Radiotherapy as an immune checkpoint blockade combination strategy for hepatocellular carcinoma

Table 1 Four key steps of a radiation-induced immune response

Major steps	Ref.
Induction of antigen release and immunogenic cell death	[20-22]
Induction of antigen-presenting cell maturation and antigen presentation	[23,24]
Induction of T-cell recruitment and infiltration	[21,29-32]
Induction of tumor cell sensitization to immune-mediated cell death	[27,28,33]

Table 2 Ongoing clinical trials investigating the combination of radiotherapy and immune checkpoint inhibitors against hepatocellular carcinoma

NCT number	Institution	Disease	Estimated enrollment	Phase	Primary endpoint	Intervention
NCT04167293	China (Sun Yat-sen University Cancer Center)	HCC with portal vein invasion	116	II/III	6-mo PFS	SBRT + sintilimab vs SBRT
NCT03817736	Hong Kong (Queen Mary Hospital)	HCC	33	II	Number of patients eligible for curative surgical interventions	TACE/SBRT + ICI
NCT03203304	United States (University of Chicago)	Unresectable HCC	50	I	Number of participants with adverse events	Nivolumab + SBRT vs nivolumab and ipilimumab + SBRT
NCT04611165	South Korea (NCC)	HCC with major vascular invasion	50	II	PFS	Nivolumab + EBRT
NCT03482102	United States (MGH)	Locally advanced/unresectable or metastatic HCC or biliary tract cancer	70	II	ORR	Tremelimumab + durvalumab + RT
NCT03316872	Canada (UHN)	HCC progression after sorafenib	30	II	ORR	Pembrolizumab + SBRT
NCT04547452	China (West China Hospital)	Metastatic HCC	84	II	PFS	SBRT + sintilimab vs sintilimab
NCT04193696	China (Guangxi Medical University)	Advanced HCC	39	II	ORR	RT+ anti-PD-1 agent

HCC: Hepatocellular carcinoma; PFS: Progression-free survival; SBRT: Stereotactic body radiation therapy; TACE: Transcatheter arterial chemoembolization; ICI: Immune checkpoint inhibitor; NCC: National Cancer Center; EBRT: External beam radiotherapy; MGH: Massachusetts General Hospital; ORR: Overall response rate; RT: Radiotherapy; UHN: University Health Network; PD-L1: Programmed cell death ligand 1.