Background
Methods
Patients and treatment characteristics
SBRT techniques
Toxicity and follow up
Statistical analysis
Results
Patients and treatment characteristics
Variable | All patients | CTP A | CTP B |
---|---|---|---|
No. (%) | No. (%) | No. (%) | |
No. of patients | 47 (100%) | 28 (60%) | 19 (40%) |
Age(years) | |||
Median (range) | 69 (29–84) | 70 (45–84) | 69 (29–83) |
BCLC stage | |||
B | 23 (49%) | 14 (50%) | 9 (47%) |
C | 24 (51%) | 14 (50%) | 10 (53%) |
CTP score | |||
A | 28 (60%) | ||
A5 | 16 (34%) | 16 | |
A6 | 12 (26%) | 12 | |
B | 19 (40%) | ||
B7 | 10 (21%) | 10 | |
B8 | 6 (13%) | 6 | |
B9 | 3 (6 %) | 3 | |
Underlying liver disease | 41 (87%) | ||
Hepatitis B | 4 (9%) | 3 (11%) | 1 (5%) |
Hepatitis C | 6 (13%) | 3 (11%) | 3 (16%) |
Alcohol related | 24 (51%) | 11 (39%) | 12 (63%) |
NASHa
| 6 (13%) | 5 (18%) | 2 (11%) |
Primary biliary cirrhosis | 1 (2%) | 1 (7%) | 0 (0%) |
None | 6 (13%) | 5 (18%) | 1 (5%) |
Previous treatmentsg
| |||
Surgery | 9 (19%) | 8 (29%) | 4 (21%) |
TACEb
| 34 (72%) | 21 (75%) | 13 (68%) |
RFAc
| 5 (11%) | 5 (18%) | 1 (5%) |
Sorafenib | 10 (21%) | 8 (29%) | 2 (11%) |
SIRTd
| 2 (4%) | 2 (7%) | 0 (0%) |
SBRTe
| 7 (15%) | 2 (7%) | 3 (16%) |
Tumor vascular thrombosis | 13 (28%) | 5 (18%) | 8 (42%) |
Extrahepatic disease | 9 (19%) | 6 (21%) | 3 (16%) |
Multiple lesions at baseline | 39 (83%) | 24 (86%) | 15 (79%) |
GTV volumef
| |||
Median (IQR) cm3
| 77 (37–229) | 69 (35–214) | 108 (38–268) |
Diameter of the lesionsf
| |||
Media(IQR) cm | 7 (5–10) | 7 (4–10) | 8 (5–10) |
Liver Volume | |||
Median (range) cm3
| 1654 (1384–2230) | 1492 (1340–2277) | 1819 (1554–1997) |
Prescription dose (Gy)f
| |||
Median (IQR) | 45 (38–48) | 45 (38–48) | 45 (44–50) |
Dmax | |||
Median (IQR) | 53 (49–59) | 54 (52–59) | 51 (48–58) |
D95% | |||
Median (IQR) | 45 (38–48) | 45 (37–48) | 45 (44–50) |
EQD210 prescribed (Gy)f
| |||
Median (IQR) | 63 (51–75) | 56 (50–71) | 71 (56–85) |
EQD210 Dmax | |||
Median (IQR) | 86 (62–104) | 91 (62–104) | 82 (61–99) |
EQD210 D95% | |||
Median (IQR) | 60 (52–76) | 56 (48–72) | 71 (56–85) |
BED10prescribed (Gy)f
| |||
Median (IQR) | 76 (62–86) | 67 (61–85) | 86 (67–102) |
BED10 Dmax | |||
Median (IQR) | 102 (75–125) | 109 (75–125) | 99 (73–115) |
BED10 D95% | |||
Median (IQR) | 72 (62–91) | 67 (57–86) | 86 (67–102) |
Mean liver dose (Gy) | |||
Median (IQR) | 17.9 (8.7–25) | 19 (9.8–25) | 16.5 (7.8–22) |
EQD22, mean liver dose
| |||
Median (IQR) | 16.5 (9.5–23) | 17.2 (9–23.5) | 15.6 (8.5–20.5) |
Local control per lesion and patterns of failure
