There’s more to cancer than the size of the tumor. Amy Kim believes that the Milan criteria—the formula adopted around the world in 1996 to determine the need and suitability for a liver transplant in patients with hepatocellular carcinoma (HCC) or cirrhosis—might be due for an update.

Twenty percent of patients who have cancer-related liver transplants have recurrences within two years of their transplant. Kim believes the technology and expertise exist to improve on the Milan criteria.
“I’m interested in identifying those recurrences sooner and managing them better—even before we do the transplant,” says Kim.

She recounts a memorable experience during her transplant fellowship at Yale, when a patient asked her how a liver cancer could return after a transplant. “The simplest answer I could offer was that it had already metastasized. But it made me wonder how the cancer, specifically HCC, could metastasize when transplants are limited to patients with very small tumors and that there wasn’t even microscopic evidence of vascular invasion.

“The patient’s question boggled my mind for months.”

The Milan criteria states a short list of guidelines to assess whether patients are good liver transplant candidates. Ideal patients can’t have cancer outside the liver, and there can be no major blood vessel involvement. No lesion can be larger than 5 centimeters or three or fewer lesions must measure less than 3 centimenters each.

But the criteria fails to take into account what Kim says is a vital element.

“We don’t look at the tumor biology,” says Kim. She says that the size of a tumor is a poor indication of a patient’s health. “Essentially, the criteria says the larger the size, the higher the risk of recurrence. But that’s such a generalized criteria. Each liver cancer is different.”

And considering the scarcity of donor livers, she wonders if livers are going to the cases with the greatest need.
Kim says patients can be left off the transplant list because of tumors that shouldn’t disqualify them. “Even if a tumor looks really bad, very often its biology tells us it won’t come back once you take out the liver.”

The Model for End-Stage Liver Disease (MELD) is another numeric scoring system to assess the severity of chronic liver disease. People with cancer get extra MELD score points, bumping them higher up the liver transplant list. “Sometimes that makes sense, but there are lots of times it doesn’t,” says Kim.

Kim’s research aims to better predict which patients are ideal transplant candidates. Along with Johns Hopkins professor of medicine and oncology Stephen Meltzer, Kim does research into precancerous biomarkers.

“Transplant hepatologists are bound by certain limitations,” Kim says. “For instance, often, it’s only when the liver is outside the body that we see things like some of the vessels already having tumor invasion. That’s why I wanted to look into biomarkers.”

She’s also working to see if tumor cells that circulate in the bloodstream might be a predictor of post-transplant cancer recurrence.

“If we find that circulating tumor cells correlate with post-transplant liver cancer recurrence, it could improve the selection of transplant candidates,” Kim says. “Donor livers would go to those with the least risk, while patients with little benefit would be spared a major abdominal surgery and commitment to immunosuppression.”