Melanie Cole, MS (Host): [00:00:00] Welcome to the podcast series from the Specialists at Penn Medicine. I'm Melanie Cole. And this is part two in our panel highlighting meningioma treatment modalities and advanced molecular imaging at Penn Medicine. Joining me in this panel are Dr. Christina Jackson, she's a neurosurgeon specializing in open, minimally invasive, and endoscopic skull-based approaches at Penn Medicine. And Dr. Emily Lebow. She's a radiation-oncologist with extensive experience in the treatment of tumors in the brain and spinal cord.

Doctors, thank you so much for joining us today, and Dr. Lebow, I'd like to start with you. As we're doing this part two, tell us about DOTATATE PET. How are you using it? What is it?

Dr. Emily Lebow: Thank you so much for having us today. DOTATATE PET is an imaging test that utilizes a radioactive tracer that binds to somatostatin receptors. And somatostatin [00:01:00] is highly expressed in meningiomas, and it's been particularly useful to us when we need to define the true extent of the tumor, and it's hard to do that based on MRI alone.

So, this is often the case in skull base meningiomas, meningiomas involving the orbit or cavernous sinus, or in cases where we're unsure of the true extent of residual disease after a surgical resection. In those cases, we are utilizing DOTATATE PET to help guide our radiation planning and define our target more confidently.

Host: Well, thank you for explaining that. So then, Dr. Jackson, what sets it apart from typical uses for imaging? Tell us a little bit about what makes it special and what outcomes you are seeing from this.

Dr. Christina Jackson: So, as Dr. Lebow mentioned, this technique tries to utilize a specific protein that's typically expressed [00:02:00] on the meningioma tumors, and we're able to more confidently identify these tumor cells on imaging with DOTATATE PET versus conventional imaging techniques like MRI, for example. As a surgeon, this is especially useful for me when targeting tumors along the skull base where there's a lot of bony involvement of the tumor. It allows me to plan my surgeries ahead of time, to know which part of the bone is involved. Therefore, I can counsel the patient in regards to resection of the bony aspect of the tumor, and also plan reconstructive techniques preoperatively so that we can even develop custom implants in anticipation for the resected bone after surgery.

And there's also a benefit of these images after surgery as well in planning potential adjuvant radiotherapy. And Dr. Lebow, I think you can comment a little bit more on how we use this imaging technique to plan your treatments, and also in terms of identifying patients [00:03:00] who may need additional treatments after initial surgery or radiation to determine what is actually tumor coming back versus treatment effects.

Dr. Emily Lebow: Yeah, thank you. That's exactly right. So, Dr. Jackson will often do amazing surgical resection, and then I'll see the patient in clinic and have a postoperative MRI or a follow-up MRI, where it's very hard to delineate the true extent of any residual disease that may be present. And that's a really critical piece of information in informing my recommendation for radiation and having an informed discussion with the patient about the risks and benefits of radiation.

And so, in those cases, I'll often rely on this modality to help better inform my understanding of the true extent of residual disease and have very informed discussions with patients.

Host: Well, thank you both for that. So now, let's talk about targeted radiotherapy with [00:04:00] lutathera. So, tell us a little bit about what this is, Dr. Lebow, and what types of cases are we using this for.

Dr. Emily Lebow: Lutathera is a really unique type of therapy, and it combines a tumor-targeting molecule—which is the DOTATATE—with a radioactive isotope, which is lutetium. So, it uses this tumor-targeting molecule or DOTATATE to identify residual meningioma or other somatostatin-expressing tumors wherever they may occur.

And so, it's really a systemic treatment, but it is able to target that radiation just to cells that are expressing the somatostatin receptor. And so we're really excited about this modality for a couple unique use cases, including patients with multifocal tumors or perhaps patients in which Dr. Jackson has resected as much tumor as possible. But because of the patient's [00:05:00] performance status or because of the location of residual tumor, the remainder is unresectable. So, we are looking forward to using this modality increasingly at Penn.

Host: Dr. Jackson, why do you feel that it's so special? What sets this type of targeted radiotherapy apart from a typical treatment plan? And what are the outcomes that you're noticing?

Dr. Christina Jackson: So, I think this is a perfect bridge from our discussion of the DOTATATE PET using a similar principle where we are really taking advantage of the fact that many meningioma cells express this receptor called SSTR2, and we're attaching essentially a radiotherapy to a molecule that recognizes that receptor.

So, one benefit of lutathera compared to other traditional radiation techniques or other therapies that we're giving through the IV, such as [00:06:00] chemotherapy and whatnot, is that it's very targeted. It really only goes to the tumor cells that have high expression of this receptor. And meningioma is a tumor that has very high expression; and therefore, it tries to limit toxicity associated with therapies by targeting meningiomas in particular.

