Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Characteristics of Patients and Response to Nivolumab
2.2. Difference between the Patients With or Without Disease-Control
2.3. Univariate and Multivariate Logistic Regression
2.4. Predictive Value of Serum NLR and PG-SGA
2.5. Progression-Free Survival in Nivolumab-Treated Patients
2.6. Immune-Related Adverse Effect (irAE) Profiles
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Nivolumab Administration
4.3. Assessment of Responses to Treatment
4.4. Clinical Profiles
4.5. Neutrophil-to-Lymphocyte Ratio
4.6. Clinical Benefits of Treatment
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Factors | n = 45 (100%) |
---|---|
Baseline conditions | |
Age (years) | 61.8 ± 9.6 |
Gender (Male) | 41 (91.1%) |
CTP score | 5.3 ± 0.6 |
ALBI score | −2.49 ± 0.39 |
Thrombocytopenia | 11 (24.4%) |
EV | 7 (15.6%) |
Ascites | 10 (22.2%) |
Cirrhosis | 41 (91.1%) |
ECOG-PS (0/1/2) | 35/9/1 |
Viral hepatitis | 38 (84.4%) |
Alcohol consumption | 8 (17.8%) |
PG-SGA score | 3.8 ± 2.9 |
Tumor-associated factors | |
Maximum tumor diameter (cm) | 7.2 ± 4.2 |
Total tumor volume (cm3) | 619.0 ± 831.1 |
Alpha-fetoprotein (ng/mL) | 82,584.2 ± 499,364.2 |
T stage (2/3/4) | 13/12/20 (28.9/26.7/44.4%) |
N stage (1) | 10 (22.2%) |
M stage (1) | 22 (48.9%) |
PVT | 19 (42.2%) |
Serum NLR | 4.0 ± 2.2 |
Medical treatment | |
Anti-viral agent | 22 (48.9%) |
Previous history of hepatectomy | 19 (42.2%) |
Previous Sorafenib | 45 (100.0%) |
Period between diagnosis and ICI (months) | 37.0 ± 32.5 |
Early drop-out of ICI treatment | 11 (24.4%) |
Response to ICI (PR/SD/PD) | 3/11/31 (6.7/24.4/68.9%) |
Factors | PR + SD (n = 14) | PD (n = 31) | p-Value |
---|---|---|---|
Age (years) | 65.2 ± 10.2 | 60.3 ± 9.1 | 0.117 |
Gender (Male) | 14 (100.0%) | 27 (87.1%) | 0.159 |
WBC (×109/L) | 6.1 ± 2.0 | 5.7 ± 2.2 | 0.571 |
Platelet(×103/μL) | 168.6 ± 76.3 | 193.4 ± 149.3 | 0.558 |
INR | 1.1 ± 0.1 | 1.2 ± 0.1 | 0.163 |
NLR | 2.9 ± 1.3 | 4.4 ± 2.3 | 0.028 |
PLR | 123.7 ± 65.4 | 190.7 ± 118.6 | 0.185 |
Creatinine (mg/dL) | 1.0 ± 0.2 | 0.9 ± 0.6 | 0.734 |
Total bilirubin (mg/dL) | 0.7 ± 0.3 | 0.9 ± 0.5 | 0.184 |
AST (U/L) | 62.3 ± 30.5 | 82.7 ± 54.7 | 0.200 |
ALT (U/L) | 48.1 ± 29.2 | 63.5 ± 49.9 | 0.291 |
Albumin (g/dL) | 4.0 ± 0.4 | 3.7 ± 0.4 | 0.059 |
CTP class (A/B) | 14/0 (100.0/0.0%) | 29/2 (93.5/6.5%) | 0.331 |
ALBI score | −2.7 ± 0.3 | −2.4 ± 0.4 | 0.042 |
EV | 3 (21.4%) | 4 (12.9%) | 0.465 |
Ascites | 2 (14.3%) | 8 (25.8%) | 0.389 |
Cirrhosis | 11 (78.6%) | 30 (96.8%) | 0.047 |
ECOG-PS (0/1/2) | 12/2/0 (85.7/14.3/0.0%) | 23/7/1 (74.2/22.6/0.3%) | 0.623 |
Viral hepatitis (Yes) | 12 (85.7%) | 26 (83%) | 0.874 |
Alcohol use (Yes) | 3 (21.4%) | 5 (16.1%) | 0.667 |
PG-SGA score | 2.3 ± 0.7 | 4.7 ± 3.2 | 0.003 |
AFP (ng/mL) | 3540.9 ± 5481.5 | 118281.2 ± 601217.5 | 0.482 |
Max. tumor diameter (cm) | 5.6 ± 3.7 | 8.0 ± 4.3 | 0.091 |
