Safety and Efficacy of Transarterial Chemoembolization in Elderly Patients with Intermediate Hepatocellular Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. Patient Selection
2.2. Elderly Definition
2.3. TACE Procedure
2.4. Ethical Approval
2.5. Data Collection and Safety Assessment
- -
- Migration to ECOG performance status of 3 or 4 after TACE;
- -
- Liver decompensation after TACE, defined by the occurrence of ascites and/or hepatic encephalopathy (EH) (early and/or delayed) and/or a grade C Child–Pugh score after TACE;
- -
- TACE-related death.
2.6. Efficacy Outcomes Analyses
3. Statistical Analysis
4. Results
4.1. Description of the Population
4.2. Safety Analyses
4.2.1. Early Adverse Events
4.2.2. Delayed Adverse Events
4.2.3. Serious Adverse Events
5. Predictive Factors of Serious Adverse Events
6. Sensitivity Analysis According to Age Threshold
7. Objective Tumor Response and Survival Outcomes
8. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical and Biological Data | Age < 70 | Age ≥ 70 | Overall Cohort | p-Value |
---|---|---|---|---|
Male * | 171 (93.4) | 78 (88.6) | 249 (91.9) | 0.17 |
Median Age (years) § | 62 (56–65) | 75 (71.5–79) | 65 (58–71) | <0.01 |
BMI (kg/m2) § | 27.1 (24.2–29.7) | 25.5 (24.2–28.8) | 26.6 (24.2–29.4) | 0.16 |
Presence of comorbidities * | ||||
Arterial hypertension | 92 (50.3) | 56 (63.6) | 148 (54.6) | 0.04 |
Cardiovascular diseases | 32 (17.5) | 26 (29.5) | 58 (21.4) | 0.02 |
Smoking | 138 (78.4) | 60 (76) | 128 (77.7) | <0.01 |
SAS | 24 (13.1) | 9 (10.2) | 33 (12.1) | 0.78 |
Chronic respiratory diseases | 14 (7.7) | 7 (8) | 21 (7.7) | 0.93 |
CKD | 14 (7.7) | 14 (15.9) | 28 (10.3) | 0.04 |
Diabetes | 72 (39.3) | 41 (46.6) | 113 (41.7) | 0.26 |
History of extrahepatic cancer * | 19 (10.4) | 23 (26.1) | 42 (15.5) | <0.01 |
Chronic liver disease etiology * | ||||
Alcohol | 135 (73.8) | 48 (54.5) | 183 (67.5) | <0.01 |
NASH | 59 (32.2) | 41 (46.6) | 100 (36.9) | 0.02 |
Chronic viral hepatitis | 66 (36.1) | 14 (15.9) | 80 (29.5) | <0.01 |
Other | 6 (3.3) | 8 (9.1) | 14 (5.2) | 0.04 |
Presence of cirrhosis * | 168 (91.8) | 63 (71.6) | 231 (85.2) | <0.01 |
History of liver decompensation * | 67 (36.6) | 19 (21.6) | 86 (31.7) | 0.01 |
ECOG grade * | ||||
0 | 147 (80.3) | 57 (64.8) | 204 (75.3) | <0.01 |
1 | 35 (19.1) | 26 (29.5) | 61 (22.5) | |
2 | 1 (0.5) | 5 (5.7) | 6 (2.2) | |
MELD § | 10 (8,12) | 9 (8,10) | 9 (8,11) | 0.13 |
Child–Pugh class * | ||||
A | 121 (72.4) | 55 (88.7) | 176 (76.9) | 0.10 |
B | 42 (25.2) | 7 (11.3) | 49 (21.4) | |
C | 4 (2.4) | 0 (0) | 4 (1.7) | |
Ascites * | 16 (8.7) | 4 (4.5) | 20 (7.4) | 0.22 |
Encephalopathy * | 4 (2.2) | 0 (0) | 4 (1.5) | 0.16 |
Albumin (g/l) § | 36 (31–41) | 38 (34–41) | 37 (32–41) | 0.03 |
PT (%) § | 78 (64–87) | 81 (72–93) | 79 (67–89.5) | <0.01 |
Total bilirubin (mol/l) § | 16 (10–25.5) | 12 (9–17) | 15 (9–22) | <0.01 |
HCC Characteristics | ||||
