Mealanie Cole (Host): Welcome to the podcast series from the Specialists at Penn Medicine. I'm Melanie Cole, and today we have a panel highlighting meningioma modalities available 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 Lebo.

She's a radiation-oncologist with extensive experience in the treatment of tumors of the brain and spinal cord. Doctors, thank you so much for joining us today. So Dr. Jackson, I'd like to start with you, what are meningiomas and speak a little bit about the prevalence and how our understanding of the biology and behavior has evolved over the past decade.

Dr Christina Jackson: Thank you, Melanie. Thank you for this opportunity. I'm happy to touch upon meningiomas for the, rest of the listeners. So for. Physicians who are not familiar with this type of tumor or don't work with these on an everyday basis, meningiomas are actually the most common primary brain tumor. They arise from the lining of the brain as well as the spinal cord, and not from the actual brain tissue itself.

While most meningiomas are considered benign under the microscope, but benign doesn't always mean harmless. Because of where these tumors arise from and where they sit, they can actually cause very real and sometimes disabling symptoms by pressing against the surrounding brain or compressing important nerves like the optic nerve that can cause vision loss or affect hormone function if they're occurring next to the pituitary gland, for example.

While the vast majority of these tumors are considered benign, but they can have major impacts on the quality of life, depending on the location And the growth pattern of these tumors. What I would like to highlight together with electro lebo is really how we're better understanding the biology of a subset of these meningiomas that are more aggressive and are considered malignant.

Either because they recur more repeatedly, they grow at a more rapid rate or show atypical or malignant features under the microscope. These higher grade meningiomas can be very difficult to control even with very aggressive surgery and radiation, and that's where newer imaging modalities, targeted therapies and advanced radiation modalities really become especially relevant in this patient population.

I would say over the past decade, there's an increasing interest and really microscope focused on better understanding the biology of these tumors. And I'm proud to say that at Penn Medicine we are at the forefront of really discovering new therapies and targets that allow us to develop. New medications for these patient's, And also to use and refine existing modalities of treatment in a novel way to better improve our diagnostic yield for these patient's and our treatment of these patient's who may have exhausted their options in terms of surgery and radiation.

But I do wanna highlight that the approach to treating these tumors really is a team effort. Of course, you're hearing from myself in the neurosurgery departments. Uh, but I would like to pass the mic over Dr. Lobo from the radiation-oncology departments, because radiation plays really a central role in the management of these tumors.

Dr Emily Lebow: Thank you so much Dr. Jackson, and thank you for having me on the podcast today. I would totally agree with everything Dr. Jackson. discussed. I would add that as we develop, increasing understanding of the underlying disease biology, we've been able to develop more biologically guided therapies, and we've been able to use our existing therapies to better target the tumor and improve our treatments.

And this includes many advanced radiation modalities, such as gamma knife, radiosurgery, and proton therapy. And we use these modalities for all different types of tumors in the brain and spine, but we've been able to adapt these modalities specifically for patient's with meningiomas to improve our options for these patient's.

Mealanie Cole (Host): Thank you both And for highlighting the multidisciplinary care that goes into these patient's. And so let's talk about standard treatment plans for these types and Dr. Jackson, when you first evaluate a newly diagnosed patient. Speak a little bit about factors that heavily influence your initial management strategy when you're talking to them and thinking about this multidisciplinary approach.

Are there cases where imaging or molecular data have changed? What would have been a straightforward surgical decision? Speak a little bit about that Management.

Dr Christina Jackson: So, you know, as with any disease process, especially in patient's with meningiomas, we like to prefer, to approach these patient's in an individualized fashion. So key factors that I'm evaluating in terms of their tumor, And it's each individual patient really is one the size of the tumor. Two, is it causing problems for the patient's?

