Sarcopenia in advanced non-small cell lung cancer (NSCLC): Clinical impact and its biological correlates

BackgroundSarcopenia, characterized by the progressive decline in skeletal muscle mass, strength, and function, poses a significant challenge in cancer care due to its negative impact on patient outcomes and quality of life. Despite its clinical significance in cancer prognosis, the underlying biological mechanisms in non-small cell lung cancer (NSCLC) remain inadequately explored. This study aims to elucidate the pathways influencing sarcopenia's development and its prognostic implications in NSCLC patients.MethodsWe analyzed data from the MATCHR prospective study (NCT 2517892). Muscle body mass (MBM) was quantified using Anthropometer3DNet, a deep learning tool, with sarcopenia defined by an MBM threshold of 5.85 kg/m2 (PMID 37678919). Comprehensive genomic profiling involved Whole Exome Sequencing using the SureSelect Human All Exon v6 kit, and transcriptomic analysis was conducted on mRNA libraries prepared with polyA enrichment, sequenced as 2 × 150 bp paired-end reads on the NovaSeq 6000 (Illumina). Additionally, a targeted proteomic analysis was performed using the Olink Explorer 3072 kit in a subset of 64 patients.ResultsThe cohort comprised 201 participants. Baseline sarcopenia was associated with significantly reduced survival in patients receiving immunotherapy (12.8 vs. 34.4 months; p=0.02), but this trend was not observed with targeted therapies. Proteomic and transcriptomic analyses identified a distinct cytokine profile correlated with sarcopenia, marked by alterations in immune regulation and muscle metabolism. Differentially expressed genes (957 total; 307 upregulated, 650 downregulated) underscored the activation of pathways critical to muscle function and development.ConclusionsOur findings not only reaffirm the profound prognostic relevance of sarcopenia in NSCLC but also reveal distinct biological underpinnings that may influence therapeutic outcomes, particularly with immunotherapies. The identified cytokines, pivotal in immune modulation and muscle metabolism, suggest potential targets for novel interventions. This study paves the way for integrating sarcopenia management into personalized cancer therapy, enhancing both treatment efficacy and patient quality of life.Clinical trial identificationNCT2517892.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.