Will the collaboration of surgery and external radiotherapy open new avenues for hepatocellular carcinoma with portal vein thrombosis?

Table 1 Summary of key studies according to the treatment method

Ref.	Study type	Number of patients	Main outcomes
Radiotherapy studies
Rim et al[33], 2018	Meta-analysis of observational studies	2111 with PVT	Pooled 1- and 2-yr OS: 43.8% and 22.3%, respectively (3DCRT)
			Pooled 1- and 2-year OS: 48.5% and 26.8%, respectively (SBRT)
			Grade 3 complications less than 5% to 10%
Huo et al[34], 2015	Comparative meta-analysis	2577 underwent TACE or RTx	TACE and RT had OS benefit compared with TACE alone
			ORs: 1.55, 1.91, 3.01, and 3.98 for 2-, 3-, 4-, and 5-yr OS rates, respectively
Yoon et al[35], 2018	Randomized trial	90 with major vascular invasion	TACE and RT had survival benefit compared with sorafenib
			Median OS 55 wk vs 43 wk, P = 0.004
			Median PFS 31 wk vs 11.7 wk, P < 0.001
Lee et al[13], 2021	Observational study using national database	444 propensity-matched patients with PVT	Local treatment including RTx had survival benefit compared with no oncologic treatment
			Median OS: 8 mo vs 2 mo, P < 0.001
			Median CSS: 8 mo vs 2 mo, P < 0.001
			OS and CSS benefit persist in the CPC A and CPC B subgroups
Surgery studies
Kokudo et al[41], 2016	Observational study using national database	2116 propensity-matched patients with PVT	Surgery had benefit compared with non-surgery
			Median OS: 2.45 yr vs 1.57 yr, P < 0.001
			Surgery benefit was not observed in the Vp4 subgroup (P = 0.242)
Wang et al[42], 2016	Retrospective study	1580 with PVT underwent (1) surgery, (2) TACE, (3) TACE with sorafenib, or (4) TACE with RTx	Median OS:
			Cheng’s type I: 15.9 vs 9.28 vs 12.0 vs 12.2 (P < 0.001)
			Cheng’s type II: 12.5 vs 4.9 vs 8.9 vs 10.6 (P < 0.001)
			Cheng’s type III: 6.0 vs 4.0 vs 7.0 vs 8.9 (P = 0.001)
Shi et al[43], 2010	Retrospective study	406 with PVT underwent surgery	Surgery showed better outcomes in Cheng’s type I and type II (1-yr OS: 52% and 38%, respectively) PVT than type III and IV (1-yr OS: 25% and 18%, respectively)
Chen et al[44], 2006	Retrospective study	438 with PVT underwent surgery	Surgery yielded satisfactory results in Cheng’s type I and II PVT (1- and 2-yr OS: 58.7% and 39.9%, respectively), not in types III and IV (1- and 2-yr OS: 39.5% and 20.4%, respectively)
Combined surgery and radiotherapy
Chong et al[46], 2018	Retrospective study	26 underwent surgery following CCRT vs 18 underwent surgery alone	Surgery following CCRT had benefit on surgery alone
			Median DSS: 62 wk vs 15 wk, P = 0.006
			Median DFS: 32 wk vs 3 wk, P = 0.002
Sun et al[47], 2019	Randomized trial	26 underwent surgery with adjuvant IMRT vs 26 surgery alone	Adjuvant IMRT significantly improved clinical outcomes
			Median OS: 18.9 mo vs 10.8 mo, P = 0.005
			Median DFS: 9.1 mo vs 4.1 mo, P = 0.001
Wei et al[49], 2019	Randomized trial	82 neoadjuvant RT vs 82 surgery alone	1- and 2-yr OS: 75.2% and 27.4%, respectively (neoadjuvant RT)
			1- and 2-yr OS: 43.2% and 9.4%, respectively (control)
			RT benefited Cheng’s type I and II PVT as well as type III PVT
Li et al[50], 2016	Comparative study	45 neoadjuvant RT vs 50 surgery alone	Neoadjuvant RT decreased the rates of HCC recurrence [49% vs 88.7%, respectively (P < 0.001)] and increased overall survival [1-yr OS: 69% vs 35.6%, respectively (P < 0.01)]

PVT: Portal vein thrombosis; OS: Overall survival; 3DCRT: 3-dimensional conformal radiotherapy; SBRT: Stereotactic body radiotherapy; TACE: Transarterial chemoembolization; RTx: Radiotherapy; PFS: Progression-free survival; CSS: Cause-specific survival; CPC: Child-Pugh class; CCRT: Concurrent chemoradiotherapy; DSS: Disease-specific survival; IMRT: Intensity-modulated radiotherapy.