Correlation of radiotherapy, targeted therapy, and immunotherapy with hepatocellular carcinoma recurrence

Table 1 The mechanism of action of radiotherapy, efficacy in hepatocellular carcinoma recurrence, main limitations and relevant improvement strategies

Type	Treatment	Mechanism	Efficacy	Limitations	Strategies	Ref.
External beam radiotherapy	3-DCRT	Adjust the direction of radiation beams based on the shape and location of the HCC lesion	3-DCRT significantly reduces the mortality and recurrence rates in resectable HCC patients with postoperative PVTT	Unsuitable for tumors with complex shapes or those located near critical organs	Replace with IMRT	Kim et al[18]; Wei et al[19]
	IMRT	Adjust the spatial distribution of a single radiation beam	The OS and RFS of patients with close surgical margins combined with IMRT are comparable to those of patients with wider surgical margins	Patients need a high number of treatment sessions and poor liver function exhibit poor tolerance	IMRT + SBRT	Wang et al[21]; Kim et al[24]
	SBRT	High-dose and high-selectivity radiation	Repeated SBRT for intrahepatic recurrent HCC is both safe and effective, with an overall 5-year local recurrence rate of only 6.3% (95%CI: 2.2%-13.4%)	High risk of liver damage outside the target area for multiple recurrent lesions	IMRT + SBRT; Repeated attempts at local control with close monitoring of liver function	Kimura et al[22];Kim et al[23];Kim et al[24];Ding et al[25]
Internal radiotherapy	IVBT (I-125)	γ-rays	Patients with high recurrence risk HCC, especially those with PVTT, demonstrate favorable treatment outcomes, with an ORR of 90% after one course of treatment	Poor systemic effects and inability to control micro-metastases; Incomplete radiation coverage; Patients with immunosuppression	TACE + sorafenib + I-125; Combined irradiation stent; 125I + CIK cells	Zhang et al[26];Huanget al[27];Lu et al[28];Zhang et al[29]
	SIRT (Y-90)	β-rays	In patients with PVTT, SIRT has been shown to significantly improve tumor response rates compared to sorafenib (19% vs 12%). Additionally, patients treated with Y-90 demonstrate a significantly reduced recurrence rate of HCC following LT and are more likely to achieve CPN	High cost; A certain risk of adverse events	Comprehensive pre-operative assessment	Gulec[30]; Hermann et al[32];Palmer et al[33];Chow et al[34];Dai et al[35];Agopian et al[36]

3-DCRT: Three dimensional-conformal radiotherapy; IMRT: Intensity-modulated radiotherapy; SBRT: Stereotactic body radiotherapy; SIRT: Selective internal radiotherapy; IVBT: Intravascular brachytherapy; HCC: Hepatocellular carcinoma; Y-90: Yttrium-90; I-125: Iodine-125; PVTT: Portal vein tumor thrombus; OS: Overall survival; RFS: Recurrence-free survival; ORR: Overall response rate; CI: Confidence interval; CPN: Complete pathological necrosis; CIK: Cytokine-induced killer; LT: Liver transplantation; TACE: Transarterial chemoembolization.