Table 1.

Lessons learned from recent comparative studies of stereotactic body radiotherapy and other locoregional therapies for unresectable HCC.

LC	Superior LC with SBRT versus TACE (∼2–4 times) [6], [7], [8]; also noted with HF-PBT [32] •Consider SBRT over TACE where high risk of TACE-related toxicity, poor response to or progression after prior TACE, HCC with MVI where LRT is considered
	Superior LC with SBRT versus RFA [11], [12], [13], [14]; also noted with HF-PBT [17] •Consider SBRT over RFA for larger tumors (especially subphrenic) and poor response to or progression after prior TACE
	Limited data comparing SBRT and TARE with Y-90 suggests comparable LC [18], [19]
OS and PFS	Similar OS following SBRT as compared to TACE [6], [7], [8], RFA [11], [13], and TARE [18], where LRT has established role
	Extrapolate superior PFS with SBRT versus TACE from HF-PBT literature [32]
	Improved median OS (Δ 3.5 months) and PFS (Δ 3.7 months) with addition of SBRT to Sorafenib for locally advanced HCC with MVI [27] •Await efficacy and safety data from future trials of current SoC systemic therapy (i.e. Atezolizumab/Pembrolizumab) +/- SBRT •Avoid off-trial concurrent SBRT and Atezolizumab/Bevacizumab, particularly when tumor proximal to luminal GI structures •Consider off-trial SBRT prior to Atezolizumab/Bevacizumab only upon MDD and individualized decision making
Toxicity and QoL	Lower toxicity with SBRT versus TACE [33], [34], [6], [7], [8]
	Similar toxicity with SBRT as RFA and Y-90 [19], [11], [12], [13]
	Similar toxicity and improved QoL when adding SBRT to Sorafenib [27] •Use SBRT if LRT is considered for patients on TKI given no increase in toxicity
Cost-effectiveness	Use of SBRT over TACE eliminates need for hospitalization [36]
	SBRT may have less treatment-related costs for patients and health systems than TACE and TARE [19], [32], [37]
Technical Considerations	SBRT allows optimized prescription of ablative dose to the entire tumor target across a range of tumor sizes and peritumor vascularity
	TACE may induce damage to peritumoral vasculature, creating hypoxic conditions promoting recurrence [9]
	RFA may be limited by the heat-sink effect, which may result in incomplete ablation of perivascular disease [15]
	TARE with Y-90 has unclear dosimetry; aggressive escalation of median (partial) doses less likely to predict treatment response than coverage of GTV with ablative dose [21], [22]

Abbreviations: LC = local control; OS = overall survival; PFS = progression-free survival; QoL = quality-of-life; SBRT = stereotactic body radiotherapy; TACE = transarterial chemoembolization; HF-PBT = hypofractionated proton beam therapy; HCC = hepatocellular carcinoma; MVI = macrovascular invasion; LRT = locoregional therapy; RFA = radiofrequency ablation; TARE = transarterial radioembolization; Y-90 = Yttrium-90; PFS = progression-free survival; SoC = standard-of-care; GI = gastrointestinal; MDD = multidisciplinary discussion; TKI = tyrosine kinase inhibitor; GTV = gross tumor volume.