Impact of Delay in Adjuvant Chemoradiation on Survival in Resected Gastric Cancer

BackgroundAdjuvant chemo(radio)therapy is known to improve survival in resected gastric cancer. However, there is scant data on the effect of delay in start of adjuvant treatment (AT) after surgery, and guidelines regarding optimal timing are mostly empirical.MethodsIn this ambispective analysis, we evaluated the survival outcome of patients who underwent upfront curative intent radical gastrectomy followed by AT at our center from 2002 through 2019. Cox proportional hazards model was used to identify predictors of recurrence-free survival (RFS) and overall survival (OS).ResultsTwo-hundred and thirty patients (median age 53 years) with stage I-III carcinoma stomach were included. Seventy-six percent patients underwent D2 lymphadenectomy; 12% received adjuvant chemotherapy alone while 88% received chemoradiotherapy. AT was initiated at a median 42 days after surgery; 17% started within 4 weeks, 55% between 4–8 weeks, and 28% after 8 weeks. Five-year RFS and OS for full cohort were 42.3±4.2% and 63.2±4.4%, respectively. On multivariate analysis, disease stage, ECOG performance status and time to AT emerged as significant predictors of RFS and OS while extent of lymphadenectomy, number of resected lymph nodes and margin positivity did not. Initiation of AT after 8 weeks was associated with significantly worse 5-year RFS (HR 2.28; 95% CI, 1.29–4.04; p=0.005) and OS (HR 2.65; 95% CI, 1.27–5.52; p=0.010).ConclusionsDelaying AT beyond 8 weeks after radical gastrectomy may be detrimental to disease recurrence and survival in patients with gastric cancer. If patients have adequately recovered, AT should preferably be initiated within 8 weeks of surgery.

Prognostic value of noggin protein expression in patients with resected gastric cancer

Background Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. Methods A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. Results RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P < 0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P < 0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35–0.97, P < 0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81–2.26, P = 0.251). Conclusions Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.