Liver Directed Therapy for Metastatic CRC

Metastatic colorectal cancer (mCRC), also called stage IV colorectal (bowel) cancer, is cancer that has spread beyond the colon or rectum to distant organs like the liver, lungs, or brain. Liver is the most common site of CRC metastasis. More than 25% of colorectal cancer patients develop liver metastasis during the course of the disease.

What is liver directed therapy for colorectal cancer?

Liver directed therapy is localized treatment for metastatic liver tumors (tumours) that have spread from a primary colon cancer or rectal cancer. Localized treatment, sometimes called locoregional therapy, is given at the site of the liver tumor itself, rather than throughout the whole body. The techniques of liver directed therapy are also used to treat primary liver malignancies, cancers that originate in the liver, such as hepatocellular carcinoma (HCC), and metastatic liver lesions from other cancers.

When is liver directed therapy used for colorectal cancer?

Liver directed therapy is generally used when surgery is not an option. This may be because the size or location of the liver tumor make it unresectable, because metastatic tumors have come back after previous surgery, or because the patient's overall health makes surgery too risky. Liver directed therapy may also be used to reduce symptoms being caused by liver metastases, such as pain.  

Liver directed therapy may be used alone or in combination with systemic therapy like chemotherapy, immunotherapy, and/or targeted therapy. Liver directed therapy may be used to shrink liver tumors to make a later surgical resection (removal) possible. In these cases, the goal of liver directed therapy may be a permanent cure. However, for many patients, liver directed therapy is used to slow progression, with the aim of increasing survival time and/or improving quality of life.  

How does liver directed therapy work?

There are several kinds of localized treatments for liver metastasis, and some treat liver tumors in more than one way. Hepatic arterial infusion and transarterial chemoembolization both involve administering chemotherapy drugs directly to the tumor. Embolization blocks blood vessels to decrease the blood supply to the tumor, starving it of the oxygen and nutrients that it needs to survive. This includes arterial embolization, transarterial chemoembolization, and radioembolization. Ablative therapy is direct destruction of tumor tissue using heat or cold, and includes radiofrequency ablation, microwave ablation, and cryoablation. Liver directed radiation uses high-energy particles or waves to kill cancer cells and can be given as selective internal radiation therapy (also called radioembolization) or stereotactic body radiation therapy.

What are the different types of liver directed therapy?

Hepatic Arterial Infusion (HAI)

Hepatic arterial infusion involves administering high doses of chemotherapy drugs through the hepatic artery, so that the drugs are delivered directly to the liver metastases. The liver extracts most or all of the drug before it can get to the rest of the body. This allows your oncology team to maximize the amount of the medication going to your liver tumor and minimize the amount of the drug that circulates to the rest of your body. Patients have fewer systemic side effects with HAI than when chemotherapy is administered to the whole body. The main side effects of hepatic arterial infusion include liver toxicity (liver cell damage), bile duct problems, and stomach ulcers.

Arterial Embolization

Arterial embolization, also called bland embolization or transarterial embolization, is the injection of very small biocompatible resin particles or beads into blood vessels that supply the liver tumor or multiple liver tumors. This blocks the blood vessel and reduces the tumor's blood supply, which in turn reduces the supply of oxygen and nutrients the tumor needs to survive.

Under local anesthesia, a small incision is made in the groin to access the femoral artery and a narrow guidewire is inserted. A delivery catheter (tube) is inserted over the wire and, with x-ray guidance (angiography), the tip of the catheter is positioned so that the particles will be delivered to the tumor's blood vessel. Particles are injected until the embolization is complete and the artery is blocked. Over the following months, the embolized vessels will permanently shrink and the tumor will decrease in size. Arterial embolization is performed by an interventional radiology physician trained in oncology procedures.

The most common side effect is post-embolization syndrome, a group of symptoms which include abdominal pain, nausea and vomiting, fever, and fatigue. Arterial embolization may also cause liver injury that affects liver function, demonstrated by elevated liver enzymes in the blood. More rarely, gallbladder inflammation (cholecystitis), pancreatic inflammation (pancreatitis), or liver abscess may occur.

Transarterial Chemoembolization (TACE)    

Transarterial chemoembolization, sometimes called just arterial chemoembolization, is similar to arterial embolization in that it involves injecting biocompatible resin particles into the blood vessels supplying the tumor, but TACE includes chemotherapy drugs with the particles. The particles then block the tumor blood supply and administer anti-cancer drugs directly to the tumor. Because of the blocked blood supply, the drugs stay in contact with the liver tumors longer, maximizing the effective dose, and the liver extracts most or all of the drug before it can get to the rest of the body, minimizing systemic side effects.

As with bland arterial embolization, after gaining percutaneous access to the femoral artery through the skin, a catheter (tube) is inserted in the artery. The tip of the catheter is positioned so that the particles will be delivered to the tumor's blood vessel. Particles are injected and the artery is blocked. Over several months, the embolized vessels permanently shrink and the tumor decreases in size. TACE is performed by interventional radiologists trained in oncology procedures.

The most common side effect of TACE is post-embolization syndrome, a group of symptoms which include abdominal pain, nausea and vomiting, fever, and fatigue. It may also cause liver cell injury, demonstrated by elevated liver enzymes in the blood. More rarely, gallbladder inflammation (cholecystitis), pancreatic inflammation (pancreatitis), or liver abscess may occur.

