Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma
Abstract
1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Toxicities
2.3. Treatment Outcomes
3. Discussion
4. Materials and Methods
4.1. Patient Eligibility
4.2. Simulation and Radiotherapy Planning
4.3. Intra-Arterial Chemotherapy
4.4. Dose-Limiting Toxicity
4.5. Follow-Up and Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviation
AFP | α-fetoprotein |
ALP | Alkaline phosphatase |
BCLC | Barcelona clinic liver cancer |
CR | Complete response |
CT | Computed tomography |
CTCAE | Common Toxicity Criteria for Adverse Events |
CTV | Clinical target volume |
DLT | Dose-limiting toxicity |
ECOG | Eastern Cooperative Oncology Group |
HCC | Hepatocellular carcinoma |
IGRT | Image-guided radiotherapy |
IMRT | Intensity-modulated radiotherapy |
INR | International normalized ratio |
IRB | Institutional Review Board |
ITV | Internal target volume |
OAR | Organs at risk |
OS | Overall survival |
PD | Progressive disease |
PFS | Progression-free survival |
PR | Partial response |
PTV | Planning target volume |
RILD | Radiation-induced liver disease |
SBRT | Stereotactic body radiotherapy |
SD | Stable disease |
TACE | Transarterial chemoembolization |
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Characteristics | Median | (Range) | No. of Patients (n = 17) | (%) |
---|---|---|---|---|
Age | 63 | (33–80) | ||
Sex | ||||
Male | 15 | (88.2) | ||
Female | 2 | (11.8) | ||
ECOG PS | ||||
0 | 8 | (47.1) | ||
1 | 9 | (52.9) | ||
Underlying liver disease | ||||
HBV | 12 | (70.6) | ||
HCV | 1 | (5.9) | ||
Without viral infections | 4 | (23.5) | ||
Underlying liver cirrhosis | ||||
No | 4 | 23.5 | ||
Yes | 13 | 76.5 | ||
AFP (ng/mL) | 45 | (2.2–38,300) | ||
>9 ng/mL | 12 | 70.6 | ||
PIVKA-II (mIU/mL) | 381.4 | (23–185,072) | ||
>35 mIU/mL | 13 | 76.5 | ||
Child-Pugh class | ||||
A5 | 14 | 82.4 | ||
A6 | 3 | 17.6 | ||
Platelet count | 163 k | (55–408 k) | 5 | 29.4 |
Mild thrombocytopenia (75–150 k/uL) | 3 | 15.8 | ||
Moderate thrombocytopenia (50–75 k/μL) | 2 | 11.8 | ||
UICC stage | ||||
T2 | 2 | 11.8 | ||
T3 | 8 | 47.1 | ||
T4 | 7 | 41.2 | ||
N0 | 16 | 94.1 | ||
N1 | 1 | 5.9 | ||
Primary tumor size (cm) | 8 | (2.6–16) | ||
Number of tumor(s) | ||||
1 | 8 | 47.1 | ||
2–4 | 7 | 41.2 | ||
≥5 | 2 | 11.8 | ||
Involved site | ||||
Right Lobe | 11 | 64.7 | ||
Left Lobe | 2 | 11.8 | ||
Both Lobes | 4 | 23.5 | ||
Vascular invasion | ||||
No | 3 | 17.6 | ||
Yes | 14 | 82.4 | ||
Previous treatment | ||||
None | 13 | 76.5 | ||
TACE | 4 | 23.5 | ||
TACI | 1 | 5.9 | ||
RFA | 1 | 5.9 |
Level 1 | Level 2 | Level 3 | Total | |||||
---|---|---|---|---|---|---|---|---|
(n = 4) | (n = 6) | (n = 7) | (n = 17) | |||||
Parameters | Median | (Range) | Median | (Range) | Median | (Range) | Median | (Range) |
PTV1 (cc) | 398 | (277–467) | 490 | (69–2086) | 355 | (260–909) | 398 | (69–2086) |
PTV2 (cc) | 819 | (561–2066) | 717 | (209–2814) | 758 | (525–1634) | 784 | (209–2814) |
Uninvolved liver volume (cc) | 1018 | (876–1643) | 1138 | (814–1393) | 1176 | (855–1511) | 1122 | (814–1643) |
Mean dose of whole liver (Gy) | 30.4 | (20.5–42.1) | 28.1 | (18.8–38.2) | 30.1 | (17.7–39.6) | 30.4 | (18.8–42.1) |
Mean dose of uninvolved liver (Gy) | 21.3 | (15.35–27.4) | 21.6 | (19.2–25.7) | 18.2 | (11.5–24.4) | 20.4 | (11.5–27.4) |
