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Glioblastoma

Humza Khizer

A glioblastoma is a tumor that can grow in the brain or spinal cord. Previously known as glioblastoma multiforme (GBM), this type of tumor forms from astrocytes, which are cells that support nerve cells. 
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Overview

Glioblastoma is the most prevalent primary brain tumor in adults, accounting for 45.2% of primary malignant brain and CNS tumors.1&nbsp;According to the 2013 CBTRUS (Central Brain Tumor Registry of the US) report, glioblastoma&#39;s average yearly age-adjusted incidence rate (IR) is 3.19 per 100,000 population.1 
&nbsp;

Glioblastoma is typically very aggressive, which means it grows and spreads quickly. This is because the tumor can generate its own blood supply, which aids in its growth and spread. Moreover, glioblastoma can easily invade normal brain tissue. Its aggressive nature makes it a highly untreatable ailment with a median survival of 15 months.1

&nbsp;

The tumor can develop at any age, but it is highly uncommon in children, and more prevalent in older individuals. Its incidence rises with age, with a peak between the ages of 75 and 84, and a decline after age 85.2&nbsp;Moreover, men have a 1.57 times higher incidence rate than women.2&nbsp;The tumor more commonly affects white people than black people.2 
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There are two types of glioblastoma based on the tumor&rsquo;s aggressiveness. These include 
&nbsp;

1.<a name="_heading=h.3znysh7"></a> Primary Glioblastoma

This type of tumor is most likely to be aggressive and advances quickly. Patients typically have&nbsp; a shorter life expectancy. Primary glioblastoma accounts for 80% of cases, and is more common in older patients with an average age of 62 years3. Moreover, men are more likely to develop primary glioblastoma 3. 
&nbsp;

2.&nbsp;<a name="_heading=h.2et92p0"></a>Secondary Glioblastoma

This kind of tumor is usually uncommon. It generally begins from a lower-grade, less advancing astrocytoma but progresses to a grade 4 tumor. However, it has a better prognosis than primary glioblastoma. 
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Secondary glioblastoma is typically found in the frontal lobe of the brain and is less necrotic. The tumor most commonly occurs in women compared to men. Moreover, younger patients with a mean age of 45 more frequently develop the tumor3. 
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Signs and Symptoms

In patients with glioblastoma, obtaining a detailed history of symptoms is critical. Symptoms vary according to the locality and size of the tumor. They are similar to those triggered by any benign or malignant brain tumor. 
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Pressure on the brain typically triggers the initial signs and symptoms. Glioblastoma manifests as a series of increasing neurological signs that can last several days to weeks. The following are the most common symptoms of glioblastoma: 
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<ul>
	<li><a href="https://merisehat.pk/disease/absence-seizures">Seizures </a>are the presenting sign in up to 25% of sufferers. They can appear at a later stage of the ailment in up to 50% of patients5</li>
	<li>Persistent <a href="https://merisehat.pk/disease/cluster-headaches">headaches</a></li>
	<li>Vomiting and nausea</li>
	<li>Difficulty thinking</li>
	<li>Alterations in mood or personality</li>
	<li>Double or blurred vision</li>
	<li>Difficulty speaking.</li>
	<li>Loss of appetite</li>
	<li>Memory issues</li>
	<li>Muscle weakness or issues with balance</li>
	<li>Nausea</li>
	<li>Speech issues</li>
	<li>Numbness, or tingling sensation 
	&nbsp;</li>
</ul>

These symptoms are frequently linked to one another. They lead to a detection within weeks or months of their commencement. 
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Causes

Several hereditary and environmental factors have been researched in glioblastoma multiforme, but no risk factor that accounts for a significant percentage of glioblastoma has been diagnosed. The cause of glioblastoma is unknown. It begins similarly to other types of cancers when cells start to advance uncontrollably and develop tumors. This cell advancement can be linked to gene modifications. If you have any of the following characteristics, you are more likely to develop this type of tumor: 
&nbsp;

<ol>
	<li><a name="_heading=h.1t3h5sf"></a> Specific Race</li>
</ol>

Glioblastoma is more prevalent in white people than in Black, Asian, or Indigenous individuals. 
&nbsp;

<ol start="2">
	<li><a name="_heading=h.2s8eyo1"></a> Specific Gender</li>
</ol>

You are more likely to develop glioblastoma if you are a male. 
&nbsp;

