Venous Thromboembolism in Asian Patients with Pancreatic Cancer Following Palliative Chemotherapy: Low Incidence but a Negative Prognosticator for Those with Early Onset
Abstract
:1. Introduction
2. Result
2.1. Patients’ Characteristics
2.2. Incidence and Predictors of Venous Thromboembolism (VTE)
2.3. Association of Khorana Risk Score with VTE Incidence
2.4. Survival Outcome
3. Discussion
4. Patients and Methods
4.1. Patient Selection
4.2. Data Collection
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Category | All Patients, n = 838 (%) | Patients Without VTE, n = 771 (%) | VTE Patients, n = 67 (%) | p |
---|---|---|---|---|---|
Age, year | median (range) | 62 (23–89) | 62 (23–89) | 63(43–83) | 0.86 |
Sex | 0.52 | ||||
male | 497(59.3) | 460 (59.6) | 37 (56.1) | ||
female | 341 (40.7) | 311 (40.3) | 30 (44.8) | ||
BMI, kg/m2 | median (range) | 22.5 (13–36.2) | 22.4 (13.0–36.0) | 22.8 (15.9–36.2) | 0.25 |
BMI, kg/m2 | >35 | 3 (0.4) | 2 (0.3) | 1 (1.5) | 0.22 |
ECOG PS | 0.48 | ||||
0–1 | 597 (71.2) | 545 (70.7) | 52 (77.6) | ||
2 | 206 (24.6) | 193 (25.0) | 13 (19.4) | ||
3 | 35 (4.2) | 33 (4.3) | 2 (3.0) | ||
CCI | 0.79 | ||||
0 | 227 (27.1) | 211 (27.4) | 16 (23.9) | ||
1 | 292 (34.8) | 265 (34.4) | 27 (40.3) | ||
2 | 193 (23.0) | 179 (23.2) | 14 (20.9) | ||
>3 | 126(15.0) | 116 (15.0) | 10 (14.9) | ||
Diabetes mellitus | presence | 313 (37.4) | 292 (37.9) | 21 (31.3) | 0.37 |
Hypertension | presence | 332 (39.6) | 302 (39.2) | 30 (44.8) | 0.36 |
Cerebrovascular disease | presence | 30 (3.6) | 28 (3.6) | 2 (3.0) | 0.99 |
Coronary artery disease | presence | 52 (6.2) | 46 (6.0) | 6 (9.0) | 0.29 |
Arrhythmia | presence | 13 (1.6) | 12 (1.6) | 1 (1.5) | 0.99 |
Tumor site | 0.12 | ||||
head | 343 (40.9) | 320 (41.5) | 23 (34.3) | ||
body | 148 (17.7) | 140 (18.2) | 8 (11.9) | ||
tail | 171 (20.4) | 156 (20.2) | 15 (22.4) | ||
overlapping | 176 (21.0) | 155 (20.1) | 21 (31.3) | ||
Tumor stage, seventh AJCC | 0.35 | ||||
III | 183 (21.8) | 172 (22.3) | 11 (16.4) | ||
IV | 655 (78.2) | 599 (77.7) | 56 (83.6) | ||
Tumor grade | 0.53 | ||||
well to moderate differentiation | 93 (11.1) | 83 (10.8) | 10 (14.9) | ||
poorly differentiation | 92 (11.0) | 86 (11.2) | 6 (9) | ||
unclassified or unknown | 653 (77.9) | 602 (78.1) | 51 (76.1) | ||
Jaundice under drainage | presence | 272 (32.5) | 248 (32.2) | 24 (32.2) | 0.59 |
Metastatic organ | liver | 438 (52.3) | 394 (51.1) | 44 (65.7) | 0.03 |
