Brain Tumors

Introduction of Brain Tumors

Brain and central nervous system (CNS) tumors represent approximately 1% of all newly diagnosed cancers and about 2% of cancer deaths. These tumors can be broadly classified as malignant and nonmalignant tumors. Brain tumors are classified based on histopathology into the following major histologic groupings: tumors of neuroepithelial tissue (also as glioma), tumors of meninges (including meningioma, and hemangioblastoma), germ cell tumors, and tumors of the region. The most common type of malignant tumors are gliomas, of which glioblastoma occurs with the most significant frequency.

Brain tumors in children represent the second most common malignancy in children. The cause for these tumors is unknown, but some predisposing conditions give rise to certain types of brain tumors. Incidence, prevalence, and survival for brain tumors vary by histologic type, age at diagnosis, sex, and race/ethnicity. Thus, brain tumors require specialized and complex care by neuro-oncologists, medical oncologists, radiation oncologists, and brain tumor neurosurgeons.

Fig.1 Distribution of primary brain and other CNS tumors by behavior and histology. (Barnholtz-Sloan, 2018)

Key Risk Factors for Brain Tumors

• Environmental Risk Factors

1. Ionizing Radiation

Exposure to therapeutic doses of ionizing radiation constitutes the only environmental factor unequivocally associated with an increased risk of brain tumors. Multiple studies have evaluated the association between even low doses of therapeutic radiation and brain tumors. Some studies have shown increased brain tumor risks in children who received prophylactic CNS irradiation for acute lymphoblastic leukemia. The higher risk of glioma in children irradiated at a very young age reflects excellent susceptibility of the developing brain to ionizing radiation.

2. Others

Many other potential environmental and behavioral risk factors have been explored for brain tumors, including diet, tobacco smoking, alcohol consumption, head injury and trauma, and exposure to electromagnetic fields. Associations between these potential factors and the risk of brain and CNS tumors have not been well replicated.

• Genetic Factors

Brain tumors are believed to develop through the progressive accumulation of genetic or epigenetic alterations that permit cells to evade standard regulatory mechanisms or escape destruction by the immune system. There is substantial epidemiologic evidence that genetic factors are associated with brain tumor risk. In addition to inherited alterations in crucial genes that control the cell cycle, such as TP53, those chemical, physical, and biological agents that damage DNA are suspected potential neurocarcinogens.

1. Familial Aggregation of Brain Tumors

Almost all cases of glioma are sporadic, but approximately 5% of glioma cases are familial, meaning that a glioma has occurred multiple times within the same family. Studies of first-degree relatives of persons with glioma have found that the incidence is 2 times higher than those without a relative with glioma. Some analyses have also shown an increased risk of other non-brain cancers in relatives of persons with brain tumors, including melanoma and sarcoma.

2. Polymorphisms in Genes Relevant to Cancer Causation or Prevention

Polymorphisms in gene encoding enzymes involved in the metabolism of chemical carcinogens or DNA repair may be associated with high susceptibility to glioma development. Genetic alterations that affect oxidative metabolism, detoxification of carcinogens, DNA stability, repair, or immune response are candidates that might plausibly confer genetic susceptibility to brain tumors and other cancers. There is a significant increase in the frequency of the functional GSTM1 allele in high-grade pediatric astrocytoma and a significant increase in the frequency of the rare GSTP1 variant 114 Val/Val.

• Allergic and Immune-Related Conditions

Persuasive evidence has accumulated over the past decade that immunologic factors related to allergy, allergic conditions, and infections impact glioma and glioblastoma risk. Several groups have reported a reduced risk of glioma or glioblastoma risk in patients attributed to allergy and allergic conditions and autoimmune diseases.

Tracers for Clinical Use

A broad range of tracers has been evaluated for clinical use in diagnosing brain tumors with PET or SPECT. Much interest and effort have been invested in developing and evaluating brain tumor tracers, such as fluorodeoxyglucose (FDG) and labeled amino acids, because they are being transferred by large-capacity specific transporters across the intact blood-brain barrier. The most widely available tracer, FDG, is a predictor of prognosis and is particularly useful for distinguishing brain lymphoma from nonmalignant lesions. It is expected that individualized patient management based on advanced PET and SPECT techniques will lead to better therapeutic outcomes in patients with gliomas and other malignant brain tumors, which still carry a rather dismal prognosis.

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Reference

1. Barnholtz-Sloan, J. S.; et al. Epidemiology of brain tumors. Neurologic clinics. 2018, 36(3), 395-419.