Malignant Brain Tumor Review

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Introduction   

Malignant brain tumors are aggressive cancers that exhibit rapid growth and can spread to other parts of the brain and spinal cord [1]. Cancerous tumors, which form when genes regulating cell growth malfunction, can develop anywhere in the body, including the brain and spinal cord, and may displace or disrupt healthy cells depending on their origin type [1]. 

The World Health Organization (WHO) developed a comprehensive grading tumor grading system, ranging from 1 to 4, to help assess tumor aggressiveness and determine the most appropriate treatment strategies [13]. In some cases, malignant brain tumors may be a combination of different tumor types or may originate from various areas within the brain. Malignant tumors, classified as grade 3 or 4, exhibit rapid growth rates and a high likelihood of recurrence after treatment. In contrast, benign (non-cancerous) tumors, often graded as 1 or 2, exhibit slow growth and carry a lower risk of recurrence [2] [3].  

A brain tumor, also known as an intracranial tumor, is an abnormal mass of tissue resulting from uncontrolled cell multiplication [4]. There are more than 150 distinct types of brain tumors, categorized into primary and metastatic tumors [4]. Primary brain tumors start within the brain itself, while most malignant brain tumors are secondary cancers that originate in another part of the body and metastasize to the brain [5]. 

The prevalence of brain tumors underscores the need for general medical providers to have a fundamental understanding of their diagnosis and management. Common types include intracranial metastases from systemic cancers, meningiomas, gliomas, and glioblastomas—the latter being the most common and aggressive malignant primary brain tumor [5]. 

Symptoms of malignant brain tumors vary depending on their size and location but often include severe, persistent headaches; seizures; persistent nausea, vomiting, and drowsiness; mental or behavioral changes like memory problems or personality shifts; progressive weakness or paralysis on one side of the body; and vision or speech difficulties [6]. 

Advancements in treatment have led to new frontiers involving cell-based and targeted therapies. Active and adoptive immunotherapies, stem cell therapies, and gene therapies have evolved due to extensive preclinical and clinical studies. Clinical trials have validated the effectiveness of antibody-based immunotherapies—such as bevacizumab—when combined with standard care [7]. Preclinical data also highlight the potential of vaccines, engineered cells, and gene therapies in preventing tumor recurrence [8]. 

A comprehensive understanding of the most common brain tumors—including their diagnosis, oncologic management, and handling of medical complications—is crucial. The new Cryosection Histopathology Assessment and Review Machine (CHARM) classification of gliomas incorporates both molecular features and histology to provide an integrated diagnosis, offering better prognostic insights [9]. Understanding these aspects is essential for improving patient outcomes and developing tailored treatment approaches for both new and recurrent gliomas. 

Primary Brain Tumors 

Primary brain tumors originate within the brain or its immediate surroundings. They include glial and non-glial types and may be benign or malignant [4]. Glial tumors arise from the brain’s supportive tissues, while non-glial tumors develop within other structures of the brain, such as nerves, blood vessels, or glands [10]. Glial tumors originate in the brain’s supportive tissues, which play a critical role in nourishing, insulating, and protecting neurons. Their presence can significantly disrupt these essential support functions [10].  

As glial tumors grow, they can interfere with nutrient supply, waste removal, and signal insulation, leading to a range of neurological deficits. This disruption can affect motor control, cognitive functions, sensory processing, and even alter personality, depending on the tumor’s location and the extent to which it compromises these supportive tissues [10]. 

Metastatic Brain Tumors 

Metastatic brain tumors originate in other parts of the body, such as the breast or lungs, and spread to the brain often through the bloodstream [11]. Metastatic brain tumors affect one in four cancer patients, with around 150,000 new cases per year [11] [12]. For example, up to 40% of individuals with lung cancer will develop metastatic brain tumors [4].  

While the prognosis for these tumors has been poor, recent advances in diagnostic techniques, surgical interventions, and radiation therapies have improved survival rates and quality of life. 

