Expert Discusses Interventional Radiology Advances in Liver-Metastatic CRC

Rahmi Oklu, MD, PhD

Rahmi Oklu, MD, PhD

Interventional radiology is making an important impact in the field of colorectal cancer (CRC), specifically in patients with CRC who have liver metastases, according to Rahmi Oklu, MD, PhD.

Phase III results of the SIRFLOX study demonstrated a significant increase in hepatic depth of response from treatment with selective internal radiation therapy (SIRT) with SIR-Spheres Y-90 resin microspheres versus standard first-line chemotherapy in patients with metastatic CRC. Experts are anticipating longer follow-up of the study, Oklu adds, to determine whether the therapy also provides an overall survival (OS) benefit.

In an interview withTargeted Oncology, Oklu, an associate professor of Radiology at Mayo Clinic, shed light on the various approaches physicians use to treat patients who have CRC with liver metastases.

TARGETED ONCOLOGY:What is important to note regarding liver metastases in CRC?

Oklu:

This is an area where interventional radiology really plays a role today. There are 3 areas in which we can make a big impact. Specifically for CRC, surgery is the preferred option and every effort should be made for these patients to have their lesions resected. Sometimes, if their lesions are isolated or low to the right side, they’re otherwise unresected because the left lobe is so small.

One area where interventional radiology can really make a big impact is portal vein embolization, where you block blood flow from the left lobe to the right lobe and you can cause hypertrophy and hypoplasia but, overall, growth of the left lobe. The whole goal here is that, after surgical resection, the right lobe will not go into polypectomy failure.

If surgery is not possible, and portal vein embolization is not possible, another area where we can have a big impact is ablation. The many types of ablation technologies we use today include cryoablation, radiofrequency ablation, microwave ablation, and there’s also non-thermal ablation, where you pulse the liver with high electric fields at 3000 volts per centimeter.

International radiology is really having a big impact in this field, specifically in lesions that are adjacent to vital structures that are otherwise not amenable to resection or to thermal ablation. With [non-thermal ablation], you can have lesions next to the portal vein, bile duct, gallbladder, and because it’s not thermal, it does not cause any injuries to adjacent structures.

Finally, I touched upon radioembolization, specifically SIRT, and what was revealed last year and the upcoming trial data.

TARGETED ONCOLOGY:What was so encouraging about the SIRFLOX data we saw last year?

Oklu:

The data that we have so far is, essentially, the endpoint of time to progression. Does it really prolong time to disease progression? The SIRFLOX data did show that it does, significantly, compared with chemotherapy alone. It didn’t really look at OS.

Does it really have an impact on OS in these patients? That is what the trials—due to be revealed some point this year—will answer. Those studies will tell us whether radioembolization does impact OS in patients when combined with chemotherapy.

TARGETED ONCOLOGY:What factors do you consider when treating a patient with CRC who has liver metastases?

Oklu:

One of the great things about Mayo Clinic is the multidisciplinary approach. We really work as a team; we try to leverage each of our colleague’s expertise. It’s not really treatment in isolation but, really, in combination. Rarely do patients just get surgery or just get radioembolization. We are in constant contact with our team members and a tumor board often reviews these patients. It doesn’t end there; it’s continuous. We try to do what we can as best as we can.

TARGETED ONCOLOGY:How have you seen these various approaches evolve?

Oklu:

One of the great things about interventional radiology is that it’s technology-based. As our technology evolves, folks come up with better delivery approaches. Today, we use particles, and maybe tomorrow we’ll use biomaterials. The tissue-engineering field is relatively on-tact in radiology. That is, in fact, one of the areas we are working on in the laboratory. We are trying to use sheathing biomaterials to deliver whatever it may be, chemotherapy or radioembolic agents. This would be not to cause an inclusion of sorts, but to deliver and then disappear without any consequence.

They are usually biocompatible, so you’ve got that whole tissue-engineering aspect which can greatly facilitate, in my opinion, drug delivery. Ultimately, it is delivery that will dictate overall outcome. Can you bring one chemotherapy drug to every cancer cell in that tumor? Treating 80% [of cancer cells] is not sufficient. You really have to treat the entire 100% of tumors that you see and tumors that you don’t see, which is why combination therapy is so critical.

TARGETED ONCOLOGY:What ongoing trials are you involved with?

Oklu:

We are working on a number of areas in our lab that are mostly bioengineering related. One area I am pretty excited to tell you about—it just got NIH funded—is not only a novel drug delivery device, but also allows you to capture the drug and outflow so you can prevent drug toxicity.

There are a lot of drugs out there that don’t go beyond phase I, or the toxicity is just too high. It may be a great drug and it could be FDA approved, such as interleukin-2—but it causes toxicity. This technology has some great potential in that you can deliver extreme doses but, yet, it will remain within the tumor bed. As it exits, it never makes it to the systemic side. We figured out an elegant way of capturing these drugs so that you can deliver very extreme levels and get away without systemic toxicity.

We are exploring that—the tissue engineering as I mentioned. We were trying to come up with a variety of chemical and electrical sensors to try to assess from a diagnostic perspective in real time. We are doing a lot. This is very exciting stuff in the lab.

The research that we do is really patient inspired. You see the patient and you beat yourself up a little bit, [wondering] “why didn’t it work? Why did my patient lose all of his hair?” That is one of the things that inspired this particular project of the drug capture. This young patient wasn’t really worried about the cancer; he was just worried about his kids finding out about the cancer itself. There is a stigma associated with cancer; some people just want to keep it private. But, if you’re losing all of your hair, then it becomes pretty obvious. That had a pretty big impact on him and it had a big impact on me.

One of the advantages I have is that I have a background in molecular biology, so you can go to the bench and then figure out whether it can be fixed. Can we prevent this from happening? The genesis is really a lot of projects that we work on in the lab that are patient inspired. A lot of people call it biology-inspired engineering. I like to call it patient-inspired biology engineering.

Reference:

Heinemann V, van Hazel, GA Sharma NK, et al. Evaluation of depth of response within a volumetric model in patients with metastatic colorectal cancer: results of the SIRFLOX study. In: Proceedings from the 2016 World Congress on GI Cancer; June 28-July 2, 2016; Barcelona, Spain. Abstract O-014.