Continuing Education Activity

Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. It remains an incurable disease with a median survival of 15 months and has been classified into wild-type and mutant isocitrate dehydrogenase (IDH) subtypes. The only well-established causative factor is exposure to high doses of ionizing radiation. GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. Formulating a treatment plan requires a multidisciplinary team, including surgical, medical, and radiation oncologists. GBM's gold-standard treatment comprises surgical resection followed by adjuvant radiochemotherapy. Clarifying patients' goals of care is essential as soon as the diagnosis is made, given the poor prognosis even with complete treatment.

This course aims to provide healthcare professionals with comprehensive insights into the current understanding of GBM, including its epidemiology, clinical presentation, diagnostic approaches, and evolving therapeutic strategies. Through this educational review, participants will gain valuable knowledge and practical skills to enhance their ability to effectively diagnose, manage, and support patients with GBM. This activity also highlights the role of the interprofessional team in optimizing care for affected patients.

Objectives:

• Identify the epidemiology and pathophysiology of glioblastoma multiforme.

• Assess strategies for the clinical and radiological evaluation of glioblastoma multiforme.

• Implement the therapeutic algorithm for the management of glioblastoma multiforme.

• Apply effective strategies to improve care coordination among interprofessional team members to facilitate positive outcomes for patients with glioblastoma multiforme.

Introduction

Glioblastoma multiforme (GBM) comprises glioma's most malignant and pervasive subtype.[1] GBM is the most common primary brain tumor in adults, accounting for 45.2% of primary malignant brain and central nervous system (CNS) tumors. Magnetic resonance imaging (MRI) shows poorly circumscribed marginal enhancement. Central hypointensity in T1 due to necrosis and peripheral hyperintensities in T2/FLAIR sequences due to edema are salient MRI features. MR spectroscopy has a choline peak. The definitive diagnosis is made through a histopathological examination that reveals poorly differentiated pleomorphic cells with predominant astrocytic differentiation. High mitotic activity, microvascular proliferation, and necrosis are hallmark features of GBM. GBM also shows glial fibrillary acidic protein (GFAP), vimentin, and S100 positivity with varying Ki-67 indices. Testing is also recommended for the presence or absence of GFAP, IDH mutation V status, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. 

GBM remains an incurable disease with a median survival of only 15 months.[2] Only 5.5% of patients survive 5 years post-diagnosis.[3] GBM has been classified into isocitrate dehydrogenase (IDH) wild-type and mutant variants. IDH variants bear the cytosine-phosphate-guanine (CpG) island methylation phenotype (G-CIMP).[1] 

IDH wild types, arising de novo, constitute almost 90% of all GBM. They are usually observed among cohorts older than age 55 years. Histologically, they comprise the giant cell, gliosarcoma, and epithelioid cell subtypes. They are associated with mutations in the epidermal growth factor receptor (EFGR), telomerase reverse transcriptase gene (TERT), or O-methylguanine DNA methyltransferase (MGMT).[4] IDH-mutants arise from precursor diffuse or anaplastic astrocytoma. They are associated with ATRX and TP53 mutations and typically affect younger patients. They comparatively have longer median survival rates.[4][5]  

Etiology

The only well-established causative factor implicated in GBM is exposure to high doses of ionizing radiation.[6] A study showed a high prevalence (17%) among patients with a history of prior therapeutic irradiation.[7] The latency between irradiation and the development of GBM varies from a few years to several decades. Studies have shown a low risk of gliomas with allergies and atopic diseases.[8] Also, less than 10 years of use of anti-inflammatory medications is associated with a protective effect of GBM in the short term.[9] There is no substantial evidence of GBM association with lifestyle factors like smoking, alcohol consumption, drug use, or exposure to N-nitroso compounds.[10] Studies have shown that using mobile phones does not increase the risk of developing GBM; however, the association with long-term use needs further confirmation.[11]