Single tumor * | 44 (24) | 23 (26.1) | 67 (24.7) | 0.71 |
Multiple tumors * | 139 (76) | 65 (73.9) | 204 (75.3) | |
Median number of tumors § | 3 (2–4) | 3 (1.5–5) | 3 (2–4) | 0.93 |
Median size of largest nodule (mm) § | 30 (20–50) | 41 (28–63) | 35 (24–51) | <0.01 |
Median tumor volume (mm) § | 58 (36–85) | 80 (44–110) | 60.5 (41–90) | <0.01 |
Partial portal thrombosis * | 13 (7.1) | 4 (4.5) | 17 (6.3) | 0.42 |
Median AFP (ng/mL) § | 13.1 (5–55) | 7.9 (4.3–80.6) | 12.5 (5–56.2) | 0.43 |
BCLC * | ||||
A | 71 (38.8) | 23 (26.1) | 94 (34.7) | 0.06 |
B | 97 (53) | 50 (56.8) | 147 (54.2) | |
C | 15 (8.2) | 15 (17) | 30 (11.1) | |
TACE Characteristics | ||||
Global * | 106 (57.9) | 50 (57.5) | 156 (57.8) | 0.94 |
Selective * | 77 (42.1) | 37 (42.5) | 114 (42.2) | |
Conventional TACE * | 174 (95.6) | 75 (86.2) | 249 (92.6) | <0.01 |
Drug-eluting beads TACE * | 8 (4.4) | 12 (13.8) | 20 (7.4) | |
Previous Treatments | ||||
Surgical resection * | 23 (12.6) | 12 (13.6) | 35 (12.9) | 0.81 |
Radiofrequency ablation * | 18 (9.8) | 14 (15.9) | 32 (11.8) | 0.15 |
Post TACE Treatments | ||||
Median TACE number * | 2 (1–3) | 2 (1–3) | 2 (1–3) | 0.32 |
Liver transplantation * | 58 (31.7) | 0 (0) | 58 (21.4) | <0.01 |
Surgical resection * | 5 (2.7) | 3 (3.4) | 8 (3.0) | 0.76 |
Radiofrequency ablation * | 37 (20.2) | 14 (15.9) | 51 (18.8) | 0.40 |
Systemic therapy * | 43 (23.5) | 28 (31.8) | 71 (26.2) | 0.14 |
SIRT * | 9 (4.9) | 3 (3.4) | 12 (4.4) | 0.57 |
Early Adverse Events | <70 | ≥70 | Overall Cohort | p-Value |
---|---|---|---|---|
Post-embolization syndrome * | 117 (63.9) | 57 (64.8) | 174 (64.2) | 0.89 |
Fever * | 52 (28.4) | 28 (31.8) | 80 (29.5) | 0.57 |
Abdominal pain * | 117 (63.9) | 56 (63.6) | 173 (63.8) | 0.96 |
Nausea/vomiting * | 30 (16.4) | 17 (19.3) | 47 (17.3) | 0.55 |
Fatigue * | 29 (15.8) | 14 (15.9) | 43 (15.9) | 0.99 |
Post-puncture hematoma * | 1 (0.5) | 4 (4.5) | 5 (1.8) | 0.02 |
Arterial complications * | 8 (4.4) | 2 (2.3) | 10 (3.7) | 0.39 |
Ischemic gastro-duodenal ulcer * | 1 (0.5) | 2 (2.3) | 3 (1.1) | 0.20 |
Ischemic cholecystitis * | 11 (6) | 6 (6.8) | 17 (6.3) | 0.80 |
Ischemic pancreatitis * | 3 (1.6) | 0 (0) | 3 (1.1) | 0.23 |
Venous thromboembolic events * | 2 (1.1) | 0 (0) | 2 (0.7) | 0.32 |
Diaphragmatic paralysis * | 2 (1.1) | 0 (0) | 2 (0.7) | 0.32 |
Bacterial infection * | 8 (4.4) | 7 (8) | 15 (5.5) | 0.23 |
AKI * | 7 (3.8) | 7 (8) | 14 (5.2) | 0.15 |
AUR * | 5 (2.7) | 8 (9.1) | 13 (4.8) | 0.02 |
Cardiac decompensation * | 12 (6.6) | 9 (10.2) | 21 (7.7) | 0.29 |
Diabetes decompensation * | 17 (9.3) | 12 (13.6) | 29 (10.7) | 0.28 |
Other metabolic disorders * | 2 (1.1) | 2 (2.3) | 4 (1.5) | 0.45 |
Ascites * | 10 (5.5) | 2 (2.3) | 12 (4.4) | 0.23 |
Encephalopathy * | 18 (9.8) | 8 (9.1) | 26 (9.6) | 0.85 |
Total bilirubin(mol/l) § | 30.5 (22, 51) | 22 (16, 30) | 27 (19, 44) | <0.01 |
PT (%) § | 63.5 (52, 76) | 72 (61, 81) | 66 (56, 78) | <0.01 |
