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Purpose: Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes. Methods: We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event‐free survival (EFS) were estimated and evaluated for association with downstaging and MSI. Results: We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10]. Conclusion: Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer. Methods: We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration’s Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS. Results: A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25–0.98; p = 0.04), 0.34 (95% CI, 0.21–0.55; p<0.0001) and 0.44 (95% CI, 0.30–0.63; p<0.0001) for one-year-OS, three-year-OS and five-year-OS, respectively. The summary RR for three-year-DFS was 0.43 (95% CI, 0.25–0.72; p = 0.002). Conclusion: Patients with resectable gastric or GEJ cancer who achieved pCR after neoadjuvant chemotherapy can gain a better outcome than patients without pCR. [ABSTRACT FROM AUTHOR]

Background/Aim: Due to the recent development of several promising chemotherapeutic agents, such as S-1, irinotecan (CPT-11) and paclitaxel, response rates for advanced gastric cancer to chemotherapy have improved. Thus far, however, the efficacy and survival benefits of sequential chemotherapy using these agents have not been evaluated. An additional benefit of outpatient sequential chemotherapy, that is, without hospitalization, would be its contribution to the maintenance of patients’ social activities. The aim of this study was to retrospectively evaluate sequential outpatient chemotherapy for advanced gastric cancer. Patients and Methods: Patients with metastatic/recurrent gastric cancer treated with sequential outpatient chemotherapy were analyzed retrospectively. The sequential treatment consisted of S1-based chemotherapy as first-line therapy, low-dose CPT-11/CDDP as second-line therapy and weekly paclitaxel administration as third-line therapy. Results: A series of 32 patients was enrolled in this study. During the sequential chemotherapy, all patients were treated at the outpatient ward of Kyoto University Hospital without hospitalization. The overall response rate was 37.5% and the median survival time was 523 days (95% confidence interval: 323–723 days). The progression-free survival for the three therapies was 135 days for S-1, 148 days for low-dose CPT-11/CDDP and 57 days for paclitaxel. Grade 4 neutropenia was observed in 1 patient (3.1%), and there were no treatment-related deaths. Univariate analysis showed that factors with significant impact on survival were pathological type (intestinal vs. diffuse), clinical response (responder vs. non-responder) and prior chemotherapy. Factors with p values <0.1, including pathological type, clinical response, prior chemotherapy and age (>75 vs. ≤75 years), were evaluated by multivariate analysis, which disclosed that clinical response and patient age were significantly related to patient prognosis. Conclusion: In terms of survival and maintenance of social activities of patients, outpatient sequential chemotherapy appears to be both feasible and effective for advanced gastric cancer. Although prospective analysis of sequential chemotherapy is difficult because of its complex treatment protocol, clinical trials to assess the survival benefits of second-line chemotherapy for advanced gastric cancer are clearly warranted. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]