Understanding the clinical outcomes of a rare but distinct low-grade glioma

Within the central nervous system lie glial cells. This group of cells forms the connective tissue of the nervous system by bridging and protecting neurons as our brains develop. The uncontrolled growth of these cells, however, can lead them to develop into gliomas, tumors which, given the ubiquitous nature of glial cells, can form across many regions of the brain. Gliomas can behave differently, depending on how quickly they grow and what types of glial cells are involved, and cover the entire spectrum of severity, ranging from low-grade to high-grade. For this reason, the classification of gliomas has been a key consideration in understanding the correct course of treatment.

“In the pediatric neuro-oncology space, there's been a lot of advances in terms of characterizing tumors and identifying subgroups and subtypes, but that's usually just in the context of the description of the tumors themselves,” said Daniel Moreira, MD, MEd, St. Jude Department of Global Pediatric Medicine and Department of Oncology. Moreira is the co-corresponding author of recent work that appeared in Neuro-Oncology, which offers a comprehensive insight into a particular type of low-grade glioma that harbors genetic alterations in the MYB or MYBL1 genes.

Not just a description, but a guide

The relative rarity of MYB/MYBL-altered pediatric low-grade gliomas means that thorough treatment and outcome data are sparse. In fact, it was only recognized as a unique type of glioma by the World Health Organization in 2021. Moreira partnered with Jason Chiang, MD, PhD, St. Jude Department of Pathology, to address this knowledge gap, but in a more patient-focused way. “What we have done is associate the tumor description with the clinical story. That way, it's not just a description, but a guide to how it translates into treatment and how it can inform clinicians,” said Moreira. “We wanted to provide insight into what the best treatment is based on historical data.”

The characterization of the glioma as a grade 1 tumor would imply a lack of severity. Indeed, limited studies have shown positive prognoses for these patients. However, due to the rarity of this type of tumor and the many unknowns, choosing the most appropriate route to treatment can be complex. “On the one hand, we can tell this is a specific type of low-grade glioma, but on the other hand, we don't really understand what kind of disease it is,” said Moreira. “We don’t know if the tumor will progress or metastasize, what the patient outcome will be, or what kind of therapy it will respond to.”

To understand this better, Moreira and Chiang pooled 24 years of cases from multiple institutions. In total, they found 33 tumors to study.

The sample size was enough to validate the general anecdotal understanding of the tumor, highlighting the good outcomes for patients despite some varying clinical, histologic, or molecular characteristics. This is especially true for patients who undergo surgery to remove the tumor outright. “These tumors, if you take them all out, or you take most of it out, the children do well,” said Chiang. “One patient had a minor remnant of the tumor for 22 years and it never changed. This tumor behavior, in general, is very good.”

Cancers are more than just their molecular makeup

Even within a sample size of 33 cases, the researchers did note some heterogeneity. “A couple of cases had metastatic disease at diagnosis, and then a couple progressed despite chemotherapy and radiotherapy. So, there is some heterogeneity to this,” Chiang emphasized. They hope that the continued expansion of this dataset will offer more insight into the diversity of this type of glioma. “Even though this is the biggest cohort,” Chiang said, “we would need dozens more to completely paint that picture. This is the first step into describing that diversity.”

The emphasis on clinically describing the tumor also raised some interesting points regarding how tumors are generally classified. The 2021 WHO classification separated MYB/MYBL1-altered pediatric low-grade glioma into two different tumor types: angiocentric glioma and diffuse astrocytoma. This separation may be a case of splitting hairs. “These two tumor types actually have overlapping patient demographics, tumor location, DNA methylation, molecule alteration, and even overlapping outcomes,” Moreira pointed out. “The data is telling us that these two tumor types may just be two ends of the same disease. And even though there is heterogeneity within the tumor, the histology is not the way to separate them.”

In many ways, the collaboration of Chiang and Moreira mirrors the ideal approach to classifying diseases such as cancer: an interdisciplinary approach that seeks to study the tumor from both molecular and clinical perspectives. “We have different expertise. We see the disease from different aspects,” Chiang highlighted. “Daniel is seeing it from the patient aspect, and I see it from the pathology perspective. When we combine our different views into the same effort, we get a more holistic view of the disease.”