Tumor Staging 

The World Health Organization (WHO) classifies tumors based on their microscopic histological features, indicating whether they are malignant or benign [13]. Key characteristics of high-grade, malignant tumors include: 

• A high degree of malignancy 
• Rapid growth and aggressive behavior 
• Extensive infiltration into surrounding tissues 
• High likelihood of recurrence 
• Prone to necrosis (tissue death) Top of Form 

Types of Malignant Tumors 

Most malignant brain tumors originate from the glial tissue, which provides support to the brain’s nerve cells [4]. These tumors, gliomas, have types based on the cells they arise from. Examples include. Brain tumors include gliomas, which account for 78% of all cases [4]. 

Gliomas develop from glial cells, which are the supportive cells of the brain, including astrocytes, oligodendrocytes, and ependymal cells [14].  

Symptomology 

Symptoms of brain tumors vary depending on their location, size, and rate of growth. Common signs include persistent headaches that may worsen over time, often more intense in the morning or severe enough to awaken the individual at night [6] [15]. Blurred or double vision can occur due to increased intracranial pressure.  

Patients experience nausea, vomiting, and loss of appetite, leading to weight loss and dehydration [6][15]. Cognitive impairments such as memory loss, difficulty concentrating, confusion, and problems with thinking, speaking, or articulating thoughts may arise when tumors impact cognitive processing regions [6][15]. Mood or personality changes are also common, as tumors affecting areas responsible for emotion and behavior can result in irritability, depression, or altered social interactions [6] [15][16].  

The sudden onset of seizures or convulsions is a significant symptom, caused by abnormal brain tissue disrupting normal electrical activity [17].  

Additional symptoms may include weakness or paralysis affecting one side of the body, loss of balance or dizziness, hearing changes, facial numbness or tingling, swallowing difficulties, and speech difficulties like slurred speech or trouble finding the right words [6] [15][16]. The presence of these symptoms warrants prompt medical evaluation, as early detection and treatment of brain tumors can improve outcomes and prevent further complications. 

Astrocytoma 

Astrocytomas are a significant subset of brain tumors originating from astrocytes—the star-shaped glial cells that provide structural and metabolic support to neurons in the central nervous system (CNS) [18]. Astrocytomas affect the brain but can also involve the cord [18]. Glial tumors constitute about 60% of brain tumors, with astrocytomas among them [18]. These tumors pose a considerable clinical challenge due to their prevalence and the serious morbidity and mortality they cause across all age groups. Early diagnosis and prompt treatment are crucial for improving patient outcomes.  

Astrocytomas originate from astrocytes, star-shaped cells that provide structural support to the brain [18][19]. They can develop in regions of the brain but develop most often in the cerebrum. While they are more frequent in middle-aged men, astrocytomas can also occur in children, where they are low-grade [18][19]. In adults, astrocytomas tend to be more aggressive [14][18]. 

The exact cause of astrocytoma remains unknown, with exposure to ionizing radiation being the only well-established risk factor [18]. Children who receive prophylactic radiation therapy for conditions like acute lymphocytic leukemia have an increased risk—up to 22 times—of developing CNS malignancies within 5 to 10 years after treatment [20] [21]. In addition, radiation therapy for pituitary adenomas has been associated with a 16-fold increased risk of glioma development [22].  

Researchers have studied associations with risk factors such as fields (e.g., from phones), head injuries, or exposures, but we have no evidence supporting these links [23]. A minority of cases show a familial predisposition in genetic conditions like Turcot syndrome, Li-Fraumeni syndrome (p53 mutations), and neurofibromatosis type 1 (NF1). Notably, about 66% of low-grade astrocytomas demonstrate p53 mutations [24] [25]. 

