Supplementary Material for: Digitally Delivered Cognitive Behavioral Therapy (CBT) and Inflammation-Guided Nutrition to Enhance Recovery and Survival After Abdominoperineal Resection (APR): A Prospective Non-Randomized Controlled Cohort Study

Background:
Abdominoperineal resection (APR) for low rectal cancer results in permanent stoma, psychosocial distress, and systemic inflammation, impairing quality of life and survival. This study evaluated whether app-based cognitive behavioral therapy (CBT) plus biomarker-guided nutrition could improve recovery and survival.

Methods:
In this prospective, single-center, non-randomized controlled cohort, 186 patients with stage I–III low rectal adenocarcinoma undergoing curative abdominoperineal resection (APR) all received standard Enhanced Recovery After Surgery (ERAS) care. Patients were managed with ERAS alone or ERAS plus an integrative program combining digital cognitive behavioral therapy (CBT) and inflammation-guided precision nutrition, tailored according to prognostic nutritional index (PNI), C-reactive protein (CRP), and interleukin-6 (IL-6). Interventions began two weeks preoperatively and continued for six months. Primary outcomes were longitudinal changes in depression, sleep quality, sexual function, and health-related quality of life. Secondary outcomes included inflammatory markers, skeletal muscle index (SMI), and two-year disease-free and overall survival.

Results:
By month 3, the intervention group showed greater improvements in all primary outcomes, sustained through 24 months (all p < 0.001). CRP and IL-6 were reduced by day 7 (both p < 0.001), with faster recovery and shorter hospitalization. SMI was better preserved at 24 months (p = 0.046). Two-year DFS (hazard ratio [HR] = 0.48, 95% confidence interval [CI] 0.26–0.89, p = 0.021) and OS (HR = 0.44, 95% CI 0.20–0.95, p = 0.036) were significantly improved. Findings remained robust in multivariable and sensitivity analyses.

Conclusions:
Among patients undergoing APR managed within an ERAS pathway, the addition of digital CBT and inflammation-guided nutrition was associated with improved multidimensional recovery and favorable survival signals. Given the non-randomized design, these results should be regarded as hypothesis-generating and support further evaluation of ERAS-based integrative strategies in randomized multicenter trials.