TACE and TARE for Liver Cancer: Selection and Technique

TACE (transarterial chemoembolisation) treats liver cancer by threading a catheter from the groin or wrist into the hepatic artery branch that feeds the tumour, injecting chemotherapy directly into it and then blocking the vessel. TARE (transarterial radioembolisation) uses the same route to deliver radioactive Yttrium-90 microspheres. Both work because liver tumours draw their blood from the hepatic artery, while the normal liver relies mainly on the portal vein.

Dr. Shobhit Singh, Consultant - Intervention Radiologist - Gastroenterology & Hepatology, BLK-Max Super Speciality Hospital, New Delhi, India, explained who is suitable for transarterial therapy, how conventional TACE has been refined with drug-eluting beads and balloon occlusion, when radioembolisation is preferred, and how ablation, TACE and radiotherapy are combined for tumours that no single treatment can clear. For the wider picture of liver cancer staging and transplant, see the complete guide to hepatobiliary interventional radiology.

How TACE and TARE treat liver cancer: the liver's dual blood supply

The principle rests on how a liver cancer is fed. The normal liver receives most of its blood from the portal vein. When the liver becomes cirrhotic, it forms regenerative nodules, and these too are supplied by the portal vein. Over time, some regenerative nodules progress to dysplastic nodules, and some dysplastic nodules become hepatocellular carcinoma (HCC).

Once HCC forms, it takes its blood from the hepatic artery, not the portal vein. A progressed HCC is characteristically fed by the hepatic artery, although some early, well-differentiated tumours are still hypovascular. Targeting the artery therefore targets the tumour, while the portal vein keeps the rest of the liver alive. That is the basis of every transarterial therapy: bland embolisation, TACE, hepatic artery infusion chemotherapy and TARE.

Bland embolisation: why blocking the artery alone is not enough

The simplest transarterial approach is bland embolisation. A catheter is passed from the femoral artery into the aorta, then into the hepatic artery and the branch supplying the tumour. The feeding vessels are blocked with gelatin sponge (gel foam), coils or another embolic agent, using very small particles. Cutting off the blood supply makes the tumour ischaemic and hypoxic, and its cells die.

That is the theory. In practice, Dr. Singh noted, papers and case reports show that bland embolisation helps only temporarily. As ischaemia sets in, the tumour recruits a blood supply from other parts of the liver, and the long-term effect is lost. Adding chemotherapy to the embolisation is what TACE was developed to do.

Who is suitable for TACE

Patient selection decides whether TACE works. Dr. Singh's criteria for conventional TACE are:

• Tumour size: larger than 3 cm and up to about 8 cm.
• Number: a single tumour is preferred, but multiple well-defined tumours are also treated.
• Enhancement: the tumour should enhance well on arterial-phase imaging, which shows that the injected drug will reach it.
• No portal vein involvement by the tumour and no extrahepatic disease (no spread outside the liver).
• Good liver function and performance status: no ascites, little or no jaundice, a good INR and good kidney function.

Factors that predict a poor result

TACE is unlikely to help much when the patient has:

• Child-Pugh class B liver function (moderately impaired; Child-Pugh grades cirrhosis from A, the best preserved, to C)
• an AFP (alpha-fetoprotein) above 4,000
• untreatable ascites
• a bilirubin above 3 mg/dL
• a performance status above 1 (on the ECOG scale, a patient who is unable to work, or more limited still)

Multiple lesions, a large tumour, an infiltrative tumour or portal vein thrombus are also drawbacks for conventional TACE. Dr. Singh's point is that newer variants, balloon-occluded TACE and drug-eluting bead TACE, now let his team offer TACE to most patients.

How conventional TACE is performed

1. Access. In the cath lab, the femoral artery in the groin or the radial artery at the wrist is punctured.
2. Selective catheterisation. The catheter is guided into the hepatic artery, and an angiogram maps the vessels supplying the tumour.
3. Chemotherapy. A chemotherapy drug, generally doxorubicin, is mixed with Lipiodol (an iodised poppy-seed oil that carries the drug and is retained by the tumour) and injected into the feeding vessels.
4. Embolisation. The feeding arteries are then blocked with particles of 300 to 500 microns, which prevents the drug washing out and adds ischaemia.

The endpoint is complete uptake of the mixture by the tumour. In one case Dr. Singh showed, a tumour in segment 7 took up the Lipiodol and doxorubicin emulsion fully; at two months, CT showed the tumour filled with retained Lipiodol (bright white on CT, not enhancement) and no active tumour.

Conventional TACE has been in use for decades and remains widely practised. Its weakness is the emulsion itself. The Lipiodol and doxorubicin mixture is unstable and separates quickly; the drug tends to escape into the systemic circulation, causing the same side effects as intravenous chemotherapy; and its regional potency falls over time.

