Introduction: Low-Grade Gliomas in Pediatric Patients

Mohamed Shebl Abdelbaki, MD, St. Louis Children’s Hospital, Washington University of Medicine in St Louis, Missouri, discusses recent advances in the understanding and management of pediatric low-grade gliomas.

In this video, Dr Abdelbaki reviews how modern molecular profiling and the updated WHO CNS tumor classifications have reshaped diagnosis and treatment strategies and emphasizes the importance of multidisciplinary care for these patients.

Watch the next video in this series.

Transcript:

Good morning and good afternoon, everyone. My name is Mohamed Shebl Abdelbaki. I'm the director of the Pediatric Neuro-Oncology Program at Washington University School of Medicine in St. Louis, and I'm very excited to be here today to discuss with you the latest advances in pediatric low gliomas. These are my disclosures that may be relevant to our discussion today.

First, I will give you a quick background about low-grade gliomas in children, and then we're going to discuss the therapy options and the new advances in this field, in addition to a very important topic, which is the response evaluation criteria that may have evolved over the past few years.

I'll first start by stating how pediatric brain tumors now are the most common tumors or cancers in children up to 14 years of age, it has surpassed leukemia as you can clearly see here in this latest data, published in 2025. In general, I think— I had a hematology-oncology first-year fellow over this last weekend who thought that most patients with pediatric brain tumors do not survive. And the reason why, I think, is related to how the IPGs [intrinsic pontine glioma] or diffuse midline gliomas typically have very poor outcomes that many researchers around the world are working on improving these outcomes, and hopefully we're going to see improvement over the next 5 to 10 years. However, this is not the case for pediatric brain tumors. We're going to discuss the most common pediatric brain tumor, which is pediatric low-grade gliomas today, or pLGG as we're going to refer to it, and you're going to see how the outcomes look like. But looking at the outcomes for the most common malignant brain tumor, which is medullablastoma, you can see there are tumors that actually are very close to 100% survivorship in terms of WnT medulloblastoma, and survivorship is pretty good for those who have other subgroups in medullablastoma as well. And this is not the case for medullablastoma only, but we've made significant improvement in our ability to treat pediatric brain tumors over the last few years.

And I think we can owe this to the significant advances that we've made in terms of investigating the molecular landscape of pediatric brain tumors and identifying new subgroups in these tumors, which has led for the first time to the integration of the pathology and the molecular biology in the 2016 WHO classification for CNS [central nervous system] tumors. And this even evolved further into identifying 22 entities, new entities in the 2021 WHO. And if we start focusing on pediatric low-grade gliomas, we're going to see how now they typically happen in 6 families, 3 of which encompass pediatric low-grade gliomas. These gliomas are present in these 6 families and 3 of them encompass pediatric low-grade gliomas. And within these 3 families that we have here, there are 6 newer entities that have been identified and they are here in bold green.

pLGGs are the most common tumor in children and adolescents. The most common of them is pylocitic astrocytoma, and this number may be actually up to 20% now, it depends on the publications, but what we know is that pilocytic astrocytoma is the most common pediatric glioma and they happen in different locations around the brain and these are the most common locations: here in the diencephalon and the cerebral hemispheres, as well as the cerebellum. But the importance of this is that we would know that in more than 50% or 60% of the cases we’re not going to be able to achieve a complete resection. Surgery is the mainstay of therapy as we're going to discuss, complete resection would be the goal safely of course, but in around 50% or 60% of the cases in the diencephalon, optic pathway, brainstem, some areas in the cerebral hemispheres, spine, you're not going to be able to achieve a complete resection. And therefore, in most of our cases, we have to look for other modalities of therapy and this is what we're going to be talking about today. But it's very important for us to know that there are other options available, not only surgery for patients with pediatric low-grade gliomas.

And I like to talk about that figure on the left. As we can see, the overall survival for patients with pLGGs is not at 100%. I say that because we get this question all the time from families: pLGGs means my child has a benign tumor. Is that correct? Yes, it's accurate, but I always refer the families to the grades of brain tumor. You have a grade 1 and 2, so that's a low-grade tumor and a grade 3 or 4, that's a high-grade tumor. And I always state that grade 1 and 2 is slow growing, not aggressive. If you resect completely, that would most probably be the end of the story. But if you cannot resect completely, this is when we would consider it like a chronic disease and your child may be requiring therapy at one time point, stop therapy, different therapy at another time point and so on. I try to stay away from the word benign because some families think of benign, that means that it would never affect their child's survivorship and as we can see, it's not 100%. In order to stay away from confusing families, I like to explain it to them rather than just responding and saying this is a benign tumor.

And on the right, for any large comprehensive program, we work very closely with our neurosurgery colleagues in a multidisciplinary fashion along with so many other specialties. We typically see patients before they go to surgery or right after surgery. It's very important that everyone is on the same page, because the families think, how much is left, how big the tumor is? It's important to share these data with the family. A complete resection, yes, the chances of the tumor coming back is very small, but we have to manage this safely. A complete and maximal safe resection is the goal. If you don't have a complete resection, that's fine. There are many other options that we're going to discuss as we're going to talk about today. And if something is left back, it doesn't matter whether this is less than 1.5 cm or more than 1.5 cm, typically the size does not make a difference. This is very important so that our neurosurgeons would, with the families, we would talk comprehensively about our goals and our goal is for our child to have a safe resection that would allow us to make the diagnosis, would allow us to have a decent progression-free survival. But if that's not going to happen, we have many other options.

I think we tend to forget that we should not be only focusing on the overall survival and progression-free survival, especially in tumors that we are aware that these are long-term survivors and those patients will live for a long period of time: they will need to get married and have a driver's license and so on and so forth and be independent in life. Therefore, we have to make sure that we work with a multidisciplinary team, because even with a complete resection, these patients will have long-term effects. It depends on the location of the tumor and so on. You have to work with endocrinology, you have to work with ophthalmology, rehabilitation medicine, neurology, of course, and now with the targeted therapies as we're going to discuss, we have to work very closely with dermatology. So making sure that we treat these patients in a multidisciplinary fashion, explain the long-term sequelae of the therapies that we're using so that the families would not be missing other appointments once they learn about, oh, the tumor is stable, I'm not going to go to the ophthalmology visit. It's not that important to follow up with endocrinology. No, it's extremely important for us to be managing our patients with pLGGs comprehensively.