Understanding the epidemiological patterns of astrocytoma is important for identifying risk factors and enhancing early detection efforts across different populations. Researchers observe minimal racial differences in astrocytoma incidence [18]. In terms of gender, pilocytic astrocytomas show no significant dominance, but studies indicate a slight male predominance in low-grade astrocytomas, with a male-to-female ratio of 1.18:1 [18] [26]. Anaplastic astrocytomas show a more pronounced male predominance, with a male-to-female ratio of about 1.87:1 [18] [26]. Age-wise, pilocytic astrocytomas are more common in the first two decades of life [18] [26]. Astrocytomas affect individuals between 30 and 40 years old, accounting for about one-fourth of cases [26]. For low-grade astrocytomas, 10% of patients are younger than 20 years, 60% are between 20 and 45 years, and 30% are older than 45 years [27]. For grade III astrocytomas (anaplastic astrocytomas), the average age at diagnosis is around 40 years [26][27]. 

The tumor’s local effects are due to multiple mechanisms, including direct invasion of surrounding brain tissue, leading to disruption of normal function, and competition with normal tissue for oxygen and nutrients, resulting in hypoxic injury [28]. The tumor microenvironment—comprising interactions with other cell types, extracellular matrix components, and blood vessels—also contributes to tumor progression. Molecular alterations such as genetic mutations and changes in signaling pathways, particularly the PI3K/AKT/mTOR and MAPK pathways, promote uncontrolled cell growth and survival [28] [29]. These mutations can disrupt normal cellular processes like cell cycle regulation, apoptosis, and differentiation. 

The complexity of these mechanisms contributes to the heterogeneity and therapeutic resistance often seen in astrocytoma cases [18][19]. Astrocytomas vary in aggressiveness, ranging from slow-growing pilocytic astrocytomas to malignant glioblastomas [18] [28]. The mass effect of the tumor can lead to various clinical signs and symptoms due to increased intracranial pressure and localized brain dysfunction. Understanding the molecular and cellular mechanisms underlying astrocytoma development is essential for advancing diagnostic methods and developing targeted therapies. 

Oligodendroglioma 

Originates from cells responsible for producing the fatty myelin sheath covering nerves [5]. Oligodendroglioma is a primary central nervous system (CNS) tumor that originates in the brain or spinal cord [30]. Diagnosis requires the identification of two specific genetic alterations: a mutation in the isocitrate dehydrogenase (IDH) gene and a co-deletion of the short arm of chromosome 1 and the long arm of chromosome 19, known as a 1p/19q codeletion [31]. Accurate diagnosis involves the surgical removal of tumor tissue for analysis by a neuropathologist. 

Pathologists classify these tumors into two grades based on their characteristics: 

• Grade II Oligodendrogliomas: These are low-grade tumors that are slow growing and invade nearby normal tissue [30]. They often develop over several years before symptoms become apparent, leading to a delayed diagnosis. 

• Grade III Oligodendrogliomas (Anaplastic Oligodendrogliomas): These are tumors that exhibit rapid growth [30].  

On magnetic resonance imaging (MRI), oligodendrogliomas appear as a single tumor with well-defined borders, often show contrast enhancement, and may exhibit surrounding swelling [30]. Researchers do not know the exact cause of oligodendrogliomas. Cancer arises due to genetic mutations that alter cell function, increasing the growth and spread of cancer cells [32]. Oligodendrogliomas form in the white matter and the cortex, the outer layer of the brain, but they can develop anywhere within the CNS. Scientists name them for their resemblance to oligodendrocytes, cells that support and insulate fibers. Although these tumors can spread to other areas of the CNS through cerebrospinal fluid (CSF), such occurrences are uncommon, and they do not often metastasize to other organs [30][33]. 

Symptoms depend on the tumor’s location. The most common sign is a seizure, experienced by about 60% of patients before diagnosis [30]. Other symptoms may include headaches, cognitive difficulties, weakness, numbness, and problems with balance and movement [30]. 

Oligodendrogliomas develop in people aged 35 to 44 but occur at other ages [30]. They are more prevalent in males and are rare in children [30]. In the United States, an estimated 14,950 people live with this tumor, and a population-based analysis of 244,808 glioma patients found that non-Hispanic white individuals have the highest incidence and lowest relative survival rates across most histology [34]. 

