Glioblastoma Care Plan Medical Research

Cancer Treatment Research

What is Glioblastoma? (heterogeneous disease, malignant brain tumor):

Glioblastoma is a fast-growing cancer that starts in the brain and spinal cord. It is acquired from astrocyte cells and mainly affects older men. Symptoms include nausea, vomiting, seizures, and blurred vision. There are two types of glioblastomas: primary and secondary. Primary glioblastomas are grade IV tumors with no lower grade tumors that precede it, while secondary tumors begin as a lower-grade tumor which later progresses to a grade IV tumor.

List of factors that contribute to genetic mutations in astrocytes (Potentials):

Spontaneous errors during DNA replication
Exposure to mutagenic agents ("Exposure to certain environmental factors has been associated with an increased risk of developing Glioblastoma. Ex. exposure to high-dose radiation therapy, certain chemicals, and specific electromagnetic fields.")
Inherited genetic composition ("In rare cases, individuals inherit certain genetic mutations that increase the chances of developing Glioblastoma. For example, hereditary cancer syndromes, such as neurofibromatosis type 1 (NF1) and Li-Fraumeni syndrome, have been linked to an increased risk of Glioblastoma.")
DNA repair defects
Epigenetic modifications ("There are certain mutations that make you more likely to develop cancer. Epigenetic changes increase your cancer risk. Ex. Having a mutation in the BRCA1 gene stops it from working properly which makes you more viable to breast/other cancers.")
Activation of oncogenes (genes involved in cell growth and division)
Inactivation of Tumor Suppressor Genes (genes responsible for regulating cell division, repairing DNA damage, and promoting cell death), inactivation or function loss of tumor suppressor genes, TP53 (p53) or PTEN, could cause abnormal growth, leading to later development of glioblastoma.

Risks & Causes (Who is more likely to get it?)

It affects people aged 45-70
Contact with chemicals, for example. Pesticides, petroleum, synthetic rubber, vinyl chloride.
Genetic conditions that cause tumors, neurofibromatosis, Li-Fraumeni syndrome, and Turcot syndrome.
Radiation therapy to the head/Central nervous system.
Chronic Inflammation in the brain

(Seasonal allergies, Ex. Hay fever could protect from Glioblastoma)

History

Glioblastoma, formerly known as "spongioblastoma multiforme", was first identified in the early 1920s. Its classification has since been changed to "glioblastoma multiforme" (GBM). The first records of gliomas date back to British scientific reports in 1800 and 1804 by Berns and Abernethy, respectively. Rudolf Virchow provided the first comprehensive histomorphological description in 1865.

Statistics on Glioblastoma

Patients usually live less than one year after diagnosis.
RT plus TMZ proved to have better survival (14.6 - 12.1 months).
TTFields have shown to improve HGG from 15.6 - 20.5 months.
Glioblastoma makes up 45.6% of malignant tumors.
Patients with Glioblastoma usually live 12-18 months after diagnosis.
22% of Glioblastoma patients are 20-44, 9% are 45-54, 6% are 55-64.
IDH-mutant (cancer) patients live 24-36 months, compared to 12-18 months for IDH-wildtype (GBM).
More than 98% extent of resurrection helps overall survival (13 months compared to 8.8).
More than 70% of the extent of resurrection helps improve overall survival (14.4 months compared to 10.5)

Diagnosis

Reflex-testing-of-the-L3-and-L4-nerve-roots-patellar-tendon-reflex.jpg

Neurologic exam

The doctor will examine your hearing, balance, strength, and reflexes. Any issues with these senses may indicate signs of glioblastoma.

Imaging tests (MRI)

CT and PET scans can detect glioblastoma tumors, but contrast MRI provides more detailed information on the location and size of the tumor.

TESTING A PIECE OF TISSUE (BIOPSY)

A biopsy is a medical procedure that involves removing a small sample of tissue from the body for laboratory testing. This procedure can help determine if the tissue contains cancerous cells or glioblastoma cells.

Symptoms

Blurred/Double vision
Headaches
Problems regarding memory
Muscle weakness
Nausea & Vomiting
Problems regarding speech
Seizures

Treatments

(Glioblastoma is an incurable brain cancer, although some treatments can increase survival rate/life expectancy.)

