Nonsurgical Treatments for HCC
The Liver Cancer Program team is skilled in providing the full range of nonsurgical treatments for hepatocellular carcinoma (HCC), including the following.
Nonsurgical Locoregional Therapy
Most people with HCC, either because of the size, number, and location of the tumors or because of poor liver function, cannot have a resection. We have a number of ways that we can treat HCC in the liver without surgery. These treatments fall into two main categories: direct destruction (ablation) either by injection of chemicals or by placing a device into the tumor to burn it or by way of the blood supply (embolization), injecting particles and/or medicines to be carried into the tumor and cut off its blood supply. Locoregional therapy may be the main treatment for people with early stage HCC (BCLC A) who are for some reason not able to have resection or a liver transplant, and for people with intermediate stage HCC (BCLC B). We at Mount Sinai are now studying whether locoregional treatment can help people with more advanced HCC (BCLC C), as well. One of the main uses of locoregional treatment is in people who are waiting for a liver transplant to keep their HCC from growing during the time it takes to get a liver.
- Ethanol injection: The injection of 95 percent ethyl alcohol (ethanol) into HCC tumors has been practiced for many years and is a very effective way to destroy small tumors (less than 2 centimeters; one inch is about 2 1/2 cm). A thin needle is placed into the tumor and the injection is guided by either ultrasound or CT scan. Ethanol injection has mostly been replaced by thermal ablation, but it still has a role to treat small tumors near structures like the gallbladder or intestine that it would be dangerous to burn.
- Thermal ablation: Over the past fifteen years thermal ablation using radiofrequency energy or, more recently, microwaves, has for the most part replaced ethanol injection. A special needle is placed into the tumor under ultrasound or CT scan guidance and is connected to a generator that causes the tumor and the surrounding liver to heat to a temperature where it is burned, and the cancer cells are killed. The chances that thermal ablation can destroy an HCC completely depend on the size of the tumor: below 2 cm it is over 90 percent successful, around 80 percent between 2-3 cm, and around 65 percent between 3-4 cm; we don’t use thermal ablation for tumors more than 4 cm in size since the chance of success is too low. All of the techniques that require putting a needle into a tumor depend on the skill of the radiologist in being able to place the needle safely and accurately; there are some locations in the liver where that can be extremely difficult or impossible. In particular tumors that sit at the top of the liver near the lungs can be difficult targets and trying to hit them risks puncturing the lung. Tumors that sit right next to large blood vessels are difficult to treat with thermal ablation because the blood flowing in the vessel keeps the tumor cool and prevents it from being killed.
- Irreversible electroporation: This is a new technology where two or more needles are placed parallel to each other around the tumor and connected to a generator that creates a very high voltage electrical field between the needles, causing irreversible injury to the cells within the field. This technology has the advantage that it does not damage normal structures the way that thermal ablation can, but the need to place multiple needles makes it technically difficult. We are developing experience now with electroporation, and its ultimate role remains to be determined.
- Chemoembolization: The liver is the only organ with two sources of blood supply. Like every organ it has an artery bringing fresh, oxygen-rich blood from the heart, called the hepatic artery; the liver, however, also has the portal vein which brings all the blood that drains from the stomach, spleen, and intestines to the liver for processing before it returns to the body. The portal vein brings about 3/4 of the total blood flow to the liver. Embolization means injecting material into a blood vessel to stop the blood flow. In any other organ, embolization of its artery would lead to severe damage, but the blood flow from the portal vein protects the liver. The tumor is not so lucky; when HCC develops, it draws all of its blood from the hepatic artery, and as a result embolization can kill HCC while leaving the normal liver relatively untouched. Embolization is performed by passing a tiny plastic tube through the blood vessels under x-ray control starting in the groin or the wrist and guiding it into the branch of the hepatic artery that supplies the tumor.
Chemoembolization combines this embolization with the injection of anticancer drugs along with the particles to increase the killing of the cancer. The standard way of doing this is to inject a mixture of a drug called doxorubicin and an oily dye called ethiodol into the tumor followed by tiny beads that are about the diameter of a human hair. The beads are carried by the circulation into the small blood vessel branches in the tumor where they get caught and stop the blood flow. At Mount Sinai we are now testing a new kind of beads for chemoembolization, called drug-eluting beads, that are mixed with doxorubicin before they are injected—the doxorubicin is absorbed into the beads and released slowly once the beads have become trapped inside the tumor. Less chemo drug escapes into the circulation with drug-eluting beads, so there are fewer side-effects, and by keeping the chemotherapy in the liver they may actually work better to kill the tumor. In general, we use chemoembolization for tumors larger than 4 cm in diameter and when there is more than one tumor. People stay overnight in the hospital after chemoembolization, but are almost always well enough to go home the next day. Chemoembolization has been proven to make people with intermediate-stage HCC live longer.
- Radioembolization: Another transarterial treatment that has been gaining popularity lately is radioembolization. Rather than combining beads with chemotherapy, the beads for radioembolization contain yttrium-90, a radioactive element. They are injected into the artery just like in chemoembolization, and once they are trapped in the tumor they gradually release their radiation and kill the tumor from within. While with chemoembolization cutting off the blood flow is an important part of why the treatment works, with radioembolization far fewer particles are injected and the effect of the treatment depends almost entirely on the radiation. We are currently studying whether radioembolization can help people with HCC that has begun to invade branches of the portal vein. In people whose portal vein is blocked by tumor, chemoembolization can cause severe liver damage since the liver isn’t protected by the blood coming in through the portal vein, but radioembolization, since there are far fewer particles, doesn’t cut off enough blood supply to cause severe damage.
Immunosuppression and HCC
After a liver transplant you have to take medicine to prevent rejection. These medicines work by suppressing your immune system. We know that immune suppression can cause cancers to develop in people who have certain infections, for example, with the papilloma virus or the Epstein-Barr virus, but immune suppression doesn’t seem to have much effect on the formation of common cancers like breast cancer, colon cancer, or HCC. While not entirely proven, the medicines that we usually use to prevent rejection, tacrolimus (Prograf) and cyclosporine, may help new HCCs to grow. There is another medicine called sirolimus (Rapamune) that in addition to preventing rejection also has anticancer properties. There is an international research study going on now to see whether the results of transplants for HCC are better when sirolimus is used. Until the results of the study are available many transplant teams, including ours at Mount Sinai, use sirolimus after transplant for people with HCC, especially in cases where the HCC was more advanced.
Chemotherapy for HCC
Despite many years of research, so far there is only one medicine, sorafenib, that can make people with HCC live longer. Sorafenib works not by killing cancer but rather by stopping its growth for a while. In the study that led to the approval of sorafenib by the FDA (which was led by Mount Sinai), the 300 people with advanced HCC who received sorafenib lived an average of 7.9 months compared to 10.7 months for the 300 people who received a placebo. Currently, sorafenib is only used in patients who are not candidates for other treatments for HCC. While an important breakthrough, sorafenib is only a beginning; at Mount Sinai we continue to lead clinical trials looking for new drugs to improve results in combination with or instead of sorafenib as well as after sorafenib stops working.
Liver Cancer Clinical Program