Abstract
PURPOSE: Cancer-related malnutrition (CRM) is characterized by nutrition impact symptoms (NIS), prominently reduced intake, and irreversible systemic inflammation (SI). This study aimed to use NIS as a phenotype to explore the etiological mechanisms of CRM and facilitate a more precise classification approach for CRM patients by symptomatic clusters. PATIENTS AND METHODS: 147 CRM patients were included in this study. Exploratory factor analysis (EFA) was used to identify the NIS clusters, analyze their regression factor score (RFS), and explore potential patient groups. Spearman correlation, Kruskal-Wallis tests, and regression analysis were used to analyze the correlation and interaction between RFS and nutrition, SI, and intake status. RESULTS: EFA identified 4 factors: RFS-1 was significantly correlated with mid-arm circumference (MAC) (r = -0.28, p = 0.001), calf circumference (r = -0.32, CC) (p < 0.001), hand grip strength (r = -0.24, p = 0.004), hemoglobin (r = -0.19, p= 0.023), albumin (r = -0.18, ALB) (p = 0.026), pre-albumin (PAB) (r = -0.26, p = 0.002), C-reactive protein (CRP) (r = 0.33, p < 0.001), neutrophil-to-lymphocyte ratio (NLR) (r = 0.32, p < 0.001), and systemic immune-inflammation index (SII) (r = 0.28, p = 0.001). RFS-2 was also significantly correlated with MAC (r = -0.21, p =0.010), CC (r = -0.19, p = 0.030), ALB (r = -0.23, p = 0.010), and PAB (r = -0.21, p = 0.010). Two-step cluster analysis identified 3 patient groups: Group 1 and Group 2 had higher MAC than Group 3 (p = 0.001) and had higher CC than Group 3 (p = 0.029). Group 1 and Group 2 had lower CRP than Group 3 (p = 0.007), presented lower NLR than Group 3 (p = 0.004), and had lower SII than Group 3 (p = 0.014). Group 2 (p < 0.001) had a lower risk of developing anorexia than Group 3, and Group 2 (p = 0.010) had a lower risk of decreasing intake. CONCLUSION: This exploratory study identified 4 NIS clusters, 2 significantly related to SI and intake status. Based on CAM etiological mechanisms, 3 potential patient groups were explored, which established a robust phenotypic framework for subsequent large-scale investigations, addressing a critical gap in CRM research and providing a standardized phenotypic tool for future multi-center analyses. These efforts will contribute significantly to enhancing the prevention, treatment, and clinical management of CRM.