Treatment for Peritoneal Malignancies

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals. Exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today I'm happy to be joined by Dr. Michael Valente, associate professor of surgery and Program Director for the Cleveland Clinic Colorectal Surgery Residency Program. He's here today to talk to us about peritoneal malignancies and their treatment. So welcome, Michael.

Michael Valente, DO: Thank you, Dr. Shepard. Glad to be here.

Dale Shepard, MD, PhD: So maybe to start, you can give us a little background on what's your role here at Cleveland Clinic? What do you do?

Michael Valente, DO: Yeah, I've been here for about 10 years. Came here right out of fellowship. I'm actually born and raised in Cleveland, Ohio, so I didn't have to travel too far to get here. As you said, I'm the program director for the fellowship. One of the oldest and largest fellowships in the country for colorectal surgeons. And as you mentioned, I'm leading the HIPEC division, essentially, of the colorectal department where we perform that operation. And I'm also recently just started up and heading the center for metastatic colorectal cancer as well here at the Cleveland Clinic. So, mostly cancer-related operations, but we do a little bit of all colorectal surgery, as most of my partners do.

Dale Shepard, MD, PhD: Okay, so we'll cover some of those topics in a little more detail. So on an earlier episode of this Cancer Advances podcast, we talked to Dr. Robert DeBernardo about HIPEC treatment for gynecologic cancers. So maybe you can tell us a little bit about this and its application for appendiceal or colorectal. And maybe since we have a really broad audience, maybe remind everyone what is HIPEC and then a little bit more about that application.

Michael Valente, DO: Absolutely. Yes. Thank you. And Dr. DeBernardo, as you mentioned, leads the gynecological oncology portion of the HIPEC. And what HIPEC means, to refresh, is hyperthermic intraperitoneal chemotherapy. And that is used when we do what we call a cytoreductive surgery or peritoneal stripping procedure, so the chemotherapy part is called the HIPEC.

And the gynecological realm is dealing with mostly ovarian tumors and some other tumors of the uterus, but from the HIPEC beginnings, it started with colorectal surgery since its inception, and essentially it went away for a while from colorectal surgery, and it was mostly being used for a low grade appendiceal tumors. You've heard of pseudo myxoma or the jelly belly, people may call it, where there's mucinous tumors. And that's where HIPEC really became the standard of the care for that particular low grade neoplastic condition. What we call low grade appendiceal mucinous neoplasms.

And then about the last 10 years or so things have come back towards colorectal malignancies where a vast... Excuse me, not a vast majority, but a large number of patients have peritoneal disease as their only set of metastases. About 4 to 5% of all colorectal patients, who have metastasis will be just to the peritoneal cavity. And those are the people that we really are focused on for the cytoreductive surgery and HIPEC. Those are the folks that we think we could achieve the most benefits, but those are the folks that we're targeting for this.

Dale Shepard, MD, PhD: When we think about this 4 to 5%, it's not very many patients, so it's important, of course, that people realize that we're back doing this. Let's just start with that. How do we get the word out to people?

Michael Valente, DO: Great, great point, and it's interesting because cytoreductive surgery, HIPEC, is immensely popular in Europe. South America, as well, Middle East. They've been doing it for colorectal cancer for quite some time. As some institutions in the United States have as well, but almost very similar to the gynecological literature there's been some good papers, some good retrospective and a few prospective trials over the last five, seven years that have shown clear benefit for cytoreductive surgery and HIPEC. And there's been some papers that said maybe the HIPEC's really not showing a benefit. So right now there's two schools of thought with what the cytoreductive surgery and HIPEC. Everyone agrees that the bulking surgery, the cytoreductive part, is by far the most important aspect of this procedure. And there's ongoing trials and studies looking at the addition of the chemotherapy is also giving some benefit.

And I think, how do you get the word out? I think it starts with patients even knowing that it's an option. You'll be surprised. Many, many patients come to me and said, "No one ever even talked about that with me as an option." And they may not be a candidate, but at least they know about it and seek our expertise to see if they might be a candidate. And besides the patients, I think getting the medical oncology community aware of it as well as a potential treatment. Something that we have in our toolbox to maybe help certain patients.

