Stereotactic Body Radiation Therapy for the Management of Hepatocellular Carcinoma: Efficacy and Safety
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods and Materials
2.1. Patients
2.2. Treatment
2.3. Follow-Up
2.4. Endpoint Definition
2.5. Statistical Analysis
3. Results
3.1. Patient and Treatment Characteristics
3.2. Efficacy
3.3. Safety
3.4. Analysis of Prognostic Value of Patient’s Characteristics and Outcomes According to Radiotherapy Parameters
3.5. Response after Liver Transplant
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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Demographic Data | ||
---|---|---|
Age | 69 | (43; 93) |
Sex | ||
Male | 269 | 84.6% |
Female | 49 | 15.4% |
ECOG Performance status (MD = 29) | ||
0 | 146 | 50.5% |
1 | 106 | 36.7% |
2 | 32 | 11.1% |
3 | 5 | 1.7% |
BMI in kg/m2 (MD = 95) | 28.9 | (13.6; 48.1) |
Underweight (<18.5) | 3 | 1.3% |
Normal build (18.5–25) | 50 | 22.4% |
Overweight (25–30) | 77 | 34.5% |
Obese (30–40) | 78 | 35.0% |
Morbidly obese (≥40) | 15 | 6.5% |
Smoking (MD = 142) | ||
Non-smoker | 45 | 25.6% |
Smoker | 29 | 16.5% |
Ex-smoker | 102 | 58.0% |
Alcohol intoxication (MD = 79) | ||
Non-drinker | 33 | 13.8% |
Drinker | 58 | 24.3% |
Former drinker | 148 | 61.9% |
Diagnosis | ||
Type of diagnosis (MD = 72) | ||
Histology | 70 | 28.5% |
Radiology | 176 | 71.5% |
Cause of cirrhosis (MD = 45) | ||
Alcohol | 160 | 58.6% |
Viral | 33 | 12.1% |
NASH | 28 | 10.3% |
Medication | 1 | 0.4% |
Hemochromatosis | 11 | 4.0% |
Combination | 37 | 13.6% |
Autoimmune | 3 | 1.1% |
Cirrhosis-Alcohol (MD = 20) | ||
No alcohol, cause of cirrhosis different from alcohol | 73 | 24.59% |
Viral | 28 | |
NASH | 19 | |
Medication | 1 | |
Hemochromatosis | 10 | |
Combination | 6 | |
Autoimmune | 3 | |
Unknown | 6 | |
Yes | 225 | 75.5% |
Cause of cirrhosis: alcohol | 160 | |
Alcohol and cause of cirrhosis different from alcohol | 65 | |
Viral | 5 | |
NASH | 9 | |
Medication | - | |
Hemochromatosis | 1 | |
Combination | 31 | |
Autoimmune | - | |
Unknown | 19 | |
Pugh-Child (MD = 82) | ||
A5 | 139 | 58.9% |
A6 | 65 | 27.5% |
B7 | 19 | 8.1% |
B8 | 9 | 3.8% |
B9 | 3 | 1.3% |
C | 1 | 0.4% |
Ascites (MD = 20) | 12 | 4.0% |
MELD score (MD = 152) | 9 | (6; 19) |
Okuda classification (MD = 105) | ||
Stage 1 | 179 | 84.0% |
Stage 2 | 34 | 16.0% |
BCLC classification (MD = 48) | ||
0 | 33 | 12.2% |
A | 128 | 47.4% |
B | 32 | 11.9% |
C | 55 | 20.4% |
D | 22 | 8.1% |
Bilirubin in µmol/L (MD = 85) | 13.9 | (3.3; 81.0) |
Albumin in g/L (MD = 101) | 37.0 | (21.9; 48.0) |
PT as a % (MD = 75) | 82 | (44; 110) |
AFP in ng/mL (MD = 67) | 9.8 | (0.9; 44,286.0) |
Portal vein thrombosis (MD = 82) | 40 | 16.9% |
Number of target lesions (MD = 1) | ||
1 | 232 | 73.2% |
2 | 66 | 20.8% |
3 | 17 | 5.4% |
4 | 2 | 0.6% |
Tumor size in mm | ||
Lesion 1 (N = 303) | 35 | (7; 105) |
