Melanie Cole, MS (Host): [00:00:00] 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 Lebow, 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. 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, 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.

What I would like to highlight together with Dr. Lebow 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 patients, and also to use and refine existing modalities of treatment in a novel way to better improve our diagnostic yield for these patients and our treatment of these patients who may have exhausted their options in terms of surgery and radiation.

But I do want to highlight that this approach to treating these tumors really is a team effort. Of course, you're hearing from myself in the neurosurgery departments. But I would like to pass the mic over Dr. Lebow 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 patients with meningiomas to improve our options for these patients.

Melanie Cole, MS: Thank you both and for highlighting the multidisciplinary care that goes into these patients. 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 patients with meningiomas, we like to prefer to approach these patients in an individualized fashion. So, key factors that I'm evaluating in terms of their tumor in each individual patient really is one the size of the tumor; two, is it causing problems for the patients? For the vast majority of patients with meningiomas, if the tumor is small, it's not causing any symptoms for the patients, 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 patients 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 patients, 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.

Melanie Cole, MS: It was such a comprehensive explanation there. And Dr. Lebow, 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 patients 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 patients. 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 Perelman 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. We're the first proton center in the Mid-Atlantic region and have treated thousands of patients 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. [00:11:00]

We're 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.

Melanie Cole, MS: 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 Penn meningioma care model?

Dr. Christina Jackson: I think that's an aspect that often [00:12:00] is passed over in our discussion with patients on expectations after treatment of these tumors, whether that be surgery or radiation. I think, you know, for a lot of these patients, 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 patients 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 patients 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 [00:13:00] 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. Lebow 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 patients of what to expect after surgery, and I'm sure Dr. Lebow will comment on what to expect after radiation, for example. And 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 patients 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.

Melanie Cole, MS: So then, Dr. Lebow, why don't you jump in here then and speak about what sets Penn apart?

Dr. Emily Lebow: Thanks, I would second everything Dr. Jackson stated. She made a lot of really excellent points. And I'll add that Penn is really utilizing new approaches to improve our treatments for meningiomas and, hopefully, minimize those long-term side effects that can really affect how patients feel months or years after finishing treatment.

So one thing that we're doing a special type of imaging modality that relies on that somatostatin receptor. It allows us to better visualize the meningiomas compared to conventional imaging with MRIs.

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.

And so, utilizing these 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.

Melanie Cole, MS: Well, it certainly is. This [00:18:00] is an absolutely fascinating conversation. I'd love to give you each a chance for a final thought here. So, Dr. Lebow, 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 patients months to years after treatment.

And so, I'm looking forward to contributing to that science, learning about it, and thinking about [00:19:00] 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 patients.

Melanie Cole, MS: 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 patients 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 and Dr. Lebow, 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 [00:20:00] 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 patients in an individualized, personalized fashion.

Alluding to what Dr. Lebow 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, are 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 [00:21:00] 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.

Melanie Cole, MS: Thank you both so much for a very enlightening discussion. Thank you for joining us. And 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 can submit your referral via our secure online referral form by visiting our website at pennmedicine.org/refer. That concludes this episode from the specialists at Penn Medicine. I'm Melanie Cole.