Impact of Subcutaneous Adipose Tissue Index Change During Neoadjuvant Chemoradiotherapy on Disease-Free Survival and Tumor Response in Patients with Locally Advanced Rectal Cancer.

Background & Aims: The heterogeneity among patients with locally advanced rectal cancer (LARC) necessitates identifying predictive markers of response to neoadjuvant chemoradiotherapy (nCRT) to enable personalized treatment strategies. Adipose tissue, which reflects nutritional status and chronic inflammation, has been implicated in tumorigenesis and disease progression. This study investigated the potential of adipose tissue as a predictive marker of nCRT response and prognosis in patients with LARC. Methods: We analyzed pre- and post-nCRT non-contrast computed tomography images at the third lumbar vertebral level to quantify adipose tissue in patients with LARC. We examined the relationship between changes in the subcutaneous adipose tissue index (SATI) and treatment outcomes, including disease-free survival (DFS), tumor regression grade (TRG), and tumor downstaging, using Cox proportional hazards and logistic regression analyses. Results: This study included 290 patients who underwent radical surgery after nCRT. Patients with significant increases in SATI had improved DFS (P = 0.002) and better short-term treatment responses, including superior TRG (P = 0.019) and more favorable tumor downstaging (P = 0.005). Multivariate analyses revealed that SATI gain was an independent prognostic factor for both long-term outcomes (DFS, P = 0.018) and short-term treatment responses (TRG, P = 0.020; tumor downstaging, P = 0.008). Additionally, calibration and decision curve analyses demonstrated the strong predictive ability of the nomogram incorporating SATI gain for DFS. Conclusions: An increase in SATI during nCRT was an independent protective factor for DFS and an independent predictor of treatment response in patients with LARC.