Muscle index, weight loss, and tumor type predict adjuvant therapy failure in periampullary cancer.

Background: Periampullary cancers frequently induce malnutrition and sarcopenia, which impair treatment tolerance and survival. Current nutritional assessment tools evaluate host status in isolation, ignoring the modifying effect of tumor biology. We developed and validated a simple nutritional risk score integrating host and tumor domains to identify high-risk patients and quantify the extent to which the association between preoperative risk and poor outcomes is mediated through a sequential pathway. Methods: This dual-center retrospective cohort study included 533 patients who underwent pancreaticoduodenectomy. Using a time-ordered split, patients were assigned to training ( Results: The cohort had mean age 64.0 ± 9.8 years, 57.8% male. Median follow-up was 23 months. During follow-up, 261 recurrence or death events (49.0%) occurred; 1-year mortality was 55.7% (95%CI 51.5-59.9%). LASSO-Cox identified three independent predictors: total muscle index (TMI, mm Conclusions: A simple three-variable score (muscle index, weight loss >5%, tumor type) enables preoperative identification of high-risk periampullary cancer patients. One-fifth of the excess recurrence risk may be mediated through a modifiable cascade of complications leading to adjuvant therapy delays, providing a clear rationale for targeted nutritional prehabilitation and perioperative interventions.