Ependymoma 

Ependymoma is a primary central nervous system (CNS) tumor originating in the brain or spinal cord [35][36]. Diagnosis involves the surgical removal of tumor tissue for analysis by a neuropathologist to ensure accuracy. Doctors classify ependymomas into three grades based on characteristics and behavior. Grade I ependymomas, which are low-grade tumors, and are less aggressive. Subependymomas, a subtype of grade I ependymomas, can arise in the brain or spine and are more common in adults than in children [35][36].  

Grade II ependymomas are also low-grade and slow growing but have a greater recurrence than grade I tumors, if not removed [35][36]. Subtypes of grade II ependymomas include myxopapillary ependymoma, which arises in the spine and is more common in adults, and conventional grade II ependymoma, which can occur in the brain or spine and varies in frequency between adults and children depending on the molecular subtype [35] [36]. Grade III ependymomas occur most often in the brain but also the spine [36].  

The location and molecular features of each ependymoma subtype can provide more accurate prognostic information than grade alone. According to the 2021 World Health Organization (WHO) classification, the main subtypes are supratentorial ependymoma (ZFTA fusion-positive and YAP1 fusion-positive), posterior fossa group A (PFA) ependymoma, posterior fossa group B (PFB) ependymoma, spinal ependymoma, spinal ependymoma with MYCN amplification, myxopapillary ependymoma, and subependymoma [35]. On magnetic resonance imaging (MRI), ependymomas appear as one or more well-defined masses that often enhance with contrast, making them appear brighter on the scan [36]. 

The exact cause of ependymomas remains unclear. Researchers have not identified the specific mutations causing ependymomas, but they do occur in individuals with certain genetic conditions, such as Neurofibromatosis Type 2 [37]. Ependymomas can form anywhere within the CNS but often develop near the ventricles of the brain and the central canal of the spinal cord. Rarely, they may form outside the CNS, such as in the ovaries [38]. These tumors originate from radial glial cells, one of the three types of glial cells that support the CNS [37[38]. 

Ependymomas can spread outside the CNS; however, they can disseminate to other areas within the CNS through cerebrospinal fluid (CSF) [37][38]. Symptoms depend on the tumor’s location. Brain ependymomas may cause headaches, nausea and vomiting, and dizziness. Spinal ependymomas may result in back pain, numbness and weakness in the arms, legs, or trunk, and sexual dysfunction or urinary and bowel problems [35]. 

Ependymomas affect both children and adults [39]. Tumors located in the lower part of the brain (posterior fossa) are more common in children, while spinal ependymomas are more prevalent in adults [37] [38[39]. They occur more often in males than females and are most common among non-Hispanic white individuals [39]. Almost 20,000 people in the United States are living with this type of tumor [35]. 

Glioblastoma Multiforme (GBM) 

Glioblastoma is the most common malignant brain tumor, accounting for 47.7% of all brain and central nervous system (CNS) tumors [4] 40]. The incidence rate is 3.21 per 100,000 individuals, with a median diagnosis age of 64 years [4][40]. It is more prevalent in men than women [4][40]. The prognosis remains poor, with 40% of patients surviving the first-year post-diagnosis, and only 17% surviving into the second year [4][40].  

Risk factors associated with GBM include prior therapeutic radiation, decreased susceptibility to allergies, impaired immune response, and certain hereditary cancer syndromes such as Li-Fraumeni syndrome and Lynch syndrome [41][42]. Symptoms vary depending on the tumor’s location but may include persistent headaches, double or blurred vision, vomiting, loss of appetite, mood and personality changes, cognitive difficulties, new-onset seizures, and gradual onset of speech difficulties [42]. 

Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, is the most aggressive and invasive form of glioma—a type of tumor arising from glial cells in the brain [4][42]. Characterized by rapid growth and extensive invasion into nearby brain tissue, GBM carries a poor prognosis [4][42]. Glioblastomas (GBMs) can develop either as primary tumors (de novo) or progress from lower grade astrocytomas, occurring in the cerebral hemispheres, especially in the frontal and temporal lobes [4][42]. 

