The Difference Between Pediatric and Adult Brain Tumors: Why the Age of the Patient Matters

When it comes to brain tumors, there is a crucial distinction between tumors found in children and those found in adults. This difference primarily stems from the fact that the pediatric brain is still developing, while the adult brain has already matured. These stages of development significantly influence not only how tumors form but also how they behave, and most importantly, how they respond to treatment.

Understanding Tumor Heterogeneity in DIPG

A classic example of the complexity of pediatric brain tumors is Diffuse Intrinsic Pontine Glioma (DIPG). One of the defining features of DIPG and similar pediatric brain cancers is their heterogeneity—meaning the cancer cells within the tumor are not all the same. These differences are driven by variations in genetic architecture, transcription mechanisms like RNA splicing, and the unique microenvironment in which they exist.

Tumor heterogeneity plays a key role in the growth rate, metabolism, and, perhaps most critically, how these cancer cells respond to treatment. In DIPG, glioma cells are often segregated into distinct regions called niches. These niches interact with neurons, glial cells, blood vessels, and immune cells, forming a complex ecosystem that helps the cancer thrive and resist therapy.

Key Differences Between Pediatric and Adult Brain Tumors

1. Cellular Origins of Tumors
   • Pediatric Brain Tumors: These tumors typically arise from cells that are still developing and differentiating. For example, developing cells are more likely to be influenced by developmental pathways like Hedgehog or WNT, which regulate cell growth and differentiation.
   • Adult Brain Tumors: In adults, brain cells have largely stopped dividing. Tumors in adults often arise from mature brain structures and are more associated with genetic mutations accumulated over time, such as those in tumor-suppressor genes.
2. Types of Brain Tumors
   • Pediatric Tumors: Tumors like medulloblastoma, ependymoma, and gliomas (such as DIPG) are more common in children. These tumors tend to occur in regions like the brainstem and cerebellum, which control balance and motor functions.
   • Adult Tumors: Adults are more prone to glioblastoma multiforme and meningiomas, which often develop in the cerebral hemispheres.
3. Molecular and Genetic Differences
   • Pediatric Tumors: These are often driven by mutations related to developmental processes, making them genetically distinct from adult tumors. For example, pediatric tumors often involve different pathways and mutation patterns than adult tumors.
   • Adult Tumors: Tumors in adults show higher levels of genomic instability due to accumulated damage from aging and environmental factors. This makes them more genetically complex, often involving mutations in genes responsible for DNA repair, such as TP53.
4. Tumor Growth and Behavior
   • Pediatric Tumors: Because the pediatric brain is actively developing, these tumors can grow aggressively, particularly during certain developmental windows. However, children's brains are also more plastic, meaning they have a greater ability to recover after treatment.
   • Adult Tumors: Tumors in adults may grow more slowly but tend to be more infiltrative, spreading into healthy brain tissue, which complicates surgical removal. For instance, glioblastomas are notoriously difficult to remove completely.
5. Response to Treatment
   • Pediatric Brain: Pediatric tumors tend to respond better to chemotherapy and radiation than adult tumors. However, because the developing brain is more sensitive to these treatments, there is a higher risk of long-term side effects, such as cognitive impairments and hormonal imbalances.
   • Adult Brain: Adult tumors are often more resistant to treatment. In addition, the adult brain has less neuroplasticity, meaning it is less capable of reorganizing and healing after damage caused by treatment.

The Importance of Personalized Treatment Approaches:

The heterogeneity of pediatric tumors like DIPG, coupled with the unique features of the developing brain, underscores the need for highly tailored treatments. In adults, the challenge often lies in managing highly aggressive and treatment-resistant tumors like glioblastoma.

While pediatric patients may have a better chance of surviving brain tumors, the focus is on minimizing the long-term side effects that can arise from aggressive treatment. In contrast, adults face more immediate life-threatening risks from highly invasive tumors, but developmental side effects are less of a concern.

Understanding the differences between pediatric and adult brain tumors is crucial for developing better, more personalized treatment strategies. The key lies in balancing aggressive treatment for pediatric patients while safeguarding their developing brains from long-term damage. For adult patients, tackling highly invasive and resistant tumors like glioblastoma remains the primary focus.

By continuing to research the biology of these tumors and their interaction with the surrounding brain environment, scientists and clinicians are gradually improving treatment outcomes for both pediatric and adult brain cancer patients.

References:

• Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., & Figarella-Branger, D. (2021). The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro-Oncology, 23(8), 1231–1251.