How does lattice radiotherapy compare to Transarterial Chemoembolization (TACE) and Transarterial Radioembolization (TARE) in the treatment of hepatocellular carcinoma?

Lattice Radiotherapy in HCC: Position Relative to TACE and TARE

Lattice radiotherapy is not mentioned in any current major hepatocellular carcinoma treatment guidelines and lacks evidence for use in HCC management, making it inappropriate to recommend over established transarterial therapies like TACE or TARE. 1, 2

Current Evidence-Based Treatment Hierarchy

First-Line Locoregional Therapy for Intermediate-Stage HCC

TACE remains the guideline-recommended standard of care for BCLC stage B (intermediate) HCC with preserved liver function (Child-Pugh A or favorable B7), no vascular invasion, and ECOG performance status 0-1. 1, 2 The American Association for the Study of Liver Diseases, European Association for the Study of the Liver, and Korean Liver Cancer Association all designate conventional TACE (cTACE) as the primary treatment option with Level A1 evidence. 1, 2

When TARE Supersedes TACE

TARE should be selected over TACE in three specific clinical scenarios: 2, 3

• Portal vein thrombosis present - TARE is safer than TACE when portal vein invasion exists, as TACE significantly increases risk of post-procedural liver failure in this setting 2, 3, 4
• Large tumors >6 cm - TARE achieves better tumor penetration and response in larger lesions compared to TACE 2, 3
• TACE failure after 2-3 sessions - Switch to TARE when no radiological response occurs after repeated TACE 2, 5

Recent multicenter data from 2025 showed TACE demonstrated superior survival over TARE in early-stage disease (mOS 60 vs 25 months in BCLC 0/A; HR 2.35, p=0.016), though TARE patients had larger baseline tumors. 6 However, TARE resulted in better quality of life and lower post-embolization syndrome rates compared to TACE. 1

External Beam Radiation Therapy Position

Conventional external beam radiation therapy (EBRT), including stereotactic body radiation therapy (SBRT) and proton beam therapy (PBT), occupies a secondary role reserved for patients unsuitable for resection, transplantation, ablation, or TACE. 1 The 2022 Korean guidelines specify EBRT is performed when:

• Liver function is Child-Pugh grade A or B7 1
• Volume receiving ≤30 Gy is ≥40% of total liver volume 1, 3
• Combined therapy after incomplete TACE response 1
• Treatment of HCC with portal vein invasion 1

SBRT may achieve comparable local control rates to RFA for HCCs ≤3 cm (C2 evidence level), but this remains lower quality evidence than TACE recommendations. 1

Critical Gap: Lattice Radiotherapy

No major HCC guideline (AASLD, EASL, KLCA-NCC, JSH, APASL, ESMO-Asia, INASL) from 2015-2025 mentions lattice radiotherapy as a treatment modality. 1, 2 The technique is absent from:

• Treatment algorithms for any BCLC stage 1, 2
• Locoregional therapy comparisons 1
• Radiation therapy sections discussing EBRT, SBRT, or PBT 1

Practical Treatment Algorithm

For unresectable HCC, follow this hierarchy: 1, 2, 5

1. Child-Pugh A, no portal vein thrombosis, tumor burden <4 nodules or <7 cm solitary → TACE first-line 2, 5

2. Child-Pugh A with portal vein thrombosis OR large tumor >6 cm → TARE preferred 2, 3, 4

3. After TACE failure (no response after 2-3 sessions within 6 months) → Switch to TARE or systemic therapy 1, 2

4. Unsuitable for TACE/TARE (decompensated cirrhosis, complete portal vein occlusion, ECOG ≥2) → Consider EBRT/SBRT if liver function permits (Child-Pugh A or B7) 1

5. EBRT/SBRT contraindicated or failed → Systemic therapy (atezolizumab + bevacizumab first-line) 1

Common Pitfalls

Avoid performing TACE when: 2, 5

• Decompensated cirrhosis (Child-Pugh C or decompensated B) exists - absolute contraindication 2
• Complete main portal vein occlusion present - use TARE instead 2, 3
• Extensive treatment planned for >50% liver volume - significantly increases liver failure risk 2

TARE requires careful patient selection: 3

• Hepatic decompensation occurs more frequently with TARE (26.0%) than TACE (13.7%) 6
• Radiation-induced liver disease (REILD) typically manifests 4-8 weeks post-TARE 3
• Contraindicated when future liver remnant <1.5L or Child-Pugh C 3

Without published evidence demonstrating safety, efficacy, or survival benefit in HCC, lattice radiotherapy cannot be recommended and should not replace guideline-supported transarterial therapies. 1, 2