When new therapies arrive, we should think more: The unseen challenges of immunotherapy-induced remodeling

Figure 3 Multidisciplinary risk mitigation framework. Translational framework for predicting and mitigating bowel wall fragility across treatment phases. Pre-treatment: Stromal gene signatures (Type III collagen/Matrix metallopeptidase 7 ratio) from biopsies predict remodeling propensity. On-treatment: Serum N-terminal type III collagen (type III collagen fragment) > 25 ng/mL and ⁶⁸Ga-FAPI positron emission tomography SUVmax > 6 signal active fibrosis. Surgical: Assess the biological resilience of intestinal wall tissue. Post-op: AI-powered digital pathology (collagen orientation index) informs stoma reversal timing. MMR: Mismatch repair; MSI: Microsatellite instability; PRO-C3: N-terminal propeptide of collagen type 3; IL-6: Interleukin-6; PET: Positron emission tomography; ICG: Indocyanine green; AI: Artificial intelligence.