Redefining the ‘Status Quo’ of IO

Progress through innovation with Dr. Riad Salem

In this interview with Riad Salem, MD, Chief of Vascular and Interventional Radiology in the Department of Radiology at Northwestern Medicine, we discuss the future of IO, unique approaches to Y-90, and what's next for the interventional oncology field in 2024. Read the full interview below. 

 
 IO Learning: 
 
Your training spans several institutions. How has exposure to different medical environments shaped your approach to interventional oncology? 
 
Dr. Salem: 
 
 Ultimately everybody is interested in providing the best patient experience and best care for the patient, and there are a few ways to deliver that. There is, of course, the academic environment that I've spent most of my career in, where things tend to be protocol-driven, algorithm-driven, really focused on the patient experience. We are responsible for, of course, generating data—good and bad—to share with our colleagues to really socialize these types of experiences. 
 
In the non-academic setting, similarly, they want ultimately the great patient experience delivered in a slightly different way potentially taking some level of guidance from established guidelines and academicians. But ultimately we all strive for common goals, which are extending overall survival per patient, improving quality of life, and making sure that the patient just has that best experience. 
 
And so, I think there are a few pathways to get to that, but depending on what environment you're in, that route might be slightly different.  
 
 
 IO Learning: 
 
When initially observing Y-90s lower side effect profile, how did you balance the adoption of a new approach with skepticism from colleagues? 
 
Dr. Salem: 
 
I trained at an institution that was a pioneer in the development of chemoembolization in the United States and worldwide, and that was the skill set that I had at the time. So, of course, that’s how I was programmed to treat liver tumors. 
 
This technique that I had learned and mastered by my mentors was great. It improved overall survival and the outcomes were outstanding, but there was a side effect profile that clearly was bothersome to patients and that had to be managed. Now something new comes along with an improved side effect profile with the same response rate and overall survival rate, and that's clearly something you need to look at. Overall survival is something we want to focus on when we think about our IO patients, but also quality of life and the ability to perform procedures on an outpatient basis so patients can recover at home with minimal side effects. 
 
Early on, I observed that Y-90 was giving me the same outcomes, but with a much lower side effect profile. I spent the next 15-20 years really investigating this therapy and, in a very systematic manner, building on that evidence and experience, both good and bad, in order to socialize this type of approach. 
 
My idea was that I'm going to make mistakes early on. Let me make the mistakes and then publish on all the mistakes so that nobody else makes them. Hopefully that would allow others to leapfrog this learning curve and go right to the excellent outcomes. 
Clearly that's what is happening now. People are leapfrogging those adverse events. They're listening to our experiences and are now getting excellent outcomes.  
 
There was skepticism at first because the other therapies were so ingrained as the standard of care that no one was really willing to look at a different way of doing things. When you combine academic and intellectual curiosity and the desire to really want to move the field forward and look for a new type of procedure to benefit patients, you have an approach that results in a new type of therapy and a new standard of care. 
 
 IO Learning: 
 
Could you discuss any pivotal moments when you realized that Y-90 had the potential to become a standard of care? 
 
Dr. Salem: 
 
When we were able to demonstrate early on that Y-90 had a tremendous impact on patients with portal vein thrombosis from tumor—a condition with no treatment at the time—that was extremely compelling and I thought would result in a new standard of care. 
 
Chemoembolization, the standard of care at the time, was relatively contraindicated in patients with portal vein thrombosis because of the risk of ischemic hepatitis and injury to the liver parenchyma, et cetera. But now, we had a new non-embolic type of therapy that would kill the tumor and portal vein thrombus. 
 
When we saw that we could even transplant some patients and resect some patients in a  population that otherwise would have been relegated to palliative care, this demonstrated the need for further investigation. That was the first time when I said this is a huge unmet need and a new way to apply embolotherapy in this very advanced patient population in a time when we had no or suboptimal systemic therapies. That really changed my view of this type of therapy and I said, "Okay, there's really a lot of substance here. Let's try to peel away all of these mysteries that we basically are observing with this therapy and see what we can do to advance the science." 
 
IO Learning: 
 
Could you share your insights on navigating or overcoming the regulatory hurdles which are often a challenge in medical research, especially in a dynamic field like IO? 
 
Dr. Salem: 
 
I guess I've become a regulatory expert by chance after attending probably about a hundred meetings at the FDA. First, you have to recognize that the FDA panelists with whom you will interact are not necessarily experts in every aspect of this field. So be humble, be creative in terms of how you present data, and be a little bit of a teacher in terms of ‘this is the science, this is what we know, this is what we don't know, and let's all learn together,’ and then insinuate yourself into the regulatory paradigm that they have to abide by. 
 
So teach them, educate them, and then, let's see how we can work together to move this forward, because ultimately that's also what they want. They have some boundaries that they have to remain within, but they're very open and welcoming to new ideas and concepts. They are there to learn with you as well, because, again, they're not going to have that same level of expertise that you have in the therapy that you are advocating for. 
 