Epidemiology

GBM is the most prevalent malignant CNS tumor.[12] GBM accounts for almost 15% of all primary CNS tumors and 50% of all malignant primary CNS tumors.[13][14] The annual incidence of glioblastoma is approximately 35 per million individuals, with a male-to-female ratio of 1.6:1.[13][15] Based on the 2013 Central Brain Tumour Registry of the United States (CBTRUS) report, the average annual age-adjusted incidence rate (IR) of GBM is 3.19 per 100,000 population.[12][14] The incidence in the pediatric population is 0.85 per 100,000.[14]  

GBM is primarily diagnosed in adults with a median age of 64 years. The incidence increases with age, peaking at 75 to 84 years and dropping after 85 years. This incidence rate among cohorts aged 65 and older has been shown to increase to 130 per million individuals.[13] The number of cases is expected to increase, given the increase in the aging population in the United States. It comprises almost half of the annual 24,000 new cases of primary malignant brain tumors in the US.[16] 

Pathophysiology

GBM shows immune escape features and high tumor heterogeneity.[6] Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM.[17][18] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations.[19] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course. Due to different triggering mutations and critical mutations in the GBM stem cells, GBM is classified into primary tumors arising from neural stem cell precursors and secondary tumors arising from mutations in mature neural cells like astrocytes. Alteration in genetic information, causing expression and suppression of genes compared to their physiological levels in healthy brain cells, leads to cellular and extracellular matrix changes, resulting in a multiform number of biochemical forms. Hence, the name multiforme is due to the extent of genotypic diversity.[20]

Dedifferentiation theory postulates astrocytes, neural stem cells (NSCs), and oligodendrocyte precursor cells (OPCs) as the cellular origin of glioblastoma. In contrast, the hierarchical model (stem cell theory) postulates cancer stem cells (CSCs) for the same.[21] Four glioblastoma subtypes described as per the “omics” approach from the data of The Cancer Genome Atlas (TCGA) Research Network include the following:

• Classical- showing amplification of chromosome 7 and loss of chromosome 10                                                                     
• Neural- expressing GABRA1, SLC12A5                                                                                                             
• Proneural- showing IDH1 point mutation                                                                                                 
• Mesenchymal- having loss of CDKN2A and NF1 but bearing mesenchymal markers like CHI3L1, MET, and CD44 [21]

The proneural and neural subtypes arise near the subventricular zone, mesenchymal and classical subtypes are distal to the subventricular zone, and other gliomas occur in the subcortical white matter.[21] N6-methyladenine (m6A), methylation at the sixth nitrogen atom of adenine and regulated by the writers, erasers, and readers enzymes, accounts for the most common form (80%) of post-transcriptional RNA modification observed in GBM.[1]

Histopathology

Histopathology of GBM shows poorly differentiated pleomorphic cells with predominant astrocytic differentiation. High mitotic activity, microvascular proliferation, and necrosis are hallmarks of GBM.[4][22] It is also reported that newly formed vessels may contain multiple Weibel-Palade bodies, usually absent in brain endothelial cells. Vessels may have thrombi that lead to endothelial damage and proliferation. Two patterns of necrotic regions are observed: 1 is a sizeable necrotic area in the center, and the other is multiple small foci surrounded by pseudopalisading features. The first is typically observed in primary glioblastoma, while the second is seen in both primary and secondary varieties.[11] Primary Scherer structures (foci of pseudopalisading necrosis) are also considered pathognomonic for GBM.[23] The molecular pattern includes the IDH-mutant and IDH-wild types that are detected by immunohistochemistry (IHC). GBM also shows positivity to GFAP, vimentin, and S100 with varying Ki-67 indices.[23]

History and Physical

It is essential to gather a detailed clinical history in patients with GBM. Symptomatology depends on the location and size of the tumor and is similar to those produced by any benign or malignant brain tumor. GBM typically presents with progressive neurological symptoms over days to weeks. Due to nonspecific symptoms, which can also occur in infectious, inflammatory, or other disease processes, physicians should have a high index of suspicion for GBM.[11]