For the vast majority of patient's with meningiomas, if the tumor is small, it's not causing any symptoms for the patient's. We actually prefer conservative management with surveillance scans at certain intervals so we can track the growth pattern of these tumors and to make sure that we keep a close eye on the growth to avoid these tumors getting out of hand and getting to a larger size that cause symptoms before we realize that it's causing problems for the patient.

For patient's that have either a very large tumor causing associated irritation or swelling to the surrounding brain region, or tumors that are causing symptoms for the patient, some of which I alluded to previously, depending on where these tumors are located for those patient's, if it's surgically feasible and safe, typically the first-line therapy we would recommend is what we call maximal safe resection, going in surgically to remove these tumors to the best of our abilities.

Ideally with what we call a gross total resection, removing all of the visible tumor as well as the involved covering of the brain where these tumors arise from, and sometimes the bone surrounding that area can also be involved with tumor and if feasible, removing that bone. Oftentimes because of the location of these tumors, one aspect that I specialize in, in particular, really is how to approach these tumors in a minimally invasive and safe way by combining different approaches.

Depending on the location of the tumor And the feasibility of resection, one imaging modality, that has really changed the way from a surgical perspective. How we plan resection of these tumors is a modality called Dotatate PEth. And what Dotatate PEth is, is a specialized type of PEth scan that takes advantage of a feature that almost all meningiomas share.

Meningioma cells actually express a receptor on their surface called somatostatin receptor two, And we actually working in conjunction with our nuclear medicine colleagues, are able to inject a tiny amount of a tracer, in this case, dotatate that locks onto that surface receptor and lights up the tumor on the.

Where the normal bone or normal brain and covering of the brain will not light up. So the contrast really is very evident and it really allows us to delineate what is actually tumor And what is not tumor. How this has impacted how I approach surgical resection for these patient's is one, It allows us to evaluate areas of healthy tissue that may be involved with tumor That is not as evident on traditional imaging modalities such as MRI or CAT scans.

And This is especially true for patient's who have tumors along the base of the skull, where oftentimes the bone can be involved with tumor And the surrounding covering of the brain can be involved with tumor. So this allows me to maximize my extent of resection to give the patient's the best chance of.

Minimizing their risk of recurrence. But even more impressively, I am now able to plan my extensive resection and merge this dotatate pets with our 3D navigation system, preoperatively and intraoperatively to design my resection and if needed, plan preoperatively the extensive reconstruction that will be needed after resection, depending on how much bone I have to remove, how much covering of the.

brain I have to remove to really allow this personalized evaluation and planning for each individual patient to optimize their outcome as well as their reconstruction after surgery.

Mealanie Cole (Host): It was such a comprehensive explanation there, and Dr. Lebo radiation therapy has become increasingly nuanced in meningioma care. So how do you. Approach this and decide between a stereotactic radiosurgery, fractionated radiation, proton. I mean, there's so many tools in your toolbox these days. So speak a little bit about working together with Dr. Jackson, but then how radiation has really changed the landscape.

Dr Emily Lebow: the number one thing for all of these patient's is multidisciplinary care. As Dr. Jackson mentioned, we really have four buckets of treatment options. That includes observation, surgical resection, radiation therapy, and oral drugs or other medications that can target these tumors. And so we need that multidisciplinary input to pick the right treatment or combination of treatments at the right time And for the right patient.

And from a radiation perspective, we're very fortunate to have many tools that we can use for these patient's. And we really take into account the unique presentation for each patient, including the size of the tumor, the location of the tumor, particularly in, relationship to critical structures in the brain, such as the brainstem, optic nerves and base of skull.

Considering all those factors together, we can use a variety of radiation approaches. this includes proton therapy at the Pearlman Center for Advanced Medicine. we're fortunate to have a very long experience with proton therapy for brain tumors. we opened over 10 years ago where the first proton center in the Mid-Atlantic region and have treated thousands of patient's, with brain tumors using proton therapy.