In playing that educator role, use precedent, other types of models that the FDA has used to try to get a clinical trial or therapy approved, and use all of the tools that are legally available to you as an investigator and as industry to navigate through that. 
 
Then ultimately what I would tell you is to be patient. It will take time. You may need two, three, four,  five meetings. Be patient. It takes time. The more comfortable they are with you as an investigator, as a scientist, and that you are really looking to move things forward, the better the outcome is going to be for everyone. 
 
IO Learning: 
 
How do you foresee industry collaboration shaping the trajectory of IO treatments in the future? 
 
Dr. Salem: 
 
 
Ultimately, our industries are the ones that have the resources to really move the field forward. Having the device and systemic therapy industries work together is going to be critical. Sometimes I find we function in silos, and device manufacturers do their own thing and drug manufacturers do their own things. But the reality is managing patients is a complex approach that requires everybody sharing in the efforts. It requires people to really collaborate, to think outside the box. 
 
This is where the physician as the intermediary comes in, to put everyone together in a room and say, "Hey, what can we do to work together? You have a therapy that augments the immune response. You have a therapy that capitalizes on the immune response. Can we work together to really improve patient outcomes?" 
 
 I see the physician as the intermediary and bringing everybody together to make sure that industry from all aspects really come together and use their resources to move the field forward.  
 
 IO Learning: 
 
Could you suggest specific areas within IO that young professionals could explore to fill unmet clinical needs? 
 
Dr. Salem: 
 
The biggest unmet clinical need we have now in the IO space is on the basic science front. There are only a few labs that really have done some work on the basic science.  We need to have a more dedicated effort to really build the basic science, the rationale for our therapies, the rationale for combining them, and then collaborate with pharma and other device companies to really bring things to the clinical space. 
 
I think people perceive us as getting too clinical a little too fast without the rationale, and I think there's some truth to that. So I think that is a wide open area with huge funding opportunities, and you could really build a name for yourself by doing basic science research.   

I took things from the clinical side to standard of care. Imagine if someone takes it from the basic science to the standard of care. That doubles the impact potentially, if not more, of what I have done, for example. And so, I really think that there's a lot of space for that. We have the skillset. We have MDs and PhDs, we have people that are extremely bright and extremely enthusiastic entering into the field of interventional radiology. We just need to put them in that right environment where they can thrive and benefit from all the resources that are available to them to really move things forward. 
 
IO Learning 
 
How do you find the right balance between caution and optimism when presenting research findings? 
 
Dr. Salem: 
 
Early on when I developed this new therapy, I probably over-report adverse events, because in a space where people are likely going to scrutinize what you are doing, the last thing you would want is to be labeled as or accused of overselling what something will do without properly reporting the adverse event profile. 
 
So, I was very careful in really over-reporting the side effects. Now, by doing that, I know that presents the highest incidence of the side effect profile. After time has passed and the therapy has been adopted, people have realized that I over-reported because the adverse event profile is much lower. If you look at the literature, I used to report 10%,15% incidence and just include every adverse event we had experienced, but the number is actually 1% or 2%. The last thing I wanted early on was to have been viewed as not having done sufficient homework or reporting on this type of therapy. 
 
And so, it's a decision that I made, and even in retrospect, I think it was the right decision, but there certainly are long-term sequela of that because, even 15 years later, people will quote a paper from 15 years ago that's noting 10%, 12% on a hundred-patient series. But when you've done 10,000, it's really 1%. 
 But I still think that anytime you're doing something new, something innovative, something that people will look at and scrutinize strictly, it's wise to be most conservative on reporting standards. 
 
IO Learning: 
 
 In overcoming the challenges of balancing clinical work, research, and teaching, can you elaborate on any specific strategies or techniques you use to maintain this equilibrium effectively? 
 
Dr. Salem: 
 
That's a tricky question. Obviously I love all of those. I have research and clinical fellows.. I've done a lot of research myself and obviously I have a very busy clinical practice. So for me, they almost all blend into one.  
 
My bias, though, is to make sure that as an interventional radiologist, as a physician scientist, you have the clinical work, expertise and technical skills, and then the research and the teaching will follow. 
 
I would be cautious for people to jump on all three of these missions upfront. Get that technical skillset done because then, when you read other manuscripts and other technical aspects, you'll really understand how challenging or how realistic something actually is. 
 
For me, it's always about making sure the clinical work is at the top, because you need to be an excellent interventionalist and understand the struggles and the challenges that the patient goes through and the struggles and the challenges that the physician goes through in delivering that care. Then research and teaching will become a natural secondary appendage to that primary work.  
 
IO Learning: 
 
How do you ensure that your research remains relevant and impactful in addressing real-world clinical practice and medical challenges? 
 
Dr. Salem: 
 
The reality is that the clinical work we do, the routine clinical work that we do, combined with some of the more complex things that we do result in us identifying potential unmet clinical needs that then morph into academic curiosity and research. 
 
