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Written by Ryan Specie, MSc Epidemiology student and CGCC Student Liaison Officer

Case study: The “Maverick” 

In July 2017, the prominent US Senator and war veteran, John McCain, went to Mayo Clinic in Phoenix, Arizona for a routine check-up. McCain told his family doctor that he had been feeling uncharacteristically fatigued, had occasional double vision and felt like his thoughts were foggy. During McCain’s physical examination, his doctor discovered a blood clot above McCain’s left eye and ordered a brain CT scan and MRI to see what may be going on.  

When the medical team received the scans, they called for McCain to return to Mayo Clinic for immediate surgery, where they confirmed the unsettling findings. The blood clot and his odd symptoms were the manifestations of a much more concerning underlying problem. McCain had a glioblastoma, an aggressive, dangerous form of brain cancer. The medical team removed all the cancerous tissue possible during McCain’s surgery and McCain returned home to recover.  

Only 11 days after the surgery, McCain returned to the US Senate floor to deliver one of two decisive votes against an effort to overturn the Affordable Care Act – a policy that had expanded health insurance coverage to millions of Americans. His improbable return to the Senate floor to vote on the bill likely set the course of US healthcare policy for decades. Indeed, the Affordable Care Act endures to this day. It was testament to his resilience, and his willingness to break from his party on certain issues, that earned him the nickname “Maverick”. 

McCain continued to serve in the US senate for several months while receiving radiation and chemotherapy on and off. However, as is typical for glioblastomas, the aggressive cancer returned. Despite advanced treatment and an unbreakable will to “fight” the cancer, McCain’s tumour worsened. In early August 2018, he decided to stop treatment. McCain passed away on 25 August 2018.  

Every year on 8 June, the world marks World Brain Tumour Day to not only raise awareness and understanding of brain tumours but also recognise the resilience of people affected by brain tumours, many of whom will have stories like McCain’s. 

What are brain tumours? 

Like other types of cancer, brain tumours occur when brain cells abnormally and uncontrollably. Like other cancers, brain tumours are also graded according to how fast they grow and how likely they are to return if treated. Grades I and II mean tumours that are “benign” and slow growing, meaning less dangerous and not likely to spread far or return if they are treated or removed surgically. Grades III and IV are called “malignant” and are much more dangerous. They spread quickly and are likely to return if treated. Brain tumours are additionally classified based on location of origin. If the brain tumour started in the brain it is called a primary tumour; if it started elsewhere in the body it is called a secondary tumour.  

Cancer Research UK lists over of brain tumours, with the tumours typically being named by the type of brain cell that became abnormal and cancerous. Brain tumours are sometimes classified into sub-categories as well. For example, “gliomas” are types of brain cancers that are named after the brain cell type, glial cells. For each of the three types of glial cells, there is a for a brain tumour that developed from these specific glial cells – for example, astrocytomas are named after a type of glial cell known as an astrocyte.   

The associated with having a brain tumour can vary based on the location of the tumour and the pressure it puts on the rest of the brain inside of the skull. Particular parts of the brain have specialised functions such as speech, balance and emotion, therefore a tumour growing in that particular location will likely cause symptoms related to its function. Less specific to location, symptoms such as headaches, seizures, drowsiness and vision problems are commonly associated with the increased pressure that brain tumours tend to create on the rest of the brain. 

How many people “beat” this cancer? The answer depends a on a few key factors: the tumour type, the grade, biomarkers (measurable characteristics), location within the brain, the size and shape, and the age of the person and their health up until diagnosis. According to , about 40% of people in England who are diagnosed with a malignant brain tumour will survive for at least one year and 15% of people of the same group will survive for at least five years. As in many areas of cancer research, treatment and diagnosis methods continue to evolve, as well as our understanding of what factors influence a good prognosis versus a bad one. 

Glioblastomas, an especially aggressive variant of brain cancer like the one that John McCain had, are known to have especially poor outcomes. reports that only about five out of 100 people will survive this type of brain tumour for five years or more. These cancers remain one of the most challenging brain tumours to treat, as well as one of the most common. 

Investigating predictive factors for brain tumour survival in England 

In the early 2020s, two faculty members of LSHTM, John Tazare, Assistant Professor and statistical pharmacoepidemiologist, and John Gregson, Associate Professor of medical statistics, collaborated with researchers at University College London Hospitals (UCLH) to study outcomes and predictive factors of people who were diagnosed with glioblastomas. Dr Tazare and I talked via video call to discuss the paper in more detail. 