Treatment of GBM presents several challenges due to its localization within the brain, inherent resistance to conventional therapies, and the limited regenerative capacity of brain tissue. Malignant cells tend to infiltrate adjacent brain areas, and the tumor’s disrupted blood supply can inhibit effective drug delivery. In addition, tumor capillary leakage often leads to peritumoral edema and intracranial hypertension [48]. Patients may also experience tumor-induced seizures and neurotoxicity from treatments directed at gliomas [48]. 

Diagnosis involves sophisticated imaging techniques to determine the tumor’s location. Providers use computed tomography (CT) scans and magnetic resonance imaging (MRI) as diagnostic tools. Intraoperative MRI can assist during surgery for tissue biopsies and tumor removal, while magnetic resonance spectroscopy (MRS) examines the tumor’s chemical profile. Conventional MRI is essential for studying astrocytomas; higher-grade tumors enhance with contrast and may show central necrosis [43]. MRI spectroscopy provides information on the tumor’s chemical composition, aiding in non-invasive tissue sampling, though it is not as definitive as a biopsy [44]. Functional MRI (fMRI) identifies brain regions activated during specific tasks, which is crucial for surgical planning to avoid critical areas responsible for speech, motor function, or vision [44]. 

After detection, a neurosurgeon obtains tumor tissue for biopsy, and a neuropathologist examines it to assign a name and grade based on the World Health Organization (WHO) classification. Histological grading assesses features such as cytologic atypia, anaplasia, mitotic activity, microvascular proliferation, and necrosis [27]. Grade II tumors exhibit cytologic atypia with variations in nuclear shape, size, and hyperchromasia [4][45]. Grade III tumors show anaplasia and increased mitotic activity, indicating higher cellularity [4][45]. Grade IV tumors, like GBM, demonstrate microvascular proliferation and necrosis, signifying the most aggressive behavior [4][45]. 

Other Types of Malignant Brain Tumors 

• Medulloblastomas: These tumors develop in the cerebellum and affect children. Although they are high-grade, they respond well to radiation and chemotherapy. 
• Oligodendrogliomas: Derived from the cells responsible for producing myelin, the protective sheath around brain nerves. These tumors can vary in aggressiveness. 
• Hemangioblastomas: Slow-growing tumors that often occur in the cerebellum. Originating from blood vessels, they can become large and are associated with cyst formation. Hemangioblastomas are most common in adults aged 40 to 60, and men more often develop them than women [4]. 
• Rhabdoid Tumors: These are rare, aggressive tumors that can spread throughout the central nervous system. They can also occur in other parts of the body, such as the kidneys. Rhabdoid tumors are more common in young children but can also occur in adults [4]. 

Pediatric Brain Tumors 

Pediatric brain tumors differ from those seen in adults, as they often arise from different tissues. Treatments that may be well-tolerated by adult brains, such as radiation therapy, can hinder normal brain development in children younger than five years old [4] [10]. These co-factors approach to treating pediatric brain tumors is more complex and nuanced. 

The Pediatric Brain Tumor Foundation reports that almost 4,200 children in the U.S. receive a brain tumor diagnosis each year, and 72% of those affected are younger than 15 years old [4] [46]. The majority of pediatric brain tumors develop in the posterior fossa, the region at the back of the brain [47]. Children with brain tumors present with symptoms of hydrocephalus (fluid buildup in the brain) or neurological deficits, such as impaired movement in the face or body. 

Certain types of brain tumors are more common in children than adults. The most frequent pediatric brain tumors include: 

• Medulloblastomas 
• Low-grade astrocytomas (pilocytic astrocytomas) 
• Ependymomas 
• Craniopharyngiomas 
• Brainstem gliomas 

Each type requires specialized treatment approaches, tailored to the child’s age and the tumor’s location and characteristics, to preserve as much normal brain function and development as possible. 

Incidence of Malignant Brain Tumors in Adults 

The incidence rate of all primary malignant and non-malignant brain and other central nervous system (CNS) tumors in the United States stands at 24.83 cases per 100,000 people, amounting to 453,623 cases overall [49]. This includes a rate of 6.94 per 100,000 for malignant tumors (126,729 cases) and 17.88 per 100,000 for non-malignant tumors (326,894 cases) [49].  

