TACE-TARE Treatment Improves Outcomes in Liver Cancer

For patients with unresectable hepatocellular carcinoma transarterial chemoembolization (TACE) or radioembolizaiton (TARE) can be used to treat liver tumors and appear to further improve outcomes when combined with systemic therapy or radio frequency ablation (RFA).^1-8

Liver cancer, or hepatocellular carcinoma (HCC), is the second most common cause of cancer-related deaths worldwide, has a poor prognosis, and few new treatment options have been available until the recent development of precision cancer medicines and immunotherapy. Systemic treatment with anti-angiogenesis, multikinase and checkpoint inhibitor medications have all recently become available and demonstrated to prolong survival for patients with advanced disease.^1-3

Local treatment of earlier stage HCC with TACE or TARE alone or in combination with newer immunotherapy based treatment regimens improves the chance of achieving a remission, and can increase the number of patients “eligible” for liver transplant.  

What is TACE?

TACE is a form of local therapy delivered directly to the liver by specially trained interventional radiologist’s that use live imaging to thread a plastic tube, called a catheter, through the blood vessels to the cancer from a small incision in the groin to the liver. The doctor then uses the catheter to deliver chemotherapy medication and/or embolization materials into the blood vessels that lead to the cancer. This allows doctors to treat tumors that are not accessible using conventional surgery or radiation treatments. 

Transarterial chemoembolization (TACE) is a minimally invasive, image-guided treatment for cancer or tumors involving the liver that delivers chemotherapy directly to a cancer in the liver. TACE often require smaller incisions, has fewer risks or complications, and take less recovery time than traditional surgery.

What is TARE?

TransArterial RadioEmbolization (“TARE”) is a minimally invasive treatment for cancers in the liver, also called radioembolization. It injects radioactive beads through a catheter and delivers high doses of radiation to the tumor, killing it over time.

The FDA approved TheraSphere™ Yttrium-90 (Y-90) Glass Microsphere for the treatment of patients with hepatocellular carcinoma HCC in 2021. TheraSphere is a selective internal radiation therapy that is comprised of millions of microscopic glass beads containing radioactive yttrium (Y-90) delivered through through a catheter directly to liver tumors, thereby reducing exposure to surrounding tissue.

The approval of TheraSphere was based on findings from the “LEGACY” clinical which included 143 patients with unresectable solitary liver lesions that were 8 cm or smaller in size who had not have had prior liver transplantation, resection, locoregional treatment, or systemic therapy. TheraSphere was given as neoadjuvant therapy with the intent to bridge patients to transplant or resection or as stand-alone treatment.

An overall response rate of 100% was achieved with Therasphere administration when used as neoadjuvant or stand-alone treatment in 143 evaluable patients with unresectable HCC. A total of 76% of patients derived a duration of response longer than 6 months and the 3-year overall survival rate was 93% in patients who had undergone transplant or resection following treatment with TheraSphere. The majority of side effects were mild and resolved without medical intervention.

TACE and TARE typically require a one night hospital stay for monitoring and most people return to a normal level of activity in one to three weeks.^9-13  Minor complications occur in ~ 20% of individuals and these include bleeding, pain, and temporary kidney injury. Two in every 100 experience major complications including liver failure, infection, or other organ damage.

Combining TACE/TARE with newer precision cancer medicines

Researchers evaluated 156 patients with unresectable HCC to be treated with TACE, or the precision cancer medicine Nexavar plus TACE, and directly compared the outcomes. Treatment continued until time to untreatable progression (TTUP), when TACE was no longer possible owing to untreatable tumor progression, deterioration to, or the occurrence of vascular invasion and/or extrahepatic spread.

The duration of overall survival without cancer progression was significantly longer; 25.² months for patients who received combination treatment as compared to 13.⁵ months for those treated with TACE alone.

The study authors stated “results clearly show that TACE in combination with systemic therapy is a treatment option that improves clinical outcomes and may be a new standard treatment for patients with intermediate-stage HCC”.

TACE + Systemic Immunotherapy

The EMERALD-1 Phase III clinical trial has demonstrated that immunotherapy administered in combination with TACE can delay cancer recurrence in patients with hepatocellular carcinoma. This is the first trial to show improved clinical outcomes for systemic therapy in combination with TACE in this setting.

