GIST and the LIVER

By Ronald P. DeMatteo, MD, FACS

Assistant Attending, Hepatobiliary Service Department of Surgery New York Memorial Hospital of Cancer and Allied Diseases. Assistant Member, Memorial Sloan-Kettering Cancer Center, Assistant Professor of Surgery Weil Medical College of Cornell University New York, NY

INTRODUCTION: GIST Support International approached renowned surgeon Dr. DeMatteo with concerns about GIST and the liver. As patients and caregivers, we know that when GIST metastasizes, it most often goes to the liver. We know that our lifesaving drugs, Gleevec and its successors, are metabolized by liver enzymes. We know that patients’ liver function is monitored through blood tests done at regular oncology visits. Please help us understand more about the liver’s importance in GIST by answering these questions.

QUESTION 1: When my oncologist orders "liver panel" blood tests, what is he/she looking for? Does Gleevec damage the liver? If my liver function test results were abnormal, would I have to stop taking Gleevec?

Imatinib, like most drugs, is metabolized or broken down in the liver. It is important to monitor your "liver function tests" while on Imatinib to make sure that the drug is not hurting your liver. In a small percentage of people, imatinib can cause elevation of liver enzymes alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), elevation of bilirubin, or reduction of albumin. Fortunately, this is uncommon. If it does occur, a brief stoppage or a slight dose reduction of the drug may be all that is required. Rarely, a patient has to stop the drug altogether. Imatinib does not cause long-term liver damage if the patient is carefully monitored.

QUESTION 2: Why is the liver frequently the site where metastasis occurs?

The liver is the most common site of metastasis for most tumors that occur in the gastrointestinal tract. The blood that drains the stomach and intestines goes directly through the liver. Because the liver normally filters the blood, any microscopic cells from a GIST that get into the bloodstream may become lodged in the liver. There also may be certain factors within the liver environment that promote the survival and growth of a single tumor cell.

QUESTION 3: Can I reduce my chances of liver metastasis by changing my diet, or otherwise protect my liver? (Conversely, could I increase the chances by eating bad stuff?)

This is a frequent question but there are not any convincing data that altering your diet will change your chances of developing liver metastases. In general, we recommend a balanced diet and avoidance of excessive alcohol use.

QUESTION 4: If I did not have liver metastases at the time of diagnosis, can my chances of developing liver metastases later be predicted? If so, how?

Doctors cannot predict accurately whether any single patient will develop liver metastasis. In general, the chance of having a GIST tumor come back anywhere is related to the location and size of the original tumor, whether it was completely removed, and how actively it was dividing under the microscope (this is called mitotic rate, often described as mitoses per high-power field).

QUESTION 5: What are the treatment options for liver metastases?

There are several treatment options for GIST liver metastases. The first choice is Imatinib therapy. Other options that may be useful in combination with Imatinib, or if the tumor is resistant to imatinib or other agents,include: radiofrequency ablation (RFA), hepatic artery embolization, and surgery. RFA is the insertion of a metal probe into a tumor in order to heat it and thereby kill it. RFA can be performed through the skin with the patient slightly sedated or during laparoscopy or open operation. We usually only use RFA when there are less than 6 tumors, the tumors are less than 5 cm in size, and the tumors are not near vital structures within the liver.

Embolization is a procedure performed by an interventional radiologist. A small tube is placed into the artery in your leg and fed upwards into the artery supplying your liver. Microscopic particles are then injected into the tumors to try to cut off their blood supply. Liver resection (surgery) is another option. In general, up to 80% of the liver can be removed because it can grow back. All 3 of these procedures are highly specialized and are usually only performed at major centers.