Table 1. Prospective studies.
| Study | Year | Type of study | Sample size | Age, median [min–max] | Dose schedule | CP-class | Median follow-up (months) | OS rate | LC | PFS | Acute toxicity |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Romero | 2006 | Phase 1/2 | 8 (HCC), 17 (Mets) | NA | 37.5 Gy/3 fx (4 pts) 30/3 (1 pt), 25/5 (3 pts) |
A: 5 B: 3 |
12.9 | Actuarial OS 75% (1-yr) 40% (2-yr) |
82% (1-yr crude) | NA | Grade 5: 1 HCC CP-B with Grade 5 toxicity (liver failure + infection → died) RILD, classic: 1 HCC RILD, non-classic: 1 HCC |
| Cardenes | 2010 | Phase 1 | 17 | 61 [46–83] | 36 Gy/3 fx 12–16 Gy/3 fx (12 pts) 8 Gy/5 fx (5 pts) |
A: 6 B: 11 |
18 | 75% (1-yr) 60% (2-yr estimated) |
100% (at median f/u of 24 mos) | NA | Classic RILD in 3/17 pts, all with CTP-B. |
| Bujold | 2013 | Phase 1/2 | 102 | 69 [40–90] | Median 36 Gy/6 fx | A: 102 | 31.4 | 55% (1-yr) 34% (2-yr) |
87% (1-yr) | Median time to progression: 6.0 mos | Classic RILD: none death from tx: 7 patients (possibly) DLT not reached in Trial 1 |
| Culleton | 2014 | Prospective/retrospective | 29 (14 prospective, 15 retrospective) |
63 [44–82] | Median: 30 Gy/6 fx | A: 0 B: 28 C: 1 |
NA | 32.3% (1-yr) (95% CI: 12.4–54.3) | NA | Progression rate: 30.3% (6 mos) 44.5% (1-yr) |
G3+ toxicity: none |
| Wang | 2014 | Feasibility | 20 | 68 [47–81] | 50 Gy/5 fx | A: 18 B: 2 |
7.4 | Mean actuarial OS: 9.6±0.9 mos (95% CI: 7.8–11.4 mos) | NA | NA | RILD (G3, 1 pt, G1/2, 6 pts) Ascites (G1, 2 pts, G2, 4 pts) Various Grade 2 toxicities |
| Lasley | 2015 | Phase 2 | 59 | 61 [24–86] | via Cardenes 2010 | A: 38 B: 21 |
CP-A: 33.3 CP-B: 46.3 |
Median OS: 44.8 (CP-A), 17.0 CP-BK-M: CP-A: 2-yr 72%, 3-yr 61% CP-B: 2-yr 33%, 3-yr 26% (P=0.03) |
CP-A: 6 mos (92%), K-M 2, 3 yr (91%) CP-B: 1, 2, 3 yr: 82% |
Median: 2.3 (CP-A), 10.0 (CP-B) 1-2-3 yr: 69.7% at 1 yr, 47.8% at 2/3 yrs (CP-A); 1-2-3 yr: 42.9% at 1yr and 22.9% at 2/3 yrs (CP-B) |
Grade 3/4 liver Toxicity: CP-A: 4 (11%) pts CP-B: 8 (38%) pts |
| Kim | 2016 | Phase 1 | 18 | 59.5 [42–83] | 36–60 Gy/4 fractions in 2 Gy increments | A: 18 | 28 | 94.4% (1-yr) 69.3% (2-yr) |
77.8% (1-yr) 71.3% (2-yr) |
55.6% (1-yr) 49.4% (2-yr) |
G3 hematologic toxicity (5 patients) G2+ GI toxicity (0 patient) |
| Weiner | 2016 | Phase 1/2 | 12 (with HCC) others with IHC |
72 [51–95] | 55 Gy/5 fractions | A: 23 B: 6 |
All pts: 8.8 | HCC: Median 9.8 mos, 1-yr (38%) | 91% (1-yr overall) | Median 5.3 mos (HCC), 1-yr 48% (HCC) | G3+ toxicity: 17 patients |
| Takeda | 2016 | Phase 2 | 90 | 73 [48–85] | 35 Gy/5 fx (10 pts) 40 Gy/5 fx (80 pts) |
A: 82 B: 8 |
41.7 | 66.7% (3-yr) | 96.3% (3-yr) | NA | G3 Lab abnormalities: LFTs (2 pts) TCP (4 pts) G4-5 liver failure: 0 pts |
| Schoenberg | 2016 | Observational | 18 | 72 [48–92] | 26 Gy/1 fx | A: 12 B: 5 |
29 | 84.8% (1-yr) 66% (3-yr) |
LC achieved in 17/18 pts with mean f/u of 29.6 | Mean recurrence-free survival 21.8 mos, tumor-free survival 79.4% (1 yr), 29.8% (3 yrs) | Mild adverse reactions (e.g., nausea): 2 pts |
| Feng | 2017 | Phase 2 | 90 (69 HCC, 4 IHC, 17 mets) | 62 [34–85] (overall) | 23–60 Gy/5 fx (most common) | A: 69 B: 21 |
All pts: 37 | NA | All: 99% (1-yr) HCC: 95% (2-yr) |
NA | G2 ascites: 1 pt G3 ascites: 1 pt |
| Scorsetti | 2015 | Observational | 43 | 72 [46–87] | 48–75 Gy/3 fx (51%) 36–60 Gy/6 fx (49%) |
A: 23 B: 20 |
8 | 77.9% (1-yr) 45.3% (2-yr) |
85.5% (1-yr) 64.4% (2-yr) |
40.9% (1-yr) | No G3+ toxicity, no classic RILD G3+ transaminases: 7 patients (16%) |
CP, Child-Pugh; RILD, radiation-induced liver disease; DLT, dose-limiting toxicity; G1, G2, G3, Grade 1, 2, 3; Gy, Grey; Fx, fraction; TCP, thrombocytopenia; IHC, intrahepatic cholangiocarcinoma; GI, gastrointestinal; Pt, patient; Tx, treatment; NA, not available/applicable.