But I also want to stress, as you talked about, not a large percentage. It's a very highly select group of patients that we're looking at for this. So I think general knowledge that it exists and, as I said, not many centers are doing it, so there's a small group of us who get together and talk about things and publish papers, and I think knowledge is the first step.

Dale Shepard, MD, PhD: We think about, clearly, HIPEC more frequently on the med-onc side. And like you said, what the appendiceal tumors, they kind of stay in the abdomen. Or like with the gynecologic tumors, they kind of stay in the... It's much more of a peritoneal disease. Is there some thought about people with limited disease in the liver, for instance, doing combined sorts of therapies, like ablate the liver lesions and do HIPEC and maybe increase the benefit to more patients?

Michael Valente, DO: Traditionally, anything extra-peritoneal disease has always been kind of a no-go, but that has changed with some of the more recent advances in stage 4 treatments in general. Especially liver. Sometimes lung as well, but liver, if you have a patient with both liver metastasis and peritoneal metastasis, that patient could theoretically undergo a cytoreductive surgeon and HIPEC, and either a combination of maybe some wedge resections of liver and/or ablation. Generally speaking, they reserve that for a very low volume disease of the liver. And in addition, it'd be a moderate to low volume of disease in the peritoneal cavity as well.

And some publications state up to three to four liver resections or wedges with the HIPEC. Now, I will tell you that is not a common situation. I mean, it is common to have both, but to take them to HIPEC is not exactly very common, but we have definitely done it here in the very select individuals, so. But I do think, as you mentioned, with some more new technologies, ablation techniques, I think we could have these patients hopefully live much longer with these new treatments.

Dale Shepard, MD, PhD: And what's the current role for systemic therapy, like in an adjutant setting, for someone who has had a debulking and had the HIPEC? You've sort of treated that intra-abdominal disease. What's the role at this point for adjuvant therapies to minimize risk for spread?

Michael Valente, DO: I wish I could give you an awesome answer to that, but no one knows for sure. I will say the vast majority of patients will have already been on chemotherapy before we get to the HIPEC. So peritoneal metastases come in two different shapes and sizes. One is synchronous and metachronous, and actually two thirds present what they say a right colon cancer with synchronous peritoneal involvement. Some of those patients could go directly towards cytoreductive surgery and HIPEC. But I would say, in our experience, the vast majority of patients that we're seeing are metachronous. They've had chemotherapy. They had their primary tumor taken out. It's a year later, two years later, maybe four years later, five years later, and now they have peritoneal disease.

So now we get into the situation they've been off chemo for a while. Those folks, we would put back on chemotherapy for a good three or four months, re-CAT scan them. Try to understand how much disease there truly, really is in there. And then if they get to the point where they do the HIPEC procedure, they don't go back on chemo right away for the most part. And that's something that we're looking at moving forward is going to be time off chemotherapy with these folks. And I think that's something that's really important for us, and for the patients to know.

So in our experience, to answer the question, the vast majority do not go back on chemotherapy after surgery initially, at least for three to six months. Now, obviously there's going to be some patients who have a large burden of disease, things may or will come back at certain points, and then they would go back on chemotherapy at that point, yes. But we are going to look at that time off chemo. I think that's critically important to understand for this group of patients.

Dale Shepard, MD, PhD: You did mention not having an awesome answer, which usually that means there's an awesome research question.

Michael Valente, DO: Exactly.

Dale Shepard, MD, PhD: So what sort of things are we doing on a research side related to HIPEC?

Michael Valente, DO: Yeah, I know you talked to Rob, and he's got a great set up. Dr. DeBernardo, with animal models looking at how the chemotherapy... how the heat's really working. I'm helping with those endeavors as well. And we have one of our new surgical oncology staff, Dr. Dan Joyce, who also joined us. He was a resident here, and he's going to be helping out with that as well.

And really some of the new things is we don't really know which chemotherapy agent really works the best for each patient. We know the cytotoxic effects of heat works well. Is it a combination of the heat and the chemotherapy? There's a lot of different avenues to explore with this right now, all throughout the world.

