Clinicopathological characteristics of GC patients after curative gastrectomy followed by S-1 AC
Table 1 shows the clinical characteristics of GC patients who received curative gastrectomy followed by S-1 AC. The mean age of the patients was 62.9 years. Of 76 patients, 47 (61.8%) were male and 29 (38.2%) were female; 30 patients were at pStage IIA, 17 patients were at pStage IIB, 17 patients were at pStage IIIA, and 12 patients were at pStage IIIB. Total gastrectomy was performed in 30 patients (39.5%), distal gastrectomy in 44 patients (57.9%), and proximal gastrectomy was performed in two patients (2.6%) for curative resection dependent on the location of the tumor. A total of 19 patients (25.0%) underwent D1+ lymphadenectomy based on their clinical stage, while the remaining patients performed D2 or D2+ lymphadenectomy [13].
Cut-off value of PDAC to stratify the prognosis and correlation between PDAC and clinicopathological factors
We performed a minimum p-value analysis for relapse-free survival (RFS) using various cut-off values for PDAC, as shown in Fig. 2. The cut-off value of 7 weeks post-surgery was confirmed to be the upper-limit to stratify the prognosis (p = 0.017; 5-year RFS: PDAC ≥ 7 weeks vs. PDAC < 7 weeks; 48.5 % vs. 77.0 %). Although there were no significant differences in 5-year overall survival (OS) rates, patients in the PDAC ≥ 7 weeks group had a poorer prognosis than those in the PDAC < 7 weeks group (p = 0.49; 5-year OS: PDAC ≥ 7 weeks vs. PDAC < 7 weeks; 74.3 % vs. 80.7 %). (Fig. 3).
Cut-off value of cumulative S-1 dose to stratify the prognosis and combined survival curves using PDAC and cumulative S-1 dose factors
To clarify the clinical effect of cumulative S-1 dose, we performed a minimum p-value analysis for RFS using various cut-off values of cumulative S-1 dose (data not shown). A cut-off value of 12,000 mg was confirmed to stratify the prognosis most (p = 0.006; 5-year RFS: cumulative S-1 dose ≥ 12,000 mg vs. < 12,000 mg; 84.7 % vs. 52.4 %).
Next, we compared survival curves between four groups: 1) PDAC ≥ 7 weeks / total S-l dose ≥ 12,000 mg; 2) PDAC < 7 weeks / total S-l dose ≥ 12,000 mg; 3) PDAC ≥ 7 weeks / total S-l dose < 12,000 mg; and 4) PDAC < 7 weeks / total S-l dose < 12,000 mg. With regard to patients who received a cumulative S-1 dose < 12,000 mg, there was a significant prognostic difference between the PDAC ≥ 7-weeks group and the PDAC < 7-weeks group for RFS (p = 0.040; 5-year RFS: PDAC ≥ 7 weeks vs. PDAC < 7 weeks; 25.0 % vs. 66.3 %). However, in patients who received a cumulative S-1 dose > 12,000 mg there was no prognostic difference between the PDAC ≥ 7-weeks group and PDAC < 7-weeks group for RFS (p = 0.64; 5-year RFS: PDAC ≥ 7 weeks vs. PDAC < 7 weeks; 85.7 % vs. 84.4 %). (Fig. 4)
Comparison of PDAC with clinicopathological factors
Next, we evaluated correlations between PDAC and clinicopathological factors using the Mann–Whitney U test. As shown in Table 2, a high peak in the C-reactive protein (CRP) cut-off value of 8 mg/dl or above was significantly associated with a delay in starting S-1 AC. In addition, the incidence of postoperative complications (Clavien–Dindo classification ≥ II) tended to be linked to longer PDAC (p = 0.065). There were no other significant differences between the groups with regard to other clinicopathological factors.
Univariate and multivariate analysis using Cox’s proportional hazard model
To elucidate the prognostic factors for recurrence-free survival, univariate and multivariate analysis using Cox’s proportional hazard model were performed. As shown in Table 2, age, gender, BMI, histological type, a postoperative peak CRP of ≥ 8 mg/dl, complications of Clavien–Dindo grade II or higher, pT-stage, pN-stage, cumulative S-1 dose, and PDAC were selected as clinical variables. The multivariate analysis showed that PDAC ≥ 7 weeks [p = 0.007; hazard ratio (HR) 3.99 (95% CI: 1.46–11.5)] and cumulative S-1 dose > 12,000 mg [p = 0.033; HR 0.38 (95% CI: 0.14–0.93)] were independent prognostic factors.