Usefulness of Circulating CYFRA21-1 in Patients as a Biomarker in Patients Taking Sorafenib or Lenvatinib for Unresectable Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Administration of SOR/LEN
2.3. Measurement of Serum CYFRA21-1
2.4. Follow-Up after Administration
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Transition of Tumor Markers Including Serum CYFRA21-1 Level
3.3. Factors Relating to Survival after SOR/LEN Administration
3.4. Characteristics in Patients with High CYFRA 21-1 Level
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All (n = 71) | SOR (n = 36) | LEN (n = 35) | p Value | |
---|---|---|---|---|
Male gender, n (%) | 62 (87) | 31 (86) | 31 (89) | 1.0 |
Etiology: HBV/HCV/others, n (%) | 13/33/25 (18/47/35) | 7/19/10 (19/53/28) | 6/14/15 (17/40/43) | 0.42 |
At the time of administration of SOR/LEN Age (years), median(range) | 70 (52–91) | 69 (56–91) | 70 (52–83) | 0.92 |
Tumor diameter (mm), median(range) | 27 (8.4–180) | 29 (8.4–160) | 27 (12–180) | 0.85 |
Tumor number, median(range) | 6 (1–10) | 10 (1–10) | 6 (1–10) | 0.046 |
Portal vein tumor thrombosis (Vp 2/3), n (%) | 16 (22) | 8 (22) | 8 (23) | 1.0 |
Extrahepatic metastasis, n (%) | 29 (41) | 19 (53) | 10 (29) | 0.054 |
ALBI grade 1/2/3, n (%) | 20/48/3 (28/68/4) | 10/24/2 (28/67/5) | 10/24/1 (29/68/3) | 1.0 |
BCLC stage B/C, n (%) | 32/39 (45/55) | 13/23 (36/64) | 19/16 (54/46) | 0.16 |
AFP (ng/mL), median(range) | 143 (1.8–421,248) | 238 (1.8–421,248) | 143 (4.0–146,670) | 0.48 |
AFP L3 index (%), median(range) | 18 (0.5–94) | 29 (0.5–87) | 15 (0.5–94) | 0.31 |
DCP (mAU/mL), median(range) | 939 (15–616,708) | 1671 (15–616,708) | 513 (25–501,890) | 0.41 |
CYFRA21-1 (ng/mL), median(range) | 2.6 (0.76–10.6) | 2.5 (0.76–10.6) | 2.7 (1.1–8.9) | 0.63 |
Administration dose, reduction/full dose, n (%) | 16/55 (22/78) | 32/4 (89/11) | 12/23 (34/66) | 0.001 |
Administration duration (weeks), median(range) | 17 (4–95) | 16 (4–95) | 21 (4–88) | 0.30 |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
HR | p Value | HR | 95%CI | p Value | ||
At the start of administration | Tumor diameter ≥ 70 mm | 3.4 | <0.001 | 2.3 | 0.97–5.3 | 0.059 |
Tumor number ≥ 4 | 1.3 | 0.44 | ||||
Portal vein tumor thrombosis (Vp 2/3) | 1.7 | 0.097 | ||||
Extrahepatic metastasis | 2.0 | 0.031 | 1.6 | 0.81–3.0 | 0.19 | |
ALBI grade 2/3 | 1.5 | 0.24 | ||||
AFP ≥ 2000 ng/ml | 3.7 | <0.001 | 2.0 | 0.91–4.6 | 0.079 | |
AFP-L3 index ≥ 15% | 2.2 | 0.020 | 2.2 | 1.1–4.6 | 0.030 | |
DCP ≥ 1000 mAU/ml | 4.9 | 0.0025 | 1.3 | 0.55–2.9 | 0.59 | |
CYFRA21-1 ≥ 3.5 ng/ml | 2.1 | 0.024 | 2.1 | 0.99–4.6 | 0.051 | |
