Turning Up the Heat: Benefits of Hyperthermia Therapy

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 Shepherd, a medical oncologist here at Cleveland Clinic overseeing our Taussig phase one and sarcoma programs. Today I'm happy to be joined by Dr. Jennifer Yu, a radiation oncologist at the Taussig Cancer Institute, and a cancer researcher in the Lerner Research Institute's Department of Cancer Biology. She's here today to talk to us about hyperthermia therapy. So welcome, Jennifer.

Jennifer Yu, MD, PhD: Thank you, Dale.

Dale Shepard, MD, PhD: So maybe as a start, I kind of told you where you're at, but give us a little bit of an idea of what you do here at the Cleveland Clinic.

Jennifer Yu, MD, PhD: I'm a physician scientist here and a radiation oncologist. My primary focus is on brain cancers, and I also am a leader of the Developmental Therapeutics program at the Case Comprehensive Cancer Center, and the founding director of the Center for Hyperthermia here at the Cleveland Clinic. And the Center for Hyperthermia is the only one of its kind in Ohio, and one of the few in the country.

Dale Shepard, MD, PhD: Excellent. So, let's just kind of jump in. We have a wide range of people who might be listening in. You say hyperthermia therapy. Tell us a little bit about what that encompasses. What exactly is that?

Jennifer Yu, MD, PhD: Hyperthermia is heating therapy. So, heat therapy has been used since ancient times to treat different diseases. If you think about the way in which our bodies have evolved, we've found ways to use hyperthermia to fight off different diseases. For example, if you have an infection, you mount a fever, and that fever helps to slow down the growth of those infectious agents and also helps your body to fight off that infection. So similarly, here we use heat therapy or hyperthermia to fight off cancers. In our case, we use local or regional heating as opposed to total body heating, such as seen in a fever.

Dale Shepard, MD, PhD: Excellent. And so, I guess just a real kind of more abstract thing, how did you get involved in hyperthermia? So, you're a radiation oncologist, and of course we think of that as a kind of a modality. How'd you get interested in hyperthermia?

Jennifer Yu, MD, PhD: Yeah, so hyperthermia is a very well-known radiation sensitizer. It can make radiation work about 50 percent better, and in the cases where you have to repeat radiation, then the hyperthermia can make radiation work up to threefold better than radiation by itself. And I was fortunate to train in a center at UCSFU, University of California, San Francisco that had a hyperthermia center, and I saw the amazing effects of hyperthermia. Just application of heat in combination with radiation or with chemotherapy can make it so effective with very few side effects.

Dale Shepard, MD, PhD: Excellent. So, you mentioned previously local hyperthermia, regional hyperthermia, whole body hyperthermia and you gave the fever example. Give us a little bit of an idea what local or regional hyperthermia might be.

Jennifer Yu, MD, PhD: Well, patients are brought into a room. It's a private room. They'll lie on a bed, and we apply non-invasive thermometers, so little wire thermometers are placed on the area that we need to heat up. And then depending on the area that we need to treat, we will use different sizes of microwave units. So, if there's just a small area that we need to treat, then the microwave unit or the hyperthermia unit will be about the size of a yogurt cup. If it's a larger area that we need to treat, then the applicator will be about the size of a shoebox. So, the treatment is given over a period of about one hour, and we try to make the patients feel as comfortable as possible and we turn down the lights and play some music. It's like a spa treatment.

Dale Shepard, MD, PhD: It's like it's a hot spa.

Jennifer Yu, MD, PhD: It's like a hot spot, but very controlled.

Dale Shepard, MD, PhD: Yeah. So, give us an idea of what kind of side effects patients might have after receiving hyperthermia.

Jennifer Yu, MD, PhD: So, patients generally do very well with hyperthermia treatments. Sometimes they might feel hot during the treatments, so we'll cool them off with a fan. Long term the patients can develop some blisters. These typically heal on their own. Sometimes there can be some ulceration. So that's particularly in patients for whom they've already received a lot of radiation treatment in the past.