Drug-eluting bead TACE

Drug-eluting beads were developed to overcome those weaknesses. They are polyvinyl alcohol particles supplied pre-packed. The chemotherapy drug is added to the vial and left for about 45 minutes, during which the beads absorb it. The loaded beads are then injected through the catheter exactly as in conventional TACE.

Once in the tumour, the beads do two jobs: they block the tumour vessels, and they release the drug slowly into the tumour cells. Because the drug is held in the beads rather than in an unstable emulsion, very little reaches the systemic circulation, and side effects are fewer.

Balloon-occluded TACE

Balloon-occluded TACE is one of the newer techniques Dr. Singh's team has recently adopted. In standard TACE, the drug injected into a feeding artery can also flow into adjacent normal liver, causing side effects.

In the balloon technique, a balloon microcatheter is placed in the artery supplying the tumour and inflated. The normal liver beyond the balloon is then supplied from the surrounding liver circulation, and flow is redistributed towards the tumour. When the drug is injected, almost all of it enters the tumour and the rest of the liver is spared. Dr. Singh described this as the principle of flow redistribution.

Radioembolisation (TARE) with Yttrium-90

Transarterial radioembolisation is the selective delivery of radiation through the arteries. Microspheres carrying Yttrium-90, a radioactive isotope, are injected through the same catheter route as TACE. The particles cause ischaemia and, more importantly, radiation necrosis of the tumour.

Yttrium-90 emits beta particles, which have a very short range in tissue: the mean penetration is about 2.5 mm. The radiation dose is therefore concentrated within the tumour and largely spares the normal liver.

Dr. Singh's team generally uses TARE for patients with portal vein tumour thrombus who still have good liver function. TARE is carried out in two stages: a planning angiogram, then the treatment itself. In one case, a large lesion in the left lobe was treated this way. A PET-CT scan after the injection showed the radioactive material entirely confined within the tumour, and imaging at two months showed no enhancement: complete necrosis.

TACE vs TARE: how the choice is made

Both TACE and TARE are available in India, and Dr. Singh's team offers both. The decision weighs three things:

• Affordability for the patient.
• Familiarity with the procedure at the treating centre.
• Tumour features. TARE is preferred when the tumour is infiltrative, when there is portal vein invasion, or when the tumour has progressed after TACE.

Treatment costs for chemoembolisation are set out in Jivo Healthcare's TACE cost guide.

Beyond HCC: liver metastases

Transarterial therapies are not limited to primary liver cancer. Dr. Singh also uses TACE and TARE for oligometastatic disease from colon cancer (a small number of liver metastases) and for neuroendocrine tumour metastases.

The principle is the same whatever the tumour: travel from the femoral artery to the aorta, then the hepatic artery, then super-selectively into the branches feeding the tumour, and deliver a very potent agent there. That agent may be chemotherapy such as doxorubicin, or radiation from Yttrium-90 spheres. The basic rule, as he put it, is that there should be no harm to the normal liver and no harm to the rest of the body; these techniques have evolved over the years precisely to achieve that.

Combination therapy for larger or complex tumours

Locoregional treatments can be combined with each other and with systemic therapy. Dr. Singh's team commonly combines TACE with ablation, or SBRT (stereotactic body radiotherapy) with TACE or TARE, for:

• lesions larger than 3 cm,
• multiple lesions, and
• lesions with portal vein thrombus.

Portal vein tumour thrombus

When tumour has grown into the portal vein, SBRT is given first to the tumour thrombus. The main tumour is then treated with TACE, TARE or ablation.

TACE first or ablation first?

Both sequences are used, and each has a rationale:

• TACE first, then ablation. Embolisation reduces perfusion-mediated cooling of the lesion, so the tumour retains more heat during ablation and becomes necrotic faster.
• Ablation first, then TACE. Ablation increases the permeability of the tumour, so more chemotherapy is retained when TACE follows.

A case where neither alone would work

One of Dr. Singh's patients had two lesions. The second lay very close to blood vessels. Microwave ablation alone would not have treated it completely because of the heat-sink effect, and TACE alone would not have treated it fully because the lesion was not very vascular.

The team ablated the first lesion. For the second, they performed TACE, injecting the drug until it filled the lesion, and then embolised the vessels adjacent to the tumour. With flow reduced, they ablated the second tumour. Blocking the vessels first neutralised the heat-sink effect, and the lesion received chemoembolisation, embolisation and ablation in a single strategy.

The individual ablation techniques used in such combinations are compared in liver tumour ablation: alcohol, radiofrequency, microwave and cryoablation. The audience's questions on TACE and TARE are answered on the live discussion page, and specialists who perform them are listed under interventional radiology.