Variable | Local control | Overall survival | ||||
---|---|---|---|---|---|---|
HR | 95% CI |
p
| HR | 95% CI |
p
| |
CTP | 1.725 | (0.406–7.335) | 0.5 | 1.806 | (0.884–3.691) | 0.1 |
Multifocality | 0.696 | (0.085–5.688) | 0.7 | 1.471 | (0.512–4.228) | 0.5 |
Diameter | 1.147 | (1.008–1.305) | 0.04 | 1.017 | (0.952–1.086) | 0.6 |
Extrahepatic disease | n.a. | 0.653 | (0.260–1.640) | 0.7 | ||
Fractionation | 0.919 | (0.755–1.118) | 0.4 | 0.952 | (0.860–1.053) | 0.3 |
SIP | 0.950 | (0.227–3.989) | 0.9 | 1.298 | (0.639–2.637) | 0.5 |
GTV Volume | 1.001 | (1.000–1.002) | 0.008 | 1.001 | (1.000–1.001) | 0.008 |
TVT | 0.977 | (0.189–5.058) | 0.9 | 1.674 | (0.781–3.590) | 0.2 |
EQD210, prescribed
| 0.952 | (0.907–0.998) | 0.04 | 1.002 | (0.978–1.026) | 0.9 |
EQD210, Dmax
| 0.992 | (0.967–1.017) | 0.5 | 0.998 | (0.988–1.008) | 0.7 |
EQD210, D95%
| 0.978 | (0.919–1.014) | 0.4 | 1.013 | (0.990–1.036) | 0.3 |
EQD22, mean liver dose
| n.a. | 1.009 | (0.967–1.054) | 0.6 | ||
BCLC | n.a. | 0.868 | (0.428–1.761) | 0.7 |
Overall survival
Toxicity
A.Toxicitiy | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
---|---|---|---|---|
No (%) | No (%) | No (%) | No (%) | |
Biochemical | ||||
ALT/AST (u/l) | 0 | 0 | 0 | |
Bilirubin (mg/dl) | 2 (4%) | 6 (13%) | 0 | |
INR | 0 | 0 | 0 | |
AP (U/l) | 1 (2%) | 0 | 0 | |
GGT (U/l) | 2 (4%) | 0 | 0 | |
GI-Toxicitiy | ||||
Gastrioduodenitis / GI bleeding | 2 (4%) | 1 (2%) | 0 | |
Liver-Toxicity | ||||
Abscess | 1 (2%) | |||
RILD | 1 (2%)b
| |||
Dekompensation | 1 (2%) | |||
B. | CTP Deteriorationa No (%) | |||
Score | ||||
1 Point | 4 | |||
2 Points | 1 (2%)b
| |||
Class | 2 (4%) |
Discussion
Author | Study | Nr. of patients | CTP | Diameter (cm)a
| Fractionation | LC@1 year | mOS | Toxicity |
---|---|---|---|---|---|---|---|---|
Mendez Romero [23] | Pr. | 5 2 | A B | 4.7 | 3-5 × 5–12 Gy | 75% | 22 | 1 lethal liver failure |
Tse [34] | Pr. | 31 | A | 173cm3b
| 6 × 4–9 Gy | 65% | 11.7 | 8 grade 3 enzyme elevations, 1 pulmonary embolism, 1 tumor-duodenal connection |
Jang [35] | Ret | 74 8 | A B | 3 | 3 × 11-20Gy | 87%@ 2 y. | 63%@ 2 y. | 5 GI toxicity grade 3 6 CTP elevation >2 |
Huang [36] | Ret | 23 4 1 | A B C | 4.4 | 10 × 4.5 Gy 18–20 × 2.5 Gy 18–20 × 1.8 Gy | 87.6% | 23 | 1 grade 3 gastric ulcer |
Bae [37] | Ret | 18 2 | A B | <3 cm (80%) 3-5 cm (20%) | 5 × 10 Gy | 85% | 100@ 1 y. | No grade 3 toxicities |
Jung [38] | Ret | 68 24 | A B | 8.6 cm3b
| 3-4 × 10-20Gy | 92%@ 3 y. | 6 patients grade 3 RILD | |
