Phase I dose-escalation study of proton beam therapy for inoperable hepatocellular carcinoma.
OBJECTIVE
The purpose of this study is to determine the optimal dose of proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients.


METHODS
Inoperable HCC patients who had naïve, recurrent, or residual tumor to treatment were considered eligible for PBT. Patients received PBT with 60 GyE in 20 fractions (dose level 1; equivalent dose in 2 Gy fractions [EQD2], 65 GyE10); 66 GyE in 22 fractions (dose level 2; EQD2, 71.5 GyE10); or 72 GyE in 24 fractions (dose level 3; EQD2, 78 GyE10). Dose-limiting toxicity was determined by grade ≥ 3 acute toxicity.


RESULTS
Twenty-seven patients were enrolled; eight, seven, and 12 patients were treated with dose levels 1, 2, and 3, respectively. Overall, treatment was well tolerated, with no dose-limiting toxicities. The complete response (CR) rates of primary tumors after PBT for dose levels 1, 2, and 3 were 62.5% (5/8), 57.1% (4/7), and 100% (12/12), respectively (p=0.039). The 3-and 5-year local progression-free survival (LPFS) rates among 26 patients, excluding one patient who underwent liver transplantation after PBT due to its probable significant effect on disease control, were 79.9% and 63.9%, respectively, and the 3-and 5-year overall survival rates were 56.4% and 42.3%, respectively. The 3-year LPFS rate was significantly higher in patients who achieved CR than in those who did not (90% vs. 40%, p=0.003).


CONCLUSIONS
PBT is safe and effective and an EQD2 ≥ 78 GyE10 should be delivered for achievement of local tumor control.
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Tae Hyun
TH
Kim
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Joong-Won
JW
Park
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Yeon-Joo
YJ
Kim
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Bo Hyun
BH
Kim
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Sang Myung
SM
Woo
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Sung Ho
SH
Moon
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Sang Soo
SS
Kim
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Young-Hwan
YH
Koh
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Woo Jin
WJ
Lee
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Sang Jae
SJ
Park
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Joo-Young
JY
Kim
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Dae Yong
DY
Kim
Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
Chang-Min
CM
Kim
Hepatocellular carcinoma; Proton therapy; Radiotherapy