The anatomical location of involvement of GBM and their relative incidence are as follows:

• Supratentorial (85%), with the involvement of the frontal lobe seen in almost 25%
• Brainstem (<5%)
• Spinal cord (<5%)
• Cerebellum (<3%) [4]

Incidence and patterns of clinical presentations among cohorts with GBM include the following:

• Intracranial hypertension (30%)
• Motor deficit (20%)
• Epilepsy (20%)
• Altered sensorium (17%)
• Confusion (15%)
• Visual deficit (13%)
• Speech deficit (13%) [4]

Evaluation

MRI brain imaging shows poorly circumscribed, marginal enhancement due to disruption of the blood-brain barrier (see Image. Peripheral Ring Enhancement Pattern of Glioblastoma Multiforme in Contrast MRI Brain). Central hypointensity in T1 due to necrosis and peripheral hyperintensities in T2/FLAIR sequences due to edema are salient MRI features.

Perfusion-weighted imaging (PWI) shows increased cerebral blood flow due to neoangiogenesis and blood-brain barrier disruption. MR spectroscopy characteristically has a choline peak.[4][11] The definitive diagnosis is through a histopathological examination.[24][25] Further testing is also recommended for the presence or absence of GFAP, IDH mutation status, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. 

Treatment / Management

Formulating a treatment plan requires a multidisciplinary team, including surgical, medical, and radiation oncologists. GBM gold standard treatment comprises surgical resection followed by adjuvant radiochemotherapy.[26]

Surgical resection allows the following:

• Cytoreduction
• Definitive histological diagnosis
• Tumor genotyping assay
• Concurrent use of gliadel wafers containing carmustine [5][13]

When feasible, gross total resection (GTR) is recommended over supramaximal resection (STR).[27] GTR, compared with STR, increases 1-year survival by almost 60%, progression-free survival at 1 year by 50%, and 2-year survival by approximately 20%.[28] Maximum tumor volume resection (at least more than 89%) leads to a better prognosis.[28] Resection of the fluid-attenuated inversion recovery (FLAIR) abnormality, in contrast to only contrast-enhanced T1 regions, improves median survival (15 months versus 10 months).[28] 

Systematic review and meta-analysis have shown the relative risk (RR) for overall survival (OS) at 12 months is 1.25, with the number needed to treat (NNT) of 6. The same RR analysis at 24 months is 1.59 with an NNT of 9. There is a significant association between the extent of resection and  OS in patients with GBM.[29] Surgical resection of butterfly GBM conferred improvement in overall survival at up to 6 months compared to biopsy alone.[30] GTR is possible in almost 80% of cohorts with the aid of intraoperative imaging, with improved or stable functional status achieved in almost 80%.[31] Fluorescence guidance resection facilitates the extent of resection (EOR).[32] GTR has been achieved in 75% of cohorts following an awake craniotomy.[33] Awake craniotomy for GBM in eloquent regions is safe and feasible.[34] In recurrence, GTR still advocated for cohorts with good performance status (DIRECTOR trial subgroup analysis).[5][35]

The level of evidence advocating resections for GBM in the current literature is as follows:

• Level II: 7%,
• Level III:66%,
• Level IV: 11%
• Level V: 16% [36]

The level of evidence for cytoreductive surgery for GBM includes the following:

• Maximal cytoreductive surgery in new supratentorial glioblastoma- Level II
• Biopsy, STR, or GTR is suggested depending on medical comorbidities, functional status, and location of tumor- Level III
• Cytoreductive surgery in "butterfly" glioblastoma- Level III
• Cytoreductive surgery for new glioblastoma in older individuals- Level III
• Role of advanced intraoperative guidance in cytoreductive surgery- Level III [37]

