Lymph-node ratio is an important clinical determinant for selecting the appropriate adjuvant chemotherapy regimen for curative D2-resected gastric cancer

Abstract

Purpose: Adjuvant chemotherapy for gastric cancer, particularly stage III, improves survival after curative D2 gastrectomy. We investigated the clinical value of the lymph-node ratio (LNR; number of metastatic lymph nodes/number of lymph nodes examined) for selecting the appropriate adjuvant chemotherapy regimen in patients with D2-resected stage II/III gastric cancer.

Methods: We reviewed the data of 819 patients who underwent curative D2 gastrectomy followed by adjuvant chemotherapy. Of them, 353 patients received platinum-based chemotherapy and 466 received TS-1. The patients were categorized into three groups according to their LNR (LNR 1, 0-0.1; LNR 2, > 0.1-0.25; and LNR 3, > 0.25), and their disease-free survival (DFS) was evaluated.

Results: The DFS curves of the patients were well separated according to stage and LNR. In multivariate analyses, an LNR > 0.1 was strongly associated with the 3-year DFS (hazard ratio 2.402, 95% confidence interval 1.607-3.590, P < 0.001). Platinum-based chemotherapy improved the 3-year DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (platinum vs. TS-1, median DFS 26.87 vs. 16.27 months, P = 0.028). An LNR > 0.1 was associated with benefiting from platinum-based adjuvant chemotherapy in stage III gastric cancer patients with lymphovascular invasion (platinum vs. TS-1, median DFS 47.57 vs. 21.77 months, P = 0.011).

Conclusions: The LNR can be used to select the appropriate adjuvant chemotherapy regimen for patients with D2-resected gastric cancer, particularly in stage III.

Keywords: Adjuvant chemotherapy; Gastrectomy; Gastric cancer; Lymph node.

Fig. 1

Resected (a) and metastatic (b) LNs according to 3 LNR groups. A median of 44 (interquartile range [IQR] 33–55) LNs were examined, involving a median of three LNs (IQR 1–7)

Fig. 2

a LNRs were initially divided into four categories (0, 0–0.1, > 0.1–025, and > 0.25). b However, the 0 and > 0–0.1 groups were merged as they had similar DFS rates; thus, the population was divided into three LNR groups (LNR 1, 0–0.1; LNR 2, > 0.1–0.25; LNR 3, > 0.25). c DFS curves of the entire population were well separated according to stage

Fig. 3

DFS curves were well separated according to LNR irrespective of adjuvant chemotherapy regimen and stage

Fig. 4

a Platinum-based chemotherapy was associated with a trend of an increased DFS in LNR 3 group of entire patients (P = 0.063). b Platinum-based chemotherapy improved the DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (P = 0.028). c LNR > 0.1 was associated with benefitting from platinum-based adjuvant chemotherapy in patients with stage III gastric cancer and LVI + (P = 0.011). d In T4 cancer, LNR > 0.1 was marginally associated with benefitting from platinum-based adjuvant chemotherapy (P = 0.069). e Cox proportional hazard regression analysis estimating the benefit of platinum-based adjuvant chemotherapy according to LNR subgroups. The solid line represents the 95% CI of the HR