<ol start="3">
	<li><a name="_heading=h.3rdcrjn"></a> Specific Ethnicity</li>
</ol>

Glioblastoma is more common in Caucasians than in other ethnic groups. 
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<ol start="4">
	<li><a name="_heading=h.lnxbz9"></a> Specific Syndromes</li>
</ol>

Patients with certain syndromes such as Lynch, Turcot type 1, or Li Fraumeni syndrome have a genetic predisposition to glioblastoma. However, it occurs in a very small percentage of cases (1%).6 
&nbsp;

<ol start="5">
	<li><a name="_heading=h.35nkun2"></a> Genetic Disorders</li>
</ol>

Around 5-10% of cases have a genetic predisposition.7&nbsp;Moreover, rare genetic disorders, such as neurofibromatosis type 1 and type 2, as well as tuberous sclerosis, have been linked to an increased occurrence of glioblastoma.7 
&nbsp;

<ol start="6">
	<li><a name="_heading=h.1ksv4uv"></a> Increased Age</li>
</ol>

As you get older, your chances of developing a brain tumor rise. Glioblastoma is more common in older people than in younger people. 
&nbsp;

<ol start="7">
	<li><a name="_heading=h.2jxsxqh"></a> Exposure to Radiation</li>
</ol>

Individuals who have been exposed to ionizing radiation are at a higher risk of developing a brain tumor. Examples of ionizing radiation involve

<ul>
	<li>Radiation therapy, which is typically used to treat cancer.</li>
	<li>Radiation exposure induced by atomic bombs. 
	&nbsp;</li>
</ul>

<ol start="8">
	<li><a name="_heading=h.z337ya"></a> Ovarian Steroid Hormones</li>
</ol>

According to research, ovarian steroid hormones may play a role in the development of GBM.7 
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Diagnosis

A neurologist may conduct a physical examination, along with taking a complete history. A computed tomography scan (CT) or magnetic resonance imaging (MRI) scan may be conducted initially. The following tests or procedures are used to detect glioblastomas: 
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<h5><a name="_heading=h.yb498nkpz74h"></a>Neurological Exam</h5>

During a neurological exam, information is gathered regarding the patient&rsquo;s signs and symptoms. The doctor may also test the patient&rsquo;s eyesight, hearing ability, coordination, balance, strength, and reflexes. Issues in one or more of these locations may reveal information about the region of the brain that is likely impacted by the brain tumor. 
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<h5><a name="_heading=h.1ci93xb"></a>Imaging Tests</h5>

These allow doctors to determine the size and site of the brain tumor. Various invasive and non-invasive imaging tests may be conducted on patients suspected of having brain tumors. 
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Invasive procedures:

<ul>
	<li>Catheter angiography 
	&nbsp;</li>
</ul>

Non-invasive tests:

<ul>
	<li>Computed tomography (CT)</li>
	<li>Magnetic resonance imaging (MRI) scans 
	&nbsp;</li>
</ul>

CT is useful for emergency imaging, whereas MRI is the ideal standard for brain tumor imaging because of its more advanced anatomical resolution and soft tissue contrast. MRI is frequently employed to detect brain tumors, and a doctor may combine it with other imaging techniques, such as functional MRI and magnetic resonance spectroscopy. 
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<h5><a name="_heading=h.2bn6wsx"></a>Biopsy</h5>

Depending on the specific situation and the locality of the tumor, the doctor may perform a&nbsp; biopsy with a needle prior to, or during, surgery to remove the glioblastoma. The collected sample is then examined in a laboratory to look for the type of cells and their

The specimen of doubtful tissue is inspected in a laboratory. It is inspected to find out the kind of cells and the level of their aggressiveness. 
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<h5><a name="_heading=h.7cysrxcypahz"></a>Staging of Glioblastoma</h5>

All brain tumors are staged on a grade of 1-4. The grade depends on the appearance of the tumor cells and how quickly these cells replicate. A tumor&rsquo;s grade allows doctors to predict its growth and the disease&rsquo;s prognosis.