Surgery to remove Glioblastoma is not possible to remove all cancer cells, additional treatments after surgery are most likely needed. (Gamma knife radiosurgery - Stereotactic radiosurgery - X-ray targets the tumor, causing less harm to healthy tissues)
Radiation therapy, X-rays, and protons are used through radiation to certain areas of the brain.
Chemotherapy - medications like pills are utilized after surgery or during/after radiation therapy to help kill cancer cells. (temozolomide - treat malignant cells)
Tumor treating therapy (TTF), is an electrical field to stop cancer cells from multiplying. (Optune device - alternating electrical field therapy)
Targeted therapy, medicines attack chemicals in cancer cells, causing cancer cells to eventually die. (Targeted drug bevacizumab
(Carmustine (BCNU) and lomustine (CCNU) - chemo drugs, slow tumor growth - Combinations of PCV regimen (procarbazine, CCNU, and vincristine))

What new treatment options are being researched?

(dendritic cell - type of immune cell found in tissues, helps immune responses by allowing antigens to surface to other cells of the immune system, phagocytes, and antigen-presenting.)

Clinical trials - immunotherapy/agents that point towards signaling pathways that could potentially control the growth of cancer cells.
Immunotherapies - dendritic cell vaccines (target antigens produced by glioblastoma cells, dendritic cells produce an immune response for the body), could help patients with advanced glioblastoma, a longer life expectancy.
CAR T-cell therapy - removing/changing the immune cells (T cells), to connect to expressed glioblastoma cells, and redirect the T cells.
Checkpoint inhibitors (drugs that help stop the tumor from weakening immune response), NCI is testing pembrolizumab with radiation therapy, temozolomide, etc.
Continuous use should help stop cancer from weakening the immune response.
New imaging technologies that help understand biomarkers related to tumor growth, help figure out if a treatment works.
Oncolytic viruses - (Poliovirus: a combination of poliovirus & rhinovirus, lead to the death of cancer cells, improved survival rate).
Phase II trial is researching the combination of DNX-2401 with Keytruda, or pembrolizumab.
Angiogenesis Inhibitors - Avastin (bevacizumab) was approved in December of 2017, fewer side effects and around 8% of people were able to survive longer.

Why is Glioblastoma difficult to treat?

The brain doesn’t allow many chemicals to enter (this includes potential treatments)
The makeup of Glioblastoma cells is different, meaning that some cells will respond to treatments/drugs, while others don’t.
Some treatments aren’t safe and could cause the death of brain cells. Or (Swelling of tissues)
The tumor expands at a fast rate.
Heterogeneity - Glioblastoma is different from other cancers as it is caused by multiple abnormal genes of cancer cells that blocking a pathway is not effective as other pathways allow the tumor to grow.
Discordance - Tumors usually create new mutations which affect growth and response to treatment, therefore, a tumor's first response to treatment will be different from how it responds the second time.
Hard to diagnose recurrence

Specific medications commonly used during treatment

The current drug, temozolomide, is moderately effective for tumor recurrences.
Carmustine (BiCNU) wafers - Implants that contain the chemotherapy drug carmustine, wafers release the medication, targeting remaining tumor cells in the area.
Bevacizumab (Avastin) - Bevacizumab is a targeted therapy that inhibits the growth of blood vessels within tumors, cutting off their blood supply. It can be used in some cases to manage symptoms and reduce tumor size temporarily; benefits in terms of survival are limited.
Lomustine (CCNU) - Lomustine can be administered orally and is used in combination with other treatments to slow tumor growth.

Additional explored medications for Glioblastoma treatment (may vary):

Irinotecan (Camptosar)
Everolimus (Afinitor)
Vorinostat (Zolinza)
Cilengitide (not yet approved)
Rindopepimut (not yet approved)
Talimogene laherparepvec (T-VEC)
Nivolumab (Opdivo)
Pembrolizumab (Keytruda)
Toca 511 & Toca FC (vocimagene amiretrorepvec and flucytosine)
Trabedersen (not yet approved)
Gliadel (carmustine implant)
Regorafenib (Stivarga)
Valproic acid (Depakene)

Make an impact

As a cure has not been found for Glioblastoma, research progression continues to thrive. With future advancements in the field of cancer, there are high hopes of finding more suitable treatments and even cures for Glioblastoma.