The other advantage of this treatment is that it can be given through the IV. So, it's easy to deliver and many physicians, including oncologists, are comfortable delivering this type of treatment versus other types of radiation, for example. And even though this is just in an emerging technique, we are seeing very compelling results in patients. For example, patients who have received lutathera therapy for higher grade meningiomas have had better progression-free survival, meaning time to recurrence of the tumor or growth of the tumor at six [00:07:00] months compared to historical controls. So, we're very excited that we're going to be able to make this therapy available for patients at Penn in 2026.

Host: That's very exciting, as you said. Now, onto GammaTile, Dr. Lebow, tell us about this treatment, the type of cases that are best suited. What are you seeing with GammaTile?

Dr. Emily Lebow: Yeah. Thank you so much. So, this is a really exciting modality that we're using now for patients with recurrent meningioma as well as other indications. And Dr. Jackson really does all the hard work here. So, a patient is taken to the operating room. And at the time of resection, radioactive tiles are placed along the edges of the resection cavity. And then, radiation is released into the immediate surrounding tissue to treat where there is a highest risk of recurrence. And I'll let Dr. Jackson talk a little more about the process of placing the brachytherapy tiles [00:08:00] and sort of what the experience is like in the OR.

Dr. Christina Jackson: Absolutely. So, I think one advantage of using GammaTile is the timing of the treatments. Oftentimes, patients with meningiomas, whether it be at initial diagnosis or in the recurrent setting, surgery can still be an option. And the beauty of this treatment is that the patient is able to get both the initial surgery or a followup surgery in addition to radiation and radiotherapy at the same time as the surgery. So after the tumor has been removed the concern is that there may be tumor cells along the margin of the cavity of resection that we may not be able to see with our naked eyes. And therefore, to minimize the risk of those microscopic cells from regrowing, what we can do is lay down these GammaTiles along the cavity to deliver local radiation to minimize that risk.

What is actually really simple and easy for me as a surgeon is that this radiotherapy is actually embedded in a material that we often use during surgery for hemostasis to prevent bleeding. And the material and the device is very simple to use. Many neurosurgeons are very familiar with it, and it doesn't add any additional time or effort or learning curve to be able to use this and allows the patients to have surgery and radiation in the same setting to prevent them from having to come back for either several days or several weeks of radiation therapy.

Host: So, what outcomes, Dr. Jackson, are you seeing from this? And what are patients saying? Because that's really outstanding that you're doing these things at the same time, and certainly for patient quality of life and convenience.

Dr. Christina Jackson: So, similar to Lutathera, you know, [00:10:00] GammaTile, it is also a newer technique and therapy. And in addition to meningiomas, we have also been using this modality and other tumor types. And from patients across different tumor types that we have been using this modality in, we do have good reports in terms of the convenience of being able to get the radiotherapy at the same time as the surgery to minimize that travel time back and forth for additional radiation.

The other benefit is we are able to use these GammaTiles in patients who may not be great candidates for additional traditional radiation therapy. And so, it does provide an additional modality that we can discuss with patients who may not have other options from traditional standard therapies.

In terms of outcomes, again, this is more preliminary, but we are seeing promising results in terms of local tumor control with placement of GammaTiles for progressive meningiomas, [00:11:00] and we're still conducting multicenter studies to be able to increase the number of patients and have longer follow-up periods to really be able to report the overall outcome for these therapies. But so far, it is looking very promising.

Host: That's great news. Now, we're going to talk about targeted therapies. We've really covered so much today, and this is such a fascinating topic. Now, Dr. Lebow, tell us a little bit about targeted therapies and what that means really in today's meningioma modality treatment plan.

Dr. Emily Lebow: Sure. Yeah. This is a very exciting area. So historically, meningiomas were not profiled molecularly in terms of specific genetic alterations. But in 2026 at Penn, we are performing molecular profiling on almost all resected meningiomas. And this gives us critical information about genetic [00:12:00] alterations and vulnerabilities biologically in these tumors, and we're able to use therapies that target specific molecular alterations that we may detect in a patient's tumor. So often, this is an oral pill that a patient may take that targets mutations present in their specific meningioma.

I think this really speaks to the importance of multidisciplinary care in meningiomas. So, we are working very closely with our molecular pathologists to assure high quality molecular profiling with our medical oncology colleagues to identify targeted therapies and help oversee the administration to patients.