According to the National Cancer Institute,9&nbsp;the cancer cells that look more normal are termed well-differentiated. Whereas terms such as &lsquo;poorly differentiated&rsquo; or &lsquo;undifferentiated&rsquo; are used for cells that are less normal. 
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<ul>
	<li>Grade 1 - Also called low-grade, it is characterized by well-differentiated cells</li>
	<li>Grade 2 - This grade is characterized by moderately differentiated cells</li>
	<li>Grade 3 - Also called high grade, it is characterized by poorly differentiated cells</li>
	<li>Grade 4 - These tumors look most abnormal and the cells are undifferentiated 
	&nbsp;</li>
</ul>

Grade 1 brain tumors are typically slow growing and less aggressive. Whereas, grade 4 tumors carry a poor prognosis due to their highly aggressive nature. Glioblastoma is classified as a grade 4 astrocytoma tumor.6,7 
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Treatment

Despite numerous international attempts, glioblastoma treatment remains the most difficult task in clinical oncology. Over the last ten years, various treatments have been looked into with very little success.

The primary challenges in glioblastoma therapy are related to the site of the tumor and its complicated and diverse biology. Progression in surgical treatment, radiotherapy, and adjuvant chemotherapy have displayed steady improvements in glioblastoma patients&#39; survival and standard of life, but the outlook remains distressing.

Quality therapy consists of the safest surgical resection possible and simultaneous radiation with temozolomide (TMZ), an oral chemotherapy agent, and then adjuvant chemotherapy with TMZ.5 
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The following are the treatment options: 
&nbsp;

<ol>
	<li><a name="_heading=h.1pxezwc"></a> Surgery</li>
</ol>

The primary component of quality care is surgery. Whenever feasible, the initial step consists of absolute macroscopic surgical removal. Surgical resection is typically recommended for patients under 70 who are in good health and have a tumor that can be completely removed.6

A multidisciplinary team consisting of surgical, medical, and radiation oncologists collaborate to develop a treatment scheme. Maximum surgical removal followed by chemoradiotherapy is the suggested treatment method. 
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Based on the kind of tumor, surgery can accomplish a variety of goals, such as

<ul>
	<li>Reduction of tumor burden</li>
	<li>Management of seizures</li>
	<li>Reversal of neurological deficits</li>
	<li>Introduction of a local therapeutic agent</li>
	<li>Improved quality of life 
	&nbsp;</li>
</ul>

The aim is to remove as much of the tumor as feasible. However, absolute removal is impossible because glioblastoma spreads into normal brain tissue.

Due to this reason, most patients get different treatments following surgical resection to target the remaining cells. The location and eloquence of the active brain region determine the range of surgical resection. Glioblastoma is a generally invasive tumor that cannot be healed fully by surgical resection. Recurrence occurs in about 80% of cases, typically within 2-3 cm of the original lesion&rsquo;s margins.7 
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<ol start="2">
	<li><a name="_heading=h.49x2ik5"></a> Radiation Therapy</li>
</ol>

Following surgery, radiotherapy can be used to kill any remaining tumor cells. Radiation therapy kills cancer cells by employing high-energy beams, for example, X-rays or protons. During radiation therapy, you will be required to lie on a table. Meanwhile, a machine will move around you, directing beams to specific points in your brain. 
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Radiotherapy aims to limit relapse by delivering radiation to the tumor and a margin of radiographically normal tissue. It has been shown to prolong the lives of patients with high-grade gliomas. Brachytherapy and stereotactic radiosurgery are successful therapies for recurrent glioblastoma, but their roles in treating newly diagnosed glioblastoma are unclear. Subgroups of patients who have had a complete gross resection may benefit from stereotactic radiotherapy. 
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<h5><a name="_heading=h.147n2zr"></a>Intensity Modulated Radiation Therapy (IMRT)</h5>

IMRT permits radiation to be delivered to the tumor while minimizing the radiation dose to surrounding normal brain tissue. 
&nbsp;

<ol start="3">
	<li><a name="_heading=h.23ckvvd"></a> Chemotherapy</li>
</ol>

Chemotherapy employs the use of drugs to destroy cancerous cells. Many chemotherapeutic agents have been tried out for their efficacy in the treatment of glioblastoma in order to enhance patient survival. Alkylating agents such as temozolomide or TMZ (methylating agent), carmustine (BCNU), and lomustine (CCNU) have shown some benefits. They are used clinically in most glioblastoma patients. 
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BCNU and CCNU are extremely cytotoxic, and their use results in the early development of resistance, further limiting their utility. As a result, temozolomide is the only quality chemotherapy for glioblastoma patients. Oral administration of TMZ as adjuvant or accompanying radiotherapy is becoming the standard of care for glioblastoma patients, at least in countries where the high cost of TMZ therapy is affordable.

