Development and validation of a novel modified cancer cachexia index in patients with locally advanced gastric cancer...

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.

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.

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 confirmed 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.

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.