Testing Aims to Personalize Treatment, Predict Transplant Outcomes in Cholangiocarcinoma

Partner | Cancer Centers | <b>Mayo Clinic Cancer Center</b>

Lewis R. Roberts, MB, ChB, PhD, discusses the past, present, and future of treatment in patients with perihilar and intrahepatic cholangiocarcinoma. &#8239;

Lewis R. Roberts, MB, ChB, PhD

A regimen of chemotherapy, radiation, and transplant has shown promise in the perihilar and intrahepatic subgroups of cholangiocarcinoma,&#8239;said Lewis R. Roberts, MB, ChB, PhD, adding that personalized approaches are on the horizon to identify patients who will best respond to this approach.

In the past, transplant was believed to be ineffective in this disease, Roberts said. Today, with transplant showing consistent benefit in select patients, the focus is shifting to explore transplant sequencing and predictive factors of response.

"Broadly speaking, we have solved a lot of the surgical and technical aspects of doing procedures, such as transplant," explained Roberts. "Now, we are beginning to study the biology of the tumors to see if a better understanding of the biology can help us to personalize the treatment that different patients get."&#8239;

In an interview with &#8239;OncLive &#8239;during the 2019 International Liver Cancer Association Conference, Roberts, a gastroenterologist, professor of medicine and director of the Hepatobiliary Neoplasia Clinic, Department of Gastroenterology and Hepatology, Mayo Clinic, discussed the past, present, and future of treatment in patients with perihilar and intrahepatic cholangiocarcinoma. &#8239;

OncLive: &#8239;What is the role of transplant in these patient subgroups and how is it changing?

Roberts: &#8239;Initially, liver transplantation was felt not to be an effective treatment for patients with cholangiocarcinoma, because they often present with more advanced disease and are prone to have their cancer&#8239; metastasize to other sites of the body.&#8239;

In early studies, those patients had liver transplants performed because they had to go on immunosuppression [after transplant] so that their bodies did not reject the new organ. However, that made them prone to recurrence.&#8239;

A number of years ago, it was found that in limited cases, particularly in the perihilar cancer subtype where the tumors are small and block the bile ducts, if we treat patients aggressively with chemotherapy and radiation and then do a liver transplant, a proportion of those patients do very well.&#8239;

Since then, the community has been trying to understand how to select individuals with &#8239;cholangiocarcinoma &#8239;who will do their best with transplant. Some patients who have underlying liver disease from the bile ducts, called primary sclerosing cholangitis, are not good candidates for surgical resection.&#8239; However, &#8239;because we know they have this underlying liver disease, we can follow them closely and diagnose the cancers very early.&#8239; In that context, we find that the patients who get a liver transplant do quite well.&#8239;

What is the newest development in this space?

We are interested in the &#8239;expansion of liver transplant for &#8239;cholangiocarcinoma to intrahepatic &#8239;cholangiocarcinomas. &#8239;We are finding that if we can identify people with intrahepatic&#8239; cholangiocarcinoma, who have small tumors and meet particular characteristics, then we know that those patients can also do very well with transplant.&#8239;

Now, in that group of individuals, we hope we can further narrow down and determine which subgroup of patients will do their best&#8239; after liver transplant; perhaps their blood tests or &#8239;tissue tests will help us determine that.

What factors play a role in selecting the right&#8239;patients with perihilar cholangiocarcinoma?

In the case of perihilar&#8239; cholangiocarcinoma, we are finding that tumor size is important, as is making sure that there is no evidence of spread outside the liver when the patient is getting transplant.&#8239;

First of all, they have to meet fairly strict criteria. Then we give them chemotherapy and radiation. Then, just before transplant, we check again [for metastasis]. Usually, we do a laparoscopy to ensure that there is no evidence of spread to lymph nodes or outside the liver.&#8239;

Are there any tests that could shed light on which patients with intrahepatic &#8239;cholangiocarcinoma will respond best?

At this point, research is being done in clinical studies. One study in particular suggests that if patients had small tumors, even if they were intrahepatic, a proportion of them will do very well with transplant.&#8239;

We're investigating whether it is possible to do blood tests or tissue tests that define a biological subtype who responds better to transplant than other different subtypes.

One of the blood tests that we often use in the case of perihilar &#8239;cholangiocarcinoma, for example, is called the CA 19-9 test. The evidence suggests that patients with high CA 19-9 are more likely to have metastasis. Those are &#8239;high-risk patients, so we tend to prefer patients who have low CA 19-9.&#8239;

We don't know if the same is true for the intrahepatic&#8239; cholangiocarcinoma; that is one of the questions.

Some colleagues have begun to do gene expression analyses of &#8239;cholangiocarcinoma tumors. [The tumors] appear to fall into two groups: one that is more like a primary liver cell in hepatocellular&#8239; carcinoma (HCC), and another that is more like a bile duct cancer cell.

Our &#8239;suspicion is those tumors that are more like a hepatocellular carcinoma cell will probably have a better outcome because we've been transplanting people with HCC for a long time now, and we know those patients [who are able to undergo transplant] have very good outcomes

What do you hope that others take away from these findings?

We hope to generate some discussion, and perhaps some opportunities for collaboration so we can continue to work on these questions as a community. [We should] work together to better define who are the best candidates for these different treatments.&#8239;