Host: Well, then, Dr. Jackson, on to you, what sets these therapies apart? And what outcomes are you seeing? Why is this so exciting?

Dr. Christina Jackson: So, I think along a similar theme of the targeted radiotherapies that we have been discussing, the [00:13:00] distinction of targeted systemic therapy really is kind of this key buzzword or keyword of precision medicine. We're looking at each patient's individual tumors separately now. We are routinely performing sequencing of the meningiomas that are being resected and treated at Penn, and it allows us to look for unique footprints that these tumors have in a particular patient so that we're not treating all patient's tumor the same way. And depending on the molecular footprint of your particular mutation or your patient's particular tumor, we can then select the right targeted drug that tries to block particular pathways that allows the tumor to grow.

And this minimizes side effects compared to traditional chemotherapy agents that are less targeted and can lead to significant side effects with normal cells outside of the tumor cells alone. But with these targeted therapies, because we're [00:14:00] only targeting the mutations that are present uniquely in the tumor and not normal cells, it does minimize the particular side effects that patients can experience.

In addition to that, if we know what pathways or signals are driving the tumor growth, these targeted therapies can have a better response compared to just broad chemotherapy agents. And this is true based on what we're seeing from a multicenter study, looking at different targeted therapies depending on the particular mutation and pathways that are activated in a particular tumor. And this is a trial that Penn is actively recruiting patients into, depending on what mutations are present in the tumor. And we are seeing some good responses in terms of six months progression-free survival and stability of the tumor based on the patient's particular tumor mutation and the appropriate targeted therapy.

Host: Well, Doctors, we've covered a lot of modalities today and [00:15:00] advanced imaging. I'd love to give you each a chance for a final thought. So, Dr. Lebow, what would you like the key takeaways to be in this panel highlighting meningioma, treatment modalities, and advanced molecular imaging at Penn Medicine and why this is really such an exciting topic.

Dr. Emily Lebow: Thanks so much. So, I think there are a lot of new treatments for meningiomas, both available at PENN now and on the horizon in 2026. And this includes GammaTile, it includes lutathera, it includes targeted therapies like MEK inhibitors. In that setting, it is so important to have an evaluation, with a multidisciplinary team who routinely cares for meningiomas and can refer patients for comprehensive sequencing, multidisciplinary evaluation, and personalized care.

Host: Dr. Jackson, last word to you, if you were to look in the future five years, where do you see the advanced molecular imaging going [00:16:00] in these treatment modalities? What would you like to see happen for meningioma treatments?

Dr. Christina Jackson: Thank you, Melanie. I couldn't agree more with Dr. Lebow's comment regarding the complexity of treating these patients with meningiomas and the importance of having these patients being evaluated at a place like Penn where we are able to have a collaborative discussion across multiple disciplines on the best therapies for these patients.

What is very exciting for me, and I think for the institution in general, is that we are really shifting into an era of precision medicine and targeted therapies for meningioma patients. Historically, these tumors have not received as much attention as other brain cancers due to the fact that a good amount of them can be benign. However, these patients can have significant morbidity and sometimes mortality associated with their tumors because after initial [00:17:00] surgery and radiation therapy, there can be limited therapies for these patients.

What is exciting for us, as Dr. Lebow alluded to, is that we are really treating each individual patient and tumor separately now. We are doing the sequencing of the tumors to really understand each patient’s tumor. And what I would like to see and I'm excited about and what Penn is contributing to, is you've heard about different targeted radiotherapy, different targeted molecular therapy.

What I want to see in the next five years is that, with better understanding of these tumors, we can take all of the molecular imaging and clinical features of each patients tumor and generate a score that tells us how likely a patient's tumor is going to progress and come back, and also allow us to predict how well a patient's tumor is going to respond to a particular targeted therapy, whether it be systemic therapy or radiation. And that will allow us to put [00:18:00] patients on the appropriate clinical trials that will give them a better chance of responding to those clinical trials to minimize time and effort wasted to put them on a therapy that may not work for their tumor.

And so, I am looking forward to really contributing to that aspect of meningioma therapy on a more personalized level, and I think Penn is a great place for those patients and we're looking forward to treating those patients.

Host: Thank you both so much. What a fascinating interview this was. Thank you both for sharing your expertise and please be sure to check out part one on meningioma modalities if you missed it. To refer your patient to Dr. Lebow or Dr. Jackson at Penn Medicine, please call our 24/7 provider-only line at 877-937-PENN, or you could submit your referral via our secure online referral form by visiting our website at pennmedicine.org/refer. Thank you so much for joining us on this episode with the [00:19:00] specialists from Penn Medicine. I'm Melanie Cole.