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Sources referred:

"Glioblastoma - Overview - Mayo Clinic". Mayoclinic.Org, 2023, https://www.mayoclinic.org/diseases-conditions/glioblastoma/cdc-20350148. Accessed 17 July 2023.

"Types Of Brain Tumors". Gliadel.Com, 2023, https://www.gliadel.com/patient/types.php?utm_source=bing&utm_medium=cpc&utm_campaign=Unbranded_Brain_Cancer_Condition&utm_term=is_brain_tumor_a_cancer&gclid=0155a055ff97161792b3c424b0f34373&gclsrc=3p.ds&. Accessed 17 July 2023.

"Astrocytes: Anatomy, Location, And Function". Verywell Health, 2023, https://www.verywellhealth.com/astrocytes-anatomy-4774354#:~:text=Astrocytes%20are%20star-shaped%20cells%20found%20in%20the%20brain.,transmitted%20within%20the%20cell%20body%20of%20the%20astrocyte. Accessed 17 July 2023.

Davis, Mary. "Glioblastoma: Overview Of Disease And Treatment". Clinical Journal Of Oncology Nursing, vol 20, no. 5, 2016, pp. S2-S8. Oncology Nursing Society (ONS), doi:10.1188/16.cjon.s1.2-8. Accessed 17 July 2023.

What is epigenetics? (2022) Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/genomics/disease/epigenetics.htm (Accessed: 17 July 2023).

"Glioblastoma: Symptoms, Causes, Treatment & Prognosis". Cleveland Clinic, 2023, https://my.clevelandclinic.org/health/diseases/17032-glioblastoma. Accessed 17 July 2023.

"Glioblastoma—Unraveling The Threads To Make Progress". National Cancer Institute, 2017, https://www.cancer.gov/news-events/cancer-currents-blog/2017/glioblastoma-research-making-progress. Accessed 17 July 2023.

Fisher, Jacob P., and David C. Adamson. "Current FDA-Approved Therapies For High-Grade Malignant Gliomas". Biomedicines, vol 9, no. 3, 2021, p. 324. MDPI AG, doi:10.3390/biomedicines9030324. Accessed 17 July 2023.

"Treating Specific Types Of Brain Tumors And Spinal Cord Tumors In Adults ". Cancer.Org, 2023, https://www.cancer.org/cancer/types/brain-spinal-cord-tumors-adults/treating/treating-specific-types.html#:~:text=Some%20examples%20include%3A%201%20Brain%20stem%20gliomas%202,plexus%20tumors%205%20Medulloblastomas%20and%20other%20embryonal%20tumors. Accessed 17 July 2023.

"What Are The Options If Your Glioblastoma Recurs?". Verywell Health, 2023, https://www.verywellhealth.com/glioblastoma-recurrence-treatment-options-4784168. Accessed 17 July 2023.

"Deadly Brain Cancer Stopped With New Compound". Medicalnewstoday.Com, 2023, https://www.medicalnewstoday.com/articles/321809#CDK5-inhibitor-stops-tumor-growth. Accessed 17 July 2023.

(No date) CDK5 inhibition resolves PKA/camp-independent activation ... - cell press. Available at: https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30545-X (Accessed: 17 July 2023).

Glioblastoma chemotherapy (no date) moffitt. Available at: https://www.moffitt.org/cancers/glioblastoma/treatment/chemotherapy/#:~:text=The%20most%20commonly%20prescribed%20glioblastoma%20chemotherapy%20medications%20include%3A,both%20medications%20are%20administered%20at%20the%20same%20time (Accessed: 17 July 2023).

"Glioblastoma: Newest Treatments May Help Patients Survive Longer". Everydayhealth.Com, 2023, https://www.everydayhealth.com/cancer/brain-tumor/glioblastoma/experimental-therapies-glioblastoma/#:~:text=There%20are%20three%20main%20reasons%3A%201%20First%2C%20the,stiff%20pudding%20inside%20a%20hard%2C%20closed%20shell.%20. Accessed 17 July 2023.

Photo citations: https://docs.google.com/document/d/1mlUhlJDjqAnH3s8byFcXvb7Ea1n0tGRbbVyKwnloy90/edit?usp=sharing

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