The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Treatment Schedule
2.3. Patient Evaluation
2.4. Endpoints and Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Oncological Outcomes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Responder | Non-Responder | p |
---|---|---|---|
Number | 53 | 107 | |
Age (year, median, IQR) | 72 (70–78) | 72 (68–78) | 0.707 |
Sex (n, %) | 0.845 | ||
Male | 41 (77.4) | 80 (74.8) | |
Female | 12 (22.6) | 27 (25.2) | |
BMI (kg/m2, median, IQR) | 22.2 (19.4–24.2) | 22.0 (19.5–24.5) | 0.988 |
ECOG-PS | |||
0 | 38 (71.7) | 56 (52.3) | 0.026 |
1 | 12 (22.6) | 29 (27.1) | |
2 | 1 (1.9) | 16 (15.0) | |
3 | 2 (3.8) | 6 (5.6) | |
Primary site (number, %) | 0.485 | ||
Upper urinary tract | 19 (35.8) | 30 (28.0) | |
Bladder | 26 (49.1) | 63 (58.9) | |
Upper urinary tract and Bladder | 8 (15.1) | 14 (13.1) | |
Location of metastases (number, %) | |||
Lung | 13 (24.5) | 53 (49.5) | 0.004 |
Liver | 5 (9.4) | 23 (21.5) | 0.077 |
Bone | 5 (9.4) | 25 (23.4) | 0.051 |
Lymph node | 36 (67.9) | 80 (74.8) | 0.452 |
Smoking history (number, %) | |||
Never | 18 (34.0) | 43 (40.2) | 0.239 |
Current | 5 (9.4) | 18 (16.8) | |
Former | 30 (56.6) | 46 (43.0) | |
Definitive therapy for primary site (number, %) | 47 (88.7) | 83 (77.6) | 0.131 |
Histological subtype (number, %) | 0.322 | ||
Pure urothelial carcinoma | 43 (82.7) | 95 (88.8) | |
Sarcomatoid variant | 3 (5.7) | 3 (2.8) | |
other variants | 7 (13.2) | 9 (17.3) | |
Follow-up period | 19 (12–26) | 6 (3–13) | <0.001 |
(months, median, IQR) |
Variables | Responder | Non-Responder | p |
---|---|---|---|
Number | 53 | 107 | |
Before the administration of pembrolizumab | |||
CRP (mg/dL, median, IQR) | 0.20 (0.10–1.40) | 1.14 (0.23–2.77) | 0.002 |
Albumin (g/dL, median, IQR) | 3.90 (3.50–4.12) | 3.60 (3.20–3.95) | 0.006 |
Hemoglobin (g/dL, IQR) | 11.10 (9.20- 12.60) | 10.50 (9.12–12.00) | 0.133 |
NLR (median, IQR) | 2.94 (2.07–4.47) | 2.96 (2.08–4.96) | 0.843 |
After two courses of pembrolizumab | |||
CRP (mg/dL, IQR) | 0.14 (0.07–0.46) | 1.05 (0.42–3.83) | <0.001 |
Albumin (g/dL, IQR) | 3.90 (3.68–4.23) | 3.60 (3.23–3.98) | <0.001 |
Hemoglobin (g/dL, IQR) | 11.90 (10.88- 13.40) | 10.80 (9.50–12.30) | 0.003 |
NLR (median, IQR) | 2.13 (1.60–3.50) | 3.30 (2.50–5.80) | <0.001 |
Best of response | ||||||
Variables | CR | PR | SD | PD | p | |
Number | 23 | 30 | 33 | 74 | ||
Before pembrolizumab administration | ||||||
CRP, <0.63 mg/dL | 19 (82.6) | 18 (60.0) | 17 (51.5) | 26 (35.1) | 0.001 | |
CRP, ≥0.63 mg/dL | 4 (17.4) | 12 (40.0) | 16 (48.5) | 48 (64.9) | ||
Albumin, <3.7 g/dL | 6 (26.1) | 11 (37.9) | 16 (48.5) | 44 (59.5) | 0.024 | |
Albumin, ≥3.7 g/dL | 17 (73.9) | 18 (62.1) | 17 (51.5) | 30 (40.5) | ||
Hemoglobin, <10.6 g/dL | 6 (26.1) | 14 (46.7) | 16 (48.5) | 40 (54.8) | 0.122 | |
Hemoglobin, ≥10.6 g/dL | 17 (73.9) | 16 (53.3) | 17 (51.5) | 33 (45.2) | ||
