Inflammatory Biomarkers From Lung Cancer, Depression May Predict Survival Outcomes

Patients with moderate to severe depression may have elevated inflammatory biomarkers shown to predict survival in lung cancer, according to recent study results.

Both lung cancer and depression have properties of inflammation, which is the body’s response to injury or infection. Chronic inflammation can damage healthy tissues, cells and organs over time. It may also affect how patients respond to treatments like immunotherapies and targeted therapies, which utilize the patient’s immune system.

Findings from the study, which were published in PLOS ONE, highlight the importance of screening for and treating depression and anxiety in patients with lung cancer.

“For patients and caregivers, it is important that practices and facilities screen their loved one for depression and anxiety,” Barbara L. Andersen, professor of psychology at The Ohio State University in Columbus, said in an interview with CURE. “Screening has been mandated by the Commission on Cancer, so it is important for patients and caregivers to prompt the medical team if screening has not been done. Once screened, it is important for patients (to) take to heart any recommendations for further assessment and provision or referral for treatment for their depression or anxiety.”

The study that Andersen and colleagues conducted included 186 patients with newly diagnosed stage 4 non–small cell lung cancer (NSCLC) who were screened for depression and anxiety at diagnosis and before treatment began. Researchers then used medical record data from blood draws at diagnosis, abstracting cell counts of neutrophils, lymphocytes and platelets. The counts were used to calculate three inflammation biomarkers, such as the ratio of neutrophils to lymphocytes.

“Being aware that both depression and lung cancer have inflammatory properties, we predicted significant effects between the severity of depression at diagnosis and increased systemic inflammation,” Andersen said.

Patients were followed, and analyses confirmed that the three biomarkers predicted two-year overall survival (the time when a patient is still alive) of the patients, which was 61%. As expected by the researchers, predictors of worse overall survival were higher neutrophil-to-lymphocyte ratio (which indicates an inflam- matory imbalance of the tumor; NLR), higher platelet-to-lymphocyte ratio (an indicator of tumor progression; PLR) and lower advanced lung cancer inflammation index (ALI; a way to assess ongoing inflammation).

Researchers tested the link between the three biomarkers and depressive symptoms. Findings demonstrated that patients with moderate or severe depressive symptoms were two to three times more likely to have poor biomarker levels.

Andersen noted that although this study focused on patients with NSCLC, it would be anticipated that significant biomarker/depression relationships would be found in patients with small cell lung cancer.

“These biomarkers — NLR and PLR — are used across tumor sites and have been predictive of survival,” she said. “The markers are not unique to lung cancer, with only ALI being lung cancer-specific. I am confident that this same effect of elevated inflammation and depression severity would be found in patients with small cell (lung cancer).”

Andersen added that she does not want people to discount depression in patients with NSCLC.

“I’ve heard people say, ‘Well, they have cancer; of course they’re depressed.’ Well, no,” she said. “(Most patients with) cancer — 70% (or) 80% of them — do not have moderate to severe symptoms. But then there’s everyone else — about 30% — (who) do have severe symptoms of depres- sion, perhaps major depressive disorder. When severe and untreated, depression is a mental health problem that shows little with time. More likely, it will continue at this level.”

Based on the findings from this study, Andersen recommended patients with NSCLC seek treatment for depression, if it is offered.

“I know that’s hard for people with depression to follow through. A symptom of depression is low motivation,” she said. “That can feed into reluctance to take a referral for care or begin psychological treatment. Major depression is an insidious illness with toxic effects when left untreated. Fortunately, there are efficacious treatments for both depressive and anxiety symptoms, with the strongest evidence for cognitive behavioral therapy and behavioral activation.”

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