Burgeoning Field of Interventional Oncology Is Poised for Takeoff: A Q&A With Dan Brown, MD

Dan Brown, MD

Interventional oncology is an emerging field in cancer care that is intended to complement existing treatment modalities. We sat down with Dan Brown, MD, the new chief of Interventional Oncology at Vanderbilt University Medical Center, to discuss the burgeoning field and its potential effect on cancer care moving forward.

OBTN: What is interventional oncology and how does it fit in with the current cancer treatment paradigm?

Dr. Brown: Interventional oncology uses image-guided technology to directly target solid tumors. It’s a complementary intervention that I hope will eventually be integrated into standard care algorithms. It gives clinicians another focused area of cancer care in which we can collaborate with other specialists. We perform targeted procedures that can be characterized as either arterial or ablative. Interventional oncology, and to some extent interventional radiology, also involves the use of biopsies for genomics analysis, in a similar way as other oncologic specialists use biopsies to help guide their biological therapies or systemic therapies.

Which patients are likely candidates for interventional oncology and how are they identified?

Vanderbilt is the second place in the country to have a formal division of interventional oncology and a backbone of our program is tumor boards. I participate in at least three tumor boards a week involving specialists in gastrointestinal oncology, liver transplantation, and neuroendocrine tumors.

The cornerstone tumor for interventional oncology is probably hepatocellular carcinoma. Chemoembolization is one of the older procedures that we perform dating back to 1980. And it became standard of care because, quite frankly, there was nothing else for years that did anything. Now we perform it very frequently. We see this in the transplant population or potential transplant population— we want to prevent patients from progressing beyond Milan criteria or to try to downstage patients back to Milan criteria if they’re beyond it.

In patients with colorectal cancer, we can either try to get a patient to surgery with portal vein embolization or we will perform radioembolization of liver metastases or ablation of liver metastases based on where they stand with their chemotherapy. If patients get toxicity from chemotherapy, particularly neurotoxicity after FOLFOX, and have residual liver disease, sometimes we treat them to give them time off of systemic therapy.

We treat a lot of patients with neuroendocrine tumors here at Vanderbilt. We perform radioembolization and bland embolization for those patients. For patients with hepatocellular and colorectal metastases, our first goal is to get them to surgery, either transplant or resection, as these treatments are potentially curative.

Can you discuss in detail some of the procedures involved with interventional oncology?

There are two main techniques that we perform— arterial interventions and ablation. For liver cancer, arterial treatment involves threading a catheter through the femoral artery to reach the primary tumor (Figure 1). The strategy is to use the tumor’s vasculature to deliver microscopic beads that contain radioactive materials or chemotherapy into the tumor. The beads leach out the chemotherapy over the course of several weeks.

Figure 1. Hepatocellular carcinoma in a poor surgical candidate. The goal was to limit progression of disease through arterial intervention to allow transplant.

a. 3-cm mass in the right lobe of the liver.

b. Catheter selecting the artery supplying the mass with enhancement of the tumor.

c. Complete tumor necrosis at follow-up imaging.

We can also infuse radioembolics in a similar way. There are two devices available—one is made of glass and the other is made of resin. In our practice, we’re treating more and more people with the radioembolic treatment because it’s an outpatient procedure. We’re starting to accumulate more data using the radioembolic treatment, especially for colon cancer and neuroendocrine tumors.

Radiofrequency ablation involves delivering an electrode into a tumor and passing a current through it. This raises the temperature in the tumor to about 60° Celsius, and kills it. Microwave ablation is a newer method used to destroy tumors with heat. It’s much more powerful, but its use is not as widespread. Finally, we can freeze tumors with cryoablation (Figure 2); this method will destroy tumor cells or regular noncancerous cells as well. Cryoablation is favored in small kidney masses, because the clinician can see the ice ball when it’s created. This has been very successful, and causes less pain than ablation that uses heat. And all these ablation types can be used in the kidney.

Figure 2. Renal cell carcinoma undergoing cryoablation in a patient who is not eligible for surgery.

a. 3.5-cm left renal mass at baseline.

b. Ice ball at the end of CT-guided cryoablation.

c. Complete tumor necrosis 4 years after treatment.

What are some of the treatments and products used in interventional oncology that are approved by the FDA?

We’ve seen a shift toward more radioembolization use. One product approved for treating hepatocellular carcinoma is TheraSphere, an FDA approved microsphere agent. SirSpheres are FDA approved for use in colorectal cancer with adjuvant chemotherapy. There are a number of prospective randomized trials going on worldwide that combine its use with first- and second-line chemotherapy regimens, and some of the first of those is called SIRFLOX. The study is designed to evaluate whether FOLFOX chemotherapy in combination with Selective Internal Radiation Therapy is more effective than chemotherapy alone. That should have data coming out some time next spring, when the data are mature enough to start analyzing.

Are there any key research studies that you’d like to highlight that have been published on interventional oncology?

There is 5-year survival data for radiofrequency ablation of renal cell carcinoma that came out of Massachusetts General Hospital. This was a longterm follow-up study published in European Urology in 2013 (Eur Urol. 2013;63[3]:486-492). That was huge because that’s the first 5-year data, and one of the limitations that we face is a lot of the techniques are new and getting long-term data are always challenging, because you have to wait long enough to let it mature.

The cryoablation data are comparable to the work of the group at Massachusetts General Hospital. Dr Debra Gervais, who’s the senior author of the study, has done a fantastic job furthering the science of renal ablation.

