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Melanie Cole (Host):  HIPEC is one of the most innovative treatments available today for complex cancers, and my guest to tell us about this is Dr. Giorgos Karakousis. He’s an associate professor of surgery at the hospital of the University of Pennsylvania. Dr. Karakousis, welcome. I’m so glad to have you join us. What a fascinating topic we’re talking about today. Tell us what is HIPEC and what’s the rationale for that and other intraperitoneal type therapies?

Dr. Giorgos Karakousis (Guest):  HIPEC is a heated intraperitoneal chemotherapy, and what that means is giving chemotherapy directly into the abdominal cavity its purpose is to treat patients who have peritoneal surface malignancies. In other words, cancers that have grown in the abdominal cavity on the surface of organs. These can be very challenging to treat by other methods. The HIPEC approach involves surgery to remove the tumors and then give high dose chemotherapy, much higher than would be able to be given intravenously, directly to where the tumors are. This is done using heat to allow for better penetration of the chemotherapy into the tissue and to destroy the cancer cells.

Host:  That was a great explanation, and so what’s the advantage of heating the chemotherapy doctor?

Dr. Karakousis:  Under heated conditions, cancer cells and tumor tissue is more fragile and allows for the chemo to penetrate more preferentially into the tumor tissue rather than the normal tissue. It spares the normal tissue some of the side effects of the chemotherapy while getting better delivery of the chemotherapy directly into the cancer cells and into the cancer tissue.

Host:  So then doctor, what cancers are not as responsive to traditional chemotherapy and what tumor types and cancers are really best treated with HIPEC?

Dr. Karakousis:  HIPEC is not for every cancer. It tends to work better for certain types of cancers. Those cancers include cancers of the appendix, which are rare cancers but can be very difficult to treat by other mechanisms. The so-called classic pseudomyxoma peritonei which is the development of large amounts of mucinous material in the abdominal cavity from appendix tumors is one such type tumor for which HIPEC is particularly useful for. Another type that it may be particularly useful for is mesothelioma.

So we may be familiar with mesothelioma occurring in the lungs and the pleura, but it can also occur in the abdominal cavity, and this can be a difficult disease to treat otherwise. Cytoreductive surgery with HIPEC can be an effective way of delivering high dose chemotherapy to this tumor as well.

Other cancers for which there has been some role for HIPEC include patients with colon cancers with more limited disease, and patients with ovarian cancer. These are the primary tumor types. Other areas are being studied and under investigation, but really the principal tumor types which HIPEC seems to have the most efficacy would be the appendix tumors and the mesothelioma.

Host:  Who would be a candidate because I would assume not everybody is? What are some clinical indications and contraindications for institution of HIPEC in certain cancer patients?

Dr. Karakousis: These are long surgeries that involve sometimes several hours of debulking surgery prior to the infusion of the chemotherapy. So there’s certain tumor factors that we look at and certain patient factors that we look at when deciding about the suitability of a patient for surgery.

In terms of the tumor factors, we’ve discussed some of the histology, but  we also look at the distribution of the tumors. Patients with tumors that have invaded into distant organs, the lungs or liver, typically are not good candidates for this procedure. Those that are best suited are those that really the disease is on the surface of organs in the abdominal cavity, but not invaded into other organs.

In terms of patient factors, we also look at the medical condition of the patient. Because these are long surgeries, it is important for patients to be under good overall general health. Age is sometimes a factor that we use in our decision making. Older patients may not be able to tolerate these longer procedures. So we use a combination of patient tumor factors. Preoperative imaging in the form of CAT scans and MRIs can give us a better idea of the distribution of the cancers and help us select patients for this procedure. In some cases, performing a laparoscopy where we look inside the abdominal cavity will give us a much better idea of whether a patient is a suitable candidate for a HIPEC procedure prior to undertaking it.

Host:  Is it a first line therapy or can certain people benefit from HIPEC as a second line, and  when does it become apparent, that other chemotherapies might be as effective and then you would look to HIPEC? Are you using right off the bat or are you waiting and seeing?

