Confronting contradiction

For Jennifer McQuade, M.D., the surprise was a counterintuitive finding that linked obesity with improved survival in male patients with metastatic melanoma.

“We know obesity increases the risk of getting many cancers and is associated with worse survival in many cancers,” she says.

So there were reasons to think – based on the same biologic pathways – metastatic melanoma would be the same, says McQuade, an assistant professor of Melanoma Medical Oncology.

She had difficulty believing the initial study findings.

“At first, I had blinders on and totally missed the obesity paradox,” she says, describing the study’s contradiction to established evidence linking obesity to mortality risk.

She proceeded carefully in examining five subsequent independent cohorts before concluding that, yes, obese males on targeted therapy were more than twice as likely to survive metastatic melanoma at two years compared with normal-weight males.

There were similar results for obese males on immunotherapy, but not on chemotherapy – and not at all for females.

“The disappointment was that I’m a strong believer in a healthy diet and exercise,” says McQuade. “I went into this study looking for evidence to support that cancer patients may be able to influence their outcomes by controlling their weight.”

Instead, now we are examining the biological basis for this obesity paradox.

“One of the biggest things this study demonstrates is the importance of asking the question correctly,” she says. “If you don’t design the experiment well, and you get unexpected results, you don’t know if those results are correct or if you just didn’t ask the question correctly.”