G is for Glioma, G is for GBM

I will preface this by saying I am not a neuro-oncologist nor any other kind of oncologist. My experience with gliomas in any direct manner is limited, and my interaction with them now (save for a very big one affecting a very important person), is as an epileptologist treating seizures which may be caused by gliomas. I wanted to shed more light on gliomas, and in putting this together, I came across a few good references which I included at the end.

Gliomas form from support cells gone rogue. They are the most common malignant primary brain tumors, with an approximate incidence rate of 6 cases per 100,000 individuals per year  in the United States (Mesfin et al. 2024). Given the population of the United States in 2026 is close to 350,000,000, 6 cases per 100,000 individuals is not an insignificant number of new cases. 

World Health Organization (WHO) classification includes four grades of gliomas: 1, 2, 3, and 4. There are low-grade and high-grade gliomas, which can include entities such as astrocytomas and oligodendrogliomas.

Then there’s the big guy, the all-caps GBM (glioblastoma multiforme), now just called glioblastoma. This is WHO Grade 4, a category that can also encompass some forms of astrocytomas as well as diffuse hemispheric gliomas (Louis et. al. 2021).

But how does it declare itself? It may be dramatic, like it did for my husband, with a seizure to herald its presence. Others may see a more insidious buildup of symptoms. Headaches which won’t relent, often worsening to the point of becoming unbearable. There could be nausea, maybe vomiting, again intensifying with each passing day. A limb grows weaker with time, perhaps speech becoming slower, halting, with no clear cause. So much of how it presents depends on where the tumor starts growing in the brain. It is a cruel lesson in neuroanatomy. 

The diagnosis, whether a GBM or other type of glioma, used to be determined through different routes. Now, along with conventional immunohistochemistry (staining the tissue and analyzing it under a microscope) it is an alphabet soup of genetic markers. To officially confirm a tumor as a GBM, it means having an isocitrate dehydrogenase (IDH) gene which is wildtype (original and unblemished). Which means, just like all roads leading to Rome, all things seem to lead back to the citric acid cycle a.k.a. Krebs cycle. Without delving too far into the minutiae, we can at least say that within the citric acid cycle, IDH has a sizable role in a cell's energy production.

The alphabet soup goes beyond IDH. There’s the MGMT gene and its methylation status (positive or negative), which can affect its response to the chemotherapeutic drug temozolomide. The MGMT gene is crucial for clearing DNA damage which can be caused by various factors, including chemicals. Except chemotherapy is there to do just that: induce damage and kill the tumor cells. What methylation does is turn off the repair gene, making it harder for tumor cells to repair damage caused by chemotherapy like temozolomide, increasing the likelihood of their death.

Then there’s EGFR, another GBM marker. Normally it helps modulate cell division but mutated forms can be thought of as the gas pedal being glued to the floor, sending the cell division mechanism hurtling forward at 120 mph, leading to uncontrollable division and the appearance of tumors. Sometimes a piece of chromosome 10 gets stuck on chromosome 7, revving up a GBM’s aggressive behavior (Ordonez-Rubiano et. al. 2025). The permutations and combinations of genes and their functioning or lack thereof continues and the list of relevant genes/genetic markers seems to increase with time. 

And here we are, hanging on to every letter as though it was a prophecy. “Hear me now,” it would say softly, “these letters tell tales of success with the trials ahead. Be well and beware of those who draw you off the path of healing.”

The overall survival for standard of care (temozolomide chemotherapy along with radiation treatment) is around 12-15 months before considering the subgroups within the alphabet soup. Some hold more promise, others more portent. Overall survival has not changed much at all since I was doing clinical research well over a decade ago.  This is the tragic reality of glioma management, particularly GBM. Though overall survival remains troublingly poor, consider that without any treatment, the overall survival drops to just a few months, if that.

It is that number that flashed before my eyes when I saw the tumor – William the Bump – on that CT image. I thought of what those months looked like, what could be done during that time. Another academic year? Preschool graduation? Another cycle of holiday celebrations? Birthdays? 

Will we see ten years together? Ten years of marriage?

I wanted to scream until my vocal cords exploded into dust.

Then came the stories of others, friends of friends, acquaintances of acquaintances, seeing months and years beyond those 12-15 months. Careers flourishing, families thriving, sunbeams poking through storm clouds. Anecdotes are beautiful, personal, and so out of place in a brain and field that seeks statistical significance and well-powered samples. But I hang on, claws digging in so deep into each of these anecdotes that they’d snap off if pushed any further.

It goes without saying that we need more funding and more research in general. GBM, with its persistently horrific prognosis, demands greater attention. Six new cases per 100,000 means thousands of new cases per year in the United States. Numbers are never the whole story. There are patients, their lives, interests, and wishes. Then there are the family members, friends, colleagues, hundreds of thousands of people touched by one diagnosis. With my husband alone, there are hundreds of additional people in his orbit who have been affected by his diagnosis, directly or indirectly. 

So reach out to organizations, reach out to your representatives, be loud. I know I will be. Until then, we wait for more letters, and with any luck, weave them into hopeful stories of our own.

Here are just a few organizations working on glioma research and advocacy, and have great resources for patients and caregivers alike:

American Cancer Society: http://www.cancer.org

American Brain Tumor Association: https://www.abta.org/

Glioblastoma Foundation: https://glioblastomafoundation.org/

National Brain Tumor Society: https://braintumor.org/ 

References

Mesfin FB, Karsonovich T, Al-Dhahir MA. Gliomas. [Updated 2024 Aug 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441874/

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-1251. doi: 10.1093/neuonc/noab106. PMID: 34185076; PMCID: PMC8328013.

Ordóñez-Rubiano EG, Ramos-Márquez A, Vega-Alvear RF, Ruiz-Forero C, Cadavid-Cobo A, Fuentes-Tapias S, Andrade-Andrade P, Cómbita AL, Payán-Gómez C, Parra-Medina R, Gómez DF, Ramón JF, Hakim F. Deciphering the Clinical Implications of Concurrent Chromosome 7 Gain and Chromosome 10 Loss in Glioblastoma: A Scoping Review. Brain Sci. 2025 Dec 31;16(1):60. doi: 10.3390/brainsci16010060. PMID: 41594781; PMCID: PMC12838677.