Comparison of Long-Term Efficacy in S-1 and Capecitabine With Oxaliplatin as Adjuvant Chemotherapy for Patients With Gastric Cancer After Curative Surgery: A Retrospective, Single-Center Observational Study.

Purpose: Various adjuvant chemotherapies have been introduced for gastric cancer patients after gastrectomy with D2 lymph node dissection. Although the mainstream regimen of adjuvant chemotherapy in Korea includes S-1 monotherapy (TS-1) and capecitabine with oxaliplatin (XELOX), few studies have compared the long-term efficacies of these 2 regimens. Methods: Between January 2010 and June 2017, 2021 patients were diagnosed with gastric cancer and underwent curative resection with adjuvant chemotherapy at our institution. Of 1461 patients with stage IB-III gastric cancer, 825 received TS-1 and 636 received XELOX as adjuvant chemotherapy. We retrospectively reviewed their medical records and analyzed the postoperative 5-year overall survival (OS) and disease-free survival (DFS) of these 2 groups. Results: The patients in the XELOX group had more advanced stage of cancer than the TS-1 group (stages III and II: 56.6% and 43.1%, respectively, in XELOX and 35.3% and 57.0% in TS-1; P < .001). The DFS did not differ significantly between the 2 study groups at any pathologic stage. The OS differed significantly only at pathologic stages IIA (P = .024) and IIB (P = .015). In a multivariate analysis of stage II patients, type of regimen was an independent prognostic factor of OS (XELOX vs TS-1; hazard ratio: 0.47, 95% confidence interval: 0.25-0.89, P = .021). Conclusion: There were similar long-term efficacies between these 2 regimens in advanced gastric cancer patients who underwent curative surgery. However, the XELOX regimen might be favorable for OS of stage II patients.

MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas.

The establishment of better selection criteria for identifying sub-populations that may benefit from treatment is a key aspect of the development and success of targeted therapy. To investigate methods for assessing MET overexpression in gastric cancer, we conducted immunohistochemistry using a new anti-Total MET monoclonal antibody in a single-institution cohort of 495 patients. As antibody is directed against a membranous and/or cytoplasmic epitope, two interpretation methods were used: (1) membranous and cytoplasmic and (2) membranous alone. In selected 120 cases, copy number gain and mRNA expression levels were measured using quantitative real-time PCR. Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in 108 cases (21.8%) and membranous alone overexpression was observed in 40 cases (8.1%). The highest correlation was observed in membranous and cytoplasmic staining of MET: MET expression scores correlated significantly with high MET mRNA levels (r=0.465, P<0.0001), increased copy number gain (r=0.393, P=0.000002) and amplification of MET gene. Moreover, patients with MET overexpression showed shorter overall survival (HR, 1.781; 95% CI, 1.324-2.395; P<0.001) and disease-free survival (HR, 1.765; 95% CI, 1.227-2.541; P=0.002) compared with patients without MET overexpression. However, membranous overexpression of MET did not highly correlate with mRNA level (r=0.274, P=0.002), copy number gain or survival (P>0.05). We developed highly correlating interpretation methods of MET immunohistochemistry in gastric carcinomas. MET overexpression is an independent prognostic factor and could be a potential target and predictor of benefit for targeted therapy with MET inhibitors.