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Understanding Stage IV Brain Cancer (Glioblastoma Multiforme) and its Treatment

What is Glioblastoma Multiforme

Glioblastoma Multiforme is the most common and highly malignant brain tumor. It is also called grade 4 astrocytoma as it originates from astrocytes, the nervous system's supportive cells.

Astrocytes perform various roles, such as providing nutrients, structure, and support to neurons, controlling neurotransmission, and keeping the blood-brain barrier maintained. Glioblastomas typically occur in the brain's cerebral hemispheres but may form in almost any brain or spinal cord area. These tumors are mainly malignant, taking into account that the tumor cells proliferate rapidly and can enter the extensive network of blood vessels that support the brain.

Glioblastoma Multiforme is a lethal grade 4 brain cancer that can cause mortality in six months or less following diagnosis if left untreated. Therefore, the patient immediately needs to seek expert medical care because it will impact their overall survival.

Brain cancer is very challenging to treat because:

  • The brain's limited ability to repair itself

  • Movement of malignant cells into surrounding tissues

  • Development of resistance to traditional treatments

  • The disruption of tumor blood supply blocks adequate delivery of drug

  • Seizures resulting from tumor

  • Capillary leakage can cause peritumoral edema (fluid accumulation around the tumor) and intracranial hypertension

Pathophysiology

Malignant cells, due to mutations, have unusual growth, proliferation, and angiogenesis. Stage 4 brain cancer is discovered to have several epigenetic and genetic mutations. Identifying and classifying these transformations will essentially help in understanding the behavior and the reason behind the treatment resistance of the tumor during the clinical course. Because of different triggering and critical mutations in the GBM stem cells, clinical experts categorize glioblastoma multiforme into primary tumors (originating from neural precursor cells) and secondary tumors (resulting from mutagenic changes in astrocytes). Modification in genetic information causes abnormal expression and suppression of genes that lead to changes in the cellular and extracellular matrix, resulting in various biochemical forms of cellular masses. Therefore, cancer gets the title multiforme from its extensive genotypic diversity.

Symptoms of Stage IV Brain Cancer

The most common symptoms glioblastoma patients experience arise from increased pressure in the brain. The pressure rises as the tumor gets bigger and fills up space, pressing healthy brain tissue with the skull. Sometimes a tumor's size grows large enough to obstruct the flow of cerebrospinal fluid, which also leads to pressure buildup in the brain.

Symptoms associated with increased intracranial pressure are:

  • Double or blurred vision

  • Nausea

  • Seizures

  • Persistent headache

  • Lack of appetite

  • Mood and personality instability

  • Inability to focus and learn

  • Difficulty in speaking with gradual onset of cancer

More specific symptoms may vary depending on the tumor's exact location and the physical functions it impacts. Such as, glioblastoma located in or near the motor cortex (area of the brain that controls body movement) will principally affect movement or cause loss of sensation in one side of the body. Tumors that form near the Broca area of the brain would give rise to speech problems.

How Common is Stage IV Brain Cancer

Glioblastoma Multiforme is the commonest and most lethal primary brain tumor type that accounts for almost 54% of all gliomas and 16% of all primary brain tumors in adults. Glioblastomas commonly occur in older adults but can also affect children. GBM in children and adolescents accounts for no more than 15% of the total cases of primary central nervous system (CNS) tumors.

Known Facts, Causes, and Risks Factors

  • GBM is more common in males than females.

  • People older than 50 and of Asian or Caucasian ethnicity are more likely to develop it.

  • A few sporadic familial syndromes are linked with brain tumors.

  • Radiation exposure is one of the major causative factors for brain tumors, such as dental x-rays and ionizing radiation.

  • A greater incidence of brain tumors is seen in people who work on farms and in the petrochemical industry

  • Researchers have found evidence suggesting that the CMV virus plays a role in glioma pathogenesis. Several other viral diseases can provoke cancer development.

Diagnosis

Physical Examination

The doctor evaluates the patient's signs and symptoms through physical observation. They may examine hearing, vision, balance, strength, coordination, and reflexes. Having issues with one or more of these physical abilities may give hints regarding the brain area that the brain tumor could have affected.

Standard Tests

Imaging tests: Advanced imaging techniques can precisely locate brain tumors. Computed tomography (CT or CAT scan) and magnetic resonance imaging (MRI) are two main diagnostic tools. Doctors use magnetic resonance spectroscopy (MRS) to study the tumor's chemical profile. Functional MRI (fMRI) helps define which brain regions are damaged and what problems these damaged areas are causing for the patient.

Testing tissue sample of tumor: A biopsy is usually performed using a needle before or during surgical removal of glioblastoma, depending on the particular location of the cancerous mass. The specimen obtained undergoes laboratory analysis to discover the types of cells and how aggressive the cancer is.

Specialized Tumor Cells Testing

Usually, the tumor cells do not remain at the primary site and instead break free and enter the bloodstream and lymph, settle in different body organs, and modify the disease. This modification is why examining the original biopsies does not yield accurate results. Cancer cells can leave the site even if the tumor is small. Later, some of these cells mutate and become resistant to the standard maximum tolerated dose of chemotherapy.

