Clinical significance of assessing systemic trace element concentrations in gastric cancer patients during anticancer drug therapy

Abstract

Introduction. Adverse events of anticancer therapy in gastric cancer remain a major clinical challenge, often limiting the completion of the full treatment course. Disruption of trace element homeostasis may contribute to the development of toxic complications and could be considered a potential basis for therapy personalization.

Aim. To assess the association between plasma concentrations of copper, zinc, selenium, and manganese and the incidence, nature, and severity of toxic complications from anticancer drug therapy in patients with locally advanced and metastatic gastric cancer.

Materials and Methods. The study included 100 patients with newly diagnosed gastric cancer who underwent four courses of chemotherapy. Trace element concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS, Varian 810-MS) immediately before the first and fifth courses of anticancer drug therapy. Adverse event severity was graded according to CTCAE v5.0. Statistical analysis employed Spearman's correlation.

Results. The absolute plasma concentrations of trace elements (copper, zinc, selenium, and manganese) in gastric cancer patients before the first and fifth courses of chemotherapy remained within established reference ranges and showed weak correlation with the incidence, nature, and severity of adverse events (p > 0.05). However, plasma trace element ratios demonstrated significant correlations. The pre-treatment copper/zinc ratio correlated with reduced severity of leukopenia (r = –0.331; p = 0.046) and diarrhea (r = –0.331; p = 0.001). The pre-treatment selenium/manganese ratio was associated with decreased severity of anemia (r = –0.211; p = 0.036). Furthermore, the pre-treatment copper/manganese ratio (r = –0.206), pre-treatment zinc/selenium ratio (r = –0.199), and the copper/zinc ratio measured after the fourth chemotherapy course (r = –0.241) all demonstrated statistically significant inverse correlations with diarrhea severity (p < 0.05 for all).

Conclusion. Predictive significance lies not in the absolute plasma concentrations of the studied trace elements before and during treatment, but in their ratios. These findings indicate the potential of incorporating trace element ratios into multivariate predictive models of toxicity, where they could serve as additional significant markers alongside genetic, clinical, laboratory, and instrumental predictors.