Wahl [12] | Ret. | 57 24 2 | A B C | <2 cm (48%) 2-3 cm (26%) 3-5 cm (23%) >5 cm (3.7%) | 3-5 × 6–10Gy | 97.4% | 74%@ 1 y. | 1 RILD, 1 GI bleeding 1 worsening ascites |
Andolino [9] | Ret. | 36 24 | A B | 3.1 cm | 3-5 × 8-16Gy | 90%@ 2 y. | 48%@ 2 y. | 20% CTP progression |
Bibault [22] | Ret. | 66 9 | A B | 3.7 cm | 3 × 8-15Gy | 89.8% | 15 | 5 liver decompensations, 1 grade 4 gastric ulcer, 3 grade 2 duodenal ulcers |
Huertas [21] | Ret. | 76 11 | A B | 2.4 cm | 3x15Gy | 99% | 82%@ 1 y. | 1 grade 5 hematemesis 2 grade > 3 gastric ulcers |
Scorsetti [24] | Ret. | 23 20 | A B | 4.8 cm | 3 × 16–25 Gy 6 × 6–10 Gy | 86% | 18 | 7 grade > 3 liver enzyme elevations |
Seo [39] | Ret. | 34 4 | A B | 40.5mlb
| 3 × 11-12 Gy | 79% | 32 | 1 grade 3 soft tissue toxicity |
Kwon [40] | Ret. | 38 4 | A | 15.4mlb
| 3 × 10-13Gy | 72% | 93%@ 1 y. | 1 radiation induced hepatic failure |
Takeda [41] | Ret. | 14 2 | A B | 1.9-7 cm | 5-7 × 5-10Gy | 100% | 100% | 1 RILD |
Price [42] | Ret. | 14 12 | A B | max. 6 cm | 3-5 × 8-16Gy | 97% | 77% | 20% CTP worsening |
Kang [43] | Pr. | 41 6 | A B | 2.9 cm | 3 × 14-20Gy | 94%@ 2 y. | 68.7@ 2 y. | 3 grade 3 GI toxicity, 2 grade 4 gastric ulcers |
Su [44] | Ret | 114 18 | A B | 1.1–5.0 cm | 1 × 28-30Gy 42–46 Gy in 3–5 fractctions | 90% | 11 patients hepatic toxicity grade ≥ 3 | |
Kang [45] | Ret | 67 34 | A B | n.s. | 6 fractions | 20–29.4 @ 2y | 12–15 | 25 cases deteriorated from grade A to B, 4 from A to C and 6 from B to C |
Sanuki [46] | Ret | 158 27 | A B | 2.7 (0.8–5) cm | 5 × 7–8 Gy | 91% @ 3 y. | 70% @ 3 y. | 13% acute grade > 3, 2 grade 5 liver failure |
Kimura [47] | Ret | 56 9 | A B | 1.6 cm | 4 × 12 Gy | 100% @ 2 y. | 76% @ 2 y. | 23% grade > 3 |
Weiner [26] | Pr. | 12 | A,B | ca. 5 cm | 5 × 8–11 Gy | 91% | 38%@ 1 y. | 9 CTP decline 2 grade 5hepatic failure |
Que [48] | Ret | 104 11 | A B | ≤ 4 cm (35%) 4–9 cm (41%) ≥10 cm (24%) | 26–40 Gy in 3–5 fract. | 85% | 15 | 3 patients grade 5 25 patients grade 3 |
Que [27] | Ret. | 22 2 | A B | 11.4 cm | 5 × 5.2-8Gy | 55.6% | 11 | 1 grade 3 liver enzyme elevation |
Bujold [10] | Pr. | 102 0 | A B | 7.2 cm | 6 × 4-9Gy | 88% | 17 | 6 grade > 3 liver failures, 1 grade 5 cholangitis, 1 grade 5 GI bleed 16 grade ≥ 3 enzyme elevations |
Culleton [33] | Pr./ Ret. | 0 29 | A B | 5.1 cm | 5–15 fractions 19.7–46.8Gyc
| n.a. | 7.9 | 63% CTP decline ≥ 2 points, 5 grade 3 thrombocytopenia, 3 > grade 3 elevation of liver enzymes |
Current study | Ret | 28 19 | A B | 7 cm | 3-12 × 4-15Gy | 77% | 9 | 1 RILD, 1 grade 5 liver decompensation, 1 grade 3 GI-bleed, 1 necrotic abscess |