Options for Treating Inoperable Liver Metastases from Colorectal Cancer
Nearly one third of patients diagnosed with colorectal cancer already have metastatic disease. Colorectal cancer that has spread to the liver is classified as metastatic disease also called Stage IV. The liver is the most common site for metastasis. If surgical resection of the metastases is not possible, and the lesion or lesions are considered inoperable, due to a variety of factors you may be deemed a good candidate for liver directed or targeted therapies. Liver directed therapies include ablation, embolization and internal radiation using yiitrium-90 microspheres. Liver directed treatments can be used alone or in combination with chemotherapy and/or biologic agents.
A variety of ablative therapies are now available; these include: Radiofrequency Ablation (RFA), Cryotherapy and Microwave Ablation (MA). These procedures are performed by a surgeon or interventional radiologists (IR) who specializes in oncology procedures. All of these techniques are applicable to patients that have a limited number of metastatic liver tumors.1 RFA, Cryotherapy and Microwave Ablation (MA) are considered beneficial for patients with unresectable liver-only disease who present with tumors less than or equal to 3-4 cm2.
- Radiofrequency Ablation (RFA) uses electrical energy to create heat in a tumor for a specific period of time. The result of this “super heating” is the death or destruction of the tumor. The procedure can be performed percutaneously, by inserting a needle through the skin under x-ray guidance, then placing a probe through the needle and positioning it in the liver tumor. The percutaneous procedure is usually performed by an interventional radiologist under local anaesthesia. Alternatively, the procedure can be done laparoscopically, using a laparoscope that is inserted through a tiny incision in the abdomen. It may also be done as an open surgical procedure. The laparoscopic and open surgical procedures are performed by a surgeon. RFA is safe, well tolerated and an effective treatment for patients with inoperable metastatic liver tumors. RFA is most effective in liver lesions that are less than or equal to 3-4 centimetres in size.3
Side Effects: Many patients experience a low grade fever for a few days following the procedure. There is a very low risk of infection, bleeding and skin burn.
Recovery: If the percutaneous method is used then the patient will go home the same day. If a laparoscopic procedure is selected then the patient usually goes home the following day. An open surgical procedure requires that an incision be made in the abdomen, general anaesthesia is needed and the recovery period will be longer.
- Cryotherapy or Cryosurgery uses super cooled nitrogen or argon gas to freeze liver lesions thereby destroying the tumor. Similar to RFA, the procedure can be performed percutaneously. In cryotherapy the doctor uses MRI or ultrasound to guide the probe and monitor the formation of an “ice ball” in the tumor and limiting damage to surrounding tissue. The procedure may also be performed by a surgeon using an open surgical procedure. Clinical and laboratory research suggest that hepatic cryotherapy is effective in patients with inoperable tumors, which are located in a difficult section of the liver (near large vessels). Like RFA, cryotherapy is most effective in liver lesions that are less than or equal to 3-4 centimetres in size.
Side Effects: Complications of cryotherapy may include bleeding, mild fever, increase in liver enzymes due to damage to the bile ducts, infection or abscess.
Recovery: If the percutaneous method is used, the patient will usually go home the same day. An open surgical procedure requires that an incision be made in the abdomen, general anaesthesia is needed and the recovery period will be longer.
- Microwave Ablation (MA) is an ablative therapy that produces coagulation of soft tissue during a percutaneous, laparoscopic or open surgical procedure. Microwave ablation (MA) uses microwave energy and an antenna to cause coagulation of tissue by creating heat by friction and vibration of water molecules in the cells. The advantage of MA over other heating systems, such as RFA, is that the microwave technique is quicker and does not cause collateral damage and can be completed in 10 minutes.
Side Effects: Many patients experience a low grade fever and pain for a few days following the procedure. Major complications include liver abscess, bile duct injury, infections, bleeding and skin burn.
Recovery: If the percutaneous method is used the patient will usually go home the same day. If a laparoscopic procedure is selected then the patient often goes home the following day. An open surgical procedure requires that an incision be made in the abdomen, general anaesthesia is used, and the recovery time will be longer.
