Table 5.
Clinical outcomes of proton therapy for hepatocellular carcinoma
| Reference | Institutions | Design | Patient number | Indication | Median size (cm) | Dose | Median f/u (range), mo | Local control | Overall survival | Adverse events |
|---|---|---|---|---|---|---|---|---|---|---|
| Chiba T, et al. [88] (2005) | Japan, Tsukuba | Retrospective | 162 | <3:27%, 3-5:56%, 5<:17% | 72 GyE/16 fx, 78GyE/ 20 fx, 84 GyE/24 fx, 50 GyE/10 fx | 87% (5-yr) | 24% (5-yr) | Very few acute reactions, 5 ≥Gr 2 toxicity | ||
| Fukuda K, et al. [95] (2017) | Japan, Tsukuba | Retrospective | 129 | CP A or B, ECOG 0-2, previously untreated | 3.9 | 77 GyE/35 fxl 72.6 GyE/22 fx, 66 GyE/10 fx (according to location) | 55 (43-67) | 94% (5-yr) | 69% (0/A stage), 66% (B stage), 25% (C stage) (5-yr) | No ≥Gr 2 late toxicity, radiation dermatitis was common, but no ≥Gr 3 toxicity |
| Bush DA, et al. [89] (2011) | United States, Loma Linda University | Phase I | 76 | CP A, B, or C, All with cirrhosis | 5.5 | 63 GyE/15 fx | Local control: 60/76 | Median PFS 36 months | 5 Gr2 toxicities, no significant overall deterioration of liver function | |
| Hong TS, et al. [91] (2014) | United States, MGH | Phase I | 15 | CP A or B | CTV: median 124 (20-581) cc | 45-75 GyE/15 fx | 69 (for survivors) | No infield recurrence, Marginal recurrence: 1/15 | 33% (3-yr), Median 12 months | 2 Gr 3 bilirubinemia, 1 Gr 3 gastrointestinal bleed, 1 Gr 5 stomach perforation |
| Kim TH, et al. [93] (2015) | Korea, NCC | Phase I | 27 | ≤6cm, CP A or B | 3.2 for dose level I, 2.3 for dose level II, 2.5 for dose level III | 60 GyE/20 fx, 66 GyE/22 fx, 72 GyE/24 fx | 71-83% (3-yr), CR: 63% for dose level I, 57% for dose level II, 100% for dose level III | 42% (5-yr), Median 38 months | No ≥Gr 2 late toxicity | |
| Kawashima M, et al. [94] (2005) | Japan, NCC Hospital East | Phase II | 30 | All with cirrhosis, R15 ≥ 15%, CP A or B | 4.5 | 76 GyE/20 fx | 31 | 96% (2-yr) | 66% (2-yr) | 8 hepatic insufficiencies, no hepatic insufficiency when ICG R15 <20% |
| Fukumitsu N, et al. [95] (2009) | Japan, Tsukuba | Phase II | 51 | CP A or B | 2.8 | 66 GyE/10 fx | 34 | 88% (5-yr) | 39% (5-yr) | 8 CPS deteriorations, late: 3 rib fractures, 1 Gr 3 radiation pneumonitis |
| Hong TS, et al. [92] (2016) | United States, MGH | Phase II | 49 | CP A or B | 5 | 58.05-67.5 GyE/15 fx | 19.5 (for survivors) | 95% (2-yr) | 63% (2-yr), Median 49.9 months | 4 Gr 3 toxicities |
| PVTT (+) | ||||||||||
| Lee SU, et al. [97] (2014) | Korea, NCC | Retrospective | 27 | PVTT(+), CP A or B | 7 | 50-66 GyE/20-22 fx | 13 (2-52) | Objective response rate: 63% for primary tumor, 56% for PVTT, local recurrence: 9/27 | 33% (2-yr), Median 13 months | No ≥Gr 3 toxicity |
| Sugahara S, et al. [98] (2009) | Japan, Tsukuba | Retrospective | 35 | PVTT(+), CP A or B | 6 | 72.6 GyE/22 fx | 21 (2-88) | CR: 8/35, PR: 21/35, local PFS: 20% (5-yr) | Median 22 months, 48% (5-yr) | 3 ≥Gr 3 acute toxicity, No ≥Gr 3 late toxicity |
| Hata M, et al. [99] (2005) | Japan, Tsukuba | Retrospective | 12 | PVTT(+), CP A or B | 6 | 50-72 GyE/10-22 fx | 28 (4-88) | CR: 2/12, PR: 10/12 | 58% (5-yr) | Mild acute toxicities, low late toxicity rate (3 mild telangiectasia) |
CP, child-pugh; ECOG, Eastern Cooperative Oncology Group; CR, complete response; PR, partial response; PFS, progression free survival; PVTT, portal vein tumor thrombosis; CTV, clinical target volume; ICG, Indocyanine green.