peritoneum | 239 (28.5) | 222 (28.8) | 17 (25.4) | 0.67 | |
lymph nodes | 150 (17.9) | 138 (17.9) | 12 (17.9) | 0.99 | |
lung | 98 (11.7) | 88 (11.4) | 10 (14.9) | 0.43 | |
CEA, ng/mL | >5 | 427 (51.0) | 387 (50.2) | 40 (59.7) | 0.16 |
CA19-9, u/mL | >37 | 666 (79.5) | 610 (79.1) | 56 (83.6) | 0.43 |
Platelet count, 109/L | >350 | 86 (10.3) | 81 (10.5) | 5 (7.5) | 0.53 |
Hemoglobin, g/dL | >10 | 734 (87.6) | 674 (87.4) | 60 (89.6) | 0.70 |
Leukocyte count, 109/L | >11 | 167 (19.9) | 146 (18.9) | 21 (31.3) | 0.024 |
Chemotherapy regimen had been exposure | Gemcitabine | 792 (94.5) | 726 (94.2) | 66 (98.5) | 0.17 |
5-FU or S-1 | 592 (70.6) | 540 (70.0) | 52 (77.6) | 0.45 | |
Platinum | 433 (51.7) | 401 (51.9) | 32 (48.5) | 0.61 | |
Khorana risk score | 0.33 | ||||
2 | 60 (7.2) | 56 (7.3) | 4 (6.0) | ||
3 | 591 (70.5) | 549 (71.2) | 42 (62.7) | ||
4 | 162 (19.3) | 144 (18.7) | 18 (26.9) | ||
5 | 25 (3.0) | 22 (2.9) | 3 (4.5) |
Location of thrombosis | n | % |
---|---|---|
DVT, lower limb | 34 | 50.7% |
DVT, upper limb | 7 | 10.4% |
PE | 14 | 20.9% |
Concomitant DVT and PE | 8 | 11.9% |
Concomitant DVT and IVC thrombosis | 2 | 3.0% |
Concomitant upper and lower limb DVT | 1 | 1.5% |
Concomitant lower limb DVT and PVT | 1 | 1.5% |
Clinical Factors | Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
HR | SE | 95% CI | p | HR | 95% CI | p | |
Clinical characteristics | |||||||
Male (vs. female) | 1.20 | 0.25 | 0.73–1.98 | 0.48 | |||
Age > 65 years (vs. ≤ 65 years) | 0.83 | 0.26 | 0.50–1.39 | 0.49 | |||
Presence of hypertension (vs. no hypertension) | 1.26 | 0.26 | 0.76–2.08 | 0.37 | |||
Presence of diabetes mellitus (vs. no diabetes mellitus) | 0.75 | 0.27 | 0.44–1.28 | 0.29 | |||
Presence of coronary artery disease (vs. no coronary artery disease) | 1.55 | 0.45 | 0.64–3.78 | 0.33 | |||
Presence of cerebrovascular disease (vs. no cerebrovascular disease) | 0.82 | 0.74 | 0.19–3.50 | 0.79 | |||
ECOG PS 0–1 (vs. > 1) | 0.70 | 0.30 | 0.38–1.26 | 0.23 | |||
CCI 0 (vs. > 0) | 1.20 | 0.30 | 0.67–2.15 | 0.54 | |||
BMI > 23 kg/m2 (≤23 kg/m2) | 1.06 | 0.26 | 0.64–1.75 | 0.82 | |||
Tumor characteristics | |||||||
Tumor site at pancreatic head (vs. other sites) | 0.74 | 0.27 | 0.44–1.24 | 0.25 | |||
Presence of jaundice under drainage (vs. no jaundice) | 1.18 | 0.27 | 0.70–1.98 | 0.54 | |||
Stage IV disease (vs. stage III) | 1.46 | 0.34 | 0.75–2.85 | 0.27 | |||
Presence of liver metastases (vs. no liver metastases) | 1.83 | 0.27 | 1.08–3.09 | 0.024 | 1.65 | 1.03–3.99 | 0.046 |