Dr. Karakousis:  In general for tumor types that are low grade, meaning not aggressive types of tumors of the appendix, for which systemic therapies given intravenously are not effective, HIPEC  sometimes takes a primary role as first line therapy because in fact we don’t have any effective second line or intravenous or systemic options.

In situations for which we do have more effective systemic therapies, such as in patients with colorectal cancers, patients would typically undergo intravenous or more standard chemotherapy first, and then depending on their response, would be reassessed for their suitability for undergoing the HIPEC procedure. I think it’s a case by case basis. We make these decisions  in a multidisciplinary fashion in conjunction with medical oncologists, pathologists, who all play into the decision making and individualize care for each patient.

As a general rule for patients with more aggressive malignancies for which we have systemic therapies, we usually proceed with those first prior to undergoing the bigger operation. In fact, the recovery can be lengthy from these surgeries, so we do not want to get into a situation where a patient undergoes a big operation and is not able to get quickly onto some intravenous or systemic chemotherapy options, which may be effective.

Host:  Is there any outcome data on the efficacy of HIPEC compared to more traditional chemos and tell us about the patient experience with this if you would , and for other providers when they are explaining this and indications for referral.

Dr. Karakousis:  So in terms of outcomes data, there are many studies that have looked at outcomes of these patients for different histologies in what’s called retrospective fashion, and much fewer  prospective or randomized trials, and this is something we really would like to increase to get a better assessment of how HIPEC may help in comparison to other treatment types compared to historical controls. For certain tumor types, like low grade appendix cancers, the addition of this heated chemo seems to offer benefit over and above surgery alone. These patients were treated in the past with simple debulking without the addition of the HIPEC.

The idea of infusing hot or heated chemotherapy into the abdominal cavity can certainly be a scary thought to any patient undergoing it, and in fact the surgeries can be lengthy and can be associated with some serious side effects or toxicities. That being said, it appears that the majority of the side effects or the toxicity from these procedures probably is related to the surgery itself, in other words, the debulking of the cancers, and less so the addition of the heated chemotherapy.

So  patients who undergo long, lengthy surgeries with removing multiple cancers probably are of similar risk to those who undergo that with the addition of the HIPEC procedure. So the HIPEC procedure, I think, probably does not add a significant amount of morbidity to the whole procedure in general. It does lengthen the time of the surgery and probably add some morbidity. In terms of recovery, these can be kind of long operations to recovery from. We certainly tell patients to anticipate a couple months recovery period. Now this is not a couple months where they’re not able to do anything, but a couple months after the surgery where they’re not quite feeling as energetic, they’re not as motivated to get up and about and do the normal activities they would do, and so it’s something to be anticipated in the recovery, just like any major abdominal surgery.

Host:  Thank you for that answer. As we wrap up, why is HIPEC usually performed at an academic medical center like Penn Medicine, and tell other providers what you would like them to know about when to refer and the importance of referring to the specialists at Penn Medicine.

Dr. Karakousis:  These are complex cases that really are best done at centers with significant experience. I think there’s a lot of data to suggest that the outcomes, both short term and longer term, are better when treated by physicians who have experience in this type of surgery, and it happens from the very onset of the process.

So when we see a patient, the multidisciplinary approach we take at a place like Penn is key to helping best select patients for this procedure. Really it takes a team approach to do these, and so that’s something we can certainly offer at Penn. What I would suggest, if you have patients for which HIPEC is even a consideration, early referral to best assess them because the initial approach is oftentimes important in terms of coordinating the overall care of these patients.

Host:  Great information, absolutely fascinating topic Dr. Karakousis, thank you so much for joining us today. That wraps up this episode from the experts of Penn Medicine. Head on over to our website at pennmedicine.org for more information and to get connected with one of our providers. If you found this podcast informative, please share with other providers, share on your social media, and be sure to check out all the other interesting podcasts in our library. Until next time, I’m Melanie Cole.