Increased Survival Associated With Surgery and Radiation Therapy in Metastatic Gastric Cancer: A SEER Database Analysis

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida. .
Cancer (Impact Factor: 4.89). 11/2012; 119(9). DOI: 10.1002/cncr.27927
Source: PubMed


Patients with metastatic gastric cancer have poor survival. The purpose of this study was to compare outcomes of metastatic gastric cancer patients stratified by surgery and radiation therapy.

The Surveillance, Epidemiology, and End Results (SEER) database was accessed to identify patients with AJCC M1 stage IV gastric cancer (based on the American Joint Committee on Cancer Cancer Staging Manual, 6th edition) between 2004 thru 2008. Patients were divided into 4 groups: group 1, no surgery or radiation; group 2, radiation alone; group 3, surgery alone; group 4, surgery and radiation. Survival analysis was determined by Kaplan-Meier and log-rank analysis. Multivariate analysis (MVA) was analyzed by the Cox proportional hazard ratio model.

A total of 5072 patients were identified. Surgery and/or radiation were associated with a survival benefit. Median and 2-year survival for groups 1, 2, 3, and 4 was 7 months and 8.2%, 8 months and 8.9%, 10 months and 18.2%, and 16 months and 31.7%, respectively (P < .00001). MVA for all patients revealed that surgery and radiation were associated with decreased mortality whereas T-stage, N-stage, age, signet ring histology, and peritoneal metastases were associated with increased mortality. In patients treated with surgery, MVA showed that radiation was associated with decreased mortality, whereas T-stage, N-stage, age, removal of < 15 lymph nodes, signet ring histology, and peritoneal metastases was associated with increased mortality. Age was the only prognostic factor in patients who did not undergo surgery.

Surgery and radiation are associated with increased survival in a subset of patients with metastatic gastric cancer. Prospective trials will be needed to address the role and sequence of surgery and radiation in metastatic gastric cancer.

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    • "Gastrectomy is the procedure of choice in selected patients, even though it has never been compared with observation in a randomized trial. Multiple previous studies reported that gastrectomy with or without metastasectomy prolonged survival in patients with metastatic gastric cancer [16,17]. In our study group, the indications for surgical intervention were: (1) adequate organ function and acceptable PS, (2) absence of extensive invasion of the primary tumor into adjacent organs, and (3) absence of extensive metastatic tumor. "
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    ABSTRACT: Background The treatment of metastatic gastric cancer is not uniform, and the prognostic factors and indications for surgery are currently unclear. This retrospective study aimed to identify the prognostic factors and clinical indications for surgery in patients with metastatic gastric cancer. Methods A total of 123 consecutive patients with gastric cancer and synchronous distant metastasis treated between January 1999 and December 2011 were reviewed. Patient, tumor, laboratory, surgical, and chemotherapy factors were analyzed, with overall survival as the endpoint. Univariate analyses were performed using the log-rank test, multivariate analyses were performed using the Cox proportional hazards model, and Kaplan-Meier curves were used to estimate survival. Significance was set at p < 0.05. Results The median overall survival time was 13.1 months. Ninety-eight patients received chemotherapy. Twenty-eight patients underwent gastrectomy with metastasectomy and 55 underwent gastrectomy without metastasectomy. The median overall survival time for patients who underwent gastrectomy with metastasectomy, gastrectomy without metastasectomy, and no surgical intervention was 21.9 months, 12.5 months, and 7.2 months, respectively (p < 0.001). Multivariate analysis identified gastrectomy with or without metastasectomy, performance status (PS) ≥3, neutrophil-to-lymphocyte ratio (NLR) >3.1, and carbohydrate antigen 19–9 (CA19-9) level >37 U/mL as predictors of poor survival. NLR and CA19-9 level were also independent prognostic factors in the group of patients who underwent surgery. Conclusions High pretreatment NLR, CA19-9 level, and PS are predictors of poor prognosis in patients with metastatic gastric cancer. In selected patients, gastrectomy can be performed safely, and may be associated with longer survival.
    Full-text · Article · Jun 2014 · BMC Cancer
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    ABSTRACT: Gastric cancer often presents in a metastasized stage. We conducted a population-based study to evaluate trends in systemic treatment and survival of metastatic noncardia gastric cancer. All patients with noncardia adenocarcinoma of the stomach, diagnosed between 1990 and 2011 in the Eindhoven Cancer Registry area in the Netherlands were included (N = 4797). We conducted multivariable logistic regression analysis to evaluate trends in administration of palliative chemotherapy and multivariable proportional hazards regression analyses to evaluate trends in crude overall survival. The proportion of patients presenting with metastatic gastric cancer increased from 24% in 1990 to 44% in 2011 (P < 0.0001). The use of palliative chemotherapy increased, from 5% in 1990 to 36% in 2011, with a strong increase in particular after 2006 (P < 0.0001). Younger patients [<50 years: adjusted odds ratio (ORadj) 3.9, P < 0.001; 50-59 years: ORadj 1.7, P = 0.01] and patients with a high socioeconomic status (ORadj 1.7, P = 0.01) more often received chemotherapy. In contrast, older patients (70-79 years: ORadj 0.3, P < 0.001; 80+ years: ORadj 0.02, P < 0.001), patients with comorbidity (ORadj 0.6, P = 0.03), linitis plastica (ORadj 0.5, P = 0.03) and multiple distant metastases (ORadj 0.5, P = 0.01) were less often treated with chemotherapy. A large hospital variation was observed in the administration of palliative chemotherapy (9%-27%). Median overall survival remained constant between 15 [95% confidence interval (CI) 11.9-17.7] and 17 (95% CI 15.0-20.0) weeks (P = 0.10). The increased administration of chemotherapy in patients with metastatic gastric cancer did not lead to an increase in population-based overall survival. Identification of the subgroup of patients which benefits from palliative chemotherapy is of utmost importance to avoid unnecessary treatment.
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    ABSTRACT: Recent studies suggest JAK2 signaling may be a therapeutic target for treatment of gastric cancer (GC). However, the exact roles of JAK2 in gastric carcinogenesis are not very clear. Here, we have targeted JAK2 to be silenced by shRNA and investigated the biological functions and related mechanisms of JAK2 in GC cell SGC7901. In this study, JAK2 is commonly highly expressed in GC tissues as compared to their adjacent normal tissues (n = 75, p < 0.01). Specific down-regulation of JAK2 suppressed cell proliferation and colony-forming units, induced G2/M arrest in SGC7901 cells, but had no significant effect on cell apoptosis in vitro or tumor growth inhibition in vivo. Interestingly, JAK2 silencing-induced activation of ERK1/2, and inactivation of ERK1/2 using the specific ERK inhibitor PD98059 markedly enhanced JAK2 shRNA-induced cell proliferation inhibition, cell cycle arrest and apoptosis. Ultimately, combination of PD98059 and JAK2 shRNA significantly inhibited tumor growth in nude mice. Our results implicate JAK2 silencing-induced cell proliferation inhibition, cell cycle arrest, and ERK1/2 inhibition could enhance apoptosis induced by JAK2 silