1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
2Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
Copyright © 2021 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The study protocol was reviewed and approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 1807-102-960). All studies were conducted according to the declaration of Helsinki.
Author Contributions
Conceived and designed the analysis: Park W, Oh DY.
Collected the data: Park W, Oh DY.
Contributed data or analysis tools: Park W, Bang JH, Nam AR, Jin MH, Seo H, Kim JM, Oh KS, Kim TY, Oh DY.
Performed the analysis: Park W, Kim TY, Oh DY.
Wrote the paper: Park W, Kim TY, Oh DY.
Conflicts of Interest
Conflicts of interest relevant to this article was not reported.
CA 19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; sPDL1, soluble form programmed death-ligand 1.
Baseline characteristics
Characteristic | No. (%) |
---|---|
Ages at diagnosis, median (range, yr) | 56 (28–80) |
Sex | |
Male | 43 (63.2) |
Female | 25 (36.8) |
Pathology | |
Adenocarcinoma, W/D | 2 (2.9) |
Adenocarcinoma, M/D | 20 (29.4) |
Adenocarcinoma, P/D | 18 (26.5) |
Poorly cohesive carcinoma | 20 (29.4) |
Mixed | 8 (11.8) |
HER2 status | |
HER2 positive | 13 (19.1) |
HER2 negative | 55 (80.9) |
Microsatellite status | |
MSI-High | 3 (4.4) |
MSI-Low | 3 (4.4) |
MSS | 27 (39.7) |
Unknown | 35 (51.5) |
Disease status | |
Relapsed after curative surgery | 10 (14.7) |
Undergone palliative surgery | 18 (26.5) |
Metastatic cancer | 40 (58.8) |
Metastatic organ | |
Liver | 15 (22.1) |
Lymph nodes | 22 (32.4) |
Peritoneum | 37 (54.4) |
Lung | 10 (14.7) |
Brain | 2 (2.9) |
Best response to 1st-line chemotherapy | |
Complete response | 0 |
Partial response | 34 (50) |
Stable disease | 29 (42.6) |
Progressive disease | 5 (7.4) |
Post progression treatment | |
1st line | 32 (47.0) |
2nd line | 25 (36.8) |
3rd line | 8 (11.8) |
4th line | 3 (4.4) |
Median OS (95% CI, mo) | 14.9 (7.3–22.5) |
Median PFS (95% CI, mo) | 8.00 (6.0–10.0) |
CI, confidence interval; HER2, human epidermal growth factor receptor 2; M/D, moderately differentiated; MSI, microsatellite instability; MSS, microsatellite stable; OS, overall survival; P/D, poorly differentiated; PFS, progression-free survival; W/D, well differentiated.
Laboratory test result
Baseline (n=68) | After 1st cycle (n=68) | Best response (n=67) | After progression (n=42) | |||||
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Median (range) | Average (95% CI) | Median (range) | Average (95% CI) | Median (range) | Average (95% CI) | Median (range) | Average (95% CI) | |
WBC (×1,000/mm3) | 6.81 (3.86–21.07) | 7.46 (6.76–8.16) | 5.45 (2.64–17.92) | 6.47 (5.70–7.24) | 4.68 (2.42–23.75) | 5.59 (4.81–6.37) | 5.52 (2.80–17.00) | 5.23 (4.81–6.37) |
| ||||||||
Hb (g/dL) | 11.6 (8.70–14.80) | 11.66 (11.26–12.06) | 11.45 (8.40–15.2) | 11.47 (11.09–11.84) | 11.2 (6.50–15.40) | 11.2 (10.79–11.61) | 10.85 (8.10–14.80) | 10.81 (10.32–11.24) |
| ||||||||
PLT (×1,000/mm3) | 279 (108–559) | 295 (270–320) | 250 (91–536) | 253 (231–276) | 205 (54–556) | 214 (190–239) | 211 (33–597) | 225.9 (192–260) |
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Neutrophil/Lymphocyte ratio | 2.38 (0.45–15.00) | 3.06 (2.43–3.69) | 1.64 (0.49–16.02) | 2.46 (1.88–3.03) | 1.3 (0.41–7.65) | 1.87 (1.48–2.26) | 2.19 (0.64–17.56) | 3.08 (2.34–4.18) |
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Monocyte/Lymphocyte ratio | 0.3 (0.13–1.24) | 0.34 (0.3–0.38) | 0.29 (0.13–0.95) | 0.36 (0.31–0.40) | 0.33 (0.12–0.94) | 0.38 (0.34–0.42) | 0.35 (0.11–2.15) | 0.46 (0.36–0.57) |
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Platelet/Lymphocyte ratio | 162.4 (53.49–427.66) | 174.65 (156.80–192.50) | 136.09 (40.47–354.42) | 148.93 (133.70–164.15) | 126.01 (31.04–608.98) | 131.81 (111.98–151.63) | 137.15 (22.24–639.35) | 166.11 (130.14–201.19) |
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CEA (ng/dL) | 2.65 (< 0.5–3,867.40) | 90.17 (0–212.772) | 2.9 (< 0.5–477.50) | 21.61 (2.96–40.26) | 2.8 (< 0.5–512.7) | 20.55 (1.96–39.14) | 4.3 (0.60–1,480.30) | 63.91 (0–143.78) |
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CA 19-9 (U/mL) | 17 (< 1.0–7,869.0) | 382.17 (76.33–664.56) | 14.2 (< 1.0–10,349) | 317.14 (0–677.56) | 17 (< 1.0–6,300) | 209 (0–416.27) | 35 (2.00–12,000) | 605.09 (0–1,228.02) |
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sPDL1 (ng/mL) | 0.8 (0.06–6.06) | 1.31 (0.98–1.63) | 0.92 (0.28–6.73) | 1.52 (1.16–1.88) | 1.01 (0.07–6.29) | 1.46 (1.11–1.81) | 1.22 (0.23–7.11) | 1.45 (1.06–1.84) |
CA 19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; CI, confidence interval; Hb, hemoglobin; PLT, platelet; sPDL1, soluble form programmed death-ligand 1; WBC, white blood cell.
Univariate and multivariate analysis for survival
Variable | Univariate analysis | Multivariate analysis | ||
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HR (95% CI) | p-value | HR (95% CI) | p-value | |
Age ≥ 60 yr (vs. < 60 yr) | 1.082 (0.612–1.915) | 0.785 | - | - |
| ||||
ECOG PS > 2 (vs. ≤ 2) | 1.851 (0.436–7.861) | 0.443 | - | - |
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Relapsed disease (vs. unresectable) | 1.496 (0.750–2.987) | 0.253 | - | - |
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Peritoneal seeding (vs. without seeding) | 1.874 (1.085–3.236) | 0.024 | 1.340 (0.726–2.697) | 0.315 |
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No. of metastasis organ > 2 (vs. ≤ 2) | 1.706 (0.793–3.669) | 0.171 | - | - |
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Undergone resection (vs. no) | 0.503 (0.284–0.891) | 0.019 | 0.603 (0.321–1.134) | 0.117 |
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1st line therapy (vs. further line) | 0.794 (0.456–1.383) | 0.415 | - | - |
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HER2-positive (vs. -negative) | 1.094 (0.561–2.132) | 0.792 | - | - |
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With anemia (vs. without anemia) | 0.892 (0.502–1.582) | 0.675 | - | - |
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CEA > 5 ng/dL (vs. ≤ 5) | 1.422 (0.793–2.548) | 0.237 | - | - |
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CA 19-9 > 37 U/mL (vs. ≤ 37) | 1.315 (0.742–2.331) | 0.349 | - | - |
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sPDL1 > 1.92 ng/mL (vs. ≤ 1.92) | 1.837 (0.975–3.458) | 0.061 | 1.448 (0.714–2.935) | 0.305 |
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NLR > 3.51 (vs. ≤ 3.51) | 3.975 (2.044–7.731) | < 0.01 | 2.381 (1.127–5.031) | 0.023 |
| ||||
MLR > 0.30 (vs. ≤ 0.30) | 2.498 (1.416–4.408) | < 0.01 | 1.565 (0.816–3.005) | 0.178 |
| ||||
PLR > 135.8 (vs. ≤ 135.8) | 2.180 (1.218–3.903) | < 0.01 | 1.525 (0.740–3.319) | 0.252 |
CA 19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; sPDL1, soluble form programmed death-ligand 1.
Dynamics of sPDL1 according to response groups
Best response | PR | SD | PD | Total | p-value |
---|---|---|---|---|---|
Baseline sPDL1 | n=34 | n=29 | n=5 | n=68 | |
Median (range) | 0.74 (0.22–6.06) | 0.90 (0.06–4.73) | 2.77 (0.25–5.03) | 0.80 (0.06–6.06) | |
Mean (95% CI) | 1.19 (0.77–1.61) | 1.17 (0.73–1.61) | 2.91 (1.20–4.62) | 1.31 (0.98–1.63) | 0.018 |
After 1st cycle | n=34 | n=29 | n=5 | n=68 | |
Median (range) | 0.86 (0.28–6.73) | 0.84 (0.31–5.44) | 1.43 (0.32–2.45) | 0.92 (0.28–6.73) | |
Mean (95% CI) | 1.45 (0.95–1.95) | 1.61 (1.04–2.18) | 1.47 (0.76–2.18) | 1.52 (1.16–1.88) | 0.912 |
At best response | n=33 | n=29 | n=5 | n=67 | |
Median (range) | 1.01 (0.07–4.85) | 0.97 (0.27–6.29) | 1.85 (0.29–7.11) | 1.01 (0.07–7.11) | |
Mean (95% CI) | 1.34 (0.95–1.73) | 1.37 (0.86–1.88) | 2.80 (0.47–5.13) | 1.46 (1.11–1.81) | 0.097 |
After progression | n=17 | n=20 | n=5 | n=42 | |
Median (range) | 1.24 (0.29–2.89) | 0.97 (0.23–3.46) | 1.85 (0.29–7.11) | 1.22 (0.23–7.11) | |
Mean (95% CI) | 1.36 (1.02–1.70) | 1.19 (0.78–1.60) | 2.80 (0.47–5.13) | 1.45 (1.06–1.84) | 0.029 |
CI, confidence interval; PD, progressive disease; PR, partial response; SD, stable disease; sPDL1, soluble form programmed death-ligand 1.
CI, confidence interval; HER2, human epidermal growth factor receptor 2; M/D, moderately differentiated; MSI, microsatellite instability; MSS, microsatellite stable; OS, overall survival; P/D, poorly differentiated; PFS, progression-free survival; W/D, well differentiated.
CA 19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; CI, confidence interval; Hb, hemoglobin; PLT, platelet; sPDL1, soluble form programmed death-ligand 1; WBC, white blood cell.
CA 19-9, cancer antigen 19-9; CEA, carcinoembryonic antigen; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; sPDL1, soluble form programmed death-ligand 1.
CI, confidence interval; PD, progressive disease; PR, partial response; SD, stable disease; sPDL1, soluble form programmed death-ligand 1.