Total tumor volume (cm3) | 397.2 ± 659.3 | 719.1 ± 889.6 | 0.233 |
T (2/3/4) | 6/5/3 (42.9/35.7/21.4%) | 7/7/17 (22.6/22.6/54.8%) | 0.110 |
N (1) | 2 (11.1%) | 8 (27.3%) | 0.389 |
M (1) | 7 (50.0%) | 15 (48.4%) | 0.920 |
PVT | 4 (28.6%) | 15 (48.4%) | 0.213 |
Anti-viral agent | 8 (57.1%) | 14 (45.2%) | 0.457 |
Period between diagnosis and IC (months) | 35.4 ± 43.2 | 37.8 ± 27.1 | 0.822 |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
HR | 95%CI | p-Value | HR | 95%CI | p-Value | |
Serum NLR | 2.07 | 1.10–3.90 | 0.025 | 2.04 | 1.10–3.80 | 0.025 |
Max. tumor size | 1.17 | 0.97–1.40 | 0.099 | |||
ALBI score | 6.11 | 1.01–37.23 | 0.050 | |||
Cirrhosis | 8.18 | 0.77–87.20 | 0.082 | |||
PG-SGA score | 2.02 | 1.08–3.80 | 0.029 | 2.30 | 1.04–5.09 | 0.039 |
Category | Total (n = 45) | Patients, N (%) a Grade 1–2 | Grade 3–4 c | Grade 5 b | Weeks to Onset Median (Range) |
---|---|---|---|---|---|
Any | 29 (64.4) | 17 (37.7) | 11 (24.4) | 1 (2.2) | |
Skin | 13 (28.9) | 13 (28.9) | 0 (0.0) | 0 (0.0) | 3.1 (0.6–7.6) |
Rash | 6 (13.3) | 6 (13.3) | 0 (0.0) | 0 (0.0) | |
Pruritus | 9 (20.0) | 9 (20.0) | 0 (0.0) | 0 (0.0) | |
Pneumonitis | 4 (8.9) | 1 (2.2) | 3 (6.7) | 0 (0.0) | 8.3 (2.0–12.0) |
Endocrine | 1 (2.2) | 1 (2.2) | 0 (0.0) | 0 (0.0) | 6.0 (NA) |
Thyroditis/hypothyroidism | 1 (2.2) | 1 (2.2) | 0 (0.0) | 0 (0.0) | |
Hypophysitis | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Gastrointestinal | 7 (15.6) | 6 (13.3) | 1 (2.2) | 0 (0.0) | 7.6 (0.6–8.9) |
Mucositis | 2 (4.4) | 2(4.4) | 0 (0.0) | 0 (0.0) | |
Esophagitis | 1 (2.2) | 1 (2.2) | 0 (0.0) | 0 (0.0) | |
Diarrhea/colitis | 5 (11.1) | 4 (8.9) | 1 (2.2) | 0 (0.0) | |
Hepatobiliary | 11 (24.4) | 2(4.4) | 9 (20.0) | 0 (0.0) | 4.6 (1.0–14.6) |
Hepatitis | 9 (20.0) | 2(4.4) | 6 (13.3) | 1 (2.2) | |
Cholangitis | 4 (8.9) | 0 (0.0) | 4 (8.9) | 0 (0.0) | |
Others | 12 (26.7) | 15 (33.3) | 0 (0.0) | 0 (0.0) | 4.3 (1.0–10.3) |
Fatigue | 7 (15.6) | 6 (13.3) | 1 (2.2) | 0 (0.0) | |
Anorexia | 7 (15.6) | 7 (15.6) | 0 (0.0) | 0 (0.0) | |
Polyarthritis | 1(2.2) | 1 (2.2) | 0 (0.0) | 0 (0.0) |
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Hung, H.-C.; Lee, J.-C.; Wang, Y.-C.; Cheng, C.-H.; Wu, T.-H.; Lee, C.-F.; Wu, T.-J.; Chou, H.-S.; Chan, K.-M.; Lee, W.-C. Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma. Cancers 2021, 13, 1607. https://doi.org/10.3390/cancers13071607
Hung H-C, Lee J-C, Wang Y-C, Cheng C-H, Wu T-H, Lee C-F, Wu T-J, Chou H-S, Chan K-M, Lee W-C. Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma. Cancers. 2021; 13(7):1607. https://doi.org/10.3390/cancers13071607
Chicago/Turabian StyleHung, Hao-Chien, Jin-Chiao Lee, Yu-Chao Wang, Chih-Hsien Cheng, Tsung-Han Wu, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou, Kun-Ming Chan, and Wei-Chen Lee. 2021. "Response Prediction in Immune Checkpoint Inhibitor Immunotherapy for Advanced Hepatocellular Carcinoma" Cancers 13, no. 7: 1607. https://doi.org/10.3390/cancers13071607