Definitive Radiotherapy for Intrahepatic Cholangiocarcinoma With Extrahepatic Metastases

Eugene Koay, MD, PhD, MD Anderson Cancer Center at the University of Texas, Houston, Texas, discusses a study which found that definitive liver radiotherapy for patients with intrahepatic cholangiocarcinoma and extrahepatic metastases was associated with a longer overall survival, compared with chemotherapy alone.

Transcript:

Hi, everybody. My name is Eugene Koay. I am an associate professor in GI radiation oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas. It's a pleasure to be here with you today and talk about the study that we recently published in Liver Cancer.

The study is entitled “Definitive liver radiotherapy for intrahepatic cholangiocarcinoma with extrahepatic metastases.” This is a multidisciplinary collaboration that involves several years of work to bring together. I want to acknowledge all of my collaborators and their inputs in support of this research.

What we were trying to do is test whether patients who have disease outside of the liver from cholangiocarcinoma, whether they benefit from liver radiation, because it's not a typical scenario where you want to try to treat the primary liver tumor, where it all started, whenever they have disease outside of the liver, such as in the lungs or in the bones, [or] lymph nodes away from the liver, for example, or even in the peritoneum. These patients have a very poor prognosis in general.

Bile duct cancer, in general, has a median survival of about 1 year, maybe just a little bit more than that with current systemic therapies. It has been a very exciting time for bile duct cancer, cholangiocarcinoma, because there are many targeted therapies and some chemotherapy combinations with immunotherapy that have shown better efficacy, compared to just standard chemotherapy alone. But even so, the prognosis is very guarded with just a 12-month median survival.

We have observed that these patients often die of liver failure from the primary tumor inside of the liver because those tumors begin to grow very large. They either obstruct the bile ducts, causing a life-threatening infection called cholangitis and/or they block the blood vessels that supply the liver. That basically removes all the nutrients and oxygen that the normal liver needs to survive and function properly. You need your liver to live.

These patients succumb quite often, about 80% of the time or maybe higher, due to what we call tumor-related liver failure. Again, this motivated this idea of testing whether we can give liver-directed radiation therapy to control the primary tumor inside the liver, where this all started for these patients with extrahepatic M1 disease.

We went back from about 2010 until present to look at our experience of treating the primary liver tumors for these patients. We excluded those patients who got other liver-directed therapies. We were primarily interested in just focusing on those who received liver-directed radiation therapy. The dose here was higher than typical palliative doses. We call these biologically effective doses (BED), that median amount of BED, that dose was 97.5 Gray. This is higher than the typical palliative radiation dose. We were being much more aggressive with the intent of controlling the tumor here.

We also found a matching cohort of patients who just got chemotherapy alone in our institution and then also within the National Cancer Database, NCDB. In total, we identified 61 patients who got this liver-directed radiation therapy that we treated here at our institution and 220 patients who just received chemotherapy alone for their intrahepatic cholangiocarcinoma with extrahepatic metastases. Then, we found a frequency-match cohort of patients who just got chemotherapy alone in the NCDB database.

We compared the outcomes across these different groups as compared to the liver-directed radiation group, the 61 patients. In all of those comparisons and even accounting for any potential biases such as the survival time that it took to get up to the point of radiation — these patients often, almost all of them, got chemotherapy before they got radiation. To get the radiation, they had to survive that amount of time — we still accounted for that in comparison to our 2 control groups: the institutional cohort of 220 who got chemotherapy alone as well as those in the NCDB cohort who just got chemotherapy alone.

Even after accounting for all those things as well as confounding prognostic variables such as patient age, gender, duration of chemotherapy, tumor size, et cetera, we found that liver radiation was one of the strongest effects on the survival time of the patients to the tune of a hazard ratio of 0.4 on the multi-variable analysis, accounting for all those other potential confounding variables.

The median overall survival from diagnosis for the NCDB chemotherapy group compared to our liver radiation group was also significantly shorter. There was 9 months median survival versus 22 months median survival comparing chemotherapy versus liver radiation, respectively. That was quite consistent with what we observed with our institutional cohort as well: 9 versus 21 months in that situation.

The other interesting observation was that the patients who got the liver-directed radiation had a much lower frequency of tumor-related liver failure. This comparison was about 82% of liver failure in the chemotherapy alone group for the institutional cohort versus 47% in the liver radiation cohort. That's a substantial reduction in the risk of dying from liver failure due to the tumor growing and blocking the bile ducts or blocking the blood vessels.

The other interesting thing was that the natural history of the disease and the failure pattern for those who got liver radiation was very different. These patients ultimately succumbed to their disease, unfortunately, but that was due to other reasons than liver failure. For example, they would die from lung metastases or from peritoneal disease. But this happened at a substantially longer time period from that proximate cause of death that causes death for the vast majority of patients who get chemotherapy alone, which is, again, liver failure.

Overall, the conclusion from this study was that our data suggests an association between liver-directed radiation and substantially prolonged survival times for these patients with intrahepatic cholangiocarcinoma and extrahepatic metastases. What we are planning to do next is do a randomized clinical trial in this exact setting. We're currently hoping to get industry support as well as grant support to help to fund this particular multi-institutional study and have actually secured some initial funding for that, as well as some donations from some of our patients to help support the study.

We're very excited about the next steps and think that if this is a prospectively validated finding in this randomized controlled trial that we're planning to do, that that will change the standard of care and introduce liver-directed radiation therapy as one of the standard things that you do for selected patients with this particular devastating disease.

Thank you for your interest in what we're trying to do. Feel free to contact me if you have any questions.

Source:

De B, Upadhyay R, Liao K, et al. Definitive liver radiotherapy for intrahepatic cholangiocarcinoma with extrahepatic metastases. Liver Cancer. 2023;12(3):198-208. doi:10.1159/000530134