Maximum dose of stomach (Gy) | 42.6 | (20.3–55.4) | 27.9 | (15.1–54.0) | 51.2 | (26.8–56.3) | 40.9 | (15.1–56.3) |
Maximum dose of duodenum (Gy) | 40.0 | (21.4–52.2) | 37.8 | (2.1–54.6) | 48.5 | (15.1–54.1) | 40 | (2.1–54.6) |
Maximum dose of spinal cord (Gy) | 29.8 | (26.8–35.2) | 25.7 | (18.7–37.4) | 36.8 | (24.7–44.0) | 30.5 | (18.7–44.0) |
Mean dose of right kidney (Gy) | 5.6 | (2.5–19.4) | 6.4 | (1.1–20.4) | 2.8 | (1.3–17.5) | 6.4 | (1.1–20.4) |
Mean dose of left kidney (Gy) | 4.6 | (0.8–16.9) | 3.2 | (0.6–6.9) | 2.4 | (0.6–7.5) | 3.2 | (0.6–16.9) |
Level 1 (n = 4) | Level 2 (n = 6) | Level 3 (n = 7) | Total (n = 17) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N (%) | N (%) | N (%) | N (%) | ||||||||||
Toxicities | G1 | G2 | G3 | G1 | G2 | G3 | G1 | G2 | G3 | G1 | G2 | G3 | |
GI toxicity | Nausea | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (14.3) | 0 | 0 | 1 (5.9) | 0 |
Vomiting | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Pain | 1 (25) | 0 | 0 | 1 (16.7) | 1 (16.7) | 0 | 1 (14.3) | 0 | 0 | 3 (17.6) | 1 (5.9) | 0 | |
Liver function | AST | 2 (50) | 1 (25) | 0 | 5 (83.3) | 0 | 0 | 6 (85.7) | 0 | 0 | 13 (76.5) | 1 (5.9) | 0 |
ALT | 2 (50) | 0 | 0 | 0 | 0 | 0 | 4 (57.1) | 0 | 0 | 6 (35.3) | 0 | 0 | |
Albumin | 3 (75) | 1 (25) | 0 | 4 (66.7) | 1 (16.7) | 0 | 4 (57.1) | 1 (14.3) | 0 | 11 (64.7) | 3 (17.6) | 0 | |
Bilirubin | 0 | 0 | 1 (25) | 0 | 2 (33.3) | 0 | 0 | 0 | 1 (14.3) | 0 | 2 (11.8) | 2 (11.8) | |
INR | 4 (100) | 0 | 0 | 6 (100) | 0 | 0 | 5 (71.4) | 0 | 0 | 15 (88.2) | 0 | 0 | |
ALP | 2 (50) | 1 (25) | 0 | 5 (83.3) | 0 | 0 | 4 (57.1) | 3 (42.9) | 0 | 11 (64.7) | 4 (23.5) | 0 | |
Hematologic | Hemoglobin | 2 (50) | 2 (50) | 0 | 2 (33.3) | 0 | 0 | 3 (42.9) | 0 | 1 (14.3) | 7 (41.2) | 2 (11.8) | 1 (5.9) |
WBC | 1 (25) | 2 (50) | 0 | 2 (33.3) | 0 | 0 | 2 (28.6) | 3 (42.9) | 0 | 5 (29.4) | 5 (29.4) | 0 | |
ANC | 2 (50) | 0 | 1 (25) | 1 (16.7) | 1 (16.7) | 0 | 0 | 4 (57.1) | 1 (14.3) | 3 (17.6) | 5 (29.4) | 2 (11.8) | |
Platelet | 2 (50) | 1 (25) | 1 (25) | 0 | 1 (16.7) | 1 (16.7) | 0 | 2 (28.6) | 0 | 2 (11.8) | 4 (23.5) | 2 (11.8) | |
Other | General weakness | 0 | 1 (25) | 0 | 3 (50) | 0 | 0 | 0 | 1 (14.3) | 0 | 3 (17.6) | 2 (11.8) | 0 |
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Cho, Y.; Kim, J.W.; Kim, J.K.; Lee, K.S.; Lee, J.I.; Lee, H.W.; Lee, K.-H.; Joo, S.-M.; Lim, J.H.; Lee, I.J. Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma. Cancers 2020, 12, 1612. https://doi.org/10.3390/cancers12061612
Cho Y, Kim JW, Kim JK, Lee KS, Lee JI, Lee HW, Lee K-H, Joo S-M, Lim JH, Lee IJ. Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma. Cancers. 2020; 12(6):1612. https://doi.org/10.3390/cancers12061612
Chicago/Turabian StyleCho, Yeona, Jun Won Kim, Ja Kyung Kim, Kwan Sik Lee, Jung Il Lee, Hyun Woong Lee, Kwang-Hun Lee, Seung-Moon Joo, Jin Hong Lim, and Ik Jae Lee. 2020. "Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma" Cancers 12, no. 6: 1612. https://doi.org/10.3390/cancers12061612
APA StyleCho, Y., Kim, J. W., Kim, J. K., Lee, K. S., Lee, J. I., Lee, H. W., Lee, K.-H., Joo, S.-M., Lim, J. H., & Lee, I. J. (2020). Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma. Cancers, 12(6), 1612. https://doi.org/10.3390/cancers12061612