Incidence rates are higher in females (27.85 per 100,000) compared to males (21.62 per 100,000) [49]. In 2023, experts expect 94,390 new cases of primary brain and other CNS tumors, comprising 26,940 malignant and 67,440 non-malignant cases [49]. 

In the United States, the incidence and mortality rates of primary brain and other central nervous system (CNS) tumors vary by age group. Among children aged 0-14, the incidence rate is 5.44 cases per 100,000 people, totaling 17,136 cases over five years, with an annual average of 3,427 new cases. Experts estimate 3,920 new cases in this group for 2023 [49].  

In adolescents aged 15-19, the incidence rate rises to 7.51 per 100,000, contributing to a five-year total of 7,863 cases, averaging 1,573 per year. Within this age range, 2,679 cases are malignant, with an incidence rate of 2.56 per 100,000, while 5,168 are non-malignant, at 4.95 per 100,000. Experts project around 1,310 new adolescent cases for 2023. Brain and CNS tumors among adolescents accounted for about 2% of all cases reported from 2015 to 2019 [49]. 

The adolescent and young adult (AYA) population, ages 15-39, has an incidence rate of 12.00 per 100,000, yielding a five-year total of 64,238 cases [49]. Non-malignant tumors occur more frequently in this group, with an incidence rate of 8.79 per 100,000 compared to 3.21 for malignant tumors. Experts project 11,660 new AYA cases in 2023 [49]. Among adults aged 40 and above, the incidence rate reaches 44.97 per 100,000, totaling 372,249 cases over five years [49]. Non-malignant tumors (33.33 per 100,000) occur more than malignant ones (11.64 per 100,000). Experts project 79,340 new cases in this age group for 2023 [49]. 

The average annual mortality rate for primary malignant brain and CNS tumors from 2016 to 2020 was 4.42 per 100,000, resulting in 86,030 deaths [49]. This included a higher rate in males (5.40 per 100,000) than in females (3.57 per 100,000), with an annual average of 17,206 deaths [49]. Lifetime risk estimates show that an individual in the U.S. faces a 0.6% chance of developing a primary malignant brain or CNS tumor and a 0.50% chance of dying from it [49] [50].  

Males have an elevated lifetime risk of developing such tumors at 0.70% and a 0.56% chance of dying from them, compared to females, who have a 0.54% risk of diagnosis and a 0.42% risk of mortality [49]. 

Brain Tumor Causes 

Brain tumors arise when damage occurs to specific genes on a cell’s chromosomes, causing them to malfunction [1]. These genes regulate the rate at which the cell divides (if it divides at all) and repair genes that fix defects of other genes, as well as genes that could cause the cell to self-destruct if the damage is beyond repair. In some cases, an individual may be born with partial defects in one or more of these genes. Environmental factors may then lead to further damage. In other cases, the environmental injury to the genes may be the only cause. It is not known why some people in an “environment” develop brain tumors, while others do not. 

Once a cell is dividing, internal mechanisms to check its growth are damaged, the cell can grow into a tumor. Another line of defense may be the body’s immune system, which could detect the abnormal cell and kill it. Tumors may produce substances that block the immune system from recognizing the abnormal tumor cells and overpower all internal and external deterrents to its growth.  

A growing tumor demands more oxygen and nutrients than the local blood supply, which is meant for normal tissue, can provide [51]. Tumors can produce substances called angiogenesis factors that promote the growth of blood vessels [51]. The new vessels that grow increase the supply of nutrients to the tumor, and the tumor becomes dependent on these new vessels. Researchers study this area, but they must expand their efforts to translate this knowledge into potential therapies. 

Testing and Diagnosis of Brain Tumors 

The diagnosis of brain tumors relies on advanced imaging techniques and specialized tests to identify the presence, location, and characteristics of the tumor. A combination of imaging modalities and, in some cases, biopsy is essential to establish a precise diagnosis. 

