Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Study Design
2.2. Analysis of Changes in Serum Growth Factors
2.3. Treatment Protocol
2.4. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Comparison of Baseline Patients’ Characteristics and Growth Factor Levels between Patients with or without Disease Control or an OR
3.3. Changes in Growth Factors between Baseline and Best Overall Response Point in Unresectable HCC Patients with Disease Control by Atezolizumab Plus Bevacizumab
3.4. Changes in Growth Factors between the Best Overall Response Point and PD Point in Unresectable HCC Patients with Disease Control by Atezolizumab Plus Bevacizumab
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Included Patients | DC (+) n = 32 | DC (−) n = 14 | p-Value | |
---|---|---|---|---|
n = 46 | ||||
Age (years), median (range) | 72 (31–84) | 68 (47–74) | 75 (47–81) | 0.0237 |
Sex (male/female) | 37/9 | 27/5 | 10/4 | 0.4226 |
Etiology, n (%) | 0.5596 | |||
HBV | 15 (32.6%) | 12 (37.5%) | 3 (21.4%) | |
HCV | 6 (13.0%) | 4 (12.5%) | 2 (14.3%) | |
NBNC | 25 (54.3%) | 16 (50.0%) | 9 (64.3%) | |
Liver condition | 0.7539 | |||
LC | 22 (47.8%) | 16 (50%) | 6 (42.9%) | |
CH | 24 (52.2%) | 16 (50%) | 8 (57.1%) | |
BCLC stage, n (%) | >0.9999 | |||
B | 16 (34.8%) | 11 (34.4%) | 5 (35.7%) | |
C | 30 (65.2%) | 21 (65.6%) | 9 (64.3%) | |
Child–Pugh class, n (%) | >0.9999 | |||
A | 46 (100%) | 32 (100%) | 14 (100%) | |
B | 0 (0%) | 0 (0%) | 0 (0%) | |
Child–Pugh score, n (%) | 0.3161 | |||
5 | 30 (65.2%) | 19 (59.4%) | 11 (78.6%) | |
6 | 16 (34.8%) | 13 (40.6%) | 3 (21.4%) | |
Biochemical analysis | ||||
Platelets, ×104/μL | 15.3 (6.1–54) | 14.45 (6.1–46.4) | 16.45 (8.5–54) | 0.5351 |
ALT, IU/L | 24.5 (7–278) | 19 (7–278) | 42.5 (19–122) | 0.0010 |
Cr, mg/dL | 0.825 (0.097–2.28) | 0.88 (0.52–2.28) | 0.705 (0.097–1.44) | 0.0913 |
AFP, ng/mL | 24.05 (2.3–57,125.2) | 19.35 (2.3–57,125.2) | 221.6 (2.4–15,009.5) | 0.2023 |
PIVKA-II, mAU/mL | 886.5 (19–213,066) | 1006 (19–213,066) | 881.5 (25–110,159) | 0.8926 |
History of operation | 24 (52.2%) | 14 (43.8%) | 10 (71.4%) | 0.1141 |
History of RFA | 14 (30.4%) | 9 (28.1%) | 5 (35.7%) | 0.7308 |
History of TACE | 25 (54.3%) | 18 (56.3%) | 7 (50%) | 0.7553 |
History of systemic therapy | 24 (52.2%) | 18 (56.3%) | 6 (42.9%) | 0.5252 |
No treatment history | 8 (17.4%) | 6 (18.8%) | 2 (14.3%) | >0.9999 |
Interruption of bevacizumab | 16 (34.8%) | 13 (40.6%) | 3 (21.4%) | 0.3161 |
Included Patients | OR (+) n = 13 | OR (−) n = 33 | p-Value | |
---|---|---|---|---|
n = 46 | ||||
Age (years), median (range) | 72 (31–84) | 68 (47–74) | 70 (31–84) | 0.0236 |
Sex (male/female) | 37/9 | 11/2 | 26/7 | >0.9999 |
Etiology, n (%) | 0.2558 | |||
HBV | 15 (32.6%) | 5 (38.5%) | 10 (30.3%) | |
HCV | 6 (13.0%) | 0 (0%) | 6 (18.2%) | |
NBNC | 25 (54.3%) | 8 (61.5%) | 17 (51.5%) | |
Liver condition | 0.7462 | |||
LC | 22 (47.8%) | 7 (53.8%) | 15 (45.5%) | |
CH | 24 (52.2%) | 6 (46.2%) | 18 (54.5%) | |