Patients that experience a relapse may need to try a different kind of chemotherapy. Other kinds of chemotherapy are frequently administered intravenously. 
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<ol start="4">
	<li><a name="_heading=h.32hioqz"></a> Tumor Treatment Fields (TTF)</li>
</ol>

A wearable device delivers low-intensity electric fields (TTFs) to the tumor through electrodes placed directly on the scalp. The electric fields interfere with cancer cells&rsquo; growth and multiplication. TTF is typically recommended following the completion of chemoradiation. 
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<ol start="5">
	<li><a name="_heading=h.1hmsyys"></a> Targeted Drug Therapy</li>
</ol>

Doctors may administer targeted therapy in place of chemotherapy. The targeted drugs focus on particular abnormalities in cancer cells that permit them to develop and advance. The drugs target the abnormalities and cause the cancer cells to die.

Bevacizumab (Avastin) inhibits the signals sent by glioblastoma cells to the body that trigger new blood vessel formation and transport blood and nutrients to cancer cells. The drug is often an alternative in patients not responding to other treatments or those experiencing a relapse. 
&nbsp;

<ol start="6">
	<li><a name="_heading=h.41mghml"></a> Wafer Therapy (Gliadel)</li>
</ol>

Doctors implant a biodegradable disc that delivers chemotherapy to any cancerous tissue that remains after surgery. 
&nbsp;

<ol start="7">
	<li><a name="_heading=h.2grqrue"></a> Nanoparticle Therapy</li>
</ol>

Tiny particles deliver chemotherapy directly into the tumor. 
&nbsp;

<ol start="8">
	<li><a name="_heading=h.3fwokq0"></a> Palliative Care</li>
</ol>

Palliative care is also essential for anyone suffering from a serious illness. It includes pain management, dealing with emotions, and other cancer-related symptoms. Palliative care specialists collaborate with the patient, their family, and other medical professionals to support the patient&rsquo;s ongoing care. The aim is to improve their living standard. Doctors can use palliative care with more aggressive treatments like surgery, chemotherapy, or radiation therapy. 
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These treatments may alleviate symptoms and put cancer into remission in a few cases. During remission, symptoms may subside or vanish for some time. Glioblastomas frequently recur. If this occurs, medical professionals may be able to treat it through surgical resection, a different type of radiation, and chemotherapy. 
&nbsp;

<div>9. New Treatments</div>

Clinical trials are underway to test new treatments for glioblastoma. These treatments include: 
&nbsp;

<ul>
	<li>
	Immunotherapy
	</li>
</ul>

Immunotherapy entails using the body&rsquo;s immune system to destroy cancer cells. 
&nbsp;

<ul>
	<li>
	Gene Therapy
	</li>
</ul>

Gene therapy entails repairing faulty genes in order to treat cancer. 
&nbsp;

<ul>
	<li>
	Stem Cell Therapy
	</li>
</ul>

Stem cell therapy entails treating cancer with early cells known as stem cells. 
&nbsp;

<ul>
	<li>
	Vaccine Therapy
	</li>
</ul>

Vaccine therapy entails boosting the body&rsquo;s immune system in order to fight cancer. 
&nbsp;

Researchers are still looking for new ways to treat glioblastoma. For the time being, treatments can alleviate signs and symptoms, and improve one&rsquo;s standard of life. 
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Glioblastoma and its therapies can have an impact on brain function. Mood swings and memory issues are common complications encountered by patients. Most glioblastoma patients must eventually cease working and driving, and may require 24-hour care. Moreover, these changes may contribute to the person feeling nervous or depressed. 
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Glioblastoma, like many primary brain tumors, has an unknown cause. However, certain factors increase the risk of developing glioblastoma. These include 
&nbsp;

<ul>
	<li><a name="_heading=h.111kx3o"></a> Age and Gender</li>
</ul>

The risk of developing a brain tumor rises with age. Glioblastoma commonly occurs in those aged 45-70 years. The mean age of primary glioblastoma is 62 years, while for secondary glioblastoma it is 45 years. Moreover, glioblastoma is more common in men. 
&nbsp;

<ul>
	<li><a name="_heading=h.3l18frh"></a> Exposure to radiation</li>
</ul>

People who have been exposed to ionizing radiation, especially to the head, are at a higher risk of developing a brain tumor.

