Ten years ago, in 2015, I officially started my nursing career. The 22nd of June was my graduation day, and I was looking forward to qualifying. However, another date that same month would become the one forever etched into my life: the 13th of June, the day my father was diagnosed with Glioblastoma Multiforme (GBM), an aggressive and incurable brain tumour.
The diagnosis struck our family like a storm; for me, it was a hurricane. I was newly qualified, full of hope and purpose, and suddenly, I found myself beside my father, who became my first patient. I felt utterly helpless. Treatment options were limited, and the disease progressed rapidly. Within weeks, my father was hemiplegic. Soon after, he had lost the ability to speak and was bedbound.
It took me two years after the events to even begin talking about it, and only now have I been able to truly revisit glioblastoma. In this blog, I reflect on the progress in glioblastoma treatment over the past decade, and current advances and trends in clinical trials.
What is GBM and why is it difficult to treat?
Glioblastoma multiforme (GBM) is the most aggressive and common form of primary brain cancer in adults, characterized by rapid growth and a high degree of resistance to conventional therapies. Around 32% of primary brain tumours diagnosed in England are Glioblastomas. Classified as a Grade IV astrocytoma by the World Health Organization, GBM arises from glial cells and typically affects the cerebral hemispheres, although it can occur anywhere in the brain or spinal cord. .
What are the current standard treatments?
Standard treatment for GBM follows a multimodal approach:
- Surgical resection: Maximal safe removal of the tumour is the first step. Complete resection is often impossible due to the infiltrative nature of GBM, but surgery can still slow down progression and relieve symptoms.
- Radiotherapy: Post-operative radiation therapy is standard to target residual tumour cells. It can also be used on its own if surgery is impossible due to the tumour’s location. Advances in technology made way to new techniques such as Stereotactic radiotherapy (SRT), which can be extremely accurate in directing the narrow beams of low-dose radiation at the tumour, from different angles.
- Chemotherapy: Concurrent or adjuvant Temozolomide (TMZ), an oral alkylating agent, has become standard care since the landmark Stupp protocol trial in 2005.
- Supportive care: treatments to help control symptoms, such as anti-epileptics (to control and prevent seizures), steroids (to reduce brain swelling), and analgesics for pain management.
Despite these treatments, the average glioblastoma survival time today is 12-18 months, with only 25% of patients surviving more than one year, and only 5% of patients surviving more than five years.
However, as bleak as these numbers can be, there is hope in ongoing clinical trials and emerging therapeutic techniques and therapies.
What advances are there in clinical trials and emerging therapies?
1. Immunotherapy: Immunotherapies revolutionised cancer treatment in the last decade. They work by activating the body’s own immune system to fight cancer cells. Different types exist, most used are the checkpoint inhibitors, monoclonal antibodies and cancer vaccines. Unfortunately, these has not been as successful in brain tumours as in other cancers, with one of the main challenges being the blood-brain barrier which prevents many substances and medicines from getting to the brain. Nonetheless:
a) Checkpoint inhibitors: Drugs like Nivolumab and Pembrolizumab, have failed as monotherapies with GBM patients, but have shown limited efficacy in some GBM populations. They are currently still being trialled as combination therapies with radiotherapy, chemotherapy, or other immunotherapies.
b) DCVax-L: A dendritic cell-based cancer vaccine, showed promising survival benefit in a large phase 3 trial when given in combination with TMZ. It offered patients nearly 3 months of additional life on average and have doubled the five-year survival for those with a newly diagnosed glioblastoma from 5.7% to 13%. It is now in the process of being reviewed by MHRA and NICE, before being appraised for potential use on the NHS if approved (Read: .
2. Oncolytic Viruses: are lab engineered viruses designed to selectively infect and kill tumour cells while stimulating immune responses. Examples include:
a) DNX-2401: an oncolytic adenovirus administered as an intratumoral injection with GBM tumours, is being trialled in combination with TMZ or a checkpoint inhibitor like Pembrolizumab.
b) Polio/Rhinovirus Recombinant: also known as PVSRIPO, a genetically engineered version of the live-attenuated Sabin type 1 poliovirus (PVS), had promising results in a phase I trial, and is currently being trialled in a phase II trial to further evaluate its efficacy. Read: .
3. CAR-T Cell Therapy: A type of Adoptive T-cell Therapy (ATC), it works by increasing the number of a person’s own tumour-fighting T-cells. The receptors on the T-cells are called chimeric antigen receptors, or CARs, hence the name CAR-T cell therapy. T-cells are collected from a patient’s blood or tumour and grown in the laboratory. Once there are enough T-cells, they are transfused back to the patient to help their immune system fight the disease. Early-phase trials using CAR-T cells targeting EGFRvIII, IL-13 Ra2 or CSPG4 proteins have shown promise in GBM, although completion of trials is still required to evaluate their clinical safety and efficacy.
4. Tumour Treating Fields (TTF): A relatively new, and non-invasive technique, TTF use alternating electric fields to disrupt tumour cell division. It involves a set of adhesive patches or bandages that hold insulated ceramic discs, called ‘transducer arrays’, onto the patient’s shaved head, forming what looks like a skull cap. TTF is FDA approved in the US, yet to be approved by NICE in the UK.
5. Cannabis Derivatives: There is conclusive evidence that use of cannabis and its products, such as cannabis oil and CBD oil can help with managing treatment side effects for patients with a brain tumour or cancer, such as pain relief and treating nausea and vomiting (cannabis-based drug, Nabilone, has a medical licence and can be legally prescribed for chemotherapy-induced nausea and vomiting). In addition, preliminary studies from the lab suggest that cannabinoid chemicals THC and CBD can stop glioblastoma (GBM) cells from growing, causing them to die and disrupting the blood supply to the tumour cells, however more trials are needed to confirm safety and efficacy. Read: .
Hope for the future
Despite modest progress in improving survival for GBM patients, ongoing clinical trials and technological innovations offer hope. Future success seems to lay likely in combination therapies, personalised approaches, and emerging novelty treatment therapies and techniques.
My father’s treatment included surgery, radiotherapy, and TMZ. He insisted on attending my graduation ceremony before the surgery and we managed to get him out of the hospital for few hours. Hiding his struggles being newly in a wheelchair, I remember him smiling throughout the entire evening. This was the last event he attended. The treatment offered a brief period of stability, but he passed away, peacefully, at home six months later, in December that same year.
As I write this blog, I cannot help but think of all the fathers, mothers, family members and partners, that were taken abruptly from their loved ones upon a GBM diagnosis. All the major events and milestones missed, and the memories never made. As we keep winning battles against cancer across many tumour groups, we are in dire need of a breakthrough with GBM. With no treatment modality being spared, and clinical trials not stopping, I am hopeful it is only a matter of time.
Even now, a decade later, I find myself flinching whenever I come across a GBM diagnosis. It’s personal. It always will be. But a GBM diagnosis cannot continue to equate an imminent death sentence. We cannot allow it.
Further resources
