Development and validation of a novel modified cancer cachexia index in patients with locally advanced gastric cancer undergoing neoadjuvant chemotherapy: a multicenter cohort study

Background: Although the cachexia index(CXI) is a well established prognostic predictor in gastric cancer(GC) patients, its effectiveness in patients with locally advanced gastric cancer(LAGC) who have undergone neoadjuvant chemotherapy(NACT) remains unclear. Methods: This multicenter study included 600 LAGC patients treated with NACT from January 2010 to June 2022. A modified CXI was constructed based on Random Forest model, calculated as (post-NACT subcutaneous adipose tissue area at L3) ×(post-NACT serum albumin)/(post-NACT platelet count) . Patients were categorized into mCXI-low and mCXI-high. Results: In the training cohort, mCXI outperformed the traditional CXI in predicting of overall survival(OS) and tumor regression grades. The mCXI-high group had a significantly higher 3-year OS(73.0% vs. 58.9%, P = 0.002), recurrence-free survival(67.7% vs. 50.2%, P = 0.002), and disease-specific survival(74.4% vs. 62.5%, P = 0.012). Multivariate analysis comfirmed that mCXI as an independent prognostic factor. The recurrence rate was significantly lower in the mCXI-high group(33.0% vs. 52.6%; P<0.001). The mCXI-high group also had a lower recurrence rate (33.0% vs. 52.6%, P < 0.001) and a delayed recurrence peak (33.51 vs. 7.11 months). Similar results were obtained in the validation cohort. Further analysis showed that in mCXI-low patients with ypStage III disease, receiving more than 4 cycles of adjuvant chemotherapy (AC) significantly improved survival (3-year OS: 43.7% vs. 25.0%, P = 0.007). In mCXI-high patients, 4–6 AC cycles yielded optimal outcomes. Conclusions: mCXI was associated with the overall prognosis in patients with LAGC underwent NACT, is superior to traditional CXI, and may serve as a decision-making tool for guiding personalized postoperative AC.