Astrocytoma is a type of brain tumor that affects men more than women. Astrocytomas are highly common in the brain but can also occur in the spinal cord. The World Health Organization (WHO) classifies astrocytomas into four grades based on their size, growth rate, and potential to spread to nearby brain tissue. 

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• Grade I

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The most common type of grade I astrocytoma is pilocytic astrocytoma which is also known as juvenile pilocytic astrocytoma or JPA. Grade I Astrocytoma grows very slowly, usually does not spread, and is considered to be noncancerous. Pilocytic astrocytomas typically occur in children and teens and make up 2% of all brain tumors.

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• Grade II

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Grade II astrocytoma is also called diffuse astrocytoma. This tumor grows slowly and can spread. Diffuse astrocytoma doesn’t have a well-defined edge, which can make it more difficult to remove completely. It occurs most often in adults between the ages of 20 and 40 years.

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• Grade III

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Grade III astrocytoma is also called anaplastic (malignant) astrocytoma. These high-grade tumors grow fast and can spread to other parts of the brain and spinal cord. Anaplastic astrocytoma occurs most often in adults between the ages of 30 and 50 years and accounts for 4% of all brain tumors.

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• Grade IV

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Grade IV astrocytoma is also called glioblastoma multiforme (GBM) and is the most aggressive brain tumor. It is most commonly found in adults between the ages of 50 and 80 years, and more common in men, and it contributes to 23% of all primary brain tumors.

Symptoms

An astrocytoma can be either asymptomatic (usually in the early stages) or symptomatic. Some of the common symptoms are: 

• Personality changes as anxiety and confusion

• Headache

• Nausea

• Vomiting 

• Memory loss 

• Seizures

• Changes in mental status

• Visual problems

• Communication problems like difficulties in understanding or expressing language or both

• Motor impairments. 

Astrocytoma is often associated with other diseases such as Li-Fraumeni syndrome (Tp53 syndrome), Turcot-Lynch syndrome (DNS mismatch repair loss), Neurofibromatosis (NF) type 1 & 2, and Tuberous Sclerosis Complex (TSC).

Diagnosis

Astrocytomas can be diagnosed by various imaging modalities such as Magnetic resonance imaging (MRI) and Computerized tomography (CT) scans. Imaging gives clarity about the size, location, and characteristics of tumors within the brain, it may also provide guidance for future surgical procedures. and Biopsy, an invasive procedure that involves removing a small part of the tissue from the tumor to determine the type and grade of the tumor helps in the confirmation of diagnosis as well as guides the treatment.

Treatment

There is no known prevention for astrocytoma. The treatment regimen depends on the grade of malignancy, anatomical site, age, and general condition of the patient. The treatment may comprise active surveillance only, maximal safe surgical resection followed by active surveillance, and/or fractionated radiotherapy, chemotherapy, and targeted therapy. Supportive or adjunctive therapy serves to alleviate the clinical symptoms of tumors and adverse effects of the conventional treatment methods. A multidisciplinary approach is crucial for planning and execution of the treatment; the team of clinicians includes a neurosurgeon, a radiation oncologist, a medical oncologist, and a neurologist.

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Low-grade astrocytoma, especially those classified as WHO grade-I are usually benign and non-infiltrative, hence, are mostly treated by maximal surgical resection, failing which (when the tumor is situated in a critical anatomical site), chemotherapy and radiotherapy are employed. The high-grade astrocytomas necessitate a more aggressive approach, such as a combination of two or more therapeutic strategies.

Surgery

Surgery can either be a conventional craniotomy or stereotactic craniotomy and is performed for two reasons – maximal debulking of tumor and to obtain a biopsy specimen. The extent of resection (EOR) of a tumor relates positively to the length of progression-free survival (PFS) and overall survival (OS) of the patient. Low-grade astrocytomas are routinely treated by supratotal resection. Additionally, a ventriculoperitoneal (VP) shunt or an external ventricular drain (EVD) may be used to drain out excess ECF and lower the raised ICP. 

Radiation therapy

Intensity Modulated Radiation Therapy (IMRT), and Stereotactic Radiotherapy are routinely used. The advanced radiotherapy techniques which include Proton Radiotherapy, and Carbon Ion Radiotherapy (CIRT) have the advantage of better tissue penetration and cause less collateral damage to the surrounding healthy brain tissue.

Chemotherapy

Chemotherapy can be systemic (oral or parenteral/intravenous administration of the drug), intrathecal (the drug is placed directly into the CSF), or regional (the drug is inserted into an organ or a body cavity). The drugs commonly used in treating malignant astrocytoma are: 

• Nitrosoureas: Carmustine  and Lomustine  and Nimustine  

• Combination Regimens: PCV – Procarbazine + CCNU + Vincristine and TPCH – Thioguanine + Procarbazine + Hydroxyurea

• Microtubule Inhibitors: Vincristine 

• Topoisomerase Inhibitors: Irinotecan, Etoposide, and Teniposide 

• Temozolomide: a newer alkylating agent, has achieved better PFS rates than PCV in randomized studies

• Angiogenesis Inhibitors: Angiostatin and Endostatin 

• Signal Transduction Inhibitors: Tamoxifen

Targeted immunotherapy

The recent immunology-based cancer therapies (most of them are still under trial) which achieve on-site drug delivery are: 

• Gene Therapy: foreign, therapeutic genetic substance (DNA/RNA) is administered directly into the tumor cell via a nanoparticle or an oncolytic immunogenic virus (special tumor-destructor virus). 

• Dendritic Cell Vaccine Therapy: it employs a vaccine made from antigens (Ag) and antigen-presenting cells(APC) against the mutant IDH enzyme. 

• Pd-1/Pd-L1 Pathway Inhibition these harmful, tumor-initiated cellular pathways hamper the human body’s natural immunity to resist/fight cancer, hence, their inhibition is necessary. The FDA-approved-PD-1 antibodies are Nivolumab, Pembrolizumab, and Cemiplimab, and the FDA-approved PD-L1 antibodies are Atezolizumab, Aduvumab, and Duravulumab. 

Supportive therapy

It aims to alleviate the clinical symptoms and adverse effects of conventional cancer therapy. It mainly comprises – Anticonvulsants (levetiracetam, phenytoin, and carbamazepine) for controlling seizures, and corticosteroids (dexamethasone) to reduce swelling around the tumor, and osmotic diuretics (mannitol) to lower the raised ICP by reducing the ECF volume in the brain.