I and my team in radiation-oncology feel very comfortable using this modality to precisely target meningiomas while minimizing any radiation dose to non-target tissues, such as normal brain tissues, brainstem, and optic nerves, and other critical structures. also very fortunate to have an extremely strong gamma knife program. This is a radiation modality that relies on extremely close collaboration with Dr. Jackson and our other neurosurgical colleagues.

And so we at Penn are so fortunate to have such a wide range of radiation and non radiation modalities, and discuss each case as a broad multidisciplinary team to pick the right approach for each patient.

Mealanie Cole (Host): Well then thinking about these, Dr. Jackson. As we talk about this multidisciplinary approach, how do you incorporate patient goals? You mentioned quality of life before those considerations, neurocognitive outcomes in long-term treatment planning, And what role does the other clinicians neuropsychology rehabilitation survivorship programs play in the pen meningioma care model?

Dr Christina Jackson: I think that's an aspect that often. Is passed over in our discussion with patient's on expectations after treatment of these tumors, whether that be surgery or radiation. I think, you know, for a lot of these patient's, by the time that they show up in my clinic, they are already exhibiting symptoms associated with the tumor.

So first and foremost, really helping the patient's understand what. It means to have a tumor, such a meningioma. While there is a subset of tumors that tend to be more aggressive, I typically try to reassure patient's that the vast majority of these tumors are benign, and a lot of the symptoms that they're experiencing are from the pressure or the mass effect of this tumor causing compression against those critical structures.

And as a surgeon, I want to reassure them of our confidence and ability to safely remove these tumors in a most minimally invasive and effective fashion. And I think. Along those lines. At Penn, we had the benefit of really working in a team along with, of course, department of Neurosurgery as well as departments in Rhinology, skull-based ENT, as well as oculoplastic And in conjunction with radiation-oncology, such as colleagues like Dr. Lebo and neuro-oncology and neuroradiology.

Where I can present all of these different options for this tumor, for each individual patient to reassure them that whatever the problem is, you are in the right place where all of these. Members of a large team constantly work together in figuring out the best treatment for you. That's kind of the first step in putting them at ease in getting care and treatment for this disease process that's impacting their function of life.

On top of that, we start a very early conversation with patient's of what to expect after surgery, and I'm sure Dr. Lebo will comment on what to expect after radiation, for example. If there are expected functional consequences, we start that evaluation and discussion of therapy early on in the process.

Many times, even before proceeding with some of these therapies, for example, we work very closely with our physical therapists, occupational therapists, speech language pathologists, and neuropsychiatrist, as you mentioned, for patient's whose lives are impacted and symptoms. That arise from these tumors can cover any of those facets of therapy that they may need even before and after surgery, and making sure that they're set up postoperatively and post-treatment wise, so they have that continuity of care before and after surgery to again reassure them that we're not just here for the treatments, we're here for the long run In terms of.

Preoperative or pre-treatment planning, the actual treatments, And then post-treatment follow-up to make sure that we get you back to your normal living and normal life as effectively and fast as possible.

Mealanie Cole (Host): So then Dr. Lebo, why don't you jump in here then and speak about. What life is like for these patient's And what outcomes are you seeing from these treatment modalities? What sets Penn apart? I mean, I think Dr. Jackson really just set it so beautifully right there, but sets Penn apart from the other's when it comes to these treatment modalities.

Dr Emily Lebow: Thanks, Melanie. Happy to speak about this incredibly important topic. I would second everything Dr. Jackson, stated. She made a lot of really excellent points, and I'll add that Penn is really. Utilizing three new approaches to improve our treatments for meningiomas and hopefully minimize those long-term side effects that can really affect how patient's feel months or years after finishing treatment.

so one thing that we're doing is using Dotatate PEth. This is a special type of imaging modality that relies on that somatostatin receptor that Dr. Jackson alluded to. It allows us to better visualize the meningiomas compared to conventional imaging with MRIs. This is particularly valuable for postoperative situations, skull base, meningiomas, or reradiation scenarios.

