Depression Tied to Inflammation and Survival in Lung Cancer

Patients who are already depressed before they receive a lung cancer diagnosis are more likely to have a worse overall survival (OS), and the driver for this may be inflammation, suggests a new study.

The findings underscore the importance of assessing and treating depression in patients with cancer, particularly given the high rate of depression among those with lung cancer vs other types of cancer, the investigators said.

The study involved 186 patients with newly diagnosed stage IV non–small cell lung cancer (NSCLC), of whom 35% had self-reported moderate to severe depressive symptoms.

Depression was reliably associated with lung-relevant systemic inflammation responses (SIRs), which included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) score.

These SIRs were prognostic for 2-year OS.

Overall mortality at 2 years was 61%. Higher NLRs and PLRs and lower ALI scores all predicted worse OS (hazard ratio [HR], 1.91, 2.08, and 0.53, respectively).

The findings were published online February 24 in PLoS ONE.

“These patients with high levels of depression are at much higher risk for poor outcomes,” but the key finding was that patients with the highest depression levels were driving the relationship, lead author Barbara Andersen, PhD, professor of psychology at The Ohio State University, stated in a press release.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she explained.

For example, 56% of patients with no depression symptoms or only mild depression symptoms had a PLR above the cutoff for dangerous levels of inflammation, compared with 42% whose PLR was below the cutoff. However, among those with high depression levels, 77% and 23% had a PLR above and below the cutoff, respectively.

“These highly depressed patients were 1.3 to 3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status,” Andersen noted.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer,” she suggested.

In a previous study, the team controlled for baseline depression and found that “the trajectory of depression from diagnosis through two years (18 assessments) predicted NSCLC patients’ survival (HR = 1.09), above and beyond baseline depression, sociodemographics, smoking status, cell type, and receipt of targeted treatments and immunotherapies.”

“Taken together, data support psychological, behavioral, and biologic toxicities of depression capable of influencing treatment response and/or survival,” they wrote.

“The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease,” she stated.

The investigators concluded that “[I]ntensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses, and longevity.”

This study was funded by The Ohio State University Comprehensive Cancer Center and Pelotonia through grants to individual authors. Andersen reported having no relevant disclosures.

PLoS One. Published online February 24, 2023. Full text

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at [email protected] or on Twitter: @SW_MedReporter

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