Background
Perioperative chemotherapy is an established treatment for advanced gastric cancer patients. Treatment selection is based on clinical staging (cT). We aimed to establish and validate a prognostic score including clinical and molecular factors, to optimize treatment decisions for these patients. Patients and methods
We analyzed 626 carcinomas of the stomach and of the gastro-oesophageal junction from two academic centers including primarily resected and pre-/perioperatively treated patients. Patients were divided into a training (N = 269) and validation (N = 357) set. Expression of11 target genes was measured by quantitative PCR in resected tumors. A risk score to predict overall survival (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by analysing 50 tumor areas from 10 patients. Results
A risk score including the expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT, tumor localization and histopathological type suggested two groups with a significant difference in OS (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.17-0.52). The risk score was successfully validated in an independent cohort (HR, 0.32; 95% CI, 0.21-0.51; P < 0.001) as well as in subgroups of primarily resected (HR, 0.30; 95% CI, 0.17-0.54; P < 0.001) and pre-/perioperatively treated patients (HR, 0.37; 95% CI, 0.17-0.81; P = 0.009). A significant difference in OS of high and low risk patients was also found in primarily resected patients with intestinal (HR: 0.45; 95% CI, 0.23-0.90;P = 0.020) and non-intestinal type carcinomas (HR: 0.1; 95% CI 0.02-0.42; P < 0.001). Intra-tumor heterogeneity analysis indicated a classification reliability of 95% for a supposed analysis of three biopsies. Conclusion
The identified risk score could substantially contribute to an improved management of gastric cancer patients in the context of perioperative chemotherapy.http://ift.tt/2iu94QN
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