Clinical‑pathological characteristics
A total of 192 gastric cancer patients who received gastrectomy after chemotherapy were enrolled between January 2012 and October 2020. Forty-four patients dropped out for different reasons (Fig. 1). Finally, this research included 148 patients with the median age of 60.0 (range, 52.0–64.8) years, Among which 122 (82.4%) were male and 26 (17.6%) were female. Ninety-four (63.5%) patients had tumors situated in the upper stomach, 19 (12.8%) in the middle stomach, and 35 (23.7%) in the lower stomach. Before NACT, 17 (11.5%) patients were at clinical stage II and 131 (88.5%) at stage III. The NACT cycle was less than three in 73 (49.3%) patients and no less than three in 75 (50.7%) patients.
As for pathological features, the proportion of tumors with high, moderate, and poor differentiation were 5.4%, 25.0%, and 69.6%, respectively. Five (3.4%) patients acquired TRG 0 grade and all of them were of pathological complete response; 15 (10.1%), 43 (29.1%), and 85 (57.4%) patients acquired the TRG of 1, 2, and 3 grade, respectively. ypTNM stages 0, I, II, III, and IV were diagnosed in 5 (3.4%), 19 (12.8%), 40 (27.0%), 74 (50.0%), and 10 (6.8%) cases, respectively.
The total postoperative morbidity was 24.3%. The median hospital stay was 10 (9–12) days. After surgery, 118 (79.7%) patients received adjuvant chemotherapy (Table 1).
Comparing the clinicopathological characteristics between the low and high LNR groups
LNR was calculated for each patient. The optimal cut-off value of LNR was 28.6% according to the receiver operating characteristic analysis. For the convenience of clinical use, we stratified LNR with a 30% boundary. Based on this value, 103 (69.6%) patients were classified as low-LNR (no more than 30% of LNR), and 45 (30.4%) patients as high-LNR (more than 30% of LNR). Comparison of the clinical‑pathological characteristics between the two cohorts is presented in Table 1. There was significant difference regarding TRG and ypT stage between the groups (P =0.012, and 0.002, respectively). High-LNR was not related to lower tumor location (P =0.620), less NACT cycle (P =0.174), less lymph nodes harvested (P =0.486), or lower tumor differentiation degree (P =0.082).
Regarding TRG, all patients with TRG 0 grade were in the low-LNR group. Precisely 52 (50.5%) patients responded to NACT at the primary site (TRG =0, 1, 2) in the low-LNR group, while 11 (24.4%) patients responded in the high-LNR group.
Comparing the prognosis of the two groups
The Kaplan–Meier survival curves according to LNR state are showed in Figure 2. The low-LNR patients got significantly longer OS and PFS than those with high-LNR. The 3-year OS and PFS were 81.9% and 72.6% in the low-LNR group and 18.5% and 13.5% in the high-LNR group (both P<0.001).
Considering the significant difference in tumor response to NACT at the primary site in the two groups, which may affect the prognosis, we included TRG in the prognostic analysis. All patients in the groups were further classified into two cohorts based on TRG: patients who responded to NACT (TRG = 0, 1, 2) and non-responders (TRG = 3). Patients who responded to NACT acquired significantly higher OS and PFS than non-responder. Figure 3 depicts the results of the subgroup analysis. In the low-LNR group, OS was longer in patients who responded to NACT compared with non-responders (3-year OS: 89.2% vs 73.2%, P =0.086). Patients who responded to NACT also had better PFS than non-responders (3-year PFS: 80.3% vs 66.5%, P =0.036). While in the high-LNR group, both OS and PFS showed no significant difference between the responders and non-responders (3-year OS: 12.1% vs 20.0%, P =0.882; 3-year PFS: 0% vs 17.4%, P=0.626).
Univariate and multivariate analyses
At the last follow-up (September 30, 2021), the median follow-up was 34.6 months. The 1-, 3-year OS was 84.5% and 62.3%, respectively, and the 1-, 3-year PFS was 72.1% and 54.7%, respectively. In the univariate analysis, the degree of differentiation, TRG, and LNR were chosen to be the predictive factors associated with OS (hazard ratio [HR]: 2.12, 95% confidence interval [CI]: 1.06–4.23, P=0.033; HR: 2.58, 95% CI: 1.40–4.79, P=0.003; HR: 8.21, 95% CI: 4.56–14.78, P<0.001) and PFS (HR: 1.92, 95% CI: 1.04–3.54, P=0.037; HR: 2.18, 95% CI: 1.27-3.75, P=0.005; HR: 6.48, 95% CI: 3.86–10.86, P<0.001) (Table 2). However, only LNR was found to be the independent predictive factor both OS (HR: 6.90, 95% CI: 3.63–13.14, P<0.001) and PFS (HR: 5.58, 95% CI: 3.17–9.82, P<0.001) in the multivariate analysis (Table 3).