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By Ritika Sakhuja

New Delhi: glioblastoma multiforme (GBM), a grade 4 glioma brain or spine tumor, is one of the most aggressive malignant cancers predominantly found in adults. The median overall survival (OS) of GBM patients is only eight months owing to the highly complex nature of the GBM tumor.

As the cancer is mostly detected when it’s too late for the patient, and chances of survival are bleak, GBM requires invasive treatment that involves surgery, followed by consistent radiation, chemotherapy, medicines, and various forms of experimental immunotherapies. Despite this, GBM displays dismal survival rates of approximately 41.4 percent in the first year following diagnosis, as per the American Cancer Society, and recurrence is mostly inevitable. As this cancer presents itself when it’s too late, and does not have a known cure or cause yet, preventive and proactive measures also seem out of the question.

Experts inform that the incidence of GBM is on the rise in India, with cases propping up even among people in their 20s. Due to the lack of understanding regarding GBM which contributes to the dreaded diagnosis, ETHealthworld spoke with experts to explore the nature of this highly aggressive cancer, the course of treatment for GBM, and the experimental therapies that can be explored as an effective response to GBM. .

The complexities of treating GBM

According to the American Association of Neurological Surgeons, Glioblastoma is the most common malignant brain and other CNS tumors accounting for 47.7 percent of all cases, with an incidence of 3.21 per 100,000 population. The median age of diagnosis is 64 years and it is more common in men as compared to women.

Detailing the symptoms that warrant doctor consultation Dr Anil D’Cruz, Director, Oncology Services, Head and Neck Cancer Specialist, Apollo Cancer Centres, Navi Mumbai said, “GBM is a very aggressive tumor and grows very rapidly. The patient usually presents with headaches and can have double vision, slurring of speech, convulsions, and vomiting when the pressure in the brain increases. All these symptoms need to be evaluated for tumors. The reason for the low survival rate in cases of GBM is because it is an aggressive malignancy which develops in such an important part of the brain that we are not able to operate with clear margins.”

The cure for glioblastoma has remained elusive because it requires complete destruction of the tumor, which is not possible in the case of GBM. GBMs usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. As a Grade 4 cancer, GBM breaks through the blood-brain barrierlimiting radical surgical ablation and systemic chemotherapy, especially at the tumor periphery, causing a small residual tumor that leads to rapid recurrence that eventually kills the patient.

Simplifying the risk of operating on a brain tumor Like GBM, Dr D’Cruz added, “The problem with these brain tumors like GBM is that they occur in the confines of the skull involving a very critical part of the body- the brain. By the time they get discovered, it is very difficult to operate and take out the tumor completely. In most cancers, we normally take out tumors with a clear margin. But if you remove a brain tumor with a clear margin you will lose a part of the normal healthy brain which will therefore have an effect on the quality of life of the patients.”

Adding to the problem detailed by Dr Cruz, Dr Suhas Aagre, Consultant Medical Oncologist and Hemato-Oncologist, Asian Cancer Institute informed, “The problem with this brain tumor is not the grade of the disease but the behavior of the disease. This is one of the most aggressive diseases we have. The site of the tumor is the most important to consider. If the tumor is lodged in a critical part of the brain, the size of the tumor doesn’t matter. Even a small tumor can be a cause for an alarm because even surgery cannot remove the entire tumor completely, as it could lead to long-term issues like paralysis.”

Advancements required in the standard treatment of GBM

The usual course of diagnosing and treating GBM begins with an MRI after a patient displays symptoms of a brain tumor. The MRI shows the first initial suspicions of the disease which is then followed up by a biopsy to confirm the diagnosis. As GBM occurs deep within the brain, biopsying the tumor requires Craniotomy which is a highly invasive surgery that involves opening up the skull. To reduce the additional health burden on the patient, doctors attempt maximum tumor resection at the time of the biopsy. Usually, the patient takes up to two to three weeks to recover from the surgery and then follows up their treatment through radiation therapy along with chemotherapy.

Expressing the need for enhancements in the treatment for GBM, Dr Agre urged, “GBM is a very aggressive disease so the treatment modalities we use and the standard of care provided are generic. We need to go into the molecular level of the disease to understand the disease biology, which may change our perspective in the future. With the current course of treatment, the median survival rate is up to eight months. Hardly five or six patients across the world have been able to survive up to five years after diagnosis.”

GBM is nothing short of a death sentence as of now, making targeted therapies through a comprehensive understanding of the disease is the need of the hour. Relaying this sentiment, Dr Salil Vaniawal, Founder, SN Gene Labs, suggested, “Comprehensive approaches are necessary to gain maximally from promising targeted therapies. Common methods used for critical evaluation of targeted therapies for glioblastoma include novel methods for targeted delivery of chemotherapy, strategies for delivery through BBB and blood-tumor barriers, innovations in radiotherapy for selective destruction of tumors, techniques for local destruction of tumors, tumor growth inhibitors , immunotherapy and cell/gene therapies.”

“To make improvements in glioblastoma therapy, I would suggest controlled targeted delivery of anticancer therapy to glioblastoma through the BBB using nanoparticles and monoclonal antibodies, direct introduction of genetically modified bacteria that selectively destroy cancer cells but spare the normal brain into the remaining tumor after resection , use of better animal models for preclinical testing, personalized/precision medicine approaches to therapy in clinical trials and translation into practice of neurosurgery and neuro-oncology. Advances in these techniques suggest optimism for the future management of glioblastoma,” added Dr Vaniawala.

Experts inform that symptoms that can be attributed to a brain tumor even slightly, should not be ignored and must be tackled with immediate medical intervention. The only way to prolong the duration of survival after the onset of GBM is an early diagnosis that can enable effective treatment before it’s too late. The experts also urged for increased clinical research and comprehensive studies to understand the disease in-depth, as this could offer a better solution that might alleviate the morbidity of a GBM diagnosis.

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