Internal Radiation Therapy:
- SIRT (Selective Internal Radiation Therapy) also known as radioembolization is a liver directed, outpatient radiation treatment for the management of inoperable liver tumors, from either primary liver cancer or colorectal metastases. SIRT delivers millions of tiny radioactive microspheres (beads) called SIR-Spheres® directly to the liver tumor to cause tumor destruction. SIRT is a non-surgical option for patients who are not candidates for surgical resection or ablation. SIR-Spheres are made of a biocompatible resin material. The SIR-Spheres microspheres or beads are very tiny (average size is 32 microns) about the diameter of a strand of human hair. SIR-Spheres preserve the blood vessels to allow for future therapies. Each yttrium-90 microsphere is charged with which will penetrate the tumor tissue up to 11 millimeters. SIR-Spheres are the only FDA-approved microsphere for patients with inoperable metastatic colorectal cancer to the liver. SIR-Spheres are administered by an interventional radiologist in the radiology suite. Under local anesthesia, a small needle puncture is made in the groin area into the femoral artery. A small flexible guidewire is inserted and positioned into the artery where the microspheres will be delivered. A narrow tube, known as a catheter is then guided over the wire and positioned into the selected artery where the SIR-Spheres will be delivered to the tumors. The advantages of radioembolization therapy, documented by clinical research, is that microspheres, when used in combination with chemotherapy or alone, provide an improvement in liver tumor control by shrinking the tumor and delaying progression in the liver.
Side Effects: Many patients experience nausea and pain which normally subside in a short time after the procedure and are treated with routine medications. Patients may also develop a mild fever that may last up to one week and fatigue which may last several weeks. Major complications are rare but may include small number of microspheres inadvertently reaching other organs in the body, such as the stomach, intestine or pancreas.
Recovery: The entire procedure takes about 90 minutes. You will be sleepy during the procedure, but able to communicate with your doctor and the team. Most patients return home four to six hours following treatment.
- Embolization therapy is performed by interventional radiologists in the radiology suite. It is a non-surgical procedure to treat inoperable metastatic liver tumors. Small particles or beads, ranging in size from 100 to 900 microns made of a biocompatible resin, are injected into selected vessels to block the blood flow feeding the tumors causing the tumor to shrink. Under local anaesthesia, a small incision is made in the groin to access the femoral artery and a narrow guidewire is inserted. A delivery catheter is inserted over the wire and under x-ray guidance (angiography) the tip of the catheter is positioned so that the particles will be delivered to the tumor. 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. Embolization can be performed with bland particles (without drug added), or with drug added which is called TACE (Transarterial Chemoembolization). Cutting off the blood supply to the tumor allows for higher doses of chemotherapy to be delivered and remain in contact with the tumor, and preventing the chemotherapy reaching healthy tissue. TACE normally contains a mixture of bland particles and two to three chemotherapy agents. TACE may also be performed using different particles made of a biocompatible resin modified for the controlled loading and delivery of drug. These particles are called drug eluting beads (DC Bead or DEBIRI) . Drug eluding beads are mixed with one chemotherapy agent (Irinotecan)4 and contrast dye. The beads will absorb the chemotherapy agent and once injected into the tumor will slowly release the drug over days.
Side Effects: The side effects will differ depending upon the type of embolization used. The most common complications reported are pain, nausea and severe post embolization syndrome (fever, pain, extreme fatigue, nausea/vomiting), hepatic injury and liver abscess.
Recovery: Most patients can be discharged a few hours after the procedure. If post embolization syndrome occurs an overnight stay is normally required.
This information was compiled with the generous help of Laura Porter, MD, Medical Consultant and Patient Advocate for the Colon Cancer Alliance, as well as Desiree Gray, Director of Health Economics & Patient Advocate for Sirtex Medical, Inc.
- Stubbs RS et al. Aust NZ J Surg 2006;76(8):696–703.
- Tol J et al. N Engl J Med 2009;360:563–72.
- Stubbs RS et al. Aust NZ J Surg 2006;76(8):696–703.
- Note: Biocompatibles DC – DEBiRI bead is 510K approved in the US as a bland particle only