NLR, <4.89 | 19 (82.6) | 21 (70.0) | 28 (84.8) | 51 (68.9) | 0.243 | |
NLR, ≥4.89 | 4 (17.4) | 9 (30.0) | 5 (15.2) | 23 (31.1) | ||
After pembrolizumab administration | ||||||
CRP, <0.67 mg/dL | 20 (90.9) | 23 (79.3) | 18 (58.1) | 15 (25.0) | <0.001 | |
CRP, ≥0.67 mg/dL | 2 (9.1) | 6 (20.7) | 13 (41.9) | 45 (75.0) | ||
Albumin, <3.7 g/dL | 5 (21.7) | 8 (27.6) | 13 (40.6) | 40 (64.5) | <0.001 | |
Albumin, ≥3.7 g/dL | 18 (78.3) | 21 (72.4) | 19 (59.4) | 22 (35.5) | ||
Hemoglobin, <10.0 g/dL | 0 (0) | 6 (20.7) | 12 (37.5) | 22 (36.1) | 0.004 | |
Hemoglobin, ≥10.0 g/dL | 23 (100.0) | 23 (79.3) | 20 (62.5) | 39 (63.9) | ||
NLR, <3.24 | 18 (81.8) | 19 (65.5) | 16 (51.6) | 24 (40.0) | 0.004 | |
NLR, ≥3.24 | 4 (18.2) | 10 (34.5) | 15 (48.4) | 36 (60.0) |
Variables | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | |
Age, ≥75 vs. <75 | 0.91 | 0.57–1.44 | 0.705 | |||
Sex, Female vs. Male | 0.87 | 0.51–1.48 | 0.610 | |||
ECOG-PS, ≥2 vs. ≤1 | 1.37 | 1.07–1.75 | 0.013 | 1.88 | 0.95–3.72 | 0.068 |
BMI, <21.9 vs. ≥21.9 | 0.82 | 0.53–1.27 | 0.378 | |||
Smoking history, yes vs. no | 0.74 | 0.47–1.16 | 0.201 | |||
Lung metastasis, yes vs. no | 1.98 | 1.28–3.07 | 0.002 | 2.02 | 1.15–3.55 | 0.014 |
Liver metastasis, yes vs. no | 2.56 | 1.55–4.24 | <0.001 | 2.65 | 1.35–5.17 | 0.004 |
Bone metastasis, yes vs. no | 1.82 | 1.1–3.03 | 0.021 | 1.11 | 0.61–2.00 | 0.720 |
Lymph node metastasis, yes vs. no | 0.95 | 0.6–1.51 | 0.830 | |||
Surgery of the primary site, yes vs. no | 0.63 | 0.37–1.07 | 0.084 | |||
Radiation therapy of the primary site, yes vs. no | 1.17 | 0.43–3.21 | 0.760 | |||
Albumin, ≥3.7 vs. <3.7 | 0.28 | 0.23–0.56 | <0.001 | 0.59 | 0.30–1.15 | 0.126 |
CRP, ≥0.67 vs. <0.67 | 1.08 | 1.04–1.11 | <0.001 | 2.28 | 1.13–4.57 | 0.020 |
Hemoglobin, ≥10.0 vs. <10.0 | 0.29 | 0.18–0.48 | <0.001 | 1.08 | 0.58–2.02 | 0.790 |
NLR, ≥3.24 vs. <3.24 | 3.21 | 1.94–5.33 | <0.001 | 2.82 | 1.50–5.31 | 0.001 |
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Tomioka-Inagawa, R.; Nakane, K.; Enomoto, T.; Tomioka, M.; Taniguchi, T.; Ishida, T.; Ozawa, K.; Takagi, K.; Ito, H.; Takeuchi, S.; et al. The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma. Biomedicines 2022, 10, 1609. https://doi.org/10.3390/biomedicines10071609
Tomioka-Inagawa R, Nakane K, Enomoto T, Tomioka M, Taniguchi T, Ishida T, Ozawa K, Takagi K, Ito H, Takeuchi S, et al. The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma. Biomedicines. 2022; 10(7):1609. https://doi.org/10.3390/biomedicines10071609
Chicago/Turabian StyleTomioka-Inagawa, Risa, Keita Nakane, Torai Enomoto, Masayuki Tomioka, Tomoki Taniguchi, Takashi Ishida, Kaori Ozawa, Kimiaki Takagi, Hiroki Ito, Shinichi Takeuchi, and et al. 2022. "The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma" Biomedicines 10, no. 7: 1609. https://doi.org/10.3390/biomedicines10071609