Change of body weight and macrophage inhibitory cytokine-1 during chemotherapy in advanced gastric cancer: what is their clinical significance?

Abstract

Background: Weight loss in advanced gastric cancer (GC) has been widely acknowledged to be a predictor for poor survival. However, very few studies have investigated the weight loss that occurs during chemotherapy. Therefore, we focused on weight loss during chemotherapy in patients with advanced GC and investigated the concentrations of macrophage inhibitory cytokine-1 (MIC-1), which has been recognized as a probable etiological factor in anorexia and weight loss.

Methods: We analyzed 384 patients with inoperable locally advanced or metastatic GC receiving first-line chemotherapy. Patients were assigned to one of two groups on the basis of their weight change during chemotherapy: >3% weight loss and ≤ 3% weight loss. Serum MIC-1 and C-reactive protein (CRP) concentrations were also assessed in these patients.

Results: The >3% weight loss group had shorter overall survival (OS; 12.0 months vs. 17.5 months, P = 0.000) than the ≤ 3% weight loss group, and the survival rates improved if the weight loss was reversed during chemotherapy. Although the MIC-1 concentrations were not correlated with weight loss before (P = 0.156) or during chemotherapy (P = 0.164), it correlated significantly with the CRP concentration (P = 0.001). Furthermore, elevated MIC-1 concentrations before chemotherapy (P = 0.017) and increased MIC-1 concentrations during chemotherapy (P = 0.001) were both found to be predictors of poor OS.

Conclusions: Changes in the body weight during chemotherapy could influence the prognosis in patients with advanced GC, and the MIC-1 might be a potential predictive and prognostic biomarker in those patients.

Figure 1. Serum MIC-1 concentrations in GC patients and ROC curve for determining MIC-1 cut-off value.

A. Serum MIC-1 concentrations in GC patients (median  = 1372 pg/ml) and controls (median  = 351 pg/ml, P = 0.000); B. ROC curve for determining MIC-1 cut-off value (the area under the ROC curve: 0.743±0.026, P = 0.000); C. Serum MIC-1 concentrations in patients with >5% weight loss (median  = 1472 pg/ml) and ≤5% weight loss before chemotherapy (median  = 1128 pg/ml, P = 0.156); D. Serum MIC-1 concentrations in patients with CRP >10 mg/l (median  = 1787 pg/ml) and in patients with CRP ≤10 mg/l (median  = 1236 pg/ml, P = 0.001) before chemotherapy.

Figure 2. Kaplan–Meier curves of overall survival (OS) of patients according to weight change before or during chemotherapy.

A. OS curve of patients grouped by weight change trends during chemotherapy (P = 0.003). B. OS curve of patients grouped by weight loss during chemotherapy (P = 0.000). C. OS curve of patients with >5% weight loss before chemotherapy grouped by weight loss during chemotherapy (P = 0.004). D. OS curve of patients with ≤5% weight loss before chemotherapy grouped by weight loss during chemotherapy (P = 0.001).

Figure 3. Kaplan–Meier curves of overall survival (OS) of patients according to macrophage inhibitory cytokine-1(MIC-1).

A. OS curve of patients grouped by serum MIC-1 before chemotherapy (P = 0.015). B. OS curve of patients grouped by serum MIC-1 change during chemotherapy (P = 0.030). C. OS curve of patients with serum MIC-1 concentrations ≤1120 pg/ml before chemotherapy grouped by serum MIC-1 change during chemotherapy (P = 0.035). D. OS curve of patients with serum MIC-1 concentrations >1120 pg/ml before chemotherapy grouped by serum MIC-1 change during chemotherapy (P = 0.078).