Impact of Sarcopenia and Inflammation on Patients with Advanced Non-Small Cell Lung Cancer (NCSCL) Treated with Immune Checkpoint Inhibitors (ICIs): A Prospective Study

SIMPLE SUMMARY: The association between sarcopenia and therapeutic response in cancer patients treated with immune checkpoint inhibitors (ICI) is still limited to a few retrospective reports. In a population of advanced non-small cell lung cancer (NCSCL) patient candidates for ICI, we demonstrated that sarcopenic status is associated with worse progression free survival and that sarcopenic patients had an 8-fold higher risk of progression disease. Sarcopenia could therefore be considered an independent unfavorable prognostic factor and predictive of a worse response to ICI. The choice to use the DXA scan, in our opinion, allows a better standardization of results than the CT scan. Moreover, patients with sarcopenia showed significantly higher inflammatory markers compared to non-sarcopenic patients. We therefore believed that sarcopenia might be a useful predictive marker for ICI therapy outcomes and that may help identify patients more likely to achieve a better response to ICI in routine clinical practice. ABSTRACT: Background: Sarcopenia is a condition characterized by loss of skeletal muscle mass associated with worse clinical outcomes in cancer patients. Data on sarcopenia in patients undergoing immune checkpoint inhibitors (ICI) therapy are still limited. The aim of this prospective observational study was to investigate the relationship between sarcopenia, ICI treatment response and immunological profile, in patients with advanced non-small cell lung cancer (NSCLC). Methods: Forty-seven stage IV NSCLC patient candidates for starting ICI, were enrolled from the Policlinico Umberto I outpatient Oncology. Patients underwent baseline blood test, inflammatory markers, cytokine assessment and body composition with dual-energy X-ray absorptiometry (DXA). Sarcopenia was defined with appendicular skeletal muscle mass over height(2) (ASM/heigh(2)). Results: Overall, 19/47 patients (40.4%) results were sarcopenic. Sarcopenic patients showed significantly shorter PFS than non-sarcopenic ones (20.3 weeks, 95% CI 7.5–33.1 vs. 61 weeks, 95% CI 22.5–99.4, p = 0.047). Specifically, they had an 8.1 times higher risk of progression disease (PD) than non-sarcopenic patients (OR 8.1, 95%, p = 0.011). Conclusions: Sarcopenic patients showed worse PFS and had a higher risk of PD compared to non-sarcopenic ones. Therefore, sarcopenia may reflect the increased metabolic activity of more aggressive tumors, which involves systemic inflammation and muscle wasting and could be considered a negative predictive factor for ICI response.