Radiotherapy comprises laser interstitial thermal therapy, brachytherapy, gamma knife (GK), stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and proton beam therapy.[32] The "Stupp protocol" is radiation therapy combined with temozolomide (TMZ).[32] Proton therapy (PT) has been shown to have superior survival benefits compared to 3-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT).[38] The Congress of Neurological Surgeons has recommended tumor-treating fields (TTFields) in their current management guidelines for GBM.[39] SRS is principally justified when surgical intervention is contraindicated.[32] Brachytherapy has also been applied to manage recurrent GBM (rGBM).[40] Hypofractionated RT (HFRT) confers reduced repopulation capacity and improved tumor killing; however, there is an increased risk of radionecrosis (RN).[16] The American Society for Radiation Oncology (ASTRO) recommends HFRT in older patients and cohorts with poor performance status and focal recurrences.[16]

The highly potent alkylating methylating agent N-methyl-N-nitrosourea (NMU) has now been replaced by procarbazine in IDH mutants (activated in the liver by cytochrome P450), and TMZ in IDH wild-type glioblastoma (spontaneously decomposing into the reactive metabolite).[26] Chloroethylating nitrosoureas (lomustine, carmustine, and nimustine) cause DNA adducts in repair-defective tumor cells following O6-methylguanine.[26] TMZ causes p53-independent Bcl-2 decline, stimulating mitochondrial apoptosis, cellular senescence, and necroptosis.[26] Nanoparticles enable the transposition of the blood-brain barrier and the current uses of ligands, thereby conferring precise targeting of chemotherapeutic agents.[41]

According to National Comprehensive Cancer Network (NCCN) guidelines, patients are divided into those aged 70 and older and those younger than 70. Each category is divided into good and poor performance status to form a treatment plan. For patients aged 70 and older with poor performance status, hypofractionated radiotherapy can be given rather than the standard 6-week course with concurrent chemotherapy. Treatment slightly varies in patients with methylated MGMT status as they are shown to have maximal benefit from TMZ, an alkylating agent. Radiotherapy alone is not recommended in these patients, whereas radiotherapy alone is sometimes recommended for unmethylated patients.

Other therapeutic strategies include immune checkpoint inhibitors, cancer vaccines, oncolytic viruses, and chimeric antigen receptor (CAR) T-cell therapy.[17][18] Active immunotherapy might benefit survival in GBM.[42] Molecular targeted therapies are comprised of the following:

• Mechanistic categories include kinase phosphorylation, cell cycle-related mechanisms, microenvironmental targets, and immunological targets.                     
• Key molecular targets include epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), and mitogen-activated protein kinase (MEK).[43] 

Cancer vaccines utilizing tumor and dendritic cells include a major proportion (51%) of the therapeutic strategies. Currently, 51% of vaccines are at phase 1 trials (phase 3 trials only 7%).[18] They are predominantly targeted for recurrent GBM (55%). 

No oncolytic viruses have progressed to phase 3 clinical trials. There have, however, been no reports of encephalitis or death. Though completed, 3 phase 3 trials of viral gene therapy have not been FDA-approved yet. Recent focus is on the role of suicide genes.[44]

Phenotyping alterations within the tumor microenvironment are reflected in the exosomes, a subtype of extracellular vesicles, thereby aiding in diagnosing and monitoring the response to the therapy.[45][46] New avenues in the management of GBM include 3D in vitro animal models, microfluidics, artificial intelligence, and machine learning.[13]

Differential Diagnosis

The differential diagnosis of GBM poses a significant challenge due to its overlapping clinical and radiological features with other brain tumors and non-neoplastic conditions. Discriminating GBM from primary and metastatic brain tumors, infectious and inflammatory processes, and vascular lesions is essential for guiding appropriate management strategies. Accurate identification hinges on a comprehensive understanding of GBM's distinct characteristics alongside nuanced clinical data interpretation and advanced imaging modalities.

