Remembering Senators Ted Kennedy and John McCain Who Both Died on This Day of Glioblastoma; What Are the Treatment Advances?

There is still no cure for glioblastoma, but the standard of care that has been in place for over a decade is starting to shift as evidenced in a number of promising studies and trials.

Glioblastoma: The Perfect Storm

Glioblastoma is a perfect storm of cancer. It grows rapidly and is located in the brain, the most protected part of the body. This means that surgery should be performed swiftly and there are few drugs that can even reach the tumor given the impenetrable blood/brain barrier.

What’s more, the cells are heterogeneous, meaning that each one must be individually targeted to slow tumor growth.

On top of all that, surgery can not remove all of the cancer because of the way the tumor burrows into the brain, so the tumor starts to grow again immediately after surgery.

The average survival rate is 15 months with treatment, and less than six if left untreated according to the National Cancer Institute. And while there is a five-year-survival rate of approximately 6%, those individuals will never be cancer-free and must continue receiving radiation and chemotherapy for the rest of their lives.

Glioblastoma: How it Grows

Dr. Jon Weingart of the Johns HopkinsComprehensive Brain Tumor Center explains that glioblastoma is a grade 4 glioma brain tumor arising from brain cells called glial cells.

The grade refers to how likely the tumor is to grow and spread, with grade 4 being reserved for only the most aggressive tumors.

In the case of glioblastoma, the tumor’s cells are abnormal, and the tumor creates new blood vessels as it grows, explains Dr. Weingart. The tumor may accumulate dead cells in its core.

And at this time, there is little more that is known about glioblastoma.

Despite all the advances in treatment, we still don’t understand what causes GBMs, says Dr. Weingart.

What is known is that glioblastoma is not hereditary, is diagnosed in adults more than children, and is slightly more common in men.

There are studies that have presented evidence which link the tumors to cell phone usage, exposure to radiation, or working in a rubber factory, but little else beyond that is known.

The number of studies and trials focusing on the cause and treatment of glioblastoma have skyrocketed over the past decade though, thanks in part to Sen. Kennedy.

Sen. Edward Kennedy Battles Glioblastoma

Sen. Kennedy shared his brain cancer diagnosis with the public on May 20, 2008, three days after suffering a seizure.

At the time, there were few who knew as much about cancer and had the power to convene the nation’s top oncologists, something Kennedy did three days later when doctors from the top cancer care centers and medical schools in the country flew to Boston or participated by phone in what may still be the most prestigious tumor board assembled in this country.

Opinion at the time was mixed, with some favoring chemotherapy and radiation, while others felt a more aggressive approach was required that would involve surgery to remove the tumor.

Two weeks after that meeting, Kennedy flew from Massachusetts to North Carolina, where he underwent a four-hour operation at Duke University Medical Center.

Dr. Allan Friedman performed that operation , noting it was “successful” and that the politician was awake during the resection, and should therefore experience no permanent neurological effects from the surgery.

Kennedy then returned to his home state where he began receiving radiation and chemotherapy treatment at Massachusetts General Hospital under the supervision of Dr. Larry Horowitz.

When he was diagnosed in May 2008, the best prognosis was that with the aggressive surgery, radiation, and chemotherapy Kennedy had a life expectancy of three to 15 months.

Kennedy rejected that at the time. He passed away on August 25, 2009, 15 months and eight days after first being diagnosed with brain cancer.

The course of treatment Kennedy received, first at Duke and then Mass General, is similar to the treatment that is currently used on patients diagnosed with glioblastoma.

Senator McCain’s Glioblastoma Battle

On July 14, 2017, McCain underwent surgery at the Mayo Clinic to remove a blood clot above his eye. During the course of that procedure, doctors noticed a growth that was later identified as a glioblastoma.

What followed next was almost a mirror image of Sen. Kennedy’s treatment.

Sen. McCain, who was 80 at the time, had surgery to remove to tumor. He underwent chemotherapy and radiation.

There were also a number of differences between the two men at the time of their diagnosis.

A melanoma survivor, McCain had a number of underlying conditions. He also developed diverticulitis that required surgery one month after he was diagnosed with his tumor.

He put on a brave face until the end, but on August 25, 2018 he lost his battle, 13 months after his diagnosis.

The Cancer Genome Atlas

In addition to Kennedy bringing awareness to the disease, research also began in 2006 as part of the The Cancer Genome Atlas.

Glioblastoma was one of the first forms of cancer -along with lung and ovarian – to be researched and examined in the multi-billon-dollar project headed up by the National Cancer Institute.

The goal was to gain a full understanding of how the disease operates and then make the information public so that researchers could use it to develop treatment options.

It was this project that confirmed the most difficult hurdle in treating glioblastoma – no two tumors were alike. And that essentially meant that no two patients had the same form of cancer.

Treatment of Glioblastoma

The biggest breakthrough in the fight against glioblastoma came in 2002 when the FDA approved temozolomide for use in patients.