Death * | 1 (0.5) | 1 (1.1) | 2 (0.7) | 0.60 |
Hospital stay (days) § | 5 (4, 7) | 4.5 (4, 7) | 5 (4, 7) | 0.60 |
Extension of hospitalization * | 97 (53) | 44 (50) | 141 (52) | 0.64 |
Early global complications * | 155 (84.7) | 75 (85.2) | 230 (84.9) | 0.91 |
Delayed Adverse Events, n (%) | <70 | ≥70 | Overall Cohort | p-Value |
---|---|---|---|---|
Post-embolization syndrome * | 13 (7.3) | 8 (9.4) | 21 (8) | 0.55 |
Fever * | 11 (6.1) | 8 (9.4) | 19 (7.2) | 0.34 |
Abdominal pain * | 25 (14) | 10 (11.8) | 35 (13.3) | 0.62 |
Nausea/vomiting * | 9 (5) | 3 (3.5) | 12 (4.5) | 0.58 |
Fatigue * | 44 (24.4) | 34 (40) | 78 (29.4) | 0.01 |
Arterial complications * | 10 (5.6) | 2 (2.4) | 12 (4.5) | 0.24 |
Ischemic gastro-duodenal ulcer * | 1 (0.6) | 1 (1.2) | 2 (0.8) | 0.59 |
Ischemic cholecystitis * | 6 (3.3) | 0 (0) | 6 (2.3) | 0.09 |
Ischemic pancreatitis * | 3 (1.7) | 1 (1.2) | 4 (1.5) | 0.76 |
Venous thromboembolic events * | 2 (1.1) | 0 (0) | 2 (0.8) | 0.33 |
Diaphragmatic paralysis * | 2 (1.1) | 0 (0) | 2 (0.8) | 0.33 |
Bacterial infection * | 8 (4.4) | 7 (8.2) | 15 (5.7) | 0.21 |
AKI * | 10 (5.6) | 5 (5.9) | 15 (5.7) | 0.91 |
AUR * | 2 (1.1) | 0 (0) | 2 (0.8) | 0.33 |
Cardiac decompensation * | 3 (1.7) | 3 (3.5) | 6 (2.3) | 0.34 |
Diabetes decompensation * | 4 (2.2) | 0 (0) | 4 (1.5) | 0.17 |
Other metabolic disorders * | 2 (1.1) | 1 (1.2) | 3 (1.1) | 0.96 |
Ascites * | 17 (9.4) | 9 (10.6) | 26 (9.8) | 0.77 |
Encephalopathy * | 9 (5) | 0 (0) | 9 (3.4) | 0.04 |
Post-TACE Child–Pugh class * | 0.83 | |||
A B C | 104 (68.8) | 35 (77.8) | 139 (70.9) | |
35 (23.3) | 7 (15.5) | 42 (21.4) | ||
12 (7.9) | 3 (6.6) | 15 (7.7) | ||
Post-TACE Child–Pugh score shift § | 0 (0; 1) | 0 (0; 1) | 0 (0; 1) | 1 |
Death * | 4 (2.2) | 0 (0) | 4 (1.5) | 0.16 |
Rehospitalization * | 33 (18.3) | 10 (11.8) | 43 (16.2) | 0.18 |
Global delayed complications * | 72 (40) | 43 (50.6) | 115 (43.4) | 0.10 |
Overall Adverse Events | ||||
Overall AEs (early + delayed) * | 158 (86.3) | 79 (89.8) | 237 (87.5) | 0.42 |
Overall serious adverse events * | 39 (21.3) | 18 (20.5) | 57 (21) | 0.87 |
Overall liver decompensations * | 39 (21.3) | 17 (19.3) | 56 (20.7) | 0.70 |
Overall serious deterioration in general condition * | 5 (2.8) | 2 (2.4) | 7 (2.6) | 0.84 |
Total deaths * | 5 (2.7) | 1 (1.1) | 6 (2.2) | 0.40 |
Univariate Analyses | OR | 95% CI | p-Value | |
---|---|---|---|---|
Age | Age ≥ 70 | 0.949 | (0.507, 1.778) | 0.8712 |
Age ≥ 75 | 1.511 | (0.738, 3.095) | 0.2591 | |
Age ≥ 80 | 1.001 | (0.319, 3.143) | 0.9983 | |
Gender | Women | 1.114 | (0.393, 3.162) | 0.8389 |
BMI | BMI ≥ 26.5 | 0.763 | (0.424, 1.372) | 0.3666 |
Arterial hypertension | 0.756 | (0.421, 1.358) | 0.3496 | |
Cardiovascular diseases | 0.736 | (0.346, 1.565) | 0.4254 | |
Smoking | 1.480 | (0.673, 3.254) | 0.3299 | |
SAS | 0.481 | (0.162, 1.431) | 0.1884 | |
Chronic respiratory diseases | 0.875 | (0.282, 2.709) | 0.8163 | |