Lesion 2 (N = 78) | 20 | (5; 65) |
Lesion 3 (N = 17) | 12 | (5; 23) |
Lesion 4 (N = 1) | 8 | (8; 8) |
Total of all lesions (N = 399, MD = 24) | 30 | (5; 105) |
Previous treatments | ||
Patients who received at least one previous treatment (MD = 3) | 111 | 35.2% |
Previous treatment received | ||
Previous local treatment (MD = 3) | 100 | 31.7% |
Previous surgery (MD = 2) | 16 | 5.1% |
Previous radiofrequency ablation (MD = 2) | 28 | 8.9% |
Previous chemoembolization (MD = 3) | 68 | 21.6% |
Previous radiotherapy (MD = 2) | 2 | 0.6% |
Previous chemotherapy (MD = 2) | 2 | 0.6% |
Previous targeted therapy (MD = 2) | 23 | 7.3% |
Cyberknife Treatment Characteristics | ||
---|---|---|
RT duration in days | 7 | (0; 28) |
The total dose in Gy (MD = 2) | 45 | (21; 54) |
Number of fractions (MD = 2) | ||
3 | 299 | 94.6% |
4 | 1 | 0.3% |
5 | 2 | 0.6% |
6 | 14 | 4.4% |
Dose per fraction in Gy (MD = 2) | 15.0 | (3.5; 15.0) |
Total dose received in Gy (MD = 2) | 45 | (15; 54) |
Early treatment discontinuation (MD = 2) | 2 | 0.6% |
Liver volume (MD = 110) | 1581.5 | (743.6; 3316.7) |
Dmax 700 cc liver (MD = 111) | 9.2 | (0.4; 34.1) |
PTV/total liver volume ratio (%) (MD = 21) | 7.2 | (0.5; 44.4) |
<10% | 196 | 66.0% |
≥10% | 101 | 34.0% |
Dosimetric data (N = 375 lesions) | ||
GTV in cm3 (MD = 1) | 21.1 | (0.4; 700.1) |
CTV in cm3 (MD = 15) | 63.3 | (2.5; 999.4) |
PTV in cm3 (MD = 9) | 90.7 | (2.6; 1067.6) |
D2% of GTV in Gy (MD = 8) | 52.4 | (25.2; 76.3) |
D50% of GTV in Gy (MD = 8) | 50.0 | (23.9; 68.4) |
D98% of GTV in Gy (MD = 8) | 46.1 | (21.1; 61.9) |
D2% of CTV in Gy (MD = 22) | 52.5 | (27.6; 75.2) |
D50% of CTV in Gy (MD = 22) | 49.7 | (25.5; 66.1) |
D98% of CTV in Gy (MD = 22) | 45.6 | (14.9; 58.3) |
D2% of PTV in Gy (MD = 16) | 52.3 | (25.1; 74.8) |
D50% of PTV in Gy (MD = 16) | 48.9 | (23.4; 63.2) |
D98% of PTV in Gy (MD = 16) | 43.6 | (13.3; 52.4) |
Type of Acute Toxicity | Toxicity (N, %) | Grade ≥ 2 Toxicity | G1 | G2 | G3 |
---|---|---|---|---|---|
Toxicity of all types combined (MD = 2) | 161 (50.9%) | 53 (16.8%) | 108 | 45 | 8 |
Fatigue (MD = 9) | 79 (25.6%) | 22 (7.1%) | 57 | 22 | - |
Pain (MD = 5) | 31 (9.9%) | 5 (1.6%) | 26 | 4 | 1 |
Nausea (MD = 10) | 47 (15.3%) | 8 (2.6%) | 39 | 8 | - |
Vomiting (MD = 5) | 22 (7.0%) | - | 22 | - | - |
Hepatitis (MD = 40) | 15 (5.4%) | 2 (0.7%) | 13 | 2 | - |
Digestive ulceration (MD = 7) | 2 (0.6%) | 2 (0.6%) | - | 2 | - |
Ascitis (MD = 5) | 28 (9.1%) | 21 (6.7%) | 7 | 14 | 7 |
Univariate Analyses | Overall Survival (N = 318) | Acute Toxicity Grade ≥ 2 (N = 316) | ||||||
---|---|---|---|---|---|---|---|---|
Characteristics | n/N | HR | 95% CI | p-Value | n/N | OR | 95% CI | p-Value |
Cause of cirrhosis (MD = 45) | 0.76 | 0.49 | ||||||
Alcohol | 120/160 | 1 | 25/160 | 1 | ||||
Viral | 28/33 | 1.09 | (0.72–1.65) | 8/33 | 1.73 | (0.70–4.26) | ||
