European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Population
2.2. Treatment and Therapeutic Concept
2.3. Assessment of Hepatic Tumor Response and Survival
2.4. Safety Analysis
2.5. Statistics
3. Results
3.1. Demographics
3.2. Treatment Characteristics
3.3. Survival Analysis
3.4. Response Analysis
3.5. Safety Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Baseline Characteristic | Number of Patients (%) |
---|---|
Cirrhosis | 109 (90%) |
Etiology of cirrhosis | |
Alcohol | 33 (30.3%) |
Viral | 41 (37.6%) |
Mixed | 15 (13.8%) |
Other | 18 (16.5%) |
Unknown | 2 (1.8%) |
Ascites | |
None | 77 (64%) |
Mild | 15 (12%) |
Moderate to severe | 29 (24%) |
Encephalopathy | |
None | 119 (98.3%) |
Grade I–II | 2 (1.7%) |
Disease extent | |
Bilobar | 77 (63.6%) |
Unilobar | 44 (36.4%) |
Number of lesions | |
Uninodular | 17 (14%) |
2–3 nodules | 30 (24.8%) |
Multinodular (>3 nodules) | 74 (61.2%) |
Largest lesion (standard deviation; range) | 4 cm (±4.3; 0.8–24.7 cm) |
Vascular invasion | 32 (26.4%) |
No | 89 (73.6%) |
PVTT (vp1–3) | 28 (23.1%) |
PVTT (vp1–3) + HVTT (vv3) | 1 (0.83%) |
PVTT (vp4) | 1 (0.83%) |
PVTT (vp4) + HVTT (vv2) | 1 (0.83%) |
HVTT (vv2) | 1 (0.83%) |
Limited extrahepatic metastases | 27 (22.3%) |
Child–Pugh-class | |
A | 79 (65.3%) |
B | 37 (30.6) |
C | 5 (4.1%) |
BCLC stage | |
A | 11 (9.1%) |
B | 64 (53.9%) |
C | 43 (35.6%) |
D | 3 (2.5%) |
ECOG | |
0 | 55 (46%) |
1 | 31 (25.6%) |
2 | 7 (5.8%) |
3 | 2 (1.7%) |
Unknown | 26 (21.5%) |
Pretreatment | 61 (50.4%) |
Resection | 19 |
Ablation | 21 |
DEB-TACE a | 21 |
cTACE b | 3 |
Radioembolization c | 19 |
Sorafenib | 20 |
Liver transplantation | 1 |
Radiation therapy | 1 |
Systemic chemotherapy | 1 |
Laboratory Value | Normal Range | ULN > 1 to 2 | ULN > 2 |
---|---|---|---|
INR (0.8–1.2) | 62.8% | 37.2% | - |
Bilirubin (0.1–1.2 mg/dL) | 56.2% | 25% | 18.8% |
Creatinine (0.8–1.2 mg/dL) | 78.1% | 21% | 0.9% |
AST (5–40 IU/L) | 32.7% | 38.5% | 28.9% |
ALT (7–56 IU/L) | 71.4% | 18.5% | 10% |
AP (44–147 IU/L) | 61.2% | 32.8% | 6.1% |
GGT (8–38 IU/L) | 5.1% | 30.3% | 64.7% |
AFP (10–20 ng/mL) | 45.6% | 10.1% | 44.3% |
Univariate Analysis | Multivariate Analysis | ||||||
---|---|---|---|---|---|---|---|
Subgroups | Number of Patients | Median OS in Months (95% CI) | HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Gender | Female | 23 | 20.8 (10.4–33.8) | 0.62 (0.38–1.03) | 0.06 | - | - |
Male | 98 | 14.4 (12.8–17.6) | 1 | - | |||
Ascites | No | 77 | 17.4 (14.3–20.6) | 0.7 (0.47–1.03) | 0.07 | - | - |
Yes | 44 | 13 (8.7–19) | 1 | - | |||
Number of nodules | Uninodular | 30 | 16.9 (9.1–27.9) | 1.47 (0.8–2.7) | 0.39 | - | - |
2–3 nodules | 17 | 13.3 (10.1–26.7) | 1.2 (0.77–1.9) | - | |||
Multinodular | 74 | 17.4 (12.7–19) | 1 | - | |||
Largest liver lesion | ≤5 cm | 72 | 15.5 (12.8–19) | 0.82 (0.55–1.22) | 0.33 | - | - |
>5 cm | 49 | 14.3 (7.6–18.7) | 1 | - | |||
Largest liver lesion | ≤7 cm | 93 | 16.9 (13.3–20.3) | 0.69 (0.44–1.08) | 0.1 | - | |
>7 cm | 28 | 12.7 (7.5–17.7) | 1 | ||||
Largest liver lesion | ≤10 cm | 109 | 16.9 (13.3–19.3) | 0.38 (0.2–0.7) | 0.006 | 0.34 (0.17–0.68) | 0.002 |
>10 cm | 12 | 11.5 (3–17) | 1 | 1 | |||
Lobar involvement | Unilobar | 44 | 19 (14–22.2) | 0.52 (0.33–0.78) | 0.0022 | 0.63 (0.4–0.98) | 0.042 |
Bilobar | 77 | 13.6 (10.9–17.4) | 1 | 1 | |||
Vascular invasion | No | 89 | 16.9 (13.3–19.3) | 0.57 (0.38–0.88) | 0.013 | 0.96 (0.48–1.38) | 0.9 |
Yes | 32 | 13.8 (7.6–18.7) | 1 | 1 | |||
Child–Pugh class a | A | 79 | 17 (13.2–20.6) | 0.23 (0.08–0.67) | 0.021 | 0.3 (0.07–1.34) | 0.17 |
