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August 2024 | George M. Pikler, M.D., Ph.D., FACP, Lead Oncology Advocate N1X10

Emotional Distress Disrupts Cancer Meds

Patients with cancer often experience emotional distress (ED) commonly characterized by symptoms of depression and/or anxiety due to multiple stressors, including the diagnosis itself, the burden of symptoms and treatments, outcome expectations, challenges in family and social relationships, and financial worries.

Preclinical studies suggest that ED can impair antitumor immune responses but few have explored the relationship between ED and the efficacy of immunotherapy, specifically its relationship with response to immune checkpoint inhibitors (ICIs).

A recent study showed that cancer patients who experience ED when receiving immunotherapy with ICIs for advanced non-small cell lung cancer (NSCLC) tend to have worse outcomes. In a study of 227 patients with NSCLC, the 111 patients who experienced anxiety and/or depression were less likely to respond to ICIs (47% versus 62%) and were less likely to survive over two years (47% versus 65%). ED could be a ‘psycho-biomarker’ that predicts immunotherapy success in combination with other factors, say the study authors.

Their study found that higher levels of cortisol (a glucocorticoid) were associated with worse survival. These findings indicated the potential role of neuroendocrine regulation in mediating the association between ED and the efficacy of ICIs. Their findings suggests that intervention strategies to alleviate ED may be a potential strategy to enhance the efficacy of ICIs. In fact, concomitant use with β-blockers was positively associated with better prognosis in patients with NSCLC receiving EGFR tyrosine kinase inhibitors, and a phase I trial showed that β-blockers combined with PD-1 inhibitors had promising efficacy in patients with advanced melanoma.

While the study suggests an association between ED and reduced efficacy of ICIs in NSCLC, a causal link cannot be established. This will require further investigation in preclinical studies and in human cohort studies with more patients. The concept of a ‘psycho-biomarker’ may be relevant for not only NSCLC but also other cancer types in the future.

Personalized comprehensive mental-health care based on different pharmacological and psychosocial approaches may be required to evaluate and manage the physical, emotional and oncogenic effects of chronic stress disruptions of cancer patients and improve their quality of life.

Nature Medicine. 2024; May 13, 2024
Cancer Cell. 2024; February 22
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Erica Cross, PA

PA

Erica is a board certified Physician Assistant. She obtained her Master’s degree in Physician Assistant studies from Our Lady of the Lake College in Baton Rouge, LA. She began practicing in 2011 and has worked clinically in Orthopedics and Dermatology. The majority of her career has been spent in a Dermatology practice where she assisted in Mohs surgery, treating various types of skin cancer. She also teaches in the medical simulation department at the University of South Alabama and enjoys every aspect of medical education.