Dale Shepard, MD, PhD: And I guess as we think about this, are there particular types of tumors that we know a little bit more about the benefits of hyperthermia? Where are we primarily doing this for in terms of tumor types?

Jennifer Yu, MD, PhD: So, hyperthermia has been studied in many, many different cancer types. In almost every cancer type, there's a benefit of hyperthermia. And this has been shown through phase three clinical trials and other types of trials as well. So, for patients that have sarcomas, for example, median survival is doubled when you add hyperthermia to the treatment regimen. For patients that have ovarian cancers or cervical cancers, there's also an improvement in survival for patients with glioblastoma, pancreatic cancer, gastric cancer, there's an improvement in survival. For patients that have superficial cancers like recurrent breast cancers that come back on the skin or skin cancers, head and neck cancers, melanomas, there's an improvement in local control when hyperthermia is used. And for patients that have bone metastases, when hypothermia is added, we see a doubling of response rates in terms of pain control for patients that receive hyperthermia. Not only has the response rate doubled, but the patients also have more durable pain control.

Dale Shepard, MD, PhD: This is very universal. So, are there coverage issues?

Jennifer Yu, MD, PhD: There are some coverage issues. So, we're limited as to the types of technologies that we have available. There are superficial heating type units, and then there's also deep regional hyperthermia programs. So here at the clinic we have a superficial unit, so that permits us to treat more superficial cancers. So, the head and neck lymph nodes, for example, skin cancers, recurrent breast cancers, some cervical cancers as well. But we're looking to develop a deep hyperthermia program that will allow us to treat patients with deep-seated tumors, retroperitoneal sarcomas, for example, large prostate cancers, pancreatic cancers, and other types of cancers.

Dale Shepard, MD, PhD: All right. So, you mentioned previously that we have a center. What exactly does that entail? What kind of people are involved in the hyperthermia center? How does that aid with patient care?

Jennifer Yu, MD, PhD: So, the center includes multiple people including different physicians. I heard this facility, our center, and we have a number of other physicians that will specialize in the treatment of hyperthermia for different sites as well. For example, in breast cancers or in head and neck cancers, our physicians are in charge of that. And we also have physicists that help to make sure that we heat appropriately, so we heat the right region to the proper temperatures and that we're not heating too high or heating too low. We also have nurses that help with wound care, or any issues associated with their treatment, whether it's hyperthermia or radiation therapy, as well as a team of therapists that help to deliver the hyperthermia.

Dale Shepard, MD, PhD: Excellent. When we think about hyperthermia centers, we've actually had a couple of podcasts in the past where we've talked about methods of using heat. We talked about laser interstitial laser therapy with Dr. Stevens. We talked about HIPEC with Dr. Demanardo. So, are those sorts of modalities also included in the center?

Jennifer Yu, MD, PhD: So those are not. The center includes mild temperature hyperthermia's that are performed on an outpatient type of basis. So HIPEC, for example, is performed by the surgeons, right, the gyno surgeons, laser ablation treatments or focused ultrasound treatments can be performed by surgeons or interventional radiologists. But our center for hyperthermia here is focused more on using mild temperature hyperthermia to enhance the effects of radiation or chemotherapy.

Dale Shepard, MD, PhD: And so, I guess if people are listening in and they have an interest in this sort of modality for their patients, give us an idea what would be an ideal patient that should be referred to the center? What kind of patient would you like to be seen in the center to optimize their therapies?

Jennifer Yu, MD, PhD: So, patients that have difficult to treat cancers, cancers that are bulky, cancers that are refractory to other types of treatments. For example, patients that have failed prior radiation or they're receiving chemotherapy but they're not achieving any response or fast enough response, those patients should be referred. Particularly those patients who have accessible cancers, patients with breast cancers, skin cancers, head and neck cancers, sarcomas of the extremities, for example, cervical cancers and patients that have bone metastases as well.

Dale Shepard, MD, PhD: And so, you also not only have your clinical responsibilities, but you also do research. Are you doing any particular research in hyperthermia that you'd like to share?

