Summary: Higher levels of inflammation, associated with worse survival rates, were two to three times more likely in lung cancer patients with depression.
source: The Ohio State University
A new study has found that 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.
The findings may help explain why a significant proportion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have resulted in significantly longer survival for many people with the disease.
“These patients with high levels of depression are at much higher risk for poor outcomes,” said Barbara Andersen, one of the study’s lead authors and a professor of psychology at Ohio State University.
“Depression levels may be as important or even more important than other factors that are associated with how people cope with lung cancer.”
The study was published online recently in the journal PLUS ONE.
Andersen and colleagues from Ohio State College of Medicine and Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute studied 186 patients newly diagnosed with advanced lung cancer (stage IV). They were interested in how levels of depression related to levels of the biomarker systemic inflammation ratio (SIR) at diagnosis.
SIRs include three biomarkers associated with inflammation in the body. More severe inflammation is more dangerous and is associated with lower survival rates.
All participants also completed a measure of depression. 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 even 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 levels of depression drove the link, Andersen said.
For example, take the platelet-to-lymphocyte ratio, one of the biomarkers in the study. For those without depressive symptoms or with mild depressive symptoms, 56 percent of patients were above the cutoff for dangerous levels of inflammation, versus 42 percent who were below.
But for those with high levels of depression, 77% were above the cutoff for high levels of inflammation and only 23% were below.
“Patients with high levels of depression had strikingly higher levels of inflammation, and that’s what really drove the correlation we saw,” she said.
These severely depressed patients were 1.3 to 3 times more likely to have high levels of inflammation, even after controlling for other factors associated with levels of inflammatory biomarkers, including demographics and smoking status.
And the analyzes showed that baseline levels of all three biomarkers predicted overall survival. Specifically, patients with elevated neutrophil-to-lymphocyte ratios (one of the inflammatory biomarkers) were roughly twice as likely to die at any point in the next two years compared to those with lower inflammation ratios.
Andersen noted that this study measured the relationship between depression and inflammation when patients were first diagnosed and still untreated.
But in a previous study by Anderson and her colleagues, they controlled for levels of depression at diagnosis and found that the trajectory of ongoing depressive symptoms afterward predicted survival. This was the first study of survival risk when depressive symptoms persisted during treatment and beyond.
Accumulating data show the importance of measuring and treating depression in patients with lung cancer, Andersen said.
She noted that there were more patients in this study with high depression/high inflammation than those with other indicators associated with poor survival in cancer patients: high school or less education, overweight status, and poor outcome on an ability test for daily work activities.
Some doctors may think it’s normal for cancer patients to be depressed, but that’s not true, she said.
“It’s normal to be upset, sad and anxious about a cancer diagnosis, but it’s not normal to have major depression,” Andersen said.
See also
“Depression should not be dismissed. This study shows the strong relationship between depression and inflammation, both of which are associated with poor outcomes.
About this news about cancer research and depression
Author: Jeff Grabmeier
source: The Ohio State University
Contact: Jeff Grabmeier – The Ohio State University
Image: Image is in the public domain
Original research: Free access.
“Depression in Relation to Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte, and Advanced Lung Cancer Inflammatory Index Biomarkers Predicting Survival in Lung Cancer” by Barbara L. Andersen et al. PLUS ONE
Summary
Depression in relation to biomarkers of neutrophil-to-lymphocyte, platelet-to-lymphocyte and advanced lung cancer index of inflammation predicting survival in lung cancer
Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has a similar dysregulation. Depression disproportionately affects patients with lung cancer, having the highest rate of any cancer.
Systemic inflammation and depression predict survival in non-small cell lung cancer (NSCLC), but the existence and extent of each co-occurrence is unknown. We examined the relationship between levels of the systemic inflammation ratio (SIR) biomarker and patients’ depressive symptoms, hypothesizing that depression severity would be significantly associated with prognostic poor inflammation.
Newly diagnosed stage IV non-small cell lung cancer (NSCLC; n = 186) enrolled patients (ClinicalTrials.gov ID: NCT03199651) and obtained self-reports of blood draw and depression (Patient Health Questionnaire-9). For SIR, neutrophil (N), lymphocyte (L), and platelet (P) cell counts were extracted for ratio (R) calculations for NLR, PLR, and advanced lung cancer inflammatory index (ALI). Patients were followed and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their applicability.
Multivariate linear regressions then tested the associations of depression with NLR, PLR, and ALI. The overall 2-year mortality rate was 61% (113/186). Cox model analyzes confirmed a higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p<0.001) together with 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 biomarkers of systemic lung inflammation, all assessed at diagnosis/pretreatment.
The same SIRs were found to be predictive of patients’ 2-year OS. Intensive research on depression combined with measurements of cell biology and inflammation is needed to extend these findings to uncover mechanisms of toxicity of depression on treatment responses and survival of NSCLC patients.