Page 29 - TD-4-2

Tumor Discovery Understanding glioblastoma invasion and therapy

account for approximately 3% of US cancer deaths, and account for the majority of high-grade gliomas that evolve
the disproportionality of this death rate is significant, from lower-grade gliomas (previously categorized as
considering that between 2014 and 2018, only 29.1% of secondary GBM). GBM is more common in individuals
12
primary CNS tumors were classified as malignant. 2 of European ancestry, and its incidence in Whites is 98%
13
higher than in Blacks and 144% higher than in Asian/
Primary malignant CNS tumors arise predominantly 2
from glial cells (80.9%) and are correspondingly called Pacific Islanders (Figure 1C). Socioeconomic status (SES)
malignant gliomas. Malignant gliomas develop within is also significantly correlated with GBM incidence, and
2
both the brain and spinal cord, with approximately 98% the highest SES is associated with a 45% higher GBM
originating in the brain. Glial cells can be categorized incidence rate than the lowest SES after controlling for self-
3,4
14
as astrocytes, oligodendrocytes, and ependymal cells, reported race.
whereas gliomas can be categorized as astrocytomas, 2. GBM risk factors
oligodendrogliomas, and ependymomas.
GBM risk factors are poorly understood. Moderate-to-
Glioblastoma (GBM) is categorized as a type of high dose ionizing radiation to the head – particularly if
astrocytoma and is the most aggressive and common administered in childhood – is the only environmental
histological subtype of malignant glioma. GBM is the risk factor known to be unequivocally associated with the
most diagnosed primary CNS malignancy and represents development of primary CNS tumors. Radiation-exposed
15
approximately half (49.1%) of diagnoses in this category children are more likely to develop a meningioma than a
of human cancer. This corresponds to a US incidence rate malignant glioma, and this risk factor accounts for very
2
15
of 3.23/100,000 people, or approximately 13,000 new GBM few cases of either pathology. Other extensively studied
diagnoses each year. 2 environmental risk factors include medications, hormone
GBM is a rapidly fatal cancer with an incredibly poor exposure, diet, body habitus and body mass index, smoking,
overall survival rate. Analysis of data collected through birth weight, cell phone usage, and electromagnetic field
16
the Surveillance, Epidemiology, and End Results Program exposure. None of these factors have been conclusively
(SEER) at the National Cancer Institute of the US National associated with GBM development. 16
Institutes of Health (NIH) shows that the median overall Heritable genetic risk factors are estimated to represent
survival time for GBM patients in the US was 8 months approximately 25% of overall GBM risk, but around 70%
2
and the 5-year overall survival rate is approximately 7% of the genetic variance underlying that risk contribution
between 2001 and 2018. This is notably lower than the 14.6- remains to be identified. At present, only 5% of GBMs
17
month median overall survival time reported by Stupp et al. are observably linked with familial disease, and only
5
18
SEER’s inclusion of data from GBM patients who chose not 1 – 4% are associated with inherited genetic disorders
to undergo treatment – for whom the median survival is known to increase glioma risk. Most of these disorders
16
6,7
reported between 1 and 3 months – likely contributed are associated with well-characterized loss-of-function
to this statistical discrepancy. However, GBM is known mutations in tumor suppressor genes. 16
for its heterogeneity, 8-10 and these data aptly highlight the
persistent challenge of epidemiologically characterizing 3. Clinical classification of CNS tumors
a clinical cohort that includes many poorly understood The aggression, extent, and spread of systemic cancers are
subcategories with readily observable survival differences.
commonly assessed and described using the American Joint
The combination of low incidence and poor survival Committee on Cancer Tumor, node, metastasis (TNM)
rate indicates that GBM is not a prevalent disease. At staging system. In this standardized clinical model, the
19
present, it is estimated that there are slightly <19,000 tumor (T) component describes the size, location, and local
Americans with a documented GBM diagnosis (0.006% invasive capacity of the primary tumor. The node (N)
19
of the 2022 US population), and the NIH correspondingly component defines the degree to which cancer infiltrates
categorizes GBM as a rare disease. 11 the lymph nodes that surround the primary tumor. The
19
The overall incidence of GBM varies greatly by age, metastasis (M) component assesses the spread of primary
sex, and ethnicity. GBM is known to develop at all ages, cancer to distant organs or tissues. 19
but the incidence increases with age and peaks between The unique environment of the CNS and the
75 and 79 years old for the individual sexes (Figure 1A). correspondingly unique behavior of primary CNS tumors
2
The average age of GBM diagnosis is 65 years old. Males make the TNM staging model poorly suited to describe
are 60% more likely to be diagnosed with GBM overall the behavior of GBM and other CNS cancers. For example,
(incidence rate ratio = 1.6) (Figure 1B), but females primary CNS tumors can be locally invasive and aggressive,
2

Volume 4 Issue 2 (2025) 21 doi: 10.36922/td.8578