Differentials for GBM include the following:

• Single cerebral metastasis
• Primary CNS lymphoma
• Cerebral abscess
• Subacute ischemic or hemorrhagic strokes
• Resolving contusions
• Tumefactive variants of demyelination
• Radiation necrosis
• Vascular malformations
• Toxoplasmosis [4][47]

Surgical Oncology

The goal of surgery is the maximum safe resection to preserve neurological function with improved survival. Since GBM infiltrates surrounding structures, GTR is not always possible.[11] Data from Surveillance, Epidemiology, and End Results (SEER) suggest GTR and STR are associated with improved survival compared to biopsy alone or no surgical intervention. The decision regarding STR vs stereotactic biopsy vs palliative surgery depends on the tumor's location, the patient's age, comorbidities, and care goals. Most of the time, surgical resection is helpful for definitive diagnosis and treatment. Postoperatively, repeat imaging should be done in 24 to 48 hours to assess the extent of resection.

Radiation Oncology

The goal of radiotherapy is to deliver radiation to the tumor and to a margin of radiographically normal tissue to limit the recurrence. The radiation dose is 50 Gy to 60 Gy, delivered over 6 weeks in fractions of 2 Gy.[48][49][50] The most common radiotherapy delivery methods include 3D conformal RT (3D-CRT) and intensity-modulated RT (IMRT).

According to NCCN guidelines, hypofractionated radiotherapy can be recommended in patients with poor performance status or aged 70 or older, irrespective of performance status or methylated status of MGMT promoter, either with or without chemotherapy. Clinical trials are ongoing regarding the role of irradiation in patients with recurrent glioblastoma. More evidence is needed regarding dose, frequency, fractionation, and prior treatments.[51]

Pertinent Studies and Ongoing Trials

Studies have shown patients who had RT doses of 50 Gy to 60 Gy had longer median survival than those who received lower postoperative RT doses.[48][49] Studies have also shown marginal or no benefit of brachytherapy for high-grade gliomas, given their infiltrative nature.[51][52] Studies testing the efficacy of proton and neutron therapy are underway. Radiation sensitizers are the compounds given along with radiotherapy to increase its therapeutic effect. None of these compounds are approved for GBM at present.

Toxicity and Adverse Effect Management

Adverse effects of radiation therapy include radiation dermatitis, neurocognitive toxicity, endocrinopathies, thalamic pain syndrome, meningioma growth, vascular dementia, gait disturbance, urinary incontinence, and ischemic strokes.[53]

Patients receiving concurrent chemotherapy with radiotherapy are at increased risk for leukopenia, thrombocytopenia, and hepatotoxicity. Weekly complete blood counts (CBCs) with differential and liver function tests (LFTs) are recommended. Severe thrombocytopenia can result in withholding of radiotherapy until blood counts are stabilized. Due to lymphopenia primarily affecting the CD4 count, pneumocystis pneumonia prophylaxis should be administered to all patients receiving daily chemotherapy while on radiotherapy.

Medical Oncology

The tumor specimens will be tested for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation (type 1 or type 2). The methylation of the MGMT promoter predicts improved survival and benefit from chemotherapy with alkylating agents.[54] The presence of the IDH 1/2 mutation doesn't guide directly towards specific treatment, but most IDH 1/2 mutant GBM has methylation of the MGMT promotor guiding therapy indirectly. Also, the IDH 1/2 mutation denotes improved prognosis and eligibility for clinical trials.

According to NCCN guidelines, patients with newly diagnosed MGMT-methylated glioblastoma, aged 70 years or younger, should be treated with TMZ and radiotherapy. Trials have shown increased overall survival at 2 and 5 years on continued follow-up in a group who received radiotherapy with concurrent daily TMZ followed by 6 monthly cycles of adjuvant TMZ. Results are similar in patients aged older than 60 and with poor prognostic factors.[55][56][57] Trials were conducted with a combined regimen of TMZ and lomustine with radiation therapy as an alternative option in MGMT-methylated GBM, which resulted in inconclusive results.[58]

Treatment is similar in MGMT-unmethylated glioblastoma patients aged 70 years or younger; however, these patients derive less benefit from TMZ when compared to the methylated group. Standard therapy with TMZ and radiotherapy is recommended if MGMT status is unknown due to the benefit from TMZ with a tolerable adverse effect profile, along with the lack of available alternatives for unmethylated tumors.

