Residency · Residency · Interventional Radiology

Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma

Hepatocellular Carcinoma Background

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the fifth most common cancer worldwide. Major risk factors include hepatitis B, hepatitis C, alcohol-related liver disease, NAFLD/NASH, and cirrhosis of any cause. The liver has a dual blood supply: the hepatic artery provides 25-30% and the portal vein provides 70-75% of blood flow. Critically, HCC derives more than 95% of its blood supply from the hepatic artery. This arterial dependence is the physiologic basis for all transarterial therapies.

BCLC Staging System

Stage 0 (Very Early) encompasses a single nodule less than 2 cm with preserved liver function (Child-Pugh A) and ECOG 0, treated with resection, ablation, or liver transplant. Stage A (Early) includes single or up to 3 nodules less than 3 cm with Child-Pugh A-B and ECOG 0, treated with resection, ablation, or transplant. Stage B (Intermediate) involves multinodular disease without vascular invasion or extrahepatic spread, in Child-Pugh A-B patients with ECOG 0, and TACE is the standard of care for this stage. Stage C (Advanced) includes portal vein invasion, extrahepatic spread, or ECOG 1-2, treated with systemic therapy (atezolizumab-bevacizumab, sorafenib, lenvatinib), though TACE may be used in select cases controversially. Stage D (Terminal) encompasses Child-Pugh C with ECOG 3-4, managed with best supportive care.

TACE Principles

TACE combines targeted chemotherapy delivery with ischemia induction. The procedure involves selective or superselective hepatic artery catheterization to the tumor-feeding arteries, delivery of a chemotherapeutic agent followed by embolic material, and a dual mechanism of action: high local drug concentration plus ischemic necrosis from arterial occlusion. Normal liver parenchyma survives because of portal venous blood supply, making a patent portal vein a critical requirement.

Conventional TACE (cTACE)

Technique

A chemotherapy agent (typically doxorubicin 50-75 mg or cisplatin 50-100 mg) is mixed with ethiodized oil (Lipiodol), which serves as both drug carrier and radio-opaque contrast agent. The mixture is injected selectively into tumor-feeding arteries, followed by embolization with gelatin sponge (Gelfoam) particles to achieve stasis. Lipiodol is preferentially retained by HCC tumor cells because they lack Kupffer cells and the reticuloendothelial system.

Lipiodol Uptake

Post-procedure non-contrast CT at 1-4 weeks assesses Lipiodol retention. Dense, homogeneous uptake correlates with tumor necrosis and treatment response, while areas without retention indicate viable residual tumor that may need retreatment.

Drug-Eluting Bead TACE (DEB-TACE)

Concept

Microspheres loaded with doxorubicin (DC Bead, HepaSphere, LifePearl) provide sustained, controlled drug release directly into the tumor bed while simultaneously embolizing with the microspheres themselves.

Bead Sizes

Available in 70-150, 100-300, and 300-500 micron ranges, with smaller beads penetrating more distally into the tumor vasculature and larger beads causing more proximal occlusion. The typical approach uses 100-300 micron beads for most HCC.

Drug Loading

Standard loading is doxorubicin 75-150 mg onto beads, with drug elution occurring over days to weeks.

cTACE vs. DEB-TACE

The PRECISION V trial showed that DEB-TACE achieved similar tumor response to cTACE with fewer systemic side effects including less doxorubicin-related toxicity such as alopecia and myelosuppression. Multiple meta-analyses have found no clear survival advantage of DEB-TACE over cTACE. DEB-TACE may be preferred in patients at higher risk for systemic toxicity, while cTACE may be preferred when Lipiodol uptake assessment is desired for treatment monitoring. Both are acceptable, and choice often depends on institutional preference and operator experience.

Patient Selection

Patients must have a confirmed HCC diagnosis (LI-RADS 5 on contrast-enhanced CT/MRI, or biopsy-proven). TACE is indicated for BCLC Stage B (intermediate), select Stage A patients not candidates for curative therapy, and select Stage C patients. Child-Pugh A or B7 is generally safe for TACE, while Child-Pugh B8-9 carries higher risk of hepatic decompensation, and Child-Pugh C is a contraindication. A patent main portal vein is essential because occluded portal vein combined with arterial embolization causes hepatic ischemia and infarction. Selective or superselective TACE may be feasible with segmental/lobar portal vein thrombosis if contralateral portal flow is maintained. ECOG performance status should be 0-1, renal function must be adequate for contrast use, and arterioportal shunting should be assessed as large shunts are relative contraindications.

Procedure Technique

Arterial access is obtained (femoral or radial), followed by celiac and SMA angiography to map hepatic arterial anatomy. Variant anatomy is common, with replaced or accessory hepatic arteries present in 20-40% of patients. Extrahepatic tumor supply from phrenic, intercostal, or omental branches should be identified. Selective catheterization of the feeding artery is performed, followed by superselective microcatheter advancement into the segmental or subsegmental artery feeding the tumor. The chemotherapy-Lipiodol mixture or drug-eluting beads are administered, and embolization proceeds to stasis (near-stasis for DEB-TACE; complete stasis for cTACE with Gelfoam). Completion angiography confirms tumor devascularization.