After the start of administration | 12-week mRECIST PD | 1.9 | 0.042 | 1.7 | 1.01–3.7 | 0.019 |
12-week AFP ratio ≥ 0.8 | 1.9 | 0.051 | ||||
12-week DCP ratio ≥ 4 | 3.0 | 0.018 | 2.5 | 1.1–6.3 | 0.047 | |
12-week CYFRA21-1 ratio ≥ 2 | 2.4 | 0.0025 | 3.6 | 1.2–11 | 0.023 | |
Administration period < 12 weeks | 2.4 | 0.0071 | 2.4 | 1.1–5.7 | 0.046 | |
ALBI grade 3 at PD | 3.9 | 0.0020 | 2.3 | 0.86–6.4 | 0.097 | |
No additional treatment after discontinuation of SOR/LEN | 2.0 | 0.041 | 2.5 | 1.1–6.1 | 0.036 |
Baseline < 3.5 ng/mL and 12-Week CYFRA21-1 Ratio < 2 (n = 46) | Baseline ≥ 3.5 ng/mL or 12-Week CYFRA21-1 Ratio ≥ 2 (n = 25) | p Value | |
---|---|---|---|
Male gender, n (%) | 41 (89%) | 21 (84%) | 0.71 |
At the time of administration of SOR/LEN Age (years), median(range) | 69 (52–86) | 72 (52–91) | 0.47 |
Tumor size ≥70 mm, n (%) | 7 (15%) | 7 (28%) | 0.22 |
Tumor number ≥4, n (%) | 38 (83%) | 17 (68%) | 0.23 |
up to 7 out, n (%) | 37 (80%) | 21 (84%) | 1.0 |
Portal vein thrombosis (Vp 2/3), n (%) | 11 (24%) | 5 (20%) | 0.78 |
Extrahepatic metastasis, n (%) | 16 (35%) | 13 (52%) | 0.21 |
ALBI grade 2or3, n (%) | 34 (74) | 17 (68) | 0.59 |
AFP ≥2000 ng/mL, n (%) | 7 (15%) | 12 (48%) | 0.005 |
AFP L3 index ≥ 15%, n (%) | 24 (52%) | 18 (72%) | 0.13 |
DCP ≥ 1000 mAU/mL, n (%) | 19 (42%) | 15 (63%) | 0.13 |
12-week mRECIST PD, n (%) | 21 (47%) | 12 (52%) | 0.80 |
TACE unsuitable pattern, n (%) | 19 (41%) | 19 (76%) | 0.006 |
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Takada, H.; Osawa, L.; Komiyama, Y.; Kato, R.; Nakakuki, N.; Muraoka, M.; Suzuki, Y.; Tatsumi, A.; Sato, M.; Takahashi, E.; et al. Usefulness of Circulating CYFRA21-1 in Patients as a Biomarker in Patients Taking Sorafenib or Lenvatinib for Unresectable Hepatocellular Carcinoma. Reports 2021, 4, 25. https://doi.org/10.3390/reports4030025
Takada H, Osawa L, Komiyama Y, Kato R, Nakakuki N, Muraoka M, Suzuki Y, Tatsumi A, Sato M, Takahashi E, et al. Usefulness of Circulating CYFRA21-1 in Patients as a Biomarker in Patients Taking Sorafenib or Lenvatinib for Unresectable Hepatocellular Carcinoma. Reports. 2021; 4(3):25. https://doi.org/10.3390/reports4030025
Chicago/Turabian StyleTakada, Hitomi, Leona Osawa, Yasuyuki Komiyama, Ryoh Kato, Natsuko Nakakuki, Masaru Muraoka, Yuichiro Suzuki, Akihisa Tatsumi, Mitsuaki Sato, Ei Takahashi, and et al. 2021. "Usefulness of Circulating CYFRA21-1 in Patients as a Biomarker in Patients Taking Sorafenib or Lenvatinib for Unresectable Hepatocellular Carcinoma" Reports 4, no. 3: 25. https://doi.org/10.3390/reports4030025