CKD | 1.287 | (0.518, 3.197) | 0.5873 | |
Diabetes | 0.774 | (0.424, 1.413) | 0.4035 | |
History of extrahepatic cancer | 0.716 | (0.3, 1.709) | 0.4517 | |
Cirrhosis | 1.606 | (0.639, 4.037) | 0.3141 | |
Alcohol | 2.065 | (1.03, 4.141) | 0.0410 | |
NASH | 0.743 | (0.399, 1.385) | 0.3498 | |
Chronic viral hepatitis | 1.387 | (0.746, 2.58) | 0.3009 | |
Other causes | 2.190 | (0.704, 6.813) | 0.1757 | |
History of liver decompensation | 3.793 | (2.066, 6.961) | <0.0001 | |
ECOG grade | ≥1 | 3.199 | (1.717, 5.962) | 0.0003 |
MELD | ≥9 | 3.804 | (1.745, 8.294) | 0.0008 |
Child–Pugh | A | 0.152 | (0.076, 0.303) | <0.0001 |
Tumor morphology | Monofocal | 1.729 | (0.914, 3.271) | 0.0923 |
Number of nodules | ≥3 | 1.396 | (0.768, 2.535) | 0.2739 |
Size of largest nodule (mm) | ≥35 | 0.981 | (0.545, 1.768) | 0.9504 |
Location | Unilobar | 1.080 | (0.602, 1.938) | 0.7958 |
Partial portal thrombosis | 1.619 | (0.546, 4.799) | 0.3852 | |
AFP (ng/mL) | ≥12.5 | 1.399 | (0.76, 2.576) | 0.2804 |
BCLC | ≥B | 2.061 | (1.047, 4.059) | 0.0364 |
Previous treatments | 0.875 | (0.43, 1.781) | 0.7121 | |
Area treated | Global | 0.736 | (0.408, 1.329) | 0.3088 |
Type of TACE | c-TACE | 1.532 | (0.433, 5.426) | 0.5082 |
Embolization of accessory tumor vasculature | Diaphragmatic arteries | 0.638 | (0.211, 1.927) | 0.4253 |
Mammary artery | 1.000 | (1, 1) | 0.9998 | |
Other artery | 1.673 | (0.418, 6.693) | 0.4669 | |
Chemotherapy | Doxorubicin | 2.921 | (0.857, 9.959) | 0.0867 |
Multivariate Analyses | OR | 95% CI | p-Value | |
Child–Pugh | ≥B | 5.034 | (2.278, 11.126) | <0.0001 |
ECOG grade | ≥1 | 3.556 | (1.6, 7.903) | 0.0019 |
MELD | ≥9 | 2.450 | (1.035, 5.798) | 0.0415 |
Tumor morphology | Multifocal | 0.423 | (0.186, 0.96) | 0.0396 |
Chemotherapy | Idarubicin | 0.177 | (0.036,0.886) | 0.0351 |
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Roth, G.S.; Hernandez, O.; Daabek, N.; Brusset, B.; Teyssier, Y.; Ghelfi, J.; Hilleret, M.N.; Sengel, C.; Bricault, I.; Decaens, T.; et al. Safety and Efficacy of Transarterial Chemoembolization in Elderly Patients with Intermediate Hepatocellular Carcinoma. Cancers 2022, 14, 1634. https://doi.org/10.3390/cancers14071634
Roth GS, Hernandez O, Daabek N, Brusset B, Teyssier Y, Ghelfi J, Hilleret MN, Sengel C, Bricault I, Decaens T, et al. Safety and Efficacy of Transarterial Chemoembolization in Elderly Patients with Intermediate Hepatocellular Carcinoma. Cancers. 2022; 14(7):1634. https://doi.org/10.3390/cancers14071634
Chicago/Turabian StyleRoth, Gael S., Olivier Hernandez, Najeh Daabek, Bleuenn Brusset, Yann Teyssier, Julien Ghelfi, Marie Noelle Hilleret, Christian Sengel, Ivan Bricault, Thomas Decaens, and et al. 2022. "Safety and Efficacy of Transarterial Chemoembolization in Elderly Patients with Intermediate Hepatocellular Carcinoma" Cancers 14, no. 7: 1634. https://doi.org/10.3390/cancers14071634