High Tumor Mutation Burden May Be Linked to Patient Depression

For years, scientists have tried to find a physical biomarker to predict who is at risk for developing depression. When it comes to patients with lung cancer, tumor mutation burden (TMB) may be the answer, according to recent research presented at the 2019 ASCO Annual Meeting.

The Inflammation-Depression Connection

Clinicians measured patients’ TMB to determine if they are likely to respond to immunotherapy agents. This is because it acts as an up-regulator of inflammation, signaling to patients’ bodies that the cancer is a foreign substance that needs to be attacked, explained study author Daniel McFarland, DO, a member of psychiatry and behavioral sciences at Memorial Sloan Kettering Cancer Center (MSK).

“It up-regulates inflammation, and then actually fights against the cancer, which is what immunotherapy does,” McFarland said.

“At the same time, there’s a lot of data to say that inflammation is predictive of developing depression. The idea behind this study is that because you have TMB as an up-regulator of inflammation around cancer, does that inflammation — which is also associated with depression – lead to depression in the scenario of people who have cancer?”

To answer this question, the researchers examined 96 patients being treated for non-small cell lung cancer or small cell lung cancer. About one quarter (24%) of patients met the scoring criteria for depression. TMB tended to be higher in patients receiving chemotherapy and immunotherapy compared to those receiving targeted therapy.

TMB was found to be an independent predictor of depression.

“We looked at something called a multivariate analysis, which basically weeds out all of the other factors involved, like demographics, age, gender, type of lung cancer and treatment type,” McFarland said. “What we found was that TMB was an independent predictor of inflammation.”

Additionally, the researchers found that C-reactive protein (CRP) levels — which is a marker for inflammation – also predicted depression. “Actually, the strength of the association was the same for people who had high TMB as those who had high CRP.” McFarland said.

Helping Clinicians Spot Depression

McFarland said that he hopes these findings — which give clinicians a physical biomarker that may be indicative of depression – will help them identify patients at risk, so that they can find them help.

“I think the main implication of this finding is that there is something biological that could be used to identify which patients may be at risk for depression or have depression,” McFarland said.

“That’s a key piece, knowing that we as oncologists are not always able to identify those patients who are suffering with depression. Getting a little bit of help along the way and looking at the biology — which is something that we’re looking at anyway – could be very beneficial.”

According to previous research, McFarland said, about 1 in 4 patients with lung cancer have clinically significant depression. Not only does the malady affect patients’ quality of life, but it can also affect outcomes, too. For those reasons, it is crucial that providers are able to get ahead of it and have it treated.

“Depression is a very common illness in the population in general, and when you’re dealing with cancer, it’s something that can be modified, treated, and dealt with,” McFarland said. “Just understanding that depression is an issue is really key.”