Table 1.

Clinical outcomes following proton radiotherapy for hepatocellular carcinoma

Study	N	Study type	Inclusion	Median dose	Child-Pugh Score	Outcome	Toxicity (≥ Gr 2)	Comments
Chiba et al. (2005)	162	Retrospective	Local HCC, <3 lesions.	72 CGE (50–88) 4.5 CGE/fx (2.9–6)	A: 50.6% B: 38.3% C: 6.2%	5 yr OS: 23.5% 5 yr LC: 86.9% Class A and solitary lesion: 5 yr OS 53.5%	Acute: 16.6% Late: 2.7%	HCV in 80%; Prior and concurrent treatment NS.
Nakayama et al. (2009)	318	Retrospective	Local HCC, <3 lesions, PS 0-2.	72.6 CGE (55/10fx-79.2/22fx)	A: 73.6% B: 24.2% C: 2.2%	5 yr OS: 44.6% 5 yr LC: NS	Acute:12.2% Late: 4%	HCV in 78%; Dose altered based upon tumor location; 56.6% treated with other local modality prior to proton.
Bush et al. (2004)	34	Prospective	Local HCC, Child score ≤ 10.	63 CGE/15 fx	Score: 5–6: 14 7–8: 7 (?) 9–10: 7 (?)	2 yr OS: 55% 2 yr LC: 75%	Acute (not graded): 60%, no hospitalizations Late: Post-treatment ascites in 17%	HCV NS; 6 patients received liver transplant post-treatment with 2 CR.
Kawashima et al. (2005)	30	Prospective	Local HCC, ≥ 20 years old, all tumors within target volume and not invasive of GI tract, no previous abdominal radiation, no recent HCC treatment, bilirubin ≤ 3.0 mg/dL, AST and ALT < 5.0 X ULN, PS 0-2.	76 CGE/20 fx	A: 67% B: 33%	3 yr OS: 62% 3 yr LC: ~95%	Acute: NS Late: HI within 6 months of treatment in 27%	HCV in 90%; ICG R15 used to determine functional liver reserve.
Fukumitsu et al. (2009)	51	Prospective	Local HCC , ≤3 tumors ≤10 cm in diameter and ≥2 cm from the porta hepatis or GI tract, PS 0-2.	66 CGE /10 fx	A: 80.4% B: 19.6%	5 yr OS: 38.7% 5 yr LC: 87.8%; CR in 57%	Acute: NS Late: 8%	HCV in 66.6%; 65% had prior local therapy.

Abbreviations: HCC – Hepatocellular carcinoma, PS –performance status, Fx – fraction, OS – overall survival, LC – local control, NS – not specified, CR – complete response, HCV – hepatitis C virus & ICG R15 - indocyanine green clearance and retention rate at 15 minutes, HI – hepatic insufficiency.