Key diagnostic tools include: 

• Computed Tomography (CT) or Computed Axial Tomography (CAT) Scan: CT scans provide detailed cross-sectional images of the brain using X-rays. These scans can detect abnormalities such as masses, bleeding, and swelling, helping to identify the presence of a brain tumor. 
• Magnetic Resonance Imaging (MRI): MRI is a powerful imaging technique that uses magnetic fields and radio waves to generate detailed images of brain tissue. MRI is often the gold standard for diagnosing brain tumors due to its superior resolution compared to CT scans.  
• Intraoperative MRI: Surgeons use intraoperative MRI during brain tumor surgery to guide tissue biopsies and assist in tumor removal. This real-time imaging allows the neurosurgeon to confirm the extent of the tumor resection while minimizing damage to surrounding healthy tissue. 
• Magnetic Resonance Spectroscopy (MRS): MRS is a non-invasive imaging technique that examines the chemical composition of a tumor, providing additional information about its nature. MRS can help differentiate between several types of brain lesions, including tumors, infections, and inflammation, based on their metabolic profiles. 
• Positron Emission Tomography (PET) Scan: PET scans use a radioactive tracer to assess metabolic activity in brain tissues. This technique is useful in detecting recurrent brain tumors and differentiating between tumor growth and treatment-related changes, such as radiation necrosis. 

Biopsy 

In many cases, a definitive diagnosis requires a biopsy, where the surgeon removes a small tumor sample and examines it under a microscope. A neurosurgeon performs the biopsy, and a pathologist analyzes the tissue sample to determine if the tumor is benign or malignant. The pathologist also assigns a grade to the tumor, which helps guide treatment decisions based on the tumor’s aggressiveness.  

• Stereotactic Biopsy: This less invasive procedure uses imaging guidance (MRI or CT) to target and remove a small piece of the tumor for examination [4]. Surgeons often perform this procedure when the tumor lies in a difficult-to-reach area or when a full resection is not feasible. The combination of imaging techniques and biopsy provides a comprehensive understanding of the tumor’s characteristics, allowing for more tailored treatment planning.  

Brain Tumor Treatment and Care 

Treatment of brain tumors, whether primary or metastatic, benign, or malignant, involves a combination of surgery, radiation therapy, and/or chemotherapy. Clinicians tailor treatment choices to each patient based on factors like tumor location, size, type, and the patient’s overall health. Radiation and chemotherapy often treat malignant, residual, or recurrent tumors, but each therapy carries potential risks and side effects that require careful consideration. 

Surgery 

Surgical removal of the tumor is often the first-line treatment, as complete or near-complete resection can improve outcomes. The goal of surgery is the preservation of essential neurological functions such as speech, mobility, and cognition [56]. In some cases, a drain (external ventricular drain, or EVD) relieves fluid buildup in the brain during recovery. 

• Surgical Navigation Systems: Introduced in the 1990s, these computerized systems use pre-operative imaging to guide the neurosurgeon during tumor resection. They enhance precision and reduce risk, making it possible to remove previously inoperable tumors. However, they rely on pre-surgical scans and cannot account for brain movements during surgery. Researchers develop new techniques using intraoperative MRI and ultrasound to overcome this limitation. 

• Intraoperative Language Mapping: For tumors affecting language areas of the brain, a patient may remain awake during surgery. Surgeons map the patient’s language function during the operation to identify tumor areas they can remove without impairing speech or comprehension. This technique is useful for large, dominant-hemisphere gliomas. 

• Ventriculoperitoneal Shunting: Some patients may develop hydrocephalus, a condition where cerebrospinal fluid (CSF) accumulates in the brain, causing increased pressure [4]. To relieve this pressure, a shunt diverts the fluid to the peritoneal cavity in the abdomen. If the shunt becomes blocked, symptoms such as headaches, vomiting, and confusion may occur [4]. 

• Endoscopic Third Ventriculostomy (ETV): In some cases, surgeons perform an ETV to bypass fluid obstructions, eliminating the need for a permanent shunt [53]. 