Jennifer Yu, MD, PhD: Sure. We are doing some research in hyperthermia, and the focus of my laboratory is really to try to make cancer treatments more effective. And there's a particular cell population, the cancer stem cell population that's very resistant to radiation and chemotherapy. And these cells play a very important role in disease recurrence. And we found that hyperthermia can suppress some resistance pathways within the cancer stem cells to make them more susceptible to radiation therapy. It can also make cancer stem cells more susceptible to chemotherapy as well. And we know that in many types of cancers that are hypoxic cancers such as glioblastomas, sarcomas, there's a lot of hypoxia and radiation does not work very effectively there, but hyperthermia can improve the oxygenation of those cancers such that the radiation works better. There's also evidence that hyperthermia can improve blood flow, so it improves perfusion and therefore it can improve chemotherapy, bringing chemotherapy into the area that needs it most, right into the tumor.

We also have found evidence that hyperthermia and others have shown this as well, but hyperthermia can impair the DNA damage response pathway and make cancer cells more susceptible to cell death pathways. So, there's a lot of benefits to hyperthermia when you use it, especially in conjunction with cytotoxic treatments like radiation and chemotherapy. And we also have some emerging data to show that hyperthermia can also improve the body's ability to fight off the cancer cells with their immune system. So, hyperthermia can make changes in the tumor microenvironment to help activate and recruit immune cells to fight off the cancer cells.

Dale Shepard, MD, PhD: I guess with those broader mechanisms, we kind of talked about more like local and regional therapies. We talked about fever of course, with the whole body. Are there techniques being developed to more effectively deliver whole body hyperthermia to make those changes that may then make chemotherapy work more effectively?

Jennifer Yu, MD, PhD: There's some development of whole-body hyperthermia, but I think more people in the field are developing local or regional techniques to improve immune therapies. And you might not need to have the entire body heated up, but just if you think about radiation or chemotherapy serving as sort of a cancer vaccine, then having hyperthermia on top of that in that local area or that regional area, it can further improve this in situ cancer vaccine. So just I think regional or local heating is going to be sufficient.

Dale Shepard, MD, PhD: So, you can essentially stimulate a whole-body response by focal treatment.

Jennifer Yu, MD, PhD: Exactly.

Dale Shepard, MD, PhD: Gotcha.

Jennifer Yu, MD, PhD: And in fact, in some of our clinical trials, in one of my clinical trials, we found that laser ablation to a brain tumor, glioblastoma can cause changes in the immune response in the periphery. So, we're following up on those changes.

Dale Shepard, MD, PhD: You mentioned sort of superficial therapy versus deeper tissue therapies. Where are the biggest gaps in our technologies and our ability to deliver hyperthermia?

Jennifer Yu, MD, PhD: Our biggest gaps are in monitoring the temperatures in a non-invasive manner, so making sure that we can heat the tumor volume to the proper temperature in real time. People are working on modeling it. Right now, you can do it with invasive thermometers or in the case of superficial cancers, of course, we can just add thermometers to the body superficially. There's also MR thermometry that can be performed as well. It takes up time on the MRI machines, so that's one barrier. But I think one of the biggest challenges is that people just don't know about hyperthermia. There needs to be education for hyperthermia. It's benefits, why it works, when to apply it, and I think that's why this podcast is very important.

Dale Shepard, MD, PhD: Yeah, excellent. I mean, I guess when we think about this as a treatment modality, I think you're right. We think radiation, we think surgery, we think chemotherapy. Don't necessarily think about these. Who do you think is the best target audience? How are we going to get the word out? This podcast, I hope, will help. Any other educational movements too, is there a particular society that's, or patient groups or anything that's helping spread the word?

Jennifer Yu, MD, PhD: Our society for thermal medicine is helping to spread the word, reaching out directly to patients so patients are aware of this and can ask their doctors about hyperthermia treatments. That's also important.

Dale Shepard, MD, PhD: That's excellent. Well, you've provided some great insight for us today. Appreciate you helping.

Jennifer Yu, MD, PhD: Thank you.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

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