Dr Tazare was brought onto the project as a consultant in statistics, planning the study’s statistical methods and developing code to make the analysis possible. The UCLH clinicians that approached both Dr Tazare and Dr Gregson were curious to explore what factors related to a longer survival time after being diagnosed with glioblastoma. Factors that predict better survival had been explored in clinical trials, but trials don’t always imitate what happens in everyday clinical care, where people’s treatment plans and decisions are not so structured. The growing adoption of electronic health records in clinical care had made it possible to explore whether patient records were consistent with data found from clinical trials.  

While keeping the patient records secure and de-identified, the team tracked the of 490 patients with glioblastoma. Similar to survival times around the globe, the group found that the 490 patients had a median (middle) survival time of 9.2 months, meaning that half of the participants studied did not, unfortunately, survive past 9.2 months after diagnosis. The group found the following factors were important predictors of better survival:  

• People who were younger (<50 years old)
• People who had “standard” chemotherapy and radiation therapy
• People who had a “debulking surgery” – a surgery to remove as much of the tumour as possible (compared to those who didn’t have surgery)
• People who had a tumour with a marker called “MGMT promotor methylation”. 

Dr Tazare noted that while the study did not bring up any new factors that hadn’t been seen before, having clinical data that matches the trial data can add to our sense of confidence in interpreting the results of clinical trials. He also noted that the relatively new field of electronic health record data studies provides opportunities for researchers and clinicians to try to answer important questions for all types of conditions in novel ways. However, Dr Tazare emphasized that these studies must be planned, designed, and executed well - whilst considering the appropriateness and potential limitations of using secondary data [data not recorded specifically for research]. 

Comparing global outcomes in brain tumour survival 

LSHTM Honorary Research Fellow and collaborator with the LSHTM , Fabio Girardi, and other contributors took a global approach to study brain tumours of all kinds. They used data from the CONCORD-3 study, a multi-national study of over 37 million people in 71 countries looking at 18 different types of cancer between the years 2000–2014 and performed a sub-analysis focused on brain cancer. included 556,237 adults from 59 countries, andbetween the ages of 15-99. Of these individuals who had brain cancer, the type of cancer was divided into 11 categories according to histology – the structure of the brain tumour under the microscope. 

According to their paper, the team were interested to see if brain cancer survival was improving worldwide. Fortunately, this was the case in many countries. To examine survival rates between countries with very different age structures (some countries with very young populations and others with very old populations), they used a measured called the “age-standardised 5-year survival rate”. This means that if each country had the same age structure, what would be the chance that someone survived up to or beyond 5 years after cancer diagnosis? 

They found that the age-standardised 5-year survival rate for two types of brain tumours, diffuse and anaplastic astrocytoma, improved substantially in Canada, multiple countries in Europe, and Australia. They also found that the age-standardised 5-year survival rate for the most aggressive primary brain cancer, glioblastoma, improved notably in all countries between 2000–2004 and 2005–2009, with the exceptions of some European countries and Israel. In addition, Girardi et al. noted “remarkable improvements” in nearly all countries surveyed in the two-year survival from glioblastoma for adults between 40–70 years old.  

Despite these encouraging developments, the in survival were not seen in all areas of the world, drawing attention to important global inequities in brain tumour care.  

The people behind the numbers 

Prior to matriculating into the MSc Epidemiology course at LSHTM, I was a practicing neurological physiotherapist in the US. I worked in a variety of clinical settings, including hospitals, inpatient rehabilitation facilities, and private healthcare clinics, with individuals with all varieties of neurological disorders.  

Some of my most memorable experiences from being a clinician were caring for those with brain cancer, including the daunting glioblastoma. While many may have heard of glioblastomas from famous individuals like Senator McCain, seeing the effects that it has on people and their families is unforgettable. One minute, the person is living a normal life. The next, they receive a devastating diagnosis that rapidly changes their ability to think, talk, walk, and everything in between.  

As we observe World Brain Tumour Day, it is of the utmost importance to remember the people behind the numbers. According to the numbers we can see from these studies and others, the vast majority of individuals who are diagnosed with glioblastoma on this day will not survive two years from now. This is a sobering realisation. 

But it can also be a call to action for global researchers, funders, decision makers, and citizen-advocates. With determined and coordinated action, attention and resources can be concentrated in the search for more effective prevention, diagnosis and treatment of brain tumours. The people behind the numbers deserve it. 

A special thanks to Dr John Tazare for generously giving his time to being interviewed.