In patients aged 70 years or older with good performance status, TMZ and radiotherapy are recommended, but a hypofractionated radiation course can be done rather than the standard course. Twelve cycles of adjuvant TMZ are recommended with hypofractionated radiotherapy rather than 6 cycles in such patients.[59] In patients aged 70 years or older with poor performance status, a single modality, either TMZ or radiotherapy, can be considered to avoid adverse effects and toxicities. MGMT methylation status can help decide between chemotherapy and radiotherapy in such cases.[60]

No substantial evidence exists for alternatives to TMZ for MGMT-unmethylated tumors, although trials have been conducted using a combination of bevacizumab/irinotecan in the past.[61]

TMZ is given orally daily during radiation therapy. Adjuvant treatment starts 4 weeks after radiotherapy, and it is provided for 6 cycles, 5 days daily in a 28-day cycle. Adverse effects include leukopenia, thrombocytopenia, hepatotoxicity, nausea, constipation, and fatigue. Regular CBC results should be checked, and therapy should be held if the absolute neutrophil count (ANC) falls below 1500/μL or platelets below 100,000/μL. 

Prophylaxis for pneumocystis pneumonia (PCP) should be given to all patients receiving concurrent chemoradiotherapy due to the high risk of CD4 T cell depletion by TMZ.

MRI with contrast is recommended within 1 month after completing radiotherapy and then frequently every 2 months during adjuvant TMZ to assess the disease status. Further recommendations, according to NCCN, include an MRI every 2 to 4 months for 2 to 3 years and less frequently after that.

Treatment recommendation guidelines (Class of recommendation: Class I A) include the following:  

• Aged older than 70 - radiotherapy plus concomitant therapy with TMZ followed by adjuvant TMZ with 6 cycles.                     
• Age younger than 70 - hypofractionated radiotherapy plus concomitant therapy with TMZ followed by adjuvant TMZ with 12 cycles.

Age and performance status are recommended while making clinical decisions in GBM patients.[59]

Prognosis

The current standard of care connotes survival of only up to 1.2 years from diagnosis.[17] A median survival time of only 15 months and a 5-year survival of a dismal 7.2% have been reported.[13][26] Age, Karnofsky performance score, and extent of surgical resection are important variables governing prognosis.[13] Young age, good performance status, MGMT methylation, and IDH mutant variant confer improved survival.[62] IDH-wildtype is a more aggressive phenotype.[13] Hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter has a favorable prognosis compared to the telomerase reverse transcriptase promoter (TERTp) variant and chromosome 10 deletion.[4] MGMT gene also governs response to TMZ.[13] 

Low case ascertainment, financial hardship, lack of a dedicated workforce, and weak infrastructure are significant hindrances to improved patient outcomes in low-income nations.[12] There is a need for identifying potent antigens to evoke immune responses to combat GBM.[63] Emphasis is also being given to promoting 'precision medicine,' which focuses on genomic heterogeneity.[64] Radiomics helps predict IDH mutation status and augments precision medicine.[16] 

Complications

The risk of surgical site infection increases with irradiation and multiple surgeries.[65] In addition to complications from chemotherapy and radiotherapy that are discussed above, the disease process itself has complications like recurrence. Recurrence after GTR and adjuvant chemoradiotherapy mainly occurs within the peritumoral brain zone (PBZ) bearing the malignant microenvironment containing tumor cells, angiogenesis-related endothelial cells, reactive astrocytes, glioma-associated microglia/macrophages (GAMs), tumor-infiltrating lymphocytes (TILs), and glioma-associated stromal cells (GASCs).[66] High local recurrence rates (80% to 90%) are observed within 2 cm of the original tumor.[16] GBM is usually associated with pseudoprogression or radionecrosis, which is a subacute worsening of MRI findings that occur within 3 months after the completion of chemoradiotherapy. It is a treatment-related effect. It is essential to distinguish between pseudoprogression and the disease's true progression to avoid abrupt treatment discontinuation. The key feature to determine is that pseudoprogression is usually asymptomatic, and MR spectroscopy characteristically reveals a lactate peak. Acute encephalopathy and radiation-induced malignancies are other notable complications associated with radiotherapy.[32]

Consultations

A multidisciplinary team is recommended, including neurology, neurosurgery, surgical, medical, and radiation oncology physicians. Also, given a poor prognosis, palliative care involvement is suggested from the early stages of diagnosis.