NASH | 17/28 | 0.86 | (0.52–1.43) | 3/28 | 0.64 | (0.18–2.31) | ||
Other | 40/52 | 1.12 | (0.79–1.63) | 10/51 | 1.32 | (0.58–2.97) | ||
Cirrhosis-alcohol (MD = 20) | 0.13 | 0.25 | ||||||
No | 57/73 | 1 | 15/73 | 1 | ||||
Yes | 168/225 | 0.79 | (0.59–1.07) | 33/223 | 0.67 | (0.34–1.32) | ||
Pugh-Child (MD = 82) | 0.003 | 0.31 | ||||||
A | 143/204 | 1 | 31/203 | 1 | ||||
B-C | 28/32 | 1.87 | (1.25–2.82) | 7/31 | 1.61 | (0.64–4.08) | ||
MELD score (MD = 152) | 0.27 | 0.13 | ||||||
/1 unit | - | 1.04 | (0.97–1.11) | - | 1.12 | (0.97–1.30) | ||
Pretreatment bilirubin (MD = 85) | 0.09 | 0.02 | ||||||
/10 µmol/L | - | 1.12 | (0.98–1.27) | - | 1.31 | (1.04–1.65) | ||
Pretreatment albumin (MD = 101) | 0.07 | 0.61 | ||||||
/10 g/L | - | 0.74 | (0.54–1.03) | - | 0.82 | (0.39–1.73) | ||
Pretreatment AFP (MD = 67) | 0.103 | 0.83 | ||||||
/103 ng/mL | - | 1.02 | (0.99–1.05) | - | 0.99 | (0.89–1.10) | ||
Portal vein thrombosis (MD = 82) | 0.02 | 0.89 | ||||||
No | 133/196 | 1 | 31/195 | 1 | ||||
Yes | 39/40 | 1.56 | (1.09–2.23) | 6/40 | 0.93 | (0.36–2.41) | ||
BCLC classification (MD = 48) | <0.001 | 0.88 | ||||||
0 | 20/33 | 1 | 4/33 | 1 | ||||
A | 87/128 | 1.31 | (0.80–2.13) | 22/128 | 1.50 | (0.48–4.71) | ||
B | 25/32 | 1.52 | (0.84–2.74) | 6/32 | 1.67 | (0.42–6.59) | ||
C | 45/55 | 1.89 | (1.11–3.21) | 7/54 | 1.08 | (0.29–4.01) | ||
D | 18/22 | 3.64 | (1.92–6.93) | 4/21 | 1.71 | (0.38–7.72) | ||
Total GTV in cm3 (MD = 20) | <0.001 | 0.02 | ||||||
/100 cm3 | - | 1.22 | (1.09–1.36) | - | 1.34 | (1.04–1.73) | ||
Total GTV in cm3 (MD = 20) | <0.001 | |||||||
Quartile 1–3 (<70) | 159/224 | 1 | ||||||
Quartile 4 (>70) | 64/74 | 1.81 | (1.34–2.42) | |||||
PTV/total liver vol ratio (%) (MD = 21) | <0.001 | 0.004 | ||||||
/10% | - | 1.34 | (1.17–1.55) | - | 1.63 | (1.17–2.26) |
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Roquette, I.; Bogart, E.; Lacornerie, T.; Ningarhari, M.; Bibault, J.-E.; Le Deley, M.-C.; Lartigau, E.F.; Pasquier, D.; Mirabel, X. Stereotactic Body Radiation Therapy for the Management of Hepatocellular Carcinoma: Efficacy and Safety. Cancers 2022, 14, 3892. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14163892
Roquette I, Bogart E, Lacornerie T, Ningarhari M, Bibault J-E, Le Deley M-C, Lartigau EF, Pasquier D, Mirabel X. Stereotactic Body Radiation Therapy for the Management of Hepatocellular Carcinoma: Efficacy and Safety. Cancers. 2022; 14(16):3892. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14163892
Chicago/Turabian StyleRoquette, Isaure, Emilie Bogart, Thomas Lacornerie, Massih Ningarhari, Jean-Emmanuel Bibault, Marie-Cecile Le Deley, Eric F. Lartigau, David Pasquier, and Xavier Mirabel. 2022. "Stereotactic Body Radiation Therapy for the Management of Hepatocellular Carcinoma: Efficacy and Safety" Cancers 14, no. 16: 3892. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14163892