One thing that has sparked a lot of interest in the European literature is... and I'll briefly talk about it, is called PIPAC or pneumatized pressurized intraperitoneal chemotherapy. So instead of doing liquid chemotherapy, we instill high pressure aerosolized chemotherapy for those folks who maybe need some down-staging or even for a palliative approach. Unfortunately, that's not FDA approved the United States right now, but there is a phase 1 trial that's currently being undertaken in a few centers in the United States.

So there's a lot of opportunity right now on the scientific and the bench side. And mostly what we do here is obviously looking at our outcomes of recurrence rates. We're looking at time off chemotherapy. That's one of our big projects right now and trying to take a look at those numbers. Because that's really what's important as well to the patients is, "How much longer can I live with this? Is this curable? And do I have to go back on chemotherapy?" So those are some of the clinical questions we're looking at.

Dale Shepard, MD, PhD: So I guess for the physicians that might be listening in and maybe not have considered this in the past, who would be the ideal patient they should send your way?

Michael Valente, DO: So, obviously, in our opinion, anyone with peritoneal disease should be evaluated by someone who has expertise in peritoneal malignancies. If that means a consult with a surgeon or at least a medical oncologist who has some good knowledge of the peritoneal-based cancer, then I think that's key. If we don't know about the patient, we'll never get enough candidates for it.

But with that being said, the key to HIPEC surgery and cytoreductive surgery is getting the patients with the least amount of disease possible. And how do we do that? Well, the medical oncologists may know that a bit from the CAT scans that are performed or the MRIs or the PET scans. But I will tell you that CAT scans, MRIs and PET scans are about 75% good at picking up peritoneal disease. Anything less than a centimeter is... You can't even see it on those modalities.

So very often CAT scans may show nothing for many years, then something pops up. Those patients should definitely be seen, and one of the first things we do with those patients is do a diagnostic laparoscopy to take a look inside the abdomen to see if they're truly a candidate for further treatment, meaning surgery. And if they're not, we get them back to chemotherapy or back on treatment as soon as we can. So, every patient who has peritoneal disease should, in my opinion, be at least considered for the next step.

Dale Shepard, MD, PhD: Very good. You mentioned the center for metastatic colorectal cancer. Tell me a little bit about that. What's that's about? Michael Valente, DO: This is something that is a brand new center that the department of colorectal surgery has developed, and it draws folks, surgeons, medical oncologists, radiation oncologists, liver surgeons, thoracic surgeons, gynecological oncologists, neurosurgeons, orthopedic and all the ancillary services. And it really brings together all of the care providers who have been providing care for these metastatic or stage 4 colorectal cancer patients.

And essentially, it's taking everyone from all the different divisions and departments that we have in addition to the disease and Taussig Cancer Center and bring it under one umbrella, one roof, to give the whole treatment to each individual patient. Because, as we know, stage four or advanced disease colorectal cancer is so different in so many different ways that peritoneal metastases is one, a lung metastasis versus a liver or combination. They're all very, very different. Bony metastases etc. The use for Gamma Knife for neurological things.

So, we're just trying to bring all of these great expertise and bring them together under one roof, collaborate, work on prospective research, looking at retrospective research as well. Bringing all of our collective efforts under one roof to get the best possible care for patients with advanced disease.

Dale Shepard, MD, PhD: And is that translated into any difference in multidisciplinary clinics or anything?

Michael Valente, DO: So great question. We have been having some good multidisciplinary clinics. I think our multidisciplinary clinics have resulted in forming a center. Maybe the other way around, because we've been doing a good job with that the last few years with the Taussig Cancer Center, where we have colorectal cancer surgeons, medical oncologists, radiation oncologists, all at the same time.

And that's what we want to do at the center. If you come in to see us with a colorectal primary, and you have a lung metastasis, you should see the group. You should see someone like myself, a thoracic surgeon, medical oncologists, radiation oncologists. They're doing some amazing things with lung lesions and SBRT or external radiation. So really the point is to try to get folks in to see the whole team and have a good roadmap moving forward.

