Advances: Liver Cancer

Advances in Surgical Oncology and Clinical Investigation in Liver Cancer

Advances in Surgical Oncology and Clinical Investigation for Liver Cancer

Advanced Surgery Techniques for Treatment of Liver Cancer

Many patients are candidates for surgical removal (resection) of their liver tumors, which is the treatment approach associated with the highest chance for cure. Liver resections are generally considered complex surgery and published data have consistently demonstrated that hospitals and centers with the highest liver surgery volume experience the lowest complication and death rates. Surgeons in the Divisions of Surgical Oncology and Transplant Surgery perform the vast majority of liver resections at the Massachusetts General Hospital.

New techniques used to minimize blood loss during surgery including use of radiofrequency energy during dissection, use of ultrasound have reduced the instances in which blood transfusions are required. The median hospital stay following major liver resection has been reduced to seven days as a result of many of these advances. For patients with unresectable liver tumors, surgical treatment options include liver transplantation, radiofrequency ablation, ethanol injection, chemoembolization, and insertion of hepatic arterial infusion pumps. (More information on hepatic arterial infusion chemotherapy can be obtained from Medtronic and from Mass General Surgical Oncology.) This team of surgeons is also poised to launch a new clinical trial involving hyperthermic isolated perfusion of the liver with Melphalan as an extension of a clinical trial in the Surgery Branch at the National Cancer Institute. The team is also developing gene therapies for unresectable liver tumors, and is poised to launch a clinical trial of Herpes simplex viral treatment of liver tumors. The development of living-related liver transplant program by Dr. Cosimi and Dr. Hertl have enabled this team to offer liver transplantation to suitable patients in a more timely fashion and avoid relatively long wait times associated with cadaveric organs. This team has worked also together with colleagues in radiology to develop the most sensitive tests for detection of liver tumors, as well as tests that allow precise mapping of liver volumes for operative planning. This team of surgeons is also experienced in performance of intraoperative ultrasound examination of the liver, which has been demonstrated to be the most sensitive method for detection of liver tumors.

Hepatic Arterial Infusion Chemotherapy for Colon and Rectal Carcinoma Liver Metastases

Colon and rectal cancers unfortunately often spread to the liver. However, it is well known that these cancers may spread to the liver and only the liver, without spread to other sites. Chemotherapy agents such as Camptosar® (CPT-11; irinotecan), 5-FU, and leucovorin are used most commonly to treat this form of cancer. These agents are commonly administered into a vein (intravenously). An attractive alternative is to administer chemotherapy directly into the arteries that feed the liver. The advantages of this approach are:

  1. A high rate (99%) of chemotherapy drug extraction by the liver on first passage of blood through the liver leads to higher chemotherapy drug concentrations in the tumors than can be achieved with intravenous drug administration.
  2. A high rate (99%) of chemotherapy drug extraction by the liver on first passage of blood through the liver leads to lower levels of drug in tissues outside the liver (e.g. bone marrow and gut), which reduces side effects of bone marrow suppression or nausea.
  3. Liver tumors are supplied principally by the arteries in the liver, which are the blood vessels into which the active chemotherapy agent is administered.
  4. The likelihood of tumor shrinkage is greater following intra-arterial chemotherapy administration directly into the liver compared to intravenous adminisration.
  5. Patients whose tumors have increased in size despite treatment with 5-FU or Camptosar® (CPT-11; irinotecan) still shrink in response to intraarterial chemotherapy in roughly 50% of instances.

In an attempt to improve upon past results with intra-arterial administration of chemotherapy, we have initiated a clinical trial that combines intra-arterial chemotherapy with systemic (intravenous) chemotherapy administration. FUDR (floxuridine) and 5-FU are administered intra-arterially, while Camptosar® (CPT-11; irinotecan) is adminstered intravenously. It is hoped that this treatment will be more effective than administration of any of these compounds alone or together via an intravenous route. Patients with colon or rectal cancer spread to the liver that are eligible for this clinical trial will have a small infusion pump (roughly the size of a hockey puck) inserted surgically into their abdomen to administer the chemotherapy. Patients that are not eligible for this trial may still benefit from intra-arterial administration of FUDR (without systemic administration of Camptosar).

