Summary: Higher levels of inflammation linked to lower survival rates are two to three times more likely in lung cancer patients with depression.
Source: Ohio State University
Lung cancer patients with moderate to severe depression are two to three times more likely to have levels of inflammation that predict poor survival rates, according to a new study.
The findings may help explain why a substantial proportion of lung cancer patients fail to respond to new immunotherapy and targeted treatments which have led to significantly longer survival for many people with the disease.
“These patients with high levels of depression are at a much higher risk for bad outcomes,” said Barbara Andersen, one of the study’s lead authors and a professor of psychology at Ohio State University.
“Levels of depression may be as important or even more important than other factors that have been associated with how people fare with lung cancer.”
The study was recently published online in the journal PLOS ONE.
Andersen and colleagues at Ohio State’s College of Medicine and Ohio State University Comprehensive Cancer Centers—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute studied 186 patients recently diagnosed with advanced (stage IV) lung cancer ). They were interested in how levels of depression correlated with levels of systemic inflammation ratio (SIR) biomarkers at diagnosis.
SIRs include three biomarkers associated with inflammation in the body. More inflammation is more dangerous and linked to lower survival rates.
All participants also completed a depression measurement. The results showed that a large proportion of patients, 35%, had moderate to severe depressive symptoms.
“Of all cancer patients, those with lung cancer are among those with the highest rates of depression, which makes our study findings all the more concerning,” Andersen said.
The results showed an association between higher depression scores and higher inflammation scores, but the key finding was that patients with the highest depression levels drove the relationship, Andersen said.
For example, take the platelet to lymphocyte ratio, one of the biomarkers in the study. For those with no or mild symptoms of depression, 56% of patients were above the cutoff for dangerous levels of inflammation, versus 42% who were below it.
But for those with high levels of depression, 77% were above the cutoff for high levels of inflammation and only 23% were below it.
“It was the patients with high levels of depression who had surprisingly higher levels of inflammation, and that’s what really drove the correlation that we saw,” she said.
These highly depressed patients were 1.3 to 3 times more likely to have high levels of inflammation, even after controlling for other factors related to levels of inflammatory biomarkers, including demographics and smoking status.
And analyzes had shown that baseline levels of all three biomarkers predicted overall survival. Notably, patients with high ratios of neutrophils to lymphocytes (one of the inflammatory biomarkers) were about twice as likely to die at any point in the next two years than those with a lower ratio of inflammation.
Andersen noted that this study measured the link between depression and inflammation when patients were first diagnosed and not yet treated.
But in an earlier study by Andersen and his colleagues, they controlled for levels of depression at diagnosis and found that the trajectory of continued depression symptoms thereafter predicted survival. This was the first examination of the survival risk posed when depressive symptoms continue during treatment and afterwards.
The accumulating data suggests the importance of measuring and treating depression in lung cancer patients, Andersen said.
He noted that there were more patients in this study with high depression/high inflammation than those with other markers associated with poor survival in cancer patients: high school or lower education, overweight status, and a poor score on a test of ability to perform daily tasks.
Some doctors might think it’s normal for cancer patients to be depressed, but that’s not true, she said.
“It’s normal to be upset and sad and anxious about a cancer diagnosis, but it’s not normal to have severe depression,” Andersen said.
“Depression shouldn’t be taken for granted. This study shows the strong link between depression and inflammation, both of which correlate with poor outcomes.”
About this news about cancer research and depression
Author: Jeff Grabmeier
Source: Ohio State University
Contact: Jeff Grabmeier – Ohio State University
Image: Image is public domain
Original research: Free access.
“Depression in association with neutrophil-lymphocyte, platelet-lymphocyte, and advanced lung cancer inflammation index biomarkers predicting lung cancer survival” by Barbara L. Andersen et al. PLOS ONE
Depression in association with neutrophil-to-lymphocyte, platelet-to-lymphocyte, and advanced lung cancer index biomarkers of inflammation predicting lung cancer survival
Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has a similar dysregulation. Depression disproportionately affects lung cancer patients, having the highest rates of all cancers.
Systemic inflammation and depression are both predictors of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence is unknown. We investigated the association between systemic inflammation ratio (SIR) biomarker levels and patients’ depressive symptoms, with the hypothesis that depression severity would be significantly associated with prognostically poor inflammation.
Newly diagnosed stage IV non-small cell lung cancer (NSCLC); No = 186) patients were enrolled (ClinicalTrials.gov Identifier: NCT03199651) and blood draws and depression self-reports were obtained (Patient Health Questionnaire-9). For SIRs, cell counts of neutrophils (N), lymphocytes (L), and platelets (P) were extracted for ratio (R) calculations for NLR, PLR, and Advanced Lung cancer Inflammation Index (ALI). Patients were followed up and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their relevance.
Next, multivariate linear regressions tested associations of depression with NLR, PLR, and ALI. Overall 2-year mortality was 61% (113/186). Analyzes of the Cox model confirmed a higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p < 0.001), together with a lower ALI (HR = 0.53; p = 0.005), to be predictive of worse OS. Adjusting for covariates, depression was reliably associated with biomarker levels (p ≤ 0.02).
Patients with moderate/severe depressive symptoms were 2 to 3 times more likely to have prognostically poor biomarker levels. New data show that patients’ depressive symptoms were reliably associated with lung-relevant biomarkers of systemic inflammation, all assessed at diagnosis/pretreatment.
The SIRs themselves were prognostic for the patients’ 2-year OS. An intensive study of depression, combined with measures of cell biology and inflammation is needed to extend these findings to uncover mechanisms of depression toxicity for treatment responses and survival of NSCLC patients.