Patients with lung cancer who have moderate to severe depression may be two to three times more likely to have inflammation levels that predict poor survival rates, according to a new study published by Andersen et al in PLOS One.
The findings may help explain why a substantial portion of patients with lung cancer fail to respond to new immunotherapies and targeted treatments that have otherwise led to significantly longer survival for many patients with the disease.
Background
“These patients with high levels of depression are at much higher risk for poor outcomes,” said co–lead study author Barbara Andersen, PhD, Professor of Psychology at The Ohio State University. “Depression levels may be as important or even more important than other factors that have been associated with how [patients] fare with lung cancer,” she added.
Systemic inflammation ratio biomarker levels include three biomarkers associated with inflammation in the body—with higher inflammation linked to a lower rate of survival.
Study Methods and Results
In the new study, the researchers included 186 patients who were newly diagnosed with stage IV lung cancer and examined how depression levels were related to systemic inflammation ratio biomarker levels at diagnosis.
All of the patients who participated in the study also completed a depression self-report. The results showed that 35% of them had moderate to severe depression symptoms.
“Of all [patients with] cancer, those with lung cancer [have] the highest rates of depression—which makes the findings of our study even more concerning,” Dr. Andersen stressed.
The researchers further showed an association between higher depression scores and higher inflammation scores—but the key finding was that patients with the highest depression levels were driving the relationship.
To demonstrate this, the researchers used the platelet-to-lymphocyte ratio as a biomarker in the analysis. For patients with mild depression symptoms, or none at all, 56% of them were above the cutoff for dangerous levels of inflammation, compared with 42% who were below.
However, for those with high depression levels, 77% were above the cutoff for high levels of inflammation, compared with only 23% who were below.
“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” Dr. Andersen underscored.
The patients with high levels of depression were 1.3 to 3 times more likely to have high levels of inflammation—even after controlling for other factors related to inflammation biomarker levels such as demographics and smoking status.
Analyses had shown that the baseline levels of all three biomarkers predicted overall survival. Specifically, patients who had elevated neutrophil-to-lymphocyte ratios were approximately twice as likely to die at any point in the next 2 years compared with those who had lower inflammation ratios.
Although the researchers measured the link between depression and inflammation when patients were first diagnosed and still untreated, in a previous study—published by Andersen et al in Psychosomatic Medicine—they controlled for depression levels at diagnosis and found that the trajectory of continuing depression symptoms thereafter predicted survival.
Conclusions
The accumulating data suggest the importance of measuring and treating depression in patients with lung cancer.
The researchers noted that there were more patients in the new study who had high levels of depression and inflammation than those with other indicators associated with poor survival—including highest education levels at or below high school, overweight status, and a poor score on a test to perform everyday activities.
Though many physicians may argue that it is normal for patients with cancer to have depression, Dr. Andersen emphasized: “It is normal to be upset, sad, and anxious about a cancer diagnosis, but it is not normal to have major depression. [It] should not be discounted. This study shows the strong link between depression and inflammation, with both related to poor outcomes,” she concluded.
Disclosure: For full disclosures of the study authors, visit journals.plos.org.