That is the chemotherapy drug that patients take after surgery and radiation.

It is also one of just five FDA-approved drugs that treat glioblastoma, along with lomustine, intravenous carmustine, carmustine wafer implants and bevacizumab.

The carmustine wafer implants were developed and tested at Johns Hopkins, and in 1996 received FDA approval.

The standard of treatment for a glioblastoma is surgery, followed by daily radiation and oral chemotherapy for six and a half weeks, then a six-month regimen of oral chemotherapy given five days a month, explains Dr. Weingart.

To start, the neurosurgeon will remove as much of the tumor as possible and may implant medicated wafers right into the brain. Developed at Johns Hopkins, these wafers dissolve naturally and gradually release chemotherapy drugs into the tumor area over time.

Then there is temozolomide, which has been used to treat advanced brain cancers since 2013, when it was granted FDA approval. The drug is taken in pill form and works by slowing down tumor growth, notes Dr. Weingart.

And for those patients who are not well enough for surgery, radiation may be used to destroy additional tumor cells and treat tumors, says Dr. Weingart.

Dr Daniel Wahl, professor of radiation and oncology at University of Michigan, notes that the downside to all of this is that there us no cure, just a delay.

Patients with GBM have effective treatment options, there’s four of them: surgery, radiation, chemotherapy, and tumor targeting fields these electric fields that we can use to treat these cancers, says Dr Wahl. But outcomes for these patients are still suboptimal. What I tell my patients is that we have these effective treatments but what they do is they delay the time to when this tumor comes back. Only in absolutely exceptional circumstances would we ever talk about getting rid of one of these cancers a few.

There is also a fifth type of treatment, targeted drug therapies.

One of those options that is on the market and available to individuals who have not responded to other treatments is Bevacizumab (Avastin).

That drug blocks glioblastoma cells from sending requests for new blood vessels. The blood vessels feed and allow tumors to grow.

New Developments in Treating Glioblastoma

Power Outage

There is also a good deal of excitement following a promising study that was published earlier this year in Nature by researchers at Columbia University.

That study focused on finding a commonality in glioblastoma tumors, a difficult task considering their cellular makeup.

In the end, the group successfully came up with four different categories for each tumor based on its core biological feature.

The group then directed its docks on the mitochondrial group, named for the mitochondria which are essentially the battery that powers and charges cells in humans.

And so, a drug that would stop the mitochondria from powering the cell could effectively stop the growth of the tumor.

Cancer Vaccine

Dr. Maria Castro, Professor of Neurosurgery and Cell and Developmental Biology at the University of Michigan, is currently at work at what could essentially be the first vaccine for patients with brain cancer.

There, researchers are infecting mice with a virus that kills some of the cancer cells while also awakening the immune system to fight the disease.

Our therapy is not only cures the animals from their initial cancers, if we give them a second cancer, with no further treatment, these animals will eliminate the second brain cancer, explains Dr. Castro.

And the reason why they can do that is because the treatment elicits what we call immunological memory, so it remembers cancer as a foreign entity. When the cancer comes back, the immune system gets reawakened, eliminates the second cancer.

Those two properties have been successful in animal models and found to be safe, but now comes the difficult transition from animals to humans.

Blinded By The Light

There is also a unique noninvasive, sonodynamic treatment using protoporphyrin that is being developed by researchers at the Ivy Brain Tumor Center at the Barrow Neurological Institute in Phoenix with the biotechnology company SonALAsense.

The drug is received intravenously and travels to the brain where it is metabolized only by glioblastoma cells.

The protoporphyrin is then activated via an ultrasound, which stimulates photodynamic energy from inside the cells.

That energy then essentially tears through the cell and kills it, while leaving behind a fluorescent stain that serves as a tumor marker for surgeons.

This means that there could be a successful removal of a glioblastoma tumor as doctors will see where the cancerous cells have burrowed into the brain thanks to their fluorescence.

That drug is in clinical trials which began in March.

It’s Electric!

Tumor treating fields have proven to be the most effective development though, extending the lives of patients by two years on average.

There’s been a very exciting development of tumor treating fields, which are electrical fields that have been applied to the brain Dr. Suriya Jeyapalan, a neurologist at Tufts Medical Center, previously told Survivor Net.

Dr. Jeyapalan, who was also a member of Sen. Kennedy’s 2008 cancer board, explained that in practice, they’re basically these adhesive pads that connect to a device … and it generates this alternating electrical current.

Patients shave their heads and then have pads taped across their entire scalp for the procedure.

The pressure build-up ultimately causes the cancer cells to split apart, which causes apoptosis.

Dr. Wahl says that at the end of the day, this research should give people hope.

I think what I would like any patient to know is that glioblastoma is a tough diagnosis, but there are effective treatments, and there are more in the pipeline, the standard approaches have not worked into develop new therapies, he notes. And so what we need are new and innovative and exciting ideas for us to study in the lab and then bring to patients.

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