1 expression | 0.023 | 0.344 | 0.193 | 0.558 | 0.196 | 0.079 | ||||||
< 1% | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
≥ 1% | 0.68(0.49–0.95) | 0.84(0.59–1.20) | 0.79(0.55–1.13) | 0.97(0.70–1.35) | 0.79(0.55–1.13) | 0.72(0.50–1.04) | ||||||
Treatment | 0.948 | 0.847 | 0.878 | 0.879 | 0.67 | 0.768 | ||||||
Monotherapy | 1 | 1 | 1 | 1 | 1 | 1 | ||||||
Combination therapy | 0.99(0.73–1.35) | 1.03(0.74–1.43) | 1.03(0.74–1.43) | 0.97(0.70–1.35) | 1.07(0.77–1.50) | 1.05(0.76–1.46) | ||||||
CEA | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 15) | 1 | 1 | ||||||||||
Normal to 3-Fold (5–15) | 0.106 | 0.71(0.46–1.08) | 0.146 | 0.73(0.47–1.12) | ||||||||
Normal (≤ 5.0) | < 0.001 | 0.39(0.26–0.57) | < 0.001 | 0.48(0.32–0.73) | ||||||||
NSE | < 0.001 | < 0.001 | ||||||||||
3-Fold(> 48.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (16.3–48.9) | < 0.001 | 0.35(0.21–0.57) | < 0.001 | 0.33(0.20–0.56) | ||||||||
Normal (≤ 16.3) | < 0.001 | 0.23(0.14–0.39) | < 0.001 | 0.22(0.13–0.37) | ||||||||
CYFRA21-1 | < 0.001 | 0.015 | ||||||||||
3-Fold(> 9.9) | 1 | 1 | ||||||||||
Normal to 3-Fold (3.3–9.9) | < 0.001 | 0.59(0.44–0.81) | 0.028 | 0.70(0.51–0.96) | ||||||||
Normal (≤ 3.3) | < 0.001 | 0.38(0.22–0.66) | 0.005 | 0.44(0.24–0.78) | ||||||||
CA19-9 | 0.616 | 0.473 | ||||||||||
3-Fold(> 81) | 1 | 1 | ||||||||||
Normal to 3-Fold (27–81) | 0.84 | 0.94(0.49–1.80) | 0.688 | 0.87(0.44–1.71) | ||||||||
Normal (≤ 27.0) | 0.238 | 0.69(0.37–1.28) | 0.353 | 0.74(0.39–1.40) | ||||||||
CA125 | 0.002 | < 0.001 | ||||||||||
3-Fold(> 105) | 1 | 1 | ||||||||||
Normal to 3-Fold (35–105) | 0.002 | 0.45(0.27–0.75) | < 0.001 | 0.38(0.22–0.64) | ||||||||
Normal (≤ 35.0) | < 0.001 | 0.37(0.22–0.62) | < 0.001 | 0.36(0.22–0.61) |
Analysis of patients with non-small cell lung cancer who received monotherapy
Analysis of patients with non-small cell lung cancer who received combination therapy
Association between STM levels and programmed apoptosis ligand 1 expression
Serum tumor markers | LUAD (N = 390) | LUSC (N = 280) | ||||
---|---|---|---|---|---|---|
PD-L1( +) | PD-L1 (-) | P value | PD-L1( +) | PD-L1 (-) | P value | |
CEA (ng/ml) | 0.161 | 0.242 | ||||
Normal (≤ 5.0) | 100 | 17 | 78 | 30 | ||
High (> 5.0) | 215 | 58 | 136 | 36 | ||
NSE (ng/ml) | 0.675 | 1 | ||||
Normal (≤ 16.3) | 137 | 30 | 89 | 27 | ||
High (> 16.3) | 178 | 45 | 125 | 39 | ||
CYFRA21-1 (ng/ml) | 0.795 | 0.104 | ||||
Normal (≤ 3.3) | 44 | 9 | 27 | 3 | ||
High (> 3.3) | 271 | 66 | 187 | 63 | ||
CA19-9 (ng/ml) | 0.043 | 0.956 | ||||
Normal (≤ 27.0) | 194 | 36 | 143 | 45 | ||
High (> 27.0) | 121 | 39 | 71 | 21 | ||
CA125 (ng/ml) | ||||||
Normal (≤ 35.0) | 114 | 23 | 0.444 | 109 | 30 | 0.524 |
High (> 35.0) | 201 | 52 | 105 | 36 |
Correlation between STM levels and tumor response
Serum tumor markers | LUAD (N = 390) | LUSC (N = 280) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
CEA group | ORR | Non-ORR | P value | DCR | Non-DCR | P value | ORR | Non-ORR | P value | DCR | Non-DCR | P value |
A* | 52 | 119 | < 0.001 | 141 | 30 | < 0.001 | 14 | 33 | 0.269 | 39 | 8 | 0.006 |
B | 51 | 51 | 95 | 7 | 23 | 44 | 56 | 11 | ||||
C | 70 | 47 | 112 | 5 | 69 | 97 | 157 | 9 | ||||
NSE group | ||||||||||||
A | 2 | 22 | < 0.001 | 11 | 13 | < 0.001 | 7 | 12 | 0.873 | 14 | 5 | 0.005 |
B | 88 | 111 | 177 | 22 | 53 | 92 | 127 | 18 | ||||
C | 83 | 84 | 160 | 7 | 46 | 70 | 111 | 5 | ||||
CYFRA21-1 group | ||||||||||||
A | 50 | 80 | 0.212 | 108 | 22 | 0.007 | 49 | 87 | 0.553 | 117 | 19 | 0.107 |
B | 96 | 111 | 188 | 19 | 43 | 71 | 107 | 7 | ||||
C | 27 | 26 | 52 | 1 | 14 | 16 | 28 | 2 | ||||
CA19-9 group | ||||||||||||
A | 13 | 26 | 0.014 | 31 | 8 | 0.001 | 7 | 10 | 0.206 | 17 | 0 | 0.013 |
B | 44 | 77 | 101 | 20 | 22 | 53 | 61 | 14 | ||||
C | 116 | 114 | 216 | 14 | 77 | 111 | 174 | 14 | ||||
CA125 group | ||||||||||||
A | 20 | 43 | 0.002 | 53 | 10 | 0.102 | 4 | 18 | 0.016 | 16 | 6 | 0.025 |
B | 77 | 113 | 167 | 23 | 39 | 80 | 110 | 9 | ||||
C | 76 | 61 | 128 | 9 | 63 | 76 | 126 | 13 |