Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368 ; EudraCT: 2014–002665-30.

Surgery is still the only curative therapy for locoregional gastric cancer. Hereby it is important to achieve negative margins (R0 resection) and to perform an adequate lymph-node dissection (D2 lymphadenectomy). Unfortunately most cases of gastric cancer are diagnosed in a locally advanced tumor stage. The poor prognosis of patients with these tumors is due to the frequent recurrences after primary resection in curative intent. This observation led to the development of (neo)adjuvant treatment concepts. Beginning with the end of the 1980s, more and more patients with locally advanced tumors were subjected to a preoperative, perioperative, or postoperative treatment in order to improve the prognosis after curative resection. However, in different regions of the world, different regiments are preferred. While adjuvant chemotherapy is the established treatment in Asia, adjuvant chemoradiotherapy is favored in the USA and perioperative chemotherapy is considered the treatment of choice in Europe. However, recently a certain convergence of the different philosophies is to be observed. This article covers the relevant studies dealing with neoadjuvant and adjuvant treatment concepts and gives an overview on the latest developments in this field.

We aimed to investigate patients with gastric/gastro-esophageal adenocarcinomas for sex- and age-specific differences regarding overall survival (OS) and response to neoadjuvant chemotherapy (CTx) under consideration of tumor specific molecular subtypes. Overall, 717 patients were analyzed, including 426 patients treated with and 291 treated without neoadjuvant CTx. Microsatellite instability (MSI) and Epstein-Barr virus positivity (EBV+) were determined previously. Females demonstrated a significantly increased OS (p = 0.035), particularly in the subgroup treated with CTx (p = 0.054). No significant differences regarding age were found. In the molecular subgroups, no sex-related differences were observed in the non-CTx group. However in the CTx group, females with MSI-high (H) tumors showed the best OS (p = 0.043), followed by the male MSI-H (p = 0.198) and female MSS (p = 0.114) compared to the male MSS group as reference. The interaction between sex and MSI in this patient group was noticeable (p = 0.053) and was included as a relevant factor in multivariable analyses. In conclusion, our results show an effect of sex on OS in gastric/gastro-esophageal cancer specifically for patients treated with neoadjuvant CTx. The superior survival of women with MSI-H tumors after neoadjuvant CTx implies that combined consideration of these factors could contribute to an individualized treatment of the patients.

The influence of perioperative transfusion (PT) on outcome following surgery for gastric cancer (GC) remains controversial, with randomized trials lacking and observational series confounded by patient risk factors. This analysis determines the association between reception of leukocyte-depleted blood products and post-operative survival for GC. Data from 610 patients who underwent curative surgery for GC in a German tertiary care clinic from 2001 to 2013 were included. Kaplan–Meier survival curves and Cox proportional hazards regression were applied to determine the association of PT and clinical and patient risk factors for overall and relapse-free survival. Propensity score analysis was performed to adjust for observational biases in reception of PT. Higher Union International Contre le Cancer/American Joint Committee on Cancer (UICC/AJCC)-stages (P <0.001), postoperative complications and severity according to the Clavien–Dindo (CD) classification (P <0.001), PT (P = 0.02), higher age (P <0.001), and neoadjuvant chemotherapy (P <0.001) were related to increased mortality rates. Higher UICC-stages (P <0.001), neoadjuvant chemotherapy (P <0.001), and type of surgery (P = 0.02) were independently associated with increased relapse rates. Patients were more likely to receive PT with higher age (P = 0.05), surgical extension to adjacent organs/structures (P = 0.002), tumor location (P = 0.003), and female gender (P = 0.03). In the adjusted propensity score weighted analysis, PT remained associated with an increased risk of death (hazard ratio (HR): 1.31, 95% CI: 1.01–1.69, P = 0.04). Because of the association of PT with negative influence on patient survival following resection for GC, risks from application of blood products should be weighed against the potential benefits.

We investigated the prognostic and predictive impact of p53 expression for gastric cancer (GC) patients treated without or with preoperative chemotherapy (CTx) and its relationship with specific molecular GC subtypes. Specimens from 694 GC patients (562 surgical resection specimens without or after CTx, 132 biopsies before CTx) were analyzed by p53 immunohistochemistry. High (H) and low (L) microsatellite instability (MSI) and Epstein–Barr virus positivity were determined previously. Our results show that aberrant p53 expression was a negative prognostic factor in uni- and multivariable analysis in the resection specimens cohort (each p < 0.01). Subgroup analysis showed the strongest prognostic effect for patients with distally located tumors or no CTx treatment. In the biopsy cohort before CTx, p53 did not predict response or survival. p53 expression was significantly different among the molecular subtypes in surgical resection and bioptic specimens with strong association of altered p53 with MSI-L. Patients with MSI-H and aberrant p53 showed the worst survival in the biopsy cohort. In conclusion, the prognostic impact of p53 in GC differs according to tumor localization and CTx. Altered p53 is characteristic for MSI-L, and the p53 status in biopsies before CTx delineates MSI-H subtypes with inverse prognostic impact.

Background: the purpose of this analysis was to analyze the outcomes of multimodal treatment that are related to Lauren histotypes in gastro-esophageal cancer (GEC). Methods: patients with GEC between 1986 and 2013 were analyzed. Uni- and multivariate regression analysis were performed to identify predictors for overall survival. Lauren histotype stratified overall survival (OS)-rates were analyzed by the Kaplan–Meier method. Further, propensity score matching (PSM) was performed to balance for confounders. Results: 1290 patients were analyzed. After PSM, the median survival was 32 months for patients undergoing primary surgery (PS) and 43 months for patients undergoing neoadjuvant chemotherapy (nCTx) ahead of surgery. For intestinal types, median survival time was 34 months (PS) vs. 52 months (nCTx+surgery) p = 0.07, 36 months (PS) vs. (31) months (nCTx+surgery) in diffuse types (p = 0.44) and 31 months (PS) vs. 62 months (nCTx+surgery) for mixed types (p = 0.28). Five-/Ten-year survival rates for intestinal, diffuse, and mixed types were 44/29%, 36/17%, and 43/33%, respectively. After PSM, Kaplan–Meier showed a survival benefit for patients undergoing nCTx+surgery in intestinal and mixed types. Conclusion: the Lauren histotype might be predictive for survival outcome in GEC-patients after neoadjuvant/perioperative chemotherapy.