Preoperative serum magnesium level as a prognostic and predictive biomarker in locally advanced gastric cancer patients receiving neoadjuvant immunochemotherapy.

BACKGROUND

The global multicenter phase III MATTERHORN trial further validated the scientific rationale and clinical value of our earlier research, demonstrating that the combination therapy significantly improved patient survival outcomes and provided critical evidence for optimizing gastric cancer treatment strategies worldwide. Nevertheless, despite the overall effectiveness of neoadjuvant immunochemotherapy (NICT), approximately half of the patients did not achieve optimal therapeutic responses. Moreover, only a few clinically useful biomarkers can predict the treatment outcomes. The relationship between pre-treatment serum electrolyte levels and treatment outcomes in patients with locally advanced gastric cancer (LAGC) after NICT remains unclear.

METHODS

A retrospective analysis was conducted on clinical data from 112 patients with LAGC who underwent radical surgery after NICT between 2020 and 2024. Serum electrolyte levels were measured prior to NICT. The associations between serum electrolyte levels and overall survival (OS) and disease-free survival (DFS) were evaluated.

RESULTS

In the Kaplan-Meier survival analysis of pre-treatment serum electrolytes, only sodium showed a significant association; however, it was not an independent prognostic factor, according to the Cox regression analysis. Low pre-treatment serum magnesium levels were significantly associated with poorer OS (HR = 21.48, P < 0.001) and DFS (HR = 8.730, P < 0.001). Multivariate Cox regression analysis confirmed that low serum magnesium was an independent prognostic factor for both OS (HR = 0.232, P = 0.007) and DFS (HR = 0.274, P = 0.004). Low magnesium levels were more prevalent in patients with signet ring cell carcinoma or positive perineural invasion. Furthermore, low serum magnesium levels were associated with a poor rate of major pathological response (P < 0.0001).

CONCLUSION

Pre-treatment serum magnesium levels are independent prognostic factors and potential biomarkers in patients with LAGC undergoing NICT. However, prospective studies are required to validate these findings.