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What Do We Know about the Brain Cancer Plaguing Sen. John McCain?

An oncology expert discusses treatment options for aggressive glioblastoma

Last night Sen. John McCain’s office announced the maverick politician had been diagnosed with a type of aggressive brain cancer called glioblastoma. This kind of tumor usually arises from star-shaped cells called astrocytes that make up the supportive tissue of the brain. It is particularly difficult to control because it does not grow as a round, well-circumscribed mass—instead, because astrocytes’ main job is to travel among the neurons, it is able to send out fingerlike projections throughout the brain, essentially creating tiny, multiple “highways” that spread malignant cells with extreme efficiency.

McCain’s diagnosis comes days after he had a blood clot removed from above his left eye. A statement from his office said it was “revealed that a primary brain tumor known as glioblastoma was associated with the blood clot.” The McCain family is now assessing treatment options, which “may include a combination of chemotherapy and radiation,” the statement said. This is not McCain’s first experience with cancer: He was diagnosed with melanoma in 2000. The 80-year-old, a Republican who has represented Arizona in the Senate for 30 years, was also a two-time presidential candidate.

Scientific American spoke about McCain’s type of cancer with Nduka Amankulor, a neurosurgeon who specializes in oncology. He is the associate director of neurosurgical oncology at the University of Pittsburgh Medical Center.


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[An edited transcript of the interview follows.]

What is glioblastoma exactly? Glioblastoma is a brain cancer. It’s a primary brain cancer, which means that it originates directly from the brain, and it’s not coming from a different kind of tumor located in another part of the body.

What are its survival rates? The survival rates can vary quite a bit, but in general even with maximum treatment—which involves surgical resection, radiation to the involved part of the brain and also chemotherapy—the average survival rate is about 18 months. So it’s generally a very aggressive type of tumor. Now, depending on the genetic profile of the tumor, patients can live longer, sometimes up to three or four years. But by the same token, if it’s a particularly aggressive tumor, then it’s possible they will live less than a year. There’s a range depending on the glioblastoma.

Several types of immunotherapy for glioblastoma are in late-stage clinical trials. What would make someone a strong candidate for that? It depends on the type of glioblastoma that they find he has. There are some types of glioblastoma that are very responsive to chemotherapy, but those generally happen in younger people. The types of tumor that can be particularly responsive to immunotherapy generally happen in older people, or people who have genetic factors that allow their tumors to acquire a lot of mutations—so that the tumor has a lot of different antigens that are recognized by the immunotherapy. Immunotherapy is certainly a consideration, and something that is an exciting option for the treatment of these tumors, but there are no validated immunotherapy trials that have yielded positive results for this type of tumor.

Why would age make a difference here? Generally tumors that happen in older people have more mutations, and for other kinds of cancers the number of mutations has been found to be related to the response to immunotherapy: Older people can have tumors that have more mutations and sometimes they can be more responsive to immunotherapy but, really, it’s just luck; there’s no hard-and-fast rule about age being related to response to immunotherapy. Sen. McCain’s doctors will likely look at the genetics of his tumor and its mutations, and try to understand whether a personalized treatment option would be a good fit based on what’s driving his particular tumor.

Do most people get their tumors genetically profiled now? It depends on the institution. There’s a basic set of mutational profiling that’s done all around the country but there are certain centers, including ours, that have access to a much wider set of genetic profiling of the tumors. I would imagine that Sen. McCain will have access to a center that will really be able to take a very deep, careful look at all the mutations in his tumor and potentially create a personalized treatment plan based on the presence of its mutations.

What has changed about care for this type of tumor since Sen. Ted Kennedy was diagnosed with it in May 2008? Immunotherapy has really matured a lot since then.But in general, unfortunately there have still been no home runs in the treatment of this tumor.

Sen.McCain has a history of skin cancer. How might that experience influence his care or treatment options? It should not limit his treatments option or affect the type of treatment he gets. The two cancers are probably not related. As we get older, our chance of having all types of cancer increases. Occasionally people have cancer syndromes where they are born with a mutation, where they get cancer early and get multiple kinds of cancers, but I very much doubt that would be the case here. Melanoma is a very common cancer and it’s related to exposure to UV radiation.

What are glioblastoma symptoms? Glioblastoma can present with seizures and headaches; those are the most common symptoms. It can also present with bleeding and with different neurological deficits including weakness, speech difficulties, confusion and difficulty walking—depending on exactly where it originates in the brain.

What do we know about risk factors for developing this form of cancer? There are very, very few risk factors for developing it. The only known risk factor that is common is a history of high levels of radiation. And that’s usually in the context of treatment for a prior cancer in the head and the historical practice many, many years ago of blasting the tumor with radiation—and so there are a few survivors of childhood cancer who then get secondary cancer from radiation. There are also a few genetic syndromes that can lead to glioblastoma, but those tumors usually manifest quite early between the third and fifth decade of life. It appears what Sen. McCain has is a standard, spontaneous glioblastoma that happened later in life.

How often does this type of cancer go into remission? Even after removal of the tumor there are microscopic cells that exist far beyond that area that was removed, and that’s why these tumors come back. With resection of the tumor—surgical removal—and radiation and chemotherapy, the tumors can go into remission. But many times that remission is short-lived—on the order of months—and then the cells that were beyond the region of treatment will begin to regrow again, and often do so more aggressively.