What is Liver Cancer?
Liver cancer is the abnormal growth of cells in the liver resulting in a liver tumor. If the abnormal cells originated as liver cells, the resulting collection of cells is called a primary liver tumor. Some liver tumors are benign, meaning they are not cancerous and do not spread to other parts of the body. Malignant liver tumors, however, can invade other organs, and spread throughout the body. Most primary malignant liver cancers are classified as hepatocellular carcinoma or called hepatomas.
A much more common cancer of the liver is a metastatic liver tumor. In this case, cancerous cells from another part of the body are carried to the liver by the blood or other bodily fluids. Metastatic liver tumors can spread to the liver from the colon, lung, breast, stomach and pancreas, as well as other sites in the body.
More than 21,300 cases of primary liver cancer are expected to be diagnosed in the United States in 2008. Primary liver cancer is expected to result in approximately 18,410 deaths during that time. Five-year relative survival rates for metastatic cancer to the liver is 3.3 percent.
How is Liver Cancer treated?
After liver cancer has been detected and staged, the doctor will discuss different treatment options. Treatments for liver cancer depend on the type of cancer and the stage. Early-stage primary liver cancer, and some metastatic tumors, may be treated with surgery, with the goal of removing the entire tumor.Alternatively, the tumor may be treated by ablation – or destroying it in place – using one of several methods, including the application of a high-temperature probe (radiofrequency ablation), a low-temperature probe (cryoablation), focused chemotherapy treatment (chemoembolization), conventional radiation therapy, local alcohol injection or CyberKnife. In some cases, the entire liver can be removed and replaced with a donor liver transplant. With more advanced cases of liver cancer, chemotherapy combined with some of the above mentioned treatments may be used.
Surgery is the common procedure for treating liver tumors that are localized and have not spread widely throughout the liver. This type of surgery, often called a partial hepatectomy, involves the surgeon making a large incision in the abdomen and cutting away a section of liver containing the tumor and some of the surrounding healthy tissue. Liver cancer surgery generally is feasible when the disease is limited. Under such conditions, resection of a primary liver tumor can lead to a five-year survival rate of 60 percent to 75 percent, and resection of a metastatic tumor may result in five-year survival rates of 25 percent to 39 percent. Unfortunately, only 20 percent to 30 percent of patients with liver cancer are eligible for surgery because their disease is too advanced and/or their liver functions are extremely poor.5 Liver cancer surgery may pose significant risk of complications, such as infection, bleeding, respiratory and cardiac problems. Approximately 2 percent to 6 percent of patients have died as a result of liver cancer surgery.
Surgery may be the only treatment necessary or it may be combined with chemotherapy or radiation for patients with widespread cancer or an advanced stage of their primary tumor.
Conventional radiation therapy, called external beam radiation therapy, typically involves delivery of wide fields of radiation that encompass both the tumor and a significant amount of surrounding healthy tissue. These wide fields of radiation, delivered in small doses over many sessions in the course of several weeks, are necessary to account for the tumor’s movement as the patient breathes. These wide radiation fields limit the total radiation dose that can be given in each treatment session because of the toxicity to the normal liver tissue included in the radiation fields, making it necessary to divide up the total treatment in 30 to 40 sessions given over weeks This type of damage to normal liver tissue from radiation has been characterized as radiation-induced liver disease (RILD), a syndrome that may occur in the first few weeks after radiation therapy, and can, in the most severe cases, lead to liver failure. Recent reports have shown patient survival rates after 1 year ranging from 47 percent to 95 percent and after 5 years from 11 percent to 25 percent, with generally better outcomes when smaller tumors are treated with higher doses.
Several techniques – such as respiratory gating and breath holding– have been developed to better compensate for movement of liver tumors with breathing.
Respiratory gating is a technique in which radiation is delivered when the tumor is thought to be in a certain location during a patient’s breathing cycle. Gating makes a number of assumptions about the location of liver tumor. These assumptions are that the tumor is always in that same location during a specific point in a patient’s breathing pattern; a patient’s breathing pattern does not change throughout a treatment; and a patient is breathing the same during a treatment as he or she was breathing during the planning phase. In reality, many patients breathe differently throughout the treatment, particularly if they are nervous or fall asleep. These changes in breathing patterns may result in errors in radiation delivery.
Breath holding involves a patient taking a full breath and then holding it for several seconds. As the patient holds his or her breath, the radiation beam is switched on and then turned off just before the patient begins to breathe normally again. Breath holding assumes a tumor will be in a certain location when the patient breathes in. This may not always be the case, depending on the depth of a patient’s breath. Breath holding also may be very difficult for patients with advanced lung disease.
Techniques such as gating and breath holding have allowed physicians to deliver much higher doses of radiation in as few as three to five sessions with a procedure called stereotactic body radiation therapy (SBRT). This alternative treatment for liver cancer has been shown to be more effective than conventional radiation therapy, with tumor control ranging from 70 percent to 100 percent 18 months after treatment, with very low rates of side effects that are generally mild. Slightly better tumor control has been reported for smaller tumors8 and metastatic lesions. Although SBRT enables doctors to spare more normal liver tissue than conventional methods, it still typically requires large margins around tumors to ensure that the radiation is delivered to the tumor and to account for the inaccuracies of gating and breath holding.
Radiosurgery devices, such as the CyberKnife offer patients a new option for liver cancer treatment. The CyberKnife System can deliver high doses of radiation with extreme accuracy because of its ability to track the location liver tumors in real-time during treatment. The CyberKnife System uses the Synchrony Respiratory Tracking System to track tumor motion as patients breathe normally, and adjusts the radiation beam accordingly. The Synchrony System correlates the rise and fall of the chest with the actual location of the tumor in X-ray images. As a result, during CyberKnife treatment, patients can lie comfortably and breathe normally without any frames, and are not asked to hold their breath or perform any complex breathing maneuvers. The Synchrony System can track moving targets with an accuracy of 1 millimeter or better, which allows clinicians to deliver radiation precisely to the tumor and limit exposure to healthy surrounding tissue.
Chemotherapy is used when cancer cells are thought to be located throughout the body or they are present in a patient’s blood or other fluids, which is often the case with metastatic tumors and advanced-stage liver cancer. Chemotherapy medication is delivered orally or through an IV, and is given to a patient either as the sole treatment or in combination with other types of liver cancer treatment. Chemotherapy affects both normal tissue and the cancer cells, so patients may experience side effects, such as severe nausea and vomiting, infections, fatigue and weight loss. Chemotherapy has not provided clinical benefit or prolonged survival for patients with advanced primary liver cancer and randomized trials have not shown any benefit of neoadjuvant therapy, a treatment that’s given first to help make the next treatment step go more smoothly, or adjuvant systemictherapy, which is a type of treatment given after surgery to target the entire body in hopes of destroying any cancer cells that may have traveled to distant body parts, but are below the level of clinical detection. HCC remains a highly lethal disease that is resistant to traditional cytotoxic chemotherapy. The last 30 years of chemotherapy clinical trials for advanced HCC have repeatedly failed to demonstrate any survival benefit for a long list of drugs. However a survival advantage was recently established for sorafenib, instituting a new standard of care for inoperable HCC.