Where it can be very difficult to delineate what is really a meningioma versus what is scar or other tissue. Being able to delineate meningioma from other tissue is so important in delivering the most precise radiation that doesn't overtreat or treat other areas that can contribute to those long-term side effects.

At Penn, we're also using other modalities, including targeted systemic therapies. Like MEK inhibitors that target specific molecular pathways implicated in meningioma growth. we're also exploring lutathera, which is a radio labeled somatostatin therapy. Unlike traditional radiation therapy, which delivers radiation dose to an anatomic target defined by imaging, the lutathera uses the tumor specific molecular features.

To deliver radiation to those cancer cells anywhere in the body. But specifically if there is multifocal disease, recurrent disease, disease that cannot be resected, we can use lutathera to effectively target those, areas of tumor. And so utilizing this wide range of advanced sort of next generation meningioma treatments. Allows us to really achieve the best possible balance between controlling the meningioma, but also minimizing those long-term side effects that can be detrimental to quality of life, and That is something that we all feel is incredibly important and planning treatment for this patient population.

Mealanie Cole (Host): Well, it certainly is. This is an absolutely fascinating conversation. I'd love to give you each a chance for a final thought here. So, Dr. Lebo, looking ahead five to 10 years, what do you think will most significantly change how we treat meningiomas from the radiation-oncology standpoint And that. Multidisciplinary approach.

What are you seeing on the horizon?

Dr Emily Lebow: I think that our improved understanding of the underlying. Disease biology will allow us to develop more precise therapies and deliver more targeted radiation that ultimately allows us to move the needle in terms of achieving disease control for some of these more aggressive meningiomas that have proven so hard to effectively control, while minimizing side effects that can really bother patient's months to years after treatment.

And so I'm looking forward to contributing to that science, learning about it, and thinking about how we can use our improved understanding of disease biology to fine tune our radiation treatments and work with our multidisciplinary colleagues on sequencing and selection of therapy for patient's.

Mealanie Cole (Host): Well, thank you and Dr. Jackson last word. To you for clinicians referring complex meningioma cases. I'd like you to give us the key takeaways from today And what distinguishes Penn Medicine's approach and when it's important that they consider sending patient's for consultation.

Dr Christina Jackson: Absolutely, Melanie. I think that's a very important and, perfect question to close this, podcast. I think as you have heard from myself, Nara Lebo Meningiomas are not created equal. It's a complex disease process that really requires the expertise across multiple different disciplines, including neurosurgery, radiation-oncology, neuro-oncology, nuclear medicine, neuroradiology, as well as pathology.

And I think what really distinguishes Penn from other centers is that we as a group and as a team. Don't think of any of these options in isolation. We have all of the tools in the toolbox available here at Penn as you have for both from myself and my colleague here.

But what is really important is that we want to focus our care and our recommendations for your patient's in an individualized, personalized fashion. Alluding to Dr. Lippo mentioned At Penn, we're actively studying these tumors in more molecular detail to really understand what drives the growth And the development of these tumors, and to be able to implement that in a clinical fashion so that when a patient comes to us for evaluation and say they have surgery with us for their treatments, able to look at their tumor.

And tell the patient what is unique about your aspect of the tumor And what that uniqueness, whether that be a certain mutation that's present in the tumor, a certain molecular feature that's unique to their tumor, That help guide us in choosing the right tools that we have available here at Penn to put everything together in one place and design a very individualized biology driven plan for specific patient and their tumor.

Mealanie Cole (Host): Thank you both so much for a very enlightening discussion. Thank you for joining us and to refer your patient to Dr. Lebo or Dr. Jackson at Penn Medicine, please call our twenty four seven provider only line at 8 7 7 9 3 7 Penn, or you can submit your referral via our secure online referral form by visiting our website@pennmedicine.org slash refer.

That concludes this episode from the specialists at Penn Medicine. I'm Melanie Cole.