Selective Internal Radiation Therapy (SIRT)

Also known as radioembolization, selective internal radiation therapy is a type of brachytherapy that delivers radiation therapy directly to the liver tumor. SIRT also blocks tumor blood supply, which in turn reduces the supply of oxygen and nutrients the tumor needs to survive. Biocompatible resin microspheres (beads) that are coated in a radioactive chemical element called yttrium-90 (Y-90 or Y90) are injected through a catheter into the blood vessels supplying the liver tumor. The procedure involves inserting a catheter (tube) into the femoral artery through small groin incision under local anesthesia. The catheter tip is positioned with x-ray guidance, and the radioactive microspheres (also known as SIR-Spheres) are injected through the catheter into the tumor-supplying blood vessels. High energy particles from the radioactive yttrium-90 kill tumor cells, and the blocked blood vessels starve the tumor of oxygen and nutrients. SIRT is performed by interventional radiologists in collaboration with radiation oncologists.

The most common side effects of SIRT are abdominal pain, fever, fatigue, and nausea. Major complications are rare but may be caused by a small number of microspheres inadvertently reaching other organs in the body, like the pancreas, gallbladder, stomach, or lungs. These complications are pancreas inflammation (pancreatitis), gallbladder inflammation (cholecystitis), stomach ulcer, or lung inflammation (pneumonitis). Patients who have SIRT may need to take safety precautions at home after radioembolization to limit radiation exposure to others.

Stereotactic Body Radiation Therapy (SBRT)  

Stereotactic body radiation therapy uses precisely targeted high dose beams of radiation to destroy the liver tumor. SBRT is delivered by a machine outside the body called a linear accelerator. It is usually performed in a single session but may be delivered over a few sessions. SBRT is a radiotherapy treatment option and not a surgical procedure, though it is sometimes called radiosurgery due to its precise tumor targeting.  

Because it is so precisely targeted, SBRT has a lower risk of side effects than other types of radiotherapy. The most common side effect of SBRT is fatigue after treatment. More rarely, patients may develop inflammation of the liver or inflammation of other organs and tissues in the path of the radiation beams.

Radiofrequency Ablation (RFA)

Radiofrequency ablation (RFA) is a type of thermal ablation therapy that uses heat created by radio waves to destroy cancer cells. RFA can be performed using a needle electrode through the skin of the abdomen (percutaneously) by an interventional radiologist (IR) who specializes in oncology procedures. Using x-ray, ultrasound, or MRI guidance, the needle is positioned at the liver tumor, and the needle is heated to a target temperature with radio waves for a few minutes to kill the cancer cells. Radiofrequency ablation can also be performed by a surgeon through laparoscopic or open surgery. For laparoscopic RFA, a few small incisions are made in the abdomen and thin tubes called trocars are placed in the incisions. Through one trocar, the surgeon operates a camera to see inside the abdominal cavity, and through another trocar, the surgeon positions the RFA needle electrode in the tumor to heat and destroy it. Open surgery involves a single long abdominal incision through which the surgeon works.

The most common side effects of radiofrequency ablation are flu-like symptoms including fever and body aches. This is sometimes called post-ablation syndrome. More rare potential complications include infection, bleeding, injury to nearby organs, and skin burns.  

Microwave Ablation (MA)  

Like radiofrequency ablation, microwave ablation is a type of ablative therapy that uses heat to destroy cancer cells, but instead of using radio waves to generate heat, microwave energy is used. Microwave ablation can be performed using a needle electrode through the skin of the abdomen (percutaneously) by an interventional radiologist (IR) who specializes in oncology procedures. Using x-ray, ultrasound, or MRI guidance, the needle is positioned at the liver tumor, and microwaves are used to heat the needle for a few minutes and destroy the cancer cells. Microwave ablation can also be performed by a surgeon through laparoscopic or open surgery. For laparoscopic microwave ablation, a few small incisions are made in the abdomen and thin tubes called trocars are placed in the incisions. Through one trocar, the surgeon operates a camera to see inside the abdominal cavity, and through another trocar, the surgeon positions the RFA needle electrode in the tumor to heat and destroy it. Open surgery involves a single long abdominal incision through which the surgeon works.

The most common side effect of microwave ablation is post-ablation syndrome, a group of flu-like symptoms including fever and body aches. More rare potential complications include infection, bleeding, injury to nearby organs, and skin burns.

Cryoablation    

Cryoablation, also known as cryosurgery or cryotherapy, uses a thin metal probe to freeze and destroy liver tumors. Cryoablation may be performed using a needle and probe through the skin of the abdomen (percutaneously) by an interventional radiologist (IR) who specializes in oncology procedures. Magnetic resonance imaging (MRI), ultrasound, or x-ray guidance is used to help the radiologist position the probe, monitor the formation of an "ice ball" in the tumor, and limit damage to surrounding tissue. Cryoablation can also be performed by a surgeon through laparoscopic or open surgery. For laparoscopic cryoablation, a few small incisions are made in the abdomen and thin tubes called trocars are placed in the incisions. Through one trocar, the surgeon operates a camera to see inside the abdominal cavity, and through another trocar, the surgeon positions the cryoablation needle and probe in the tumor to freeze and destroy it. Open surgery involves a single long abdominal incision through which the surgeon works. The possible side effects of cryoablation include fever, bleeding, infection, and bile duct or liver damage.