Melanie Cole, MS (Host): Welcome to the podcast series from the specialists at Penn Medicine. I'm Melanie Cole. And today, our discussion focuses on heated intraperitoneal chemotherapy or HIPEC. Joining me is Dr. Nawar Latif. He's an Assistant Professor of Gynecologic Oncology and the Surgical Director of the Living Donor Uterus Transplant Program at Penn Medicine.

Dr. Latif, it's such a pleasure to have you with us today. I'd like you to speak about what exactly HIPEC is and what is its place in the care of patients with ovarian cancer.

Nawar Latif, MD: Thank you for discussing with me that topic. Hyperthermic intraperitoneal chemotherapy, or we call it HIPEC is essentially one of the treatment option that we offer a patient with ovarian cancer. The treatment for ovarian cancer is a combination of surgery to remove the cancer, cytOreductive surgery, and chemotherapy. The data that had been published has shown that the addition of HIPEC during the surgery has shown that it's beneficial for patient in terms of their overall outcomes. So, essentially, HIPEC is the administration of heated chemotherapy at the time of the surgical resection and the debulking of ovarian cancer.

Melanie Cole, MS: So, is this typically done as an adjunct to what we think of as regular chemo or cytoreductive surgery? How does its mechanism of action enhance these therapies in patients with ovarian cancer? And you said It was done during cytoreductive surgery. So explain a little bit about this process. How does this work?

Nawar Latif, MD: To answer your first question, it's an adjunct to the chemotherapy that we give you regularly before or after surgery. Essentially, the way we do it, the way we describe the standard of care is to do the cytoreductive surgery, do the resection of the tumor, and then the second phase of that surgery essentially doing the HIPEC, the additional 90 plus minutes of administration of chemotherapy into the abdominal cavity at the end of the surgical resection of the cancer during the debulking surgery for ovarian cancer.

Going back to your question about the mechanism of action, there are so many research and theories about how it works. But essentially, the idea behind its effect is mainly that the absorption of the chemotherapy through the peritoneal surfaces increase significantly when you administer it directly to the peritoneum. And also, that can have significant effect on the cancer cells, but also can minimize the toxicity systemically because it has minimal absorption to the patient system.

The effect of the heat, so we are heating the peritoneal cavity to 42 degrees, that has shown it increased the absorption of the chemotherapy and also has shown that it can potentiate the effect of chemotherapy on cancer cells.

Melanie Cole, MS: Wow. That really is amazing technology. And Dr. Latif, speak about patient selection. Who is this indicated for at this point?

Nawar Latif, MD: At this point, there are two main group of patients that we at least evaluate them for HIPEC. The first group of patients is patients who had neoadjuvant chemotherapy for ovarian cancer for epithelial ovarian cancer, so a patient who received three to four cycles of chemotherapy for ovarian cancer. Then, we are preparing them for the interval cytoreductive surgery. This is the group of the patient that we will evaluate for the benefit and the use of the HIPEC. There are more specific criteria for, these patients to be included for the evaluation for HIPEC at the time of their interval debulking surgery.

The second group of patient is usually the patient who have unfortunately a recurrence of ovarian cancer and we also give them chemotherapy to treat that and then we are planning and aiming for further cytoreductive surgery that has shown also benefit to patient to offer them HIPEC in that setting.

Melanie Cole, MS: So, the timing, can the timing be shifted? I mean, it takes place during the surgery whenever that happens, right?

Nawar Latif, MD: Exactly. So, the timing is usually we go for the surgery and, as long as we achieve the optimal resection and debulking of the cancer, then we offer HIPEC in that setting.

Melanie Cole, MS: Because HIPEC is pretty intense. Dr. Latif, can it be done a second time in patients who are refractory to the standard of care treatments?

Nawar Latif, MD: That is a very good question. So far, we don't have any data to support that. I think we try to offer HIPEC one time, which is like at the time of the interval cytoreductive surgery, or in the time of the recurrence. There's no data published on the concept of repeating HIPEC and whether there's any benefit from doing that.

Melanie Cole, MS: Then, let's talk about the side effects. We've all heard about those for chemotherapy. Now, speak about what the patient goes through if they undergo HIPEC therapy and how are these managed?

Nawar Latif, MD: Usually, the side effects of HIPEC, we discussed this with the patient, and one of the side effects is the delay turn of the bowel function, ileus. Also, it can affect the kidney function. It can sometimes cause kidney damage that we have to monitor for. Also at the time of the cytoreductive surgery, if we are doing bowel resection, there's a potentially slight increase risk of leak from the bowel anastomosis. So, we have to also think about that as we do the surgery.

So far, overall, the side effect and toxicity from administering HIPEC is small and most of them are resolvable, as long as we make sure that we stick to the standard of administering of the HIPEC.

The other potential side effect is the kidney damage. And in that situation, we make sure that we keep the patient and the kidneys well hydrated. And we administer, sodium thiosulfate, which is a protective agent to the kidneys as we administer the HIPEC to the patient during surgery.

Melanie Cole, MS: This is really such an exciting time in your field, Dr. Latif, and such an interesting topic. As we wrap up, what would you like the key takeaways to be about HIPEC done for ovarian cancer at Penn Medicine, and how would someone contact you or the department to discuss this?

Nawar Latif, MD: Yeah. I always talk to the patient about these options. I think we have to be very judicious and careful in administering and offering HIPEC to our patient. We offer it to patients who are relatively healthy, who have stage III disease and who can undergo long surgery, to make sure that when we perform and do this procedure and in addition of the HIPEC, that they will recover well and they'll get back to their treatment as soon as possible.

So, we always make sure that like we have good conversation and discussion with our patients about, these options and to properly select what's the best for them and engage them in that decision-making regarding their care for ovarian cancer. For the patient referral, we always tell our partners and colleagues across the area that they can call our referral center to refer a patient for evaluation for cytoreductive surgery or option of HIPEC. And we're happy, obviously, to see the patient evaluate them and at least talk to them about that option, and make sure that when we offer to them, that's going to be a safe option and beneficial option for them.

Melanie Cole, MS: Thank you so much, Dr. Latif, for sharing your expertise with us today and for joining us. To refer your patient to Dr. Latif at Penn Medicine, please call our 24/7 provider-only line at 877-937-PENN, or you can submit your referral via our secure online referral form by visiting our website at pennmedicine.org/referyourpatient. That concludes this episode from the specialists at Penn Medicine. I'm Melanie Cole. Thanks so much for joining us today.