Circulating cytokines and outcome in metastatic colorectal cancer patients treated with regorafenib

Figure 1 Plasma cytokines levels. Basal evaluation of 6 cytokines in non-responder patients (n = 12), Responder patients (n = 5) and in healthy volunteers (n = 6). Cytokine concentration is expressed in pg/mL. Data are shown as median with range. The difference in median values was computed using the non-parametric Mann Whitney U test. P < 0.05 was considered the statistical significance. ^aP < 0.05 NR vs R; ^cP < 0.05 NR vs Healthy. NR: Non-responder; R: Responder; TNF-α: Tumor necrosis alpha; TGF-β: Transforming growth factor alpha; VEGF: Vascular endothelial growth factor; CCL-2: Chemokine ligand 2; CCL-4: Chemokine ligand 4; CCL-5: Chemokine ligand 5.

Figure 2 Correlation analysis. A: Correlation between tumor necrosis alpha and progression free survival in all metastatic colorectal cancer (mCRC) patients (n = 17) (r_s = -0.52, P = 0.033); B: Correlation between transforming growth factor alpha and progression free survival in all mCRC patients (n = 17) (r_s = -0.52, P = 0.038); C: Correlation between tumor necrosis alpha and transforming growth factor alpha in all mCRC patients (n = 17) (r_s = 0.53, P = 0.028). P < 0.05 was considered the statistical significance. Each dot represents the value of one patients. Transforming growth factor alpha and tumor necrosis alpha are expressed as a concentration (pg/mL). Progression free survival is expressed in months. PFS: Progression free survival; TNF-α: Tumor necrosis alpha; TGF-β: Transforming growth factor alpha.

Figure 3 Receiver operating characteristic curve analysis, progression free survival and overall survival Kaplan-Meier curves. A: Receiver operating characteristic curve with area under the curve (0.908, 95CI: 0.758–1.000, P = 0.010) for predicting survival by plasma TNF-α basal levels in patients with metastatic colorectal cancer treated with regorafenib according to the baseline TNF-α levels ≤ (―, n = 5) or > (―, n = 12) the cut-off value (determined by receiver operating characteristic curve analysis); B: Progression free survival (5.2 vs 2.6 mo, Log-rank test, P = 0.005); one patient in Group A is not shown because of a graphic choice; C: Overall survival (16.6 vs 7.3 mo, Log-rank test, P = 0.010). PFS: Progression free survival; OS: Overall survival; ROC: Receiver operating characteristic; TNF-α: Tumor necrosis alpha; TGF-β: Transforming growth factor alpha.

Figure 4 Univariate Cox analysis to predict risk of disease progression. Difference between the two survival curves was assessed by long rank test, the HR with 95%CI was calculated by the Cox regression model (HR = 7.203; 95%CI: 1.531–33.882; P = 0.012). PFS: Progression free survival; TNF-α: Tumor necrosis alpha.