Both John McCain and Jimmy Carter have contended with brain tumors, but the two political icons have had vastly different treatment results.
The Arizona senator died Saturday after a year in treatment while the former president was declared cancer-free just four months after he started therapy in 2015.
How could these two men have such opposite outcomes?
The answer has to do with the specific physical and genetic characteristics of their tumors.
McCain’s malignancy was a glioblastoma. These cancers originate in the brain and are the most common — and most aggressive — type of brain tumor.
Carter has metastatic melanoma, a type of skin cancer that has spread throughout his body, including to his brain.
Until recently, both glioblastoma and metastatic melanoma had similarly dire prognoses: Most patients didn’t live more than a few years after getting their diagnosis.
But the advent of immunotherapy drugs has dramatically changed the survival odds for those with melanoma.
“Metastatic melanoma, due to immunotherapy, is now on the complete other end of the spectrum from glioblastoma,” said Dr. Ezra Cohen, associate director of Moores Cancer Center at UC San Diego. “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 remains stuck in the one- to two-year range.
Why hasn’t glioblastoma seen the same kind of progress?
Cohen said it all comes down to mutations.
Mutations are common with melanoma, and that makes it one of the toughest forms of cancer to treat after it has spread from its initial location, he said. But having a high mutation rate also makes it more likely that melanoma cells will have abnormal features that the body’s immune system will recognize as foreign, paving the way for a counterattack.
Glioblastoma tumors have fewer mutations, and are less likely to set off the immune system’s 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.
Carter’s recovery came courtesy of an immunotherapy drug called Keytruda. This “checkpoint inhibitor” lifts the brakes that halt the immune system’s initial assault on cancer, allowing the fight to proceed.
So far, the checkpoint inhibitors that are getting dramatic results with many forms of cancer have not worked well against glioblastoma. But some researchers think that may change. They suspect that what looks like continued cancer growth after immunotherapy treatment may actually be the inflammation that indicates a strong immune response.
A large trial is underway to determine the exact effect of checkpoint inhibitors on glioblastoma. Smaller trials are attempting to target these tumors based on other unique characteristics they possess.
Dr. Charles Redfern, an oncologist with Sharp HealthCare’s Laurel Amtower Cancer Institute in San Diego, said it has been difficult seeing some patients benefit from new therapies while others continue to suffer. But he noted that, with melanoma, there were many years of incremental advances before the sudden sea change brought by the latest crop of drugs.
“I have a patient like Jimmy Carter where his disease has pretty much gone into remission,” Redfern said. “We would love to have that same kind of result in glioblastoma.”