Presence of peritoneal metastases (vs. no peritoneal metastases) | 0.84 | 0.29 | 0.48–1.49 | 0.55 | |||
Presence of lung metastases (vs. no lung metastases) | 1.36 | 0.36 | 0.67–2.76 | 0.39 | |||
Presence of distant lymph nodes metastases (vs. no distant lymph node metastases) | 1.01 | 0.33 | 0.52–1.92 | 0.99 | |||
Biological data | |||||||
CEA > 5 ng/mL (vs. < 5 ng/mL) | 1.47 | 0.26 | 0.88–2.44 | 0.14 | 1.27 | 0.75–2.14 | 0.37 |
CA19-9 > 37 u/mL (≤37 u/mL) | 1.34 | 0.34 | 0.69–2.62 | 0.39 | |||
Platelet count > 350 × 109/L (vs. ≤ 350 × 109/L) | 0.69 | 0.48 | 0.27–1.76 | 0.43 | |||
Hemoglobin > 10 g/dL (vs. ≤ 10 g/dL) | 1.23 | 0.41 | 0.55–2.78 | 0.61 | |||
Leukocyte count > 11,000/μL (vs. ≤ 11,000/μL) | 1.95 | 0.28 | 1.13–3.38 | 0.016 | 1.75 | 1.07–3.03 | 0.032 |
Use of anticancer drugs | |||||||
Chemotherapy with platinum (vs. without platinum) | 0.90 | 0.26 | 0.55–1.48 | 0.68 | |||
Chemotherapy with gemcitabine (vs. without gemcitabine) | 4.09 | 1.02 | 0.56–30.2 | 0.17 | 4.27 | 0.58–21.0 | 0.16 |
Chemotherapy with 5-FU or S-1 (vs. without 5-FU or S-1) | 1.21 | 0.27 | 0.72–2.03 | 0.48 | |||
Khorana risk score 4–5 (vs. score 2–3) | 1.66 | 0.28 | 0.97–2.87 | 0.067 | 1.12 | 0.36–2.64 | 0.66 |
Khorana Risk Score | Overall, n = 838 | 2, n = 60 | 3, n = 591 | 4, n = 162 | 5, n = 25 |
---|---|---|---|---|---|
Venous thromboembolism, n | 67 | 4 | 42 | 18 | 3 |
Person-years | 676.9 | 39.2 | 510.7 | 113.8 | 13.2 |
Incidence rate, per 1000 person-years | 99.0 | 102.0 | 82.2 | 158.2 | 227.3 |
Crude HR (95% CI) | 1 | 0.90 (0.32–2.50) | 1.73 (0.59–5.12) | 2.24 (0.50–10.0) | |
Adjusted HR* (95% CI) | 1 | 0.97 (0.35–2.70) | 1.20 (0.31–4.67) | 1.23(0.21–7.19) |
Clinical Factor | Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
HR | SE | 95% CI | p | HR | 95% CI | p | |
Clinical characteristics | |||||||
Male (vs. female) | 1.31 | 0.08 | 1.13–1.52 | <0.001 | 1.27 | 1.09–1.47 | 0.002 |
Age > 65 years (vs. age ≤ 65) | 1.21 | 0.07 | 1.05–1.40 | 0.011 | 1.07 | 0.91–1.25 | 0.41 |
ECOG PS 0–1 (vs. ECOG PS >1) | 0.37 | 0.08 | 0.31–0.43 | <0.001 | 1.78 | 1.48–2.14 | <0.001 |
CCI 0 (vs. CCI > 0) | 0.66 | 0.08 | 0.56–0.78 | <0.001 | 1.37 | 1.15–1.63 | <0.001 |
BMI > 23 kg/m2 (vs. ≤ 23 kg/m2) | 0.93 | 0.07 | 0.81–1.08 | 0.33 | |||
Tumor characteristics | |||||||
Tumor site at pancreatic head (vs. other sites) | 1.07 | 0.07 | 0.93–1.24 | 0.35 | |||