Radiation Therapy 

Radiation therapy uses high-energy X-rays to destroy cancer cells and shrink tumors [52].  

Standard External Beam Radiotherapy uses targeted radiation beams to treat the tumor while sparing surrounding healthy tissue. Newer delivery methods, such as intensity-modulated radiotherapy (IMRT), allow for even more precise targeting and reduce the risk of long-term radiation damage [54]. 

• Proton Beam Therapy: A type of radiation therapy that uses protons to deliver radiation to the tumor with minimal impact on nearby healthy tissues.  

• Stereotactic Radiosurgery (SRS): Techniques such as Gamma Knife, CyberKnife, and Novalis deliver focused radiation beams to the tumor from multiple angles, minimizing damage to surrounding tissues [55].  

Chemotherapy 

Physicians often use chemotherapy to treat certain pediatric tumors, lymphomas, and some oligodendrogliomas. For the most malignant primary brain tumors, chemotherapy can improve survival in 20% of patients, although predicting who will benefit is challenging [4]. Some physicians may opt not to use chemotherapy due to its potential side effects, which can include nausea, immune system suppression, and lung scarring. 

Chemotherapy works by damaging cancer cells, which are less capable of repairing themselves than normal cells [57]. However, resistance to chemotherapy can occur when tumor cells survive treatment or when the drugs cannot penetrate the brain due to the blood-brain barrier [57]. Researchers are exploring methods to improve drug delivery, such as disrupting the blood-brain barrier or injecting chemotherapy directly into the tumor. 

Chemotherapy-Imbued Wafers: The FDA approved these wafers in 1996. Surgeons implant them during procedures, allowing the wafers to release chemotherapy drugs into the tumor site, which reduces systemic side effects [58].  

Laser Interstitial Thermal Therapy (LITT) 

LITT is a newer, less invasive technique used to treat smaller brain tumors in hard-to-reach areas. Providers insert a catheter into the tumor and use laser energy to destroy the tumor tissue. While promising, the long-term efficacy of this treatment is still under investigation [59]. 

Investigational Therapies 

Researchers are studying emerging therapies for tumors with poor prognoses under conventional treatment. These investigational treatments include: 

• Immunotherapy: Aims to enhance the body’s immune system to better recognize and attack tumor cells. 
• Anti-Angiogenesis Therapy: Seeks to block the formation of new blood vessels that tumors need to grow. 
• Gene Therapy: Attempts to repair or modify the genes involved in tumor growth. 
• Targeted Toxin Therapy: Involves attaching toxins to molecules that specifically target tumor cells, sparing normal tissue. 

Comprehensive Care 

Malignant brain tumors pose complex challenges due to their aggressive nature and the intricate involvement of central nervous system structures. Originating from genetic mutations that disrupt normal cell growth, these tumors vary in type and location, with primary malignant tumors often forming in the brain and secondary tumors spreading from other body regions. The World Health Organization (WHO) tumor grading system, which ranges from grade 1 to 4, assists clinicians in assessing tumor aggressiveness and selecting appropriate treatment approaches [13]. Common malignant brain tumors include glioblastomas, astrocytomas, oligodendrogliomas, and ependymomas, each presenting unique characteristics and requiring targeted therapeutic interventions [5]. Symptoms often vary based on tumor size and location, ranging from headaches and seizures to personality changes and cognitive deficits [6].  

Advancements in treatment, including immunotherapy, gene therapy, and precision-targeted radiation, offer new hope, with tools like intraoperative MRI and functional mapping enhancing surgical precision and preserving neurological function [4][30]. Continued research and an understanding of molecular pathways driving these tumors are essential to improving diagnosis, treatment options, and survival outcomes for individuals affected by malignant brain tumors. 

Successful brain tumor treatment requires a multidisciplinary approach, involving neurosurgeons, oncologists, radiologists, and other specialists. The goal is to tailor treatment to the individual’s specific tumor characteristics while minimizing damage to normal brain tissue and preserving quality of life. Continuous advancements in technology and research are paving the way for more effective and less invasive treatment options. 

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