There are many problems based on our clinical work that we have yet to solve in interventional radiology. I'll give you an example. Most of my work is based on Y-90, but my more recent work over the last decade or so has been based on TIPS and portal vein recanalization. There was a group of patients that for 15-20 years have been deemed unTIPSable, where this TIPS procedure to decompress portal hypertension in these varices has been deemed impossible and cannot be done. And so, that's an unmet need. We focused on that and figured out a way to solve that. So, now there really is no unTIPSable patient. On 9 out of 10 of those patients we are now using new techniques where we puncture the spleen, the mesentery and the superior mesenteric vein and other structures which allows us to build and reconstruct the venous system that has been occluded and clotted for decades in a piecemeal manner. 
 
But you have to be academically curious. You have to want to spend time solving this problem, and then it makes a big difference. 
 
In the cases for the problem I just described,  it used to take me 10 to 12 hours of procedure time to solve the problem, to build that block and fix those occluded veins. Now it takes me 2 to 3 hours, and people are doing them in other countries and in other centers in the United States. I have people in Brazil, Chile, Spain, and Asia texting and showing me images, and I help them work through that same sort of puzzle. It really is about identifying the unmet needs. Then people will listen and try to figure it out, because that unmet need that I have here in Chicago is the same in New York City, Philadelphia, Miami, and Los Angeles. Those same patients exist.It's very relevant for everyone to pay attention when someone else is tackling a problem and potentially has found a solution for something that's been so challenging for so long. 
 
IO Learning: 
 
 How do you think the collaborative spirit among specialties will evolve and how will it contribute to the future of IO? 
 
Dr. Salem: 
 
The only way to move forward and succeed is through some type of collaborative model. I certainly am very proud about the model that we have developed here at Northwestern. If you look at what we have done here and what we have published, there's always a surgeon on our projects, and medical oncologists, a hepatologist, an IR, a radiologist, because collaboration is really the way to succeed moving forward because no single subspecialty has the answer to every issue that arises with patients. 
 
For me, at least in the IO space, the most natural collaboration is with transplant surgery, with hepatology, and with medical oncology, because we all,  as a puzzle, have unmet needs that the other group can solve. With this kind of collaboration comes a unified universal solution that we present to the patient and move the patient algorithm forward by having everyone collaborating.  
 
IO will not be able to succeed without this kind of collaboration. Functioning in a silo is not the way to do things, because patient management is multispecialty and multidisciplinary, and patients jump from specialty to specialty and discipline to discipline as they are being managed. Sometimes you need a resection, then you get some chemotherapy, then you see an IR for an ablation, then you see a hepatologist for liver disease. Patients jump from team to team, and collaborating is really the only way to function. 
 
IO Learning: 
 
 What core personal qualities do you believe have most contributed to your accomplishments in both clinical practice and research? Furthermore, what has been the most rewarding aspect of your career so far? 
 
Dr. Salem: 
 
I'm very academically curious. When I read about a topic or see something that's challenging, I'm very curious about it. When I see unmet needs, I try to sit down with my colleagues, my team, and my fellows to try to find a solution. Academic and intellectual curiosity is something I'm blessed to have. 
 
I'm also quite patient. Some of these projects take years to complete. First to even synthesize, then to execute on, to complete, and then publish and share. You also have to be humble and know that you're going to make mistakes and that others are going to know more about this field than you. You have to learn from them as well. I think if you put all of these things together, you have the recipe for a very nice combination of a clinical practice, research, and development of new therapies. 
 
In terms of the most rewarding aspect so far, it would have to be the role of mentorship that I have played to many individuals. Many of my colleagues that now have become smarter, faster, more clever, more technically skilled than me. They take what you've built and they build on that. That's really a humbling and amazing thing to see. So for me, the role of mentorship is one that I'm extremely proud of on that professional side. 
 
On the research groundbreaking side, I am obviously proud of the ability to bring a new therapy to standard of care with full FDA approval with the first Y-90 device to do that. Then, the work now that I'm doing with portal vein recanalization and treating patients that would be relegated to basically palliative type therapies lifelong is also something I'm extremely proud of. 
 
IO Learning: 
 
What message would you like to convey to the next generation of IO professionals, particularly those who aspire to have a meaningful impact in both clinical practice and research? 
 
Dr. Salem: 
 
My message to the next generation of IO is to be academically curious. Be patient, try to really look for unmet needs and develop a niche, because then you will become a global expert in that area. You have to be naturally attracted to this field, and hopefully that unmet area is what you are looking at and what interests you. Then become very specialized, because we need specialists to move these sorts of things forward that then become democratized or socialized to other areas as well. 
 
I think when you do that, you really can develop a meaningful impact. Start small, be focused, and grow. You're not going to solve all the problems by going right to the biggest issue, but start small and build your team of individuals that have complementary skill sets to you, and you'll be very successful.