Presence of jaundice under drainage (vs. no jaundice) | 1.11 | 0.08 | 0.95–1.29 | 0.21 | |||
Stage IV disease (vs. stage III) | 1.99 | 0.09 | 1.66–2.40 | <0.001 | 2.04 | 1.69–2.46 | <0.001 |
Biological data | |||||||
CEA > 5 ng/mL (vs. ≤ 5 ng/mL) | 1.28 | 0.07 | 1.11–1.48 | 0.001 | 1.10 | 0.95–1.28 | 0.21 |
CA19-9 > 37 u/mL (vs. ≤ 37 u/mL) | 1.06 | 0.09 | 0.88–1.26 | 0.56 | |||
Platelet count > 350 × 109/L (vs. ≤ 350 × 109/L) | 1.09 | 0.09 | 0.87–1.40 | 0.44 | |||
Hemoglobin > 10 g/dL (vs. ≤ 10 g/dL) | 0.64 | 0.11 | 0.51–0.79 | <0.001 | 1.15 | 0.92–1.45 | 0.22 |
Leukocyte count > 11,000/μL (vs. ≤ 11,000/μL) | 1.69 | 0.09 | 1.41–2.01 | <0.001 | 1.24 | 1.03–1.49 | 0.02 |
Use of anticancer drugs | |||||||
Chemotherapy with platinum (vs. without platinum) | 0.62 | 0.07 | 0.53–0.71 | <0.001 | 1.42 | 1.21–1.66 | <0.001 |
Chemotherapy with gemcitabine (vs. without gemcitabine) | 0.50 | 0.16 | 0.37–0.68 | <0.001 | 2.22 | 1.59–3.10 | <0.001 |
Chemotherapy with 5-FU or S-1 (vs. without 5-FU or S-1) | 0.44 | 0.08 | 0.38–0.51 | <0.001 | 1.93 | 1.64–2.27 | <0.001 |
Occurrence of VTE | |||||||
Occurrence of any VTE (vs. no VTE) | 1.15 | 0.13 | 0.89–1.50 | 0.29 | |||
Early onset of venous thromboembolism (vs. no VTE) | 4.86 | 0.24 | 3.02–7.80 | <0.001 | 3.80 | 2.34–6.18 | <0.001 |
Late onset of venous thrombosis (vs. no VTE) | 0.88 | 0.16 | 0.64–1.91 | 0.39 |
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Chen, J.-S.; Hung, C.-Y.; Chang, H.; Liu, C.-T.; Chen, Y.-Y.; Lu, C.-H.; Chang, P.-H.; Hung, Y.-S.; Chou, W.-C. Venous Thromboembolism in Asian Patients with Pancreatic Cancer Following Palliative Chemotherapy: Low Incidence but a Negative Prognosticator for Those with Early Onset. Cancers 2018, 10, 501. https://doi.org/10.3390/cancers10120501
Chen J-S, Hung C-Y, Chang H, Liu C-T, Chen Y-Y, Lu C-H, Chang P-H, Hung Y-S, Chou W-C. Venous Thromboembolism in Asian Patients with Pancreatic Cancer Following Palliative Chemotherapy: Low Incidence but a Negative Prognosticator for Those with Early Onset. Cancers. 2018; 10(12):501. https://doi.org/10.3390/cancers10120501
Chicago/Turabian StyleChen, Jen-Shi, Chia-Yen Hung, Hung Chang, Chien-Ting Liu, Yen-Yang Chen, Chang-Hsien Lu, Pei-Hung Chang, Yu-Shin Hung, and Wen-Chi Chou. 2018. "Venous Thromboembolism in Asian Patients with Pancreatic Cancer Following Palliative Chemotherapy: Low Incidence but a Negative Prognosticator for Those with Early Onset" Cancers 10, no. 12: 501. https://doi.org/10.3390/cancers10120501