Treatment Response Assessment

The mRECIST criteria, based on enhancement of viable tumor on contrast-enhanced imaging, define complete response as disappearance of arterial enhancement in all target lesions, partial response as greater than 30% decrease in the sum of diameters of viable (enhancing) target lesions, stable disease as not meeting criteria for PR or PD, and progressive disease as greater than 20% increase in viable tumor or new lesions. MRI with contrast (preferred) or CT at 4-8 weeks post-treatment is obtained, and TACE is repeated every 6-12 weeks until complete response or treatment failure.

Repeat Treatments and the Concept of TACE Failure

TACE is typically performed in multiple sessions. TACE failure or refractoriness is defined as failure to achieve objective response after 2 consecutive sessions, or development of vascular invasion or extrahepatic spread after TACE. Once refractory, patients should transition to systemic therapy (atezolizumab-bevacizumab) or consider Y-90 radioembolization. The ART score and ABCR score can help predict benefit of retreatment.

Complications

Post-embolization syndrome (pain, fever, nausea) is the most common complication. Hepatic decompensation with worsening liver function, ascites, and encephalopathy can occur, with risk increasing with poor baseline function. Liver abscess is rare but has higher risk with bilioenteric anastomosis. Non-target embolization can cause gallbladder infarction (cystic artery) or gastric/duodenal ulceration. Biliary injury from ischemic cholangiopathy and vascular injury including hepatic artery dissection or spasm are additional risks.

<image>Illustration of the dual blood supply to the liver and the principle of TACE. A diagram showing the liver with the portal vein providing 70-75% of blood flow to normal hepatocytes and the hepatic artery providing 25-30%. A magnified inset shows an HCC tumor nodule receiving >95% of its blood supply from the hepatic artery. Arrows demonstrate the TACE concept: chemotherapy-Lipiodol mixture or drug-eluting beads delivered selectively through the hepatic artery to the tumor, causing ischemic necrosis while normal liver parenchyma survives on portal venous blood flow.</image>

<image>Comparison of conventional TACE and drug-eluting bead TACE. Two parallel panels: Left panel shows cTACE with a syringe injecting doxorubicin-Lipiodol emulsion through a microcatheter, with an inset showing Lipiodol droplets carrying doxorubicin within tumor vessels and a subsequent CT showing dense Lipiodol uptake in the treated tumor. Right panel shows DEB-TACE with microspheres loaded with doxorubicin being injected, with an inset showing beads lodged in tumor arterioles releasing drug over days, and a subsequent MRI showing lack of arterial enhancement (mRECIST complete response). A comparison table below lists drug delivery mechanism, systemic side effects, and response assessment method for each.</image>

<image>Angiographic sequence of a selective TACE procedure. Four panels: (1) Celiac angiogram showing the hepatic arterial anatomy with a hypervascular mass in the right lobe; (2) Selective right hepatic arteriogram showing the tumor blush with hypertrophied feeding arteries; (3) Superselective microcatheter position in the segmental feeding artery with injection of chemoembolization agent; (4) Post-TACE angiogram showing complete devascularization of the tumor with no residual blush. Labels identify the celiac trunk, common hepatic artery, right hepatic artery, and the tumor.</image>

Clinical Pearls

TACE is the standard of care for BCLC Stage B (intermediate) HCC, so knowing the staging system is essential. A patent main portal vein is required for safe TACE, as embolic therapy with a completely thrombosed main portal vein risks hepatic failure. Superselective catheterization minimizes non-target embolization and preserves liver function, so the most selective position possible should always be the goal. Variant hepatic artery anatomy is present in 20-40% of patients, making celiac and SMA angiography mandatory to identify replaced or accessory arteries. The mRECIST (not standard RECIST) is the appropriate response assessment criterion for HCC because it measures viable enhancing tumor rather than total tumor size. TACE failure should be recognized early (no response after 2 sessions) and patients transitioned to systemic therapy rather than repeating ineffective treatments. Post-embolization syndrome is expected and should be differentiated from complications such as abscess or hepatic decompensation.

References

• Lammer J et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of HCC (PRECISION V). Cardiovasc Intervent Radiol 2010
• Defined by the EASL Clinical Practice Guidelines on HCC. J Hepatol 2018
• Defined by the AASLD Practice Guidance on HCC. Hepatology 2023
• Defined by the SIR Quality Improvement Guidelines for TACE. J Vasc Interv Radiol 2017
• Defined by Defined by the BCLC Strategy for HCC Prognosis Prediction and Treatment Recommendation. Hepatology 2022

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