Dale Shepard, MD, PhD: And how has this translated into changes in tumor boards and that sort of interaction as well?

Michael Valente, DO: Tumor board has become, believe it or not, more robust than even... We've had to add more tumor boards, because there's more cases coming in of different complexity. And I think one thing about, like I said, I've been here for 10 years, and I've been some other places for training. The collaboration between the departments is so great here, and people are so energetic to get together and work on these difficult cases. And I think it's been a great collaboration thus far. We're pretty in our infancy. It's only been a few months since we started but as I said, it's everything we've always been doing. Just bringing it all together now under one home.

Dale Shepard, MD, PhD: And, of course, you have owned that you're in your infancy, and it's relatively new in an era of a pandemic and so that, of course, would present challenges. How has that affected patients and their access to getting multidisciplinary opinions? Has it improved thanks to virtual visits? Is it less likely they get opinions, because they don't seek those opinions? What's the world look like now?

Michael Valente, DO: Now things are, I think, stabilizing a bit in terms of access. A few points on this. I know from a colorectal standpoint, some folks are obviously missing colonoscopies and missing some of their screenings and maybe not following up with some imaging, which did have an impact, of course, with cancer rates, maybe recurrence rates, lack of getting proper treatment. But I think that is turning around. People are getting out and getting their examinations and screening colonoscopies.

Now in terms of, for my particular practice, virtual visits have been great in a way, in multiple ways. During the pandemic, of course, travel was minimized. And so I was able to get to a large group of patients from all over the country. Some international patients as well, of course, who are looking for a consultation for a cytoreductive surgery or HIPEC or stage 4 recurrent cancer.

So, I think that the virtual platform has enabled to reach more patients and to at least save them a trip coming in across the country or even from two hours away. We could talk and get a good understanding of if maybe you will be a good candidate for surgery. Or, "You know what? We need to get a liver surgeon involved. Let me set up a virtual with them." And it's very convenient for the patients. Very nice. It's great for the patient who's undergoing chemotherapy in Indiana who wants to get an opinion, and it takes time to travel. And it's really been really good. I think things are starting to turn around, but I do think virtual visits are something that I definitely would like to keep, moving forward. That's for sure.

Dale Shepard, MD, PhD: I mean, certainly in something specialized like HIPEC, it provides that opportunity to so many more people who may not have had the opportunity in the past, so that's great.

Michael Valente, DO: Absolutely.

Dale Shepard, MD, PhD: And so that's good to hear that that will continue to be pursued. Where would you like things to go? What are the biggest gaps? What are the biggest barriers? How do we make the next big step?

Michael Valente, DO: Yeah, I would love that I could come to work and maybe just treat hemorrhoids and anorectal conditions and have no cancer to operate on. That'd be fantastic. So, we could get there a couple of different ways. There's obviously screening. Everyone get a colonoscopy, and let's prevent colon cancer from starting to begin with. Obviously, working on dietary, lifestyle changes is important.

Now, in terms of what's on the horizon for what we're doing here. I think a lot of it's going to be what you do, Dr. Shepard. It's going to be medical advances in treatments, immune therapy etc. Things that are really going to take the stage four patient and prolong life, maybe cure. Maybe situations where patients who've had their tumor out for five, six years now. They've been making this a chronic condition, where maybe something like cytoreductive surgery or HIPEC may never be needed. But if it is needed, it would be in conjunction with good chemotherapeutic immune therapy agents, which would once again make this more of a chronic lingering disease than a life-ending disease. That would be my hope is I don't get to operate anymore. That'd be great. I love operating, but not for cancer. It'd be great to get that out.

Dale Shepard, MD, PhD: Yeah, no, that's great. So I certainly appreciate that insight on HIPEC, and to refer your patient for a HIPEC consultation you can call the referring physician hotline at 855.733.3712. Again, that's the referring physician hotline 855.733.3712. So I certainly appreciate all your insights, all your hard work in this area. Thanks for being with us.

Michael Valente, DO: Thank you, Dr. Shepherd. My pleasure.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget you can access real-time updates from Cleveland Clinic's cancer center experts on our consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.