Deterrence and Patient Education

GBM, the most common primary brain cancer, is aggressive. It develops from a type of brain cell called the glial cell. As the tumor grows, it causes pressure on surrounding brain cells, resulting in symptoms like headache, seizures, memory problems, personality changes, vision, language difficulty, weakness, and paralysis. Some of the symptoms may mimic a stroke. It is unknown what causes GBM. Studies report that a history of radiation treatment in early life can increase the risk of being affected.

Deterrence and prevention strategies for GBM primarily revolve around mitigating known risk factors and promoting early detection. While the exact cause of GBM remains elusive, minimizing exposure to potential environmental carcinogens such as ionizing radiation and certain chemicals may reduce the likelihood of developing the disease. Additionally, advocating for lifestyle modifications, including maintaining a healthy weight, regular exercise, and a balanced diet rich in antioxidants, may contribute to overall brain health and potentially lower the risk of GBM. 

GBM is diagnosed by CT/MRI, followed by biopsy for definitive confirmation. If the imaging shows the typical appearance and other characteristics, then the suspicion of GBM is high. A management strategy is formulated after extensive discussion with the patient, family, and medical and surgical oncology teams. The mainstay of treatment includes radiotherapy and chemotherapy after surgical resection. Given its aggressive nature, even with maximal therapy, GBM has poor overall survival and a high rate of recurrence. The survival rate ranges from 1 to 2 years in most patients. Due to high recurrence, frequent follow-ups with repeat imaging are recommended even after completion of treatment.

Fostering awareness about the importance of early symptom recognition and seeking prompt medical evaluation can facilitate timely diagnosis and intervention, potentially improving treatment outcomes for affected individuals. Continued research into the underlying mechanisms of GBM development and the identification of novel preventive measures are essential to effectively combat this aggressive malignancy.

Enhancing Healthcare Team Outcomes

An interdisciplinary team involving nurses, advanced care practitioners, palliative care specialists, and care coordinators, in addition to medical, surgical, and radiation oncologists, is critical in holistically managing patients with GBM. Primary care physicians and neurologists most commonly refer these patients.

Due to the aggressive nature of the tumor, palliative care should be initiated as soon as the diagnosis is made. It is essential to determine the goals of care and patients' wishes throughout the continuum of care. Patients and family members must discuss prognosis to set expectations about the disease. The overall goal is to maintain the patient's quality of life as long as possible with adequate management of their symptomatology. Nevertheless, discussions regarding newer therapeutic avenues and clinical trials should be had in eligible patients.[67]

Developing comprehensive treatment plans tailored to each patient's unique circumstances is essential. This involves considering factors such as tumor location, extent of resection, molecular characteristics, patient preferences, and comorbidities. Strategic decision-making ensures optimal therapeutic outcomes while minimizing adverse effects and maximizing quality of life. Ethical considerations are paramount in GBM care, particularly regarding treatment decisions, end-of-life care, and participation in clinical trials.

Regular interdisciplinary meetings facilitate collaboration, information sharing, and consensus-building. Clear and concise communication ensures that all team members are aligned with treatment goals and plans, minimizing errors and optimizing patient outcomes. Healthcare professionals must collaborate closely to ensure seamless transitions between surgery, radiation therapy, chemotherapy, rehabilitation, and supportive care. Care coordination efforts aim to prevent gaps in care, reduce treatment delays, and improve overall experience and outcomes in patients with GBM.