B | 37 | 15.2 (10.4–19) | 0.34 (0.12–1.003) | 0.42 (0.1–1.9) | |||
C | 5 | 8.95 (4.3–10.9) | 1 | 1 | |||
BCLC stage b | A | 11 | 20.9 (8.9–.) | 0.1 (0.02–0.5) | 0.0005 | 0.24 (0.03–2.1) | 0.43 |
B | 64 | 17.7 (14.3–21.8) | 0.2 (0.04–0.7) | 0.3 (0.05–2.6) | |||
C | 43 | 12.7 (7.7–15.2) | 0.3 (0.07–1.32) | 0.48 (0.05–4.1) | |||
D | 3 | 6.6 (4.3–8.8) | 1 | 1 | |||
Prior therapy | No | 60 | 14.6 (12.4–20.8) | 1.3 (0.89–1.9) | 0.19 | - | - |
Yes | 61 | 15.8 (11.2–19.3) | 1 | - | |||
Extrahepatic metastases | No | 94 | 17.7 (14–20.2) | 0.46 (0.29–0.73) | 0.002 | 0.6 (0.35–1.03) | 0.07 |
Yes | 27 | 11.2 (8–14.3) | 1 | 1 |
Univariate Analysis | |||||
---|---|---|---|---|---|
Subgroups | Number of Patients | Median OS in Months (95% CI) | HR (95% CI) | p-Value | |
Chemotherapeutic drug a | Epirubicin | 43 | 17.7 (13.3–21) | 0.91 (0.62–1.4) | 0.34 |
Doxorubicin | 75 | 13.6 (11.2–17.6) | 1 | ||
Doxorubicin + Mitomycin C | 3 | 19.3 (17.7–.) | 0.43 (0.11–1.7) | ||
Embolization pattern a | Selective | 49 | 15.5 (11.2–19.25) | 1 | 0.12 |
Unilobar | 39 | 17.6 (9.1–23.3) | 0.7 (0.43–1.1) | ||
Bilobar | 33 | 14.3 (9.5–20.6) | 1.12 (0.71–1.78) | ||
Lipiodol added b | No | 89 | 15.8 (13–18.7) | 1 | 0.64 |
Yes | 32 | 14.2 (7.6–21) | 1.1 (0.71–1.75) |
Parameter | Grade | All Patients | Bilobar | Lobar | Selective | Pearson Correlation (p-Value) |
---|---|---|---|---|---|---|
Bilirubin (n = 266) | 0 | 129 (48.5%) | 47 (46.5%) | 62 (55.4%) | 20 (61%) | p = 0.28 |
1 | 69 (25.9%) | 32 (31.6%) | 32 (28.6%) | 5 (15.2%) | ||
2 | 64 (32%) | 19 (18.8%) | 18 (16.1%) | 7 (21.2%) | ||
3 | 4 (1.5%) | 3 (3%) | - | 1 (3%) | ||
4 | - | - | - | - | ||
AST (n = 282) | 0 | 131 (46.5%) | 40 (40%) | 69 (49.6%) | 22 (50%) | p = 0.18 |
1 | 98 (34.8%) | 32 (32%) | 54 (28.8%) | 12 (27%) | ||
2 | 31 (11%) | 16 (16%) | 9 (6.5%) | 6 (13.6%) | ||
3 | 20 (7.1%) | 10 (10%) | 6 (4.3%) | 4 (9.1%) | ||
4 | 2 (0.71%) | 1 (1%) | 1 (0.7%) | - | ||
ALT (n = 242) | 0 | 159 (65.7%) | 68 (68.7%) | 77 (70%) | 14 (42.4%) | p = 0.006 |
1 | 70 (28.9%) | 24 (24.2%) | 29 (26.4%) | 17 (51.2%) | ||
2 | 7 (2.9%) | 6 (6.1%) | 0 (0%) | 1 (3%) | ||
3 | 6 (2.4%) | 1 (1%) | 4 (3.6%) | 1 (3%) | ||
4 | - | - | - | - | ||
GGT (n = 244) | 0 | 236 (96.7%) | 93 (92.1%) | 111 (100%) | 32 (100%) | p = 0.003 |
1 | 8 (3.3%) | 8 (7.9%) | - | - | ||
2 | - | - | - | - | ||
3 | - | - | - | - | ||
4 | - | - | - | - | ||
AP (n = 238) | 0 | 227 (95.4%) | 97 (97%) | 99 (93.4%) | 31 (96.9%) | p = 0.43 |
1 | 11 (4.6%) | 3 (3%) | 7 (6.6%) | 1 (3.1% | ||
2 | - | - | - | - | ||
3 | - | - | - | - | ||
4 | - | - | - | - | ||
INR (n = 240) | 0 | 230 (97%) | 95 (96.9%) | 103 (97.2%) | 32 (97%) | p = 0.99 |
1 | 7 (3%) | 3 (3.1%) | 3 (2.8%) | 1 (3%) | ||
2 | - | - | - | - | ||
3 | - | - | - | - |
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Ludwig, J.M.; Iezzi, R.; Theysohn, J.M.; Albrecht, T.; Posa, A.; Gross, A. European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden. Cancers 2021, 13, 5122. https://doi.org/10.3390/cancers13205122
Ludwig JM, Iezzi R, Theysohn JM, Albrecht T, Posa A, Gross A. European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden. Cancers. 2021; 13(20):5122. https://doi.org/10.3390/cancers13205122
Chicago/Turabian StyleLudwig, Johannes M., Roberto Iezzi, Jens M. Theysohn, Thomas Albrecht, Alessandro Posa, and Alexander Gross. 2021. "European Multicenter Study on Degradable Starch Microsphere TACE: The Digestible Way to Conquer HCC in Patients with High Tumor Burden" Cancers 13, no. 20: 5122. https://doi.org/10.3390/cancers13205122