More prevalent types of radiation, such as electromagnetic fields emitted by power lines and radiofrequency radiation emitted by microwave ovens, have not been demonstrated to raise the incidence of this cancer. 
&nbsp;

It is unknown whether smartphone use raises the chance of developing brain cancer. Some research has discovered a link between smartphone use and a kind of brain cancer known as acoustic neuroma. Many other studies have found no link. Because smartphones are a newer component, additional long-term research is required to fully understand their possible impact on cancer risk. For the time being, if you&#39;re worried about the probable association between cell phones and cancer, doctors advise reducing your access by utilizing a speaker or hands-free device that distances the mobile from the head. 
&nbsp;

<ul>
	<li><a name="_heading=h.206ipza"></a> Genetic Predisposition</li>
</ul>

Certain genetic conditions, such as neurofibromatosis type 1 and 2, Turcot syndrome, and Li-Fraumeni syndrome have been shown to increase the risk of glioblastoma. 
&nbsp;

<ul>
	<li><a name="_heading=h.ymrjb0lekja1"></a> Exposure to Chemicals</li>
</ul>

Exposure to chemicals such as pesticides, vinyl chloride, petroleum products, and synthetic rubber has been associated with an increased risk of glioblastoma. 
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There is no curative therapy for glioblastoma. Several risk factors can raise the likelihood of developing a brain tumor. These include brain radiation therapy and certain hereditary illnesses. 
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<div style="border-bottom:black 1.0pt; border-style:none; border-top:black 1.0pt; padding:11.0pt 0in 11.0pt 0in">
Novel Pharmacological Treatment Options in Pediatric Glioblastoma&mdash;A Systematic Review8
</div>

Childhood glioblastoma is an aggressive brain tumor that has an extremely poor prognosis. Surgery, irradiation, and temozolomide chemotherapy are all standard treatments. However, there are no effective medications for pediatric glioblastoma patients at this time. A team of researchers recently conducted a systematic review of existing novel pharmacological treatment options for pediatric glioblastoma. 
&nbsp;

According to the review, none of the investigated treatments demonstrated any advantage in terms of overall survival or the duration of stable illness.

However, autoimmune-modified treatments as well as further tumor-specific receptor targeting provided encouraging preclinical findings. 
&nbsp;

<a name="_heading=h.3ygebqi"></a>Novel therapy techniques based on molecular biologies, such as immunotherapeutic approaches and pharmacologically susceptible tumor-specific targets, showed encouraging preclinical outcomes. Thus, the review emphasizes the need for further research on such novel treatment approaches. 
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Key Points

<ul>
	<li>Glioblastoma is a highly aggressive form of brain cancer. It is the most prevalent primary malignant brain tumor in adults..</li>
	<li>Due to the tumor&rsquo;s rapid spread, increased pressure on the brain is frequently the initial symptom. This can lead to headaches, seizures, vision problems, and speech issues.</li>
	<li>Although there is no cure, there are therapies that can help alleviate symptoms.</li>
	<li>Experts are unsure what triggers glioblastoma. However, several factors may increase your chances of developing this condition. These include increasing age and exposure to ionizing radiation. 
	&nbsp;</li>
</ul>
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[1] Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol biomarkers Prev  a Publ Am  Assoc Cancer Res cosponsored by Am Soc Prev Oncol. 2014 Oct;23(10):1985–96.

[2] Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors  Diagnosed in the United States in 2009-2013. Neuro Oncol. 2016 Oct;18(suppl_5):v1–75.

[3] Kanderi T, Gupta V. Glioblastoma multiforme. In: StatPearls [Internet]. StatPearls Publishing; 2021.

[4] Urbańska K, Sokołowska J, Szmidt M, Sysa P. Glioblastoma multiforme - an overview. Contemp Oncol (Poznan, Poland). 2014;18(5):307–12.

[5] Davis ME. Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs. 2016;20(5):S2.

[6] Gilard V, Tebani A, Dabaj I, Laquerrière A, Fontanilles M, Derrey S, et al. Diagnosis and management of glioblastoma: A comprehensive perspective. J Pers Med. 2021;11(4):258.

[7] Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU. Glioblastoma multiforme: a review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pacific J cancer Prev APJCP. 2017;18(1):3.

[8] Wyss J, Frank NA, Soleman J, Scheinemann K. Novel Pharmacological Treatment Options in Pediatric Glioblastoma—A Systematic Review. Cancers (Basel). 2022;14(11):2814.