 

Radiofrequency Ablation of Liver TumorsRadiofrequency ablation is a treatment that can be applied to some liver tumors that are unresectable. The technique involves placement of a thin electrode (similar to a needle) into the center of a liver tumor, usually with the assistance of either CAT scan or ultrasound imaging. The electrode can be inserted through the skin often times, such that an operation is not required, much as a liver biopsy can be performed without the need for an operation. Local anesthesia is commonly used to minimize the discomfort of electrode insertion. The electrode is then connected to an electrical generator, and as current passes from the electrode tip to a grounding pad, the tumor is heated to a point where it is destroyed. This portion of the procedure generally does not produce any discomfort. During the procedure, vital signs, tumor temperature, and electrical properties of the tumor are monitored. The efficacy of treatment is assessed by CAT scan one month following treatment. Re-treatments are often necessary. Risks of the procedure include bleeding, although this is extremely rare.

In November of 1996, Dr. Kenneth Tanabe and Dr. Nahum Goldberg performed the first radiofrequency ablation of a patient with a liver tumor in the United States. This history-making procedure was performed in the operating rooms of the Massachusetts General Hospital as part of an Institutional Research Board approved clinical research protocol. The experimental procedure was deemed a success in both efficacy and safety. Following this initial trial, researchers in the Division of Surgical Oncology at the Massachusetts General Hospital have continued to lead the way in making cutting edge advances in this field. Nonetheless, it is important to point out that:

  1. radiofrequency ablation remains experimental
  2. radiofrequency ablation is not a substitute for resection (surgical removal) whenever possible, as removal of the tumor is considered the "gold standard" for treatment in appropriate patients
  3. the chances of successful (complete) tumor destruction is about 75% -- less for tumors larger than 3 cm and more for tumors smaller than 3 cm
  4. it is exceedingly rare that pateints with liver metastases from cancer of the pancreas, lungs, stomach, or esophagus are candidates for radiofrequency ablation unless they have no more than two tumors measuring no more than 4.0 cm in size.

 

Isolated Hepatic Perfusion for Unresectable Liver Tumors Liver cancer and liver tumors pose a difficult challenge for oncologists. Unfortunately, it is frequently not possible to surgically remove liver tumors. Radiofrequency ablation and cryosurgical ablation are possible in patients with a limited number of tumors that are relatively small (no larger than 3 – 5 cm). Patients that are not candidates for surgical removal or ablation of their liver tumors are most often treated with chemotherapy. Intravenous administration of chemotherapy may temporarily shrink liver tumors.

Liver specialists in the Division of Surgical Oncology and Division of Transplant Surgery have opened a clinical trial to study an aggressive and novel approach to treatment of unresectable liver tumors. The treatment involves an operation in which the blood vessels that supply the liver and drain the liver are isolated to create a blood flow circuit for the liver that is separate from the rest of the body. The liver is heated to 40° C (hyperthermia) and an extremely high dose of a chemotherapy agent (melphalan) is circulated in the liver. Because the blood flow in the liver is isolated from the blood flow of the remainder of the body, only the liver itself is subjected to the high dose of chemotherapy and the hyperthermia. The hyperthermia and chemotherapy together more effectively destroy cancer than either modality alone. At the end of the operation, the normal blood flow of the liver is re-established. This procedure has been performed on over 150 patients at the National Cancer Institute, with demonstration of safety and efficacy. This clinical trial at the Massachusetts General Hospital is performed as a collaboration between liver specialists in the Surgical Oncology and Transplant surgery, and is designed to examine safety and feasibility of this treatment when performed at a center other than the National Cancer Institute. Patients with unresectable liver tumors from colon or rectal cancer, ocular melanoma, neuroendocrine tumors (including carcinoid), and cholangiocarcinoma are eligible. Patients must have no evidence of cancer outside the liver, and should not have either hepatitis or cirrhosis.