Silver Cancer Institute and Center for Chronic Disease uses tumor DNA testing to detect the cause behind the brain tumor's growth and mutations for chemotherapy resistance.

New personalized cancer tests are now available at Silver Cancer Institute for:

  • Genomic Cancer Testing - to analyze your circulating cancer cells and detect genetic driver mutations

  • Chemosensitivity Testing - to evaluate which type of chemotherapy will work efficiently for the patient, how a particular patient will react to a specific chemotherapeutic agent, and which is most efficient

  • Natural Testing - to identify which nontoxic and well-tolerated natural substances can restore drug sensitivity in cancer cells and repress resistance to chemotherapy

Personalized genomic brain cancer testing allows Dr. Dean R. Silver to use more precise and revolutionized treatment approaches for brain cancer and enable the patient to take advantage of multiple helpful treatment options at one time.

Prognosis

GBM is a severe neoplasm with a median survival of only three months if left untreated after diagnosis. The way a patient responds to glioblastoma treatment depends on various factors, such as the tumor's location, size, and mass remaining after surgical removal. Additional important factors are the age of the patient and their overall health. Generally, children are more likely to have a favorable prognosis as compared to adults. Surgery is an essential component in managing GBM. Unfortunately, most solid tumors have already metastasized at the time of diagnosis, so surgery does not remove all tumors. As a result, glioblastomas usually recur over time. It is necessary to monitor the patients for tumor recurrence regularly and treat them according to requirements. Many experimental therapies aside from standard care document beneficial results for most patients because every patient is unique and responds well to customized treatments. Therefore, combinations of established approaches and modern therapies aiming to suppress angiogenesis, apoptosis, or cancer cell signaling pathways may provide the best opportunity to make prognosis better.

Treatment

Standard Treatment Options for Brain Cancer

  • Surgical removal of the tumor: The target is to eliminate as much of the tumorous mass as possible. But due to glioblastoma's growth into the healthy brain tissue, doctors cannot ensure complete removal.

  • Chemotherapy: Standard chemotherapy uses drugs to kill brain cancer cells. In most cases, chemotherapy resistance is induced following the use of high-dose chemotherapy in the patient as cancer cells mutate and adapt to the new environment, which is a significant hindrance in chemotherapy usage in clinical practice.

  • Radiation therapy: Cancer cells are killed using high-energy beams, like X-rays or protons. Radiation therapy is often performed after surgery and sometimes in combination with chemotherapy. Radiation therapy and chemotherapy are used as primary treatments in patients who cannot have surgery.

  • Tumor treating fields (TTF) therapy: Doctors use an electrical field to disturb the tumor cells' capacity to multiply and grow. In TTF, adhesive pads are applied to the patient's scalp, and a portable device connected to these pads generates the electrical field.

  • Palliative care: This specialized medical care allows the patient some relief from pain and other severe symptoms of GBM. Palliative care professionals work with the patient, their family, and other doctors to render additional support to complement the ongoing treatment.

Personalized Multimodal Synergistic Treatment

Silver Cancer Institute and Center for Chronic Disease offers a multimodal treatment plan involving personalized patient testing and brain cancer management using different modalities, including:

  • Personalized Genomic Molecular Profiling: Personalized brain cancer testing and treatment at SCI enable every patient to take advantage of a customized treatment plan uniquely tailored for each patient. The measure of circulating tumor DNA cells in the bloodstream predicts how much the tumor has spread, chances of remission, and disease prognosis. By monitoring the circulating cancer cells in your blood, our team will make sure to model the most effective treatment strategy for you.

  • Low-dose Metronomic Chemotherapy: New studies have revealed that high-dose chemo may increase the circulating cancer cells and cause them to spread, leading to chemotherapy resistance and metastasis. Low-dose chemotherapy and additional treatments at SCI can reverse the resistant pathways, offering each patient a higher success rate in their treatment. The chemotherapy is metronomic and genetically targeted to each patient. Not administering the maximum tolerated high dose of traditional chemotherapy eliminates most of the serious side effects.

  • Natural Synergistic Substances: More than 3000 plant species have been proved to have anticancer activity. Utilization of these synergistic and nontoxic natural substances in patients blocks "molecular biomarkers pathways," thus controlling cancer aggressiveness and metastasis.

  • Immunotherapy w/ Checkpoint inhibitors: Solid brain tumor metastasis is a lot more common now than it ever was. Surgical resection and radiation are not adequate, but according to new investigations, combining both with immunotherapy has proven very beneficial. The use of immune checkpoint inhibitors, including PDL-1, PD1, and CTLA–4, when combined synergistically with radiation therapy, demonstrates extraordinary results in inhibiting brain metastasis in patients.

  • Immunotherapy w/ Autologous Whole Tumor Vaccine, Dendritic Cell Vaccine, and Supportive Oligonucleotides (SOT): Personalized vaccines produced against cancer are also available at SCI. These vaccines are precisely made from the circulating cancer cells in the patient's blood and administered to them three times a year or as needed because underlying immunity optimization is of paramount importance.

For more information on stage IV brain cancer and its customized treatment, please call us at 480-860-2030 or visit www.silvercancerinstitute.com.

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