Redefining Treatment Approaches in Advanced HCC - Episode 2
A panel of experts discuss practical considerations for TACE in patients with unresectable BCLC stage B HCC, as well as define TACE-refractoriness and what to do if a patient fails treatment.
Richard S. Finn, MD: That’s a great segue to think about some of the practical considerations for using TACE [transarterial chemoembolization]. Laura, you’re a busy hepatologist at Northwestern University and play an active role in treating patients with liver cancer, as well as contributing to the intermediate space. What are you thinking about when considering a patient as a TACE candidate in practical terms?
Laura M. Kulik, MD: Since the BCLC [Barcelona Clinic Liver Cancer staging system] started— it’s the 20-year anniversary, congratulations to Dr Llovet—there has been a lot of refining. Originally, you could have a Child-Pugh score of A/B. But now it has become clear that it is very important that the more the patient is doing well from a liver standpoint, the more you could expect them to tolerate TACE, and hence, have more of a response because you can deliver the treatment that you’re wanting to.
Dr Llovet brought up a couple of prognostic factors, the 6-and-12 score is one of them, the up-to-7 score is another. This is taking the tumor burden, which is defined by the largest lesion plus the number of lesions, so you get this linear equation. If you have 1 tumor that is 6 cm, and that’s the largest tumor, and you have 2 tumors, that would be 6 plus 2, which is 8. Up-to-7 has recently been defined as how you may start to think of patients who would deserve to go onto systemic therapy, or at least consider systemic therapy.
I would say as a transplant hepatologist though that some of those patients would be in the realm of consideration for downstaging in terms of upper limit. When we think of transplant, we don’t have a ceiling of anything and try to downstage, because the chances become less the more tumor burden you have.
I think you have to look at the patient overall, their age, their overall health, as to whether this patient will be a transplant candidate. Vincenzo Mazzaferro, MD, who was the grandfather of coming up with the Milan Criteria, recently published a randomized, controlled trial looking at transplant vs locoregional therapy and/or systemic therapy, which is remarkable that you can do this in this day and age. And not surprisingly, the overall survival was significantly improved at 5 years in patients who were transplanted.
You always have to consider the potential of downstaging, but we know there are patients, going back to your question, who are not going to be good TACE candidates. They’re either going to be refractory, have an infiltrative tumor, or they’re starting out with ALBI, which is the albumin plus bilirubin, and it’s also a linear equation, a 1, 2, 3. With these factors, we know that they probably won’t tolerate TACE well, and moving to systemic therapy earlier in those patients is becoming more of the thought process, as opposed to waiting.
Richard S. Finn, MD: You bring up some important points that are practical and speak to the point that hepatocellular carcinoma is a multidisciplinary disease, not only oncology and hepatology, but interventional radiology and surgery, such as hepatobiliary surgery and transplant. The criteria for transplant are somewhat fluid, especially in the United States. It is not so orthodox anymore that a patient gets assigned intermediate stage and stays there. Patients will migrate to become advanced eventually, and they may even migrate a little earlier, and there are opportunities for curative therapies for some of these patients.
Amit, when you see a patient and you’re considering TACE, how do you pay attention to their liver function? How does that impact your decision?
Amit G. Singal, MD, MS: Laura started to talk about this to some degree in terms of when we consider somebody for chemoembolization or radioembolization, or any locoregional therapy. It is important that you consider the liver function, and we’ve gone beyond just considering the Child-Pugh score; many of our centers also add the ALBI score, which is adds value to the Child-Pugh score. We do this because whenever you treat with locoregional therapy, you’re trying to induce some degree of tumor response with the idea of either downstaging and/or improving survival. There’s also the concomitant risk of liver injury. Whenever we do a chemoembolization, radioembolization, SBRT [stereotactic body radiation therapy], etc, we have to watch the liver function carefully, because you can see patients who have deterioration, whether that’s new decompensation or increase in their bilirubin.
The stronger a patient’s liver comes in, the more likely they are to tolerate that chemoembolization or other locoregional therapy. This is a critical factor to consider as we go through this, and if you see a patient whose liver function gets worse—to your point of stage migration—that’s another consideration in terms of stopping locoregional therapy and switching to systemic therapy.
Richard S. Finn, MD: You bring up some important points. To put it in context historically, before the approval of sorafenib in 2007 and 2008, we didn’t have a proven systemic treatment. Josep led one of the pivotal studies that established TACE as a standard of care, but in a confined population anatomically, as well as liver function. And TACE and locoregional treatment expanded to fill the void over time, in that we didn’t have any systemic treatment, so TACE was used in patients who were probably not optimal candidates. Maybe they had vascular invasion, maybe they had progression after a TACE, and it was TACE beyond progression even, because we didn’t have anything else to offer these patients other than maybe clinical trials.
I remember back in the day offering patients octreotide because there were early data there, tamoxifen, eventually cytotoxic agents—capecitabine, doxorubicin—even though there weren’t data to support that. But we wanted to offer patients something or a clinical trial.
Dan, when you see a patient at your multidisciplinary program who had TACE, how do you assess response, and when do you decide TACE is no longer working?
Daneng Li, MD: I think it’s done, as you mentioned, in a multidisciplinary fashion. Usually, we would assess for a TACE response anywhere between 6 to 8 weeks post-TACE procedure, initially with imaging. How do you characterize response? You want to see that the tumor has died out and is not necessarily lighting up on the scan.
You want to assess whether you get clearage of that entire tumor or there’s residual enhancement. This is an important point because we know a lot of times with incomplete TACE, the tumor becomes a little more resistant moving forward. There are a lot of preclinical data to suggest that an incomplete TACE can lead to an increase in tumor hypoxia and ultimately rev up pathways involved in angiogenesis, which can be problematic in developing somewhat more resistant tumors.
How do you make that characterization of whether someone’s potentially TACE-refractory over time? I think there are a lot of different criteria in terms of whether you get an incomplete response, and not a complete response, where you’ve done the embolization. But also, whether new lesions show on that first scan afterward is suggestive of a somewhat refractory disease and may be an indication to transition to systemic therapy much earlier.
Transcript Edited for Clarity