Inflammation Linked to Lung Cancer and Depression Affects Survival Outcomes

Inflammation is a complex biological response forming part of the body's natural defense against injury or infection. It helps eliminate harmful stimuli and heal tissues. However, chronic inflammation plays an important role in the development of various diseases, including cancer. Its link to cancer is explained by its ability to cause cellular DNA damage, promote cell growth and division, and, in the tumor microenvironment, alter immune responses. These properties represent one of the “14 hallmarks of cancer”, because sustained inflammation can support cancer-cell growth, spread, and metastasis. This shows that chronic inflammation is a key factor in cancer development and progression.

Research Highlighting the Importance of Emotional Well-Being After Diagnosis

New research found that inflammation associated with lung cancer and depression may affect patients' survival despite immunotherapy and targeted treatments. People with moderate or severe depression had high levels of inflammatory biomarkers that could predict the course of lung cancer and patient survival.

Both lung cancer and depression have features of inflammation, the body's response to injury or infection. Chronic inflammation can damage healthy tissues, cells, and organs over time. It may also affect patients' responses to treatments such as immunotherapies and targeted therapies.

Published on 24 February 2023 in PLOS ONE, the study's findings highlight the importance of screening for and treating depression and anxiety in patients with lung cancer.

The Importance of Screening for Depression and Anxiety

Lead researcher and psychology professor Barbara L. Andersen says it is important for patients and caregivers to know whether their medical practices and facilities screen their loved ones for depression and anxiety. If this has not been done, the medical team should initiate screening. Patients who are screened should take recommendations for further evaluation and treatment of depression or anxiety seriously.

Study Methods and Findings

Andersen and colleagues studied patients with newly diagnosed stage 4 non-small cell lung cancer (NSCLC). The study included 186 patients, screened for depression and anxiety at diagnosis before treatment began. Researchers calculated three inflammatory biomarkers using cell counts from blood tests performed at diagnosis.

Andersen says the researchers knew that both depression and lung cancer had inflammatory features and expected important interactions between depression severity and systemic inflammation at diagnosis.

Follow-up confirmed that the three biomarkers predicted patients' two-year overall survival (the time a patient remains alive). As expected, worse overall survival was indicated by a high neutrophil-to-lymphocyte ratio (NLR, indicating inflammatory imbalance in the tumor), a high platelet-to-lymphocyte ratio (PLR, an indicator of tumor progression), and a low advanced lung cancer inflammation index (ALI, a way to assess ongoing inflammation).

The Relationship Between Depression and Biomarkers

The researchers tested the relationship between the three biomarkers and depressive symptoms. Patients with moderate or severe depressive symptoms were two to three times more likely to have unfavorable biomarker levels.

Andersen says that although this study focused on NSCLC patients, the researchers expect important biomarker-depression relationships in small cell lung cancer as well. She explains, “These biomarkers—NLR and PLR—are used across tumor sites and predict survival. Except for ALI, they are not specific to lung cancer. I am confident that patients with small cell lung cancer would show the same elevated inflammation and depression severity.”

The Importance and Treatment of Depression

Andersen adds that depression should not be dismissed in NSCLC patients. “I have heard people say, 'Of course they are depressed; they have cancer.' No,” she says. “70-80% of people with cancer do not have moderate to severe symptoms. But approximately the remaining 30% have serious depressive symptoms, possibly major depressive disorder. When severe and untreated, depression is a mental health problem that does not diminish over time. Rather, it tends to persist at that level.”

Based on these findings, Andersen encourages NSCLC patients to accept depression treatment when offered. “I know it can be difficult for people with depression to follow through,” she says. “One symptom of depression is low motivation. This can make people reluctant to see a psychiatrist or begin psychological treatment. Untreated major depression is an insidious illness with toxic effects. Fortunately, effective treatments for depressive and anxiety symptoms exist, with the strongest evidence for cognitive behavioral therapy and behavioral activation.”