by Dr. C.H. Weaver M.D. updated 10/2019
For patients with unresectable hepatocellular carcinoma transarterial chemoembolization (TACE) can be used to treat smaller liver tumors and appears 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 several precision cancer medicines. Systemic treatment with anti-angiogenesis, multikinase and checkpoint inhibitor medications have all recently become available and demonstrated to prolong survival. (1-3)
Transarterial chemoembolization (TACE) is a minimally invasive, image-guided treatment for cancer or tumors involving the liver. It is performed by specially trained “interventional radiologists” using real-time image guidance. TACE often require smaller incisions, has fewer risks of complication, and take less recovery time than traditional surgery.
During TACE a specially trained interventional radiologist uses live imaging to thread a plastic tube, called a catheter, through the blood vessels from a small incision in the groin to the liver. The doctor then uses the catheter to deliver both chemotherapy medication and 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. TACE typically requires a one night hospital stay for monitoring and most people return to a normal level of activity in one to three weeks.
TACE appears to be least effective in persons who have a high serum level of alfa-fetoprotein, blockage of the portal vein, the presence of severe cirrhosis, and/or the presence of cancer in more than 50% of the liver. Individuals with HCC and these risk factors should discuss the risks and benefits of TACE carefully with their doctor. (4)
Combining TACE with newer precision cancer medicines is a new treatment approach that bears promise.
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 Nexavar is a treatment option that improves clinical outcomes and may be a new standard treatment for patients with intermediate-stage HCC".
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.
- Gastrointestinal Cancers Symposium (GICS) 2018. Abstract 206, presented January 19, 2018.
- World Health Organization. Cancer. Available from: <a href="http://www.who.int/mediacentre/factsheets/fs297/en/.">http://www.who.int/mediacentre/factsheets/fs297/en/.</a> Last accessed: April 2017.
- World Health Organization. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Available from: <a href="http://globocan.iarc.fr/Pages/fact\_sheets\_cancer.aspx.">http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.</a> Last accessed: April 2017.
- Cancer, Vol 88, No 12, pp 50-57, 2000.
- Llovet J, Real M, Montana X, et al. Arterial embolization or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized uncontrolled trial. The Lancet. 2002;359:1734-1739.
- Cancer, Vol 92, No 6, pp 1516-1524, 2001
- Cancer, Vol 88, No 9, pp 1986-1991, 2000.
- International Journal of Radiation Oncology, Biology and Physics, Vol 47, No 1, pp 435-442, 2000