Diffuse Midline Glioma

Patricia Nicole Tan

Exploring the Complex Journey of Diagnosis, Treatment, and Hope

What would you do if your little child were diagnosed with a brain tumor? You’d probably feel scared and anxious, right? This is exactly what most parents experience when their children are diagnosed with diffuse midline glioma. 

Diffuse midline glioma (DMG) is a fast-growing brain tumor that forms in the central parts of the nervous system (Diffuse Midline Glioma (DMG) | Boston Children’s Hospital, n.d.). Most of these tumors are found in the brainstem, responsible for crucial functions like breathing, swallowing, and regulating heart rate. However, they can also appear in other areas such as the thalamus and spinal cord (Diffuse Midline Glioma | UCSF Brain Tumor Center, n.d.). But why does this happen? What can be done about it? Let’s explore these questions further in this article.

Diagnosis

DMG is most commonly diagnosed using imaging techniques, especially Magnetic Resonance Imaging (MRI) (Sharie et al., 2023). However, even though the tumor’s midline location and infiltrative growth pattern can be identified through imaging, a biopsy is crucial for confirming the diagnosis and guiding treatment decisions. It is also necessary to detect the presence of the H3K27M mutation, a key factor in these tumors. (Yoon et al., 2021). 

Research on the H3K27 mutant glioma has intensified in recent years, but efforts are still ongoing to translate this growing understanding into better clinical outcomes for DMG patients (Saratsis et al., 2023). Unfortunately, DMGs are known for having a poor prognosis. Their resistance to treatment, difficulty in surgical removal, and the challenge of developing effective drugs contribute to the uncertainty surrounding their origins (Noon & Galban, 2023). Even with radiotherapy, survival rates have not significantly improved, with many patients surviving less than a year (Lapin et al., 2017). 

The signs and symptoms of DMGs can include vision problems, headaches, difficulty walking or maintaining balance, droopy eyelids, and trouble chewing or swallowing (Cleveland Clinic, n.d.). While these symptoms can provide some indication, ongoing research continues to seek better treatments.

Medical Professions Involved

When it comes to treating DMG, a multidisciplinary team is essential, and two key medical professionals play a crucial role. The first is a neurosurgeon, a physician specializing in the diagnosis and surgical treatment of disorders affecting the central and peripheral nervous systems, including tumors  (What Is a Neurosurgeon - Neurosurgery - Highland Hospital - University of Rochester Medical Center, n.d.). To become a neurosurgeon, one must first complete a pre-med course, then take the Medical College Admissions Test (MCAT) to apply for medical school. Afterward, they must complete a residency, which typically lasts seven years, and they may also choose to pursue a fellowship in a specific area of neurosurgery (Torres, 2023). According to the National Health Service of the United Kingdom, neurosurgeons earn between $108,744 and $144,177 per year.

The second vital professional is an oncologist, a specialist in the study and treatment of cancer (WebMD Editorial Contributor, 2023). Like neurosurgeons, oncologists must complete a pre-med course, take the MCAT, attend medical school, and complete a residency. They may also choose to pursue a fellowship in a specific area of oncology (Katakam, 2024). Oncologists generally earn between $200,000 and $500,000 per year, according to the American Society of Clinical Oncology (Browse Jobs | ASCO Career Center | by Relevance, n.d.). 

These two professionals are essential in the battle against DMG, working together to explore and develop alternative treatments. While current treatments has not yielded a definitive cure, the efforts of neurosurgeons and oncologists are crucial in trying to prolong the survival of patients with DMG and in the ongoing search for more effective treatments.

Treatments

Radiation therapy remains the primary treatment for diffuse midline glioma (DMG), aiming to slow the tumor’s progression and reduce its size to alleviate symptoms. However, despite this approach, tumors almost always recur, leading to the unfortunate reality that DMG is still considered incurable, with patients typically surviving only 9 to 12 months (Noon & Galban, 2023). 

In the search for more effective treatments, researchers are exploring the potential of immunotherapy. One promising area of study is the combination of immunotherapy with radiotherapy. This approach could make tumor cells more sensitive to treatment, which may inspire further research into DMG. Another avenue being investigated is oncolytic virotherapy (OV), which may increase the expression of immune checkpoint proteins on tumor cells, offering another potential treatment strategy (Bernstock et al., 2022).  

Epigenetic-agent based immunotherapy is also under investigation. Although epigenetic therapy alone has not shown the desired results in DMG patients, and even combined treatments have not met expectations, ongoing studies suggest that these approaches could eventually enhance the effectiveness of immunotherapy in treating DMG (Jing et al., 2023). 

Additionally, researchers have found that DMG tumors heavily rely on methionine, an amino acid found in food. This discovery has led to the development of drugs that target the methionine-processing machinery in cancer cells, potentially paving the way for new, non-invasive treatments (Golbourn et al., 2022). 

Statistics

DMGs are the second most common malignant brain tumors in children, primarily affecting those between 3 and 10 years old. In the United States, around 200 to 300 new cases are diagnosed each year (Tosi & Souweidane, 2024). Unfortunately, the outlook for these patients is grim, with survival rates so poor that most do not live beyond two years.

However, there are rare cases that challenge this bleak prognosis. One notable example is a 12-year-old boy with DMG who has lived a normal life for more than six years. His treatment involved high-dose radiotherapy and extensive surgical resection, followed by bevacizumab. While this approach has proven effective for him, it’s important to note that its success can vary significantly from patient to patient, and it may not be a viable option for everyone (Ono et al., 2021). 

Impact and Awareness

The impacts of DMGs on children is profound, affecting not only their physical abilities, but also their overall quality of life. The symptoms of this devastating condition, including difficulties with movement, speech, and basic functions like swallowing, can be life-altering (The Brain Tumour Charity, 2024).

The emotional toll on families is also immense, as they grapple with a diagnosis that currently offers limited hope. Raising awareness about DMGs is important, as it promotes support for ongoing research and development of new treatments.

With continued efforts, there is hope that future advancements will lead to better outcomes and improved quality of life for these young patients.

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