Why John McCain and Jimmy Carter brain tumours had such different outcomes
United States senator died after a year of treatment, whereas former US president beat cancer after four months of therapy; the difference was that McCain had a glioblastoma, whereas Carter had metastatic melanoma treatable by immunotherapy
Deadly brain tumours have challenged both Jimmy Carter and John McCain in recent years, but the two US political icons have had vastly different treatment results.
Arizona senator McCain, who died on Saturday, had announced to the world just a day earlier that he was stopping treatment after a year, while former president Carter was declared cancer-free just four months after he started therapy in 2015.
How could these two men have such opposite outcomes?
The answer, said Dr Ezra Cohen, associate director of Moores Cancer Centre at the University of California, San Diego, has to do with the specific physical and genetic characteristics involved.
Carter’s brain tumour was caused by metastatic melanoma which started in a distant part of the 39th US president’s body and travelled to his brain. McCain’s tumour was a malignancy called a glioblastoma, the most common kind of brain tumour.
For most of human history, both metastatic melanoma and glioblastoma had similarly dire prognoses. Most patients didn’t live more than a few years after diagnosis.
But the advent of immunotherapy drugs has dramatically changed the survival odds for melanoma.
“Metastatic melanoma, due to immunotherapy, is now on the complete other end of the spectrum from glioblastoma,” Cohen said. “We’re now seeing melanoma patients who are nearly a decade from treatment and are still showing no signs of recurrence. We’re beginning to think that these patients are cured.”
Not so for glioblastoma. Survival after diagnosis continues to range from one to two years.
Why hasn’t glioblastoma seen the same kind of progress? Cohen said it all comes down to mutation.
Melanoma, Cohen noted, has a highly mutated form of cancer which has made it one of the toughest forms of to treat once it spreads from its initial location. But having a high mutation rate also makes it more likely that the body’s immune system will detect melanoma cells and respond to them.
Mutation just makes it more likely that there will be all sorts of abnormal features on the outside of melanoma cells that the body’s immune system will recognise as foreign and attack.
New “checkpoint” immunotherapies such as Keytruda, the drug that produced Carter’s miraculous recovery, rev up the immune systems’ response in patients that cancer cells have tricked into semi-dormancy.
But other forms of cancer such as glioblastoma have fewer mutations, and fewer abnormal features that set off immune system alarms. Revving up the immune system, Cohen noted, doesn’t do much good if it has not adequately detected the cancer in the first place.
“Glioblastoma has 100-fold less mutation than melanoma does, and that makes it a poorer target for these drugs,” Cohen said.
Though the checkpoint inhibitors that are getting dramatic results in many forms of cancer have significantly less effect for glioblastoma, some think they may actually be capable of some change. Though initial trials have shown poor results, some researchers have speculated that what looks like continued growth after immunotherapy treatment may actually be the inflammation that indicates a strong immune response.
A large trial is currently under way to determine the exact effect of checkpoint inhibitors on glioblastoma, while other, smaller trials are attempting to target these tumours based on other unique characteristics they possess.