Combined treatments in hepatocellular carcinoma: Time to put them in the guidelines?

Table 7 Radiofrequency ablation combined with immunotherapy

Ref.	BCLC, n (%)	Treatment, n (%)	Results	Level of evidence
Cui et al[100], 2014	A (10); B (10); C (10)	RFA and cellular immunotherapy 8-11 d after RFA vs RFA alone	Higher PFS (P < 0.001). Six courses had better survival prognosis than three courses	III
Ma et al[99], 2010	A (7)	RFA and autologous RAK cells 14 d after RFA	No severe adverse events, recurrences or deaths during a seven month follow-up	IV
Duffy et al[98], 2017	C (21)	Tremelimumab every 4 wk and subtotal RFA on day 36	Median OS-12.3 mo. Median time to progression–7.4 mo. A significant increase of CD3+ and CD8+ immune cells infiltrates in lesions not treated by RFA	III
Lee et al[102], 2015	A (114)	PEI (13); RFA (69); Surgery (32) and adjuvant CIK cells vs PEI, RFA or Surgery alone	OS was significantly longer in the immunotherapy group than in control group (P = 0.006). CSS was significantly longer in the immunotherapy group (P = 0.02)	II
Tu et al[103], 2014	A and B	RFA and monoclonal antibody (131I-chTNT) injection during ablation vs RFA alone	Increased OS. Improved progression-free survival. Increased circulating white blood cells	IV
Bian et al[104], 2014	0 + A (94); B (33)	RFA and adjuvant 131I metuximab vs RFA alone	Prevention of tumor recurrence	II
Lee et al[101], 2019	0 and A (239)	RFA or PEI or Surgery plus CIK vs RFA or PEI or surgery alone	Increased recurrence-free survival and OS	I

BCLC: Barcelona Clinic Liver Cancer Classification; RFA: Radiofrequency ablation; PEI: Percutaneous ethanol injection; CIK: Cytokine-induced Killer; OS: Overall survival; CSS: Cyberchondria severity scale; PFS: Progression-free survival.