There are two gold standard articles on chemoembolization providing superior survival to best supportive care that were published in 2002, one from Barcelona, and one from Hong Kong. Those are randomized perspective trials. One was published in Hepatology (2002;35[5]:1164-1171) and one was published in The Lancet (2002;359[9319]:1734-1739).

It’s such a broad specialty it’s hard to pick one or two things, but those are the kind of things that we’re aiming for. I think when the SIRFLOX trial (NCT00724503) is complete that that’s going to be a huge deal as far as showing the potential benefits of combining yttrium-90 (Y-90) with chemotherapy, because that gets back to my first point of things being collaborative. Patients who benefitted the most from oncologic therapies have generally received a combination of treatments. When oxaliplatin was added to 5-FU for colorectal cancer, that was a whole paradigm shift, and that’s hopefully what adding things like radioactive Y-90 to systemic chemotherapy for certain tumors can be as well.

What are some of the side effects that arise with various interventional oncology procedures and how are they managed?

The ablation needles all have 510(k) approval and they are approved for soft tissue ablation, which gives us a wide berth for using them. As far as toxicities and side effects, they’re generally very minimal. We often treat the people that just can’t have surgery because they have other medical comorbidities and the surgeons are hesitant to cut because they’re worried about the recovery. For most of what I do, patients undergoing chemoembolizations will go home the next day. Most ablations can go home the same day. Some patients will be held for observation overnight. All the radioembolization patients go home the same day. We see patients in clinic afterward, assess them, and make sure they’re doing okay. Our nurse practitioner will call most patients that we treat and ensure that they’re doing okay a couple days later, so the toxicity is very limited.

Are interventional oncology procedures generally reimbursed?

Some are, some aren’t. Some procedures are billed as an unspecified code, which means we don’t get paid very much for it. We get preapproval for our patients to make sure they don’t receive an enormous bill. The interventions and procedures that we’re performing have been documented to be safe and effective, but sometimes we have disagreements with the insurance company—but so does every other specialist in American medicine.

How widespread is the use of interventional oncology in the United States?

I’m chairing the 2014 Society of Interventional Radiology Scientific Meeting. That meeting has 5000 attendees—physicians, extenders, and industry. Attendees were surveyed about areas that they were most interested in. The number one interest by far was interventional oncology. It garnered just over 50% of the vote, and 75% of people listed it in their top three. So this is an area of tremendous interest. Having a formal division demonstrates that we have the same interest and motivation to treat these patients that surgical, medical, and radiation oncologists do. All those specialists do is treat cancer and that’s what this division is about—building a service that only deals with cancer. That level of commitment has to be present from the beginning. I don’t know if a medical oncologist is going to be as agreeable to collaborate with someone who can’t attend a tumor board because they’re ablating varicose veins or doing a fibroid embolization. Those things are important and people need to do them, but the cancer patient is where my passion lies, and that’s how I’ve chosen to focus on this area.

What is the process for physician training in interventional oncology?

There’s no formal fellowship. That’s a point of discussion among like-minded people around the country. When it was announced that I was joining Vanderbilt this past January, I got calls from a number of colleagues at other large NCI comprehensive centers that do a lot of the interventional oncology work at those centers and they asked about how I was going to do this, because they were interested in doing something like that themselves. They want to be able to just completely focus on one area. So right now, training involves having interventional radiology fellows go to centers that perform a lot of interventions so that they just get immersed in it as much as they can be in the year. I personally would like one of our goals to be to develop a fellowship program here at Vanderbilt that will allow an extra year of training for people who have completed an interventional radiology fellowship, to allow them to subspecialize in interventional oncology.

How does your interventional oncology division collaborate with the other oncology divisions at Vanderbilt?

As far as patient care goes, it starts with the tumor board. A lot of these patients are discussed during the tumor board consult. If a patient sees me directly, but who I think is best served by a surgeon, I make sure that he sees a surgeon. So we have discussions at our tumor board about what’s the best option for this patient and that’s how that starts off. As far as research goes, I’m just getting started with that, but I’ve had opportunities to collaborate with VISE, which is the Vanderbilt Initiative in Surgery and Engineering. That is an engineering arm here that is trying to develop new technologies, especially targeted therapies and minimally invasive techniques maintenance. This is some of the technology that I use, and there’s a lot of potential synergy there. I am looking forward to meeting with Dr Carlos Arteaga, the director of the Center for Cancer Targeted Therapies, and presenting to his group to investigate ways to collaborate. I’m just getting started here but there’s been a lot of interest among other specialists to find ways to put our skills together, and I think that’s one of the things about Vanderbilt that makes it a good place to be.

What do you see as the future of this practice over the next 10 years?

I think that Vanderbilt has taken a leadership role in this process and I think other institutions are going to evolve in a similar fashion where there are people who focus solely on interventional oncology. That shows a commitment to the other oncologic specialists that this is what I want to do. I’m not a dilettante who does this as part of a practice. This is the practice, and this is the focus of the practice. I just think that demonstrates a commitment and allows me to focus on the literature and other changes so we can stay up-to-date and communicate at the highest levels, which is the best outcome for the patient. That’s what this is all about.

Prior to joining Vanderbilt, Dan Brown, MD, was chief of Interventional Radiology and professor of Radiology at Thomas Jefferson University Hospital in Philadelphia. Brown is a graduate of Hahnemann Medical College, now Drexel University College of Medicine. He completed a residency program in radiology at Bryn Mawr Hospital and completed a fellowship in Interventional Radiology at Pennsylvania State University. He practiced at Washington University in St. Louis for nine years before moving to Thomas Jefferson.