Deadly brain tumors have challenged both Jimmy Carter and John McCain in recent years, but the two American political icons have had hugely different treatment outcomes.
Arizona senator McCain, who died on Saturday, had announced to the world a day earlier that he stopped treatment after a year, while former president Carter was declared cancer free only four months after he started the therapy in 2015.
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How can these two men have such opposite results?
The answer, said Dr. Ezra Cohen, associate director of Moores Cancer Center at the University of California, San Diego, has to do with the specific physical and genetic characteristics involved.
Carter's brain tumor was caused by a metastatic melanoma that began in a distant part of the body of the 39th US president and traveled to his brain. McCain's tumor was a malignancy called a glioblastoma, the most common form of brain tumor.
For the majority of human history, both metastatic melanoma and glioblastoma had similar prognoses. Most patients lived no more than a few years after the diagnosis.
But the arrival of immunotherapy drugs has drastically changed the chances of survival for melanoma.
"Metastatic melanoma, due to immunotherapy, is now on the other end of the spectrum of glioblastoma," Cohen said. "We now see melanoma patients who have been removed from treatment for almost a decade and are still showing no signs of relapse, and we are beginning to think these patients are cured."
Not so for glioblastoma. Survival after diagnosis continues to vary from one to two years.
Why did glioblastoma not see the same progress? Cohen said it all amounts to mutation.
We now see melanoma patients who have been removed from treatment for almost a decade and still show no signs of recurrence
Dr. Ezra Cohen
Melanoma, Cohen noted, has a highly mutated form of cancer, making it one of the most difficult forms to treat as soon as it spreads from its original location. But due to a high rate of mutation, it is also more likely that the body's immune system will detect and respond to melanoma cells.
Mutation only makes it more likely that there are all kinds of abnormal features on the outside of melanoma cells that will recognize the body's immune system as alien and attack.
New "checkpoint" immunotherapies such as Keytruda, the drug that produced the miraculous recovery of Carter, increase the response of the immune system in patients who have misled cancer cells to semi-rest period.
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But other forms of cancer such as glioblastoma have fewer mutations and fewer abnormal features that cause the immune system to alarm. Upgrading the immune system, Cohen noted, does not do much good if it has not adequately detected the cancer.
"Glioblastoma has 100-fold less mutation than melanoma, which makes it less of a target for these drugs," says Cohen.
Although the control point inhibitors who get dramatic results in many cancers have significantly less effect on glioblastoma, some think they may be capable of some change. Although initial studies have shown poor results, some researchers have speculated that what appears to be persistent growth after immunotherapy treatment may actually be the inflammation indicating a strong immune response.
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A large study is currently underway to determine the exact effect of control point inhibitors on glioblastoma, while other smaller studies try to target these tumors based on other unique characteristics they possess.