• About Emerald-1

TACE and RFA is more effective than either treatment alone

Studies suggest that the combination of TACE and RFA may produce better survival than treatment with TACE alone.^4,8 Researchers in China conducted a study in 291 patients diagnosed with liver cancer larger than 3 centimeters. Patients were randomly assigned to receive treatment with either TACE alone, RFA alone, or a combination of TACE and RFA. The goal of the study was to evaluate survival benefits as well as response rates to these various techniques.

• After an average follow up of 28.5 months, the average survival times were 24 months among the patients who received TACE, 22 months for patients who received RFA, and 37 months among those who received TACE and RFA.
• Further analysis revealed that treatment of multiple tumors within the liver with combination therapy produced better outcomes than treatment of single tumors with RFA or TACE alone.
• Response rates that were sustained for six months were highest among patients treated with TACE and RFA (54%) compared with 35% for patients treated with TACE alone and 36% among patients treated with RFA alone.

For patients with larger liver tumors, a combination of TACE and RFA was successful in improving overall survival outcomes.

TACE Plus PEI Reduces Recurrences with Early-Stage Hepatocellular Cancer

TACE and percutaneous ethanol injection (PEI) therapy is superior to PEI alone for the treatment of patients with small hepatocellular carcinomas.

Both TACE and ethanol (alcohol) injection have demonstrated anti-cancer properties for HCC tumors. TACE involves surgically implanting a catheter into the major artery (hepatic) that supplies blood to the liver. Through this catheter, chemotherapy drugs are injected directly into the liver. This augments the anti-cancer effects of chemotherapy beyond the effects offered by systemic (full body) delivery through a few mechanisms: 1) the chemotherapy agent does not become diluted by mixing with the rest of the blood from the body prior to reaching the cancer, 2) the chemotherapy agent is not broken down in the body through biochemical processes prior to reaching the cancer, 3) larger amounts of the chemotherapy agent can reach the cancer with fewer associated systemic side effects.

Following intra-arterial chemotherapy administration, a small gelatin sponge is placed into the hepatic artery to block blood flow to the cancer. This reduces the volume of blood in the cancer, which allows the chemotherapy agent to spread throughout the cancer and remain there in sufficient concentrations.

Percutaneous ethanol injection is a procedure in which ethanol is injected directly into the cancer(s). One to three needles are placed through the skin into the cancer through CT image guidance. Ethanol, which kills cancer cells through dehydration, coagulation and clot formation, is then administered through the needles, which are left in place for 5 to 10 minutes to prevent reflux of the ethanol. The reduced blood volume achieved by TACE augments the anti-cancer effects of ethanol in the same way it augments chemotherapy.

Researchers from Japan recently conducted the first clinical trial evaluating the efficacy of combining TACE with PEI versus PEI alone in 52 patients with small HCC lesions. In this study, all patients had one to three lesions that measured less than 3 centimeters in diameter. Half of the patients were treated with both TACE and PEI, while the other half were treated with PEI alone. Three years following treatment, the group of patients who received the combination therapy had a 20% reduced incidence of residual disease (cancer growth at the site of the original cancer) and a 60% reduced incidence of new cancer lesions compared to patients receiving PEI alone. The overall survival rates at 1, 3, and 5 years following therapy were 100%, 81% and 40.4%, respectively in patients treated with TACE-PEI and 91.3%, 65.9% and 37.7%, respectively in patients treated with PEI only.⁴

It is important to note that patients with lesions measuring less than 2 centimeters in diameter achieved the most benefit from treatment with TACE-PEI compared to PEI alone. Three years following therapy in this subgroup of patients, not one patient treated with the TACE-PEI combination had any detectable residual disease, compared with 31.8% of those treated with PEI alone. In addition, all patients with lesions less than 2 cm treated with TACE-PEI were alive at 3 years following therapy, compared to 62.4% of these patients treated with PEI alone.

These results indicate that TACE-PEI improves survival compared with PEI alone in patients with small HCC, particularly those smaller than 2 cm. Future clinical trials will help to further establish the role of combination TACE-PEI therapy in the treatment of small HCC tumors.

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