Modified frailty index and systemic immune-inflammation enable biological risk stratification in geriatric colorectal cancer surgery

Figure 2 Biological interplay between frailty, inflammation, and surgical stress in geriatric colorectal cancer patients. This figure illustrates the self-reinforcing cycle between frailty and inflammation, with frailty (including sarcopenia and malnutrition) exacerbating systemic inflammation and vice versa. The interaction between immunosenescence/inflammaging (e.g., elevated interleukin-6, tumor necrosis factor-α), amplified inflammation (measured by systemic immune-inflammation index), and surgical stress creates a vicious cycle that leads to worsened postoperative outcomes, including increased risk of infection, organ failure, and delirium. Optimizing chronic disease management, minimizing surgical trauma, and addressing frailty through prehabilitation may reduce the negative clinical consequences and improve recurrence-free survival. SII: Systemic immune-inflammation index; mFI: Modified frailty index; CRP: C-reactive protein; NLR: Neutrophil-to-lymphocyte ratio; RFS: Recurrence-free survival; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α.