BCLC stage, n (%) | 0.7441 | |||
B | 16 (34.8%) | 5 (38.5%) | 11 (33.3%) | |
C | 30 (65.2%) | 8 (61.5%) | 22 (66.7%) | |
Child–Pugh class, n (%) | >0.9999 | |||
A | 46 (100%) | 13 (100%) | 33 (100%) | |
B | 0 (0%) | 0 (0%) | 0 (0%) | |
Child–Pugh score, n (%) | 0.3095 | |||
5 | 30 (65.2%) | 7 (53.8%) | 23 (69.7%) | |
6 | 16 (34.8%) | 6 (46.2%) | 10 (30.3%) | |
Biochemical analysis | ||||
latelets, ×104/μL | 15.3 (6.1–54) | 17.2 (7.6–46.4) | 15.2 (6.1–54) | 0.9568 |
ALT, IU/L | 24.5 (7–278) | 19 (7–43) | 31 (7–278) | 0.0639 |
Cr, mg/dL | 0.825 (0.097–2.28) | 0.78 (0.52–1.42) | 0.89 (0.097–2.28) | 0.3487 |
AFP, ng/mL | 24.05 (2.3–57,125.2) | 18.1 (2.3–2945.4) | 80.1 (2.3–57,125.2) | 0.4145 |
PIVKA-II, mAU/mL | 886.5 (19–213,066) | 277 (19–3217) | 1616 (20–213,066) | 0.0699 |
History of operation | 24 (52.2%) | 6 (46.2%) | 18 (54.5%) | 0.7462 |
History of RFA | 14 (30.4%) | 5 (38.5%) | 9 (27.3%) | 0.4934 |
History of TACE | 25 (54.3%) | 8 (61.5%) | 17 (51.5%) | 0.7437 |
History of systemic therapy | 24 (52.2%) | 9 (69.2%) | 15 (45.5%) | 0.1968 |
No treatment history | 8 (17.4%) | 3 (23.1%) | 5 (15.2%) | 0.6689 |
Interruption of bevacizumab | 16 (34.8%) | 4 (30.8%) | 12 (36.4%) | >0.9999 |
Included Patients | |
---|---|
n = 28 | |
Age (years), median (range) | 70 (31–84) |
Sex (male/female) | 23/5 |
Treatment response | |
CR | 2 (7.1%) |
PR | 7 (25.0%) |
SD | 19 (67.9%) |
Etiology, n (%) | |
HBV | 9 (32.1%) |
HCV | 4 (14.3%) |
NBNC | 15 (53.6%) |
Liver condition | |
LC | 14 (50.0%) |
CH | 14 (50.0%) |
BCLC stage, n (%) | |
B | 10 (35.7%) |
C | 18 (64.3%) |
Child–Pugh class, n (%) | |
A | 28 (100%) |
B | 0 (0%) |
Child–Pugh score, n (%) | |
5 | 16 (57.1%) |
6 | 12 (42.9%) |
Biochemical analysis | |
Platelets, ×104/μL | 13.7 (6.1–41.3) |
ALT, IU/L | 23 (7–278) |
Cr, mg/dL | 0.89 (0.52–2.28) |
AFP, ng/mL | 19.4 (2.3–57,125.2) |
PIVKA-II, mAU/mL | 1852 (20–213,066) |
History of operation | 11 (39.3%) |
History of RFA | 8 (28.6%) |
History of TACE | 15 (53.6%) |
History of systemic therapy | 15 (53.6%) |
No treatment history | 4 (14.3%) |
Interruption of bevacizumab | 13 (46.4%) |
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Yang, Z.; Suda, G.; Maehara, O.; Ohara, M.; Yoda, T.; Sasaki, T.; Kohya, R.; Yoshida, S.; Hosoda, S.; Tokuchi, Y.; et al. Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma. Cancers 2023, 15, 593. https://doi.org/10.3390/cancers15030593
Yang Z, Suda G, Maehara O, Ohara M, Yoda T, Sasaki T, Kohya R, Yoshida S, Hosoda S, Tokuchi Y, et al. Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma. Cancers. 2023; 15(3):593. https://doi.org/10.3390/cancers15030593
Chicago/Turabian StyleYang, Zijian, Goki Suda, Osamu Maehara, Masatsugu Ohara, Tomoka Yoda, Takashi Sasaki, Risako Kohya, Sonoe Yoshida, Shunichi Hosoda, Yoshimasa Tokuchi, and et al. 2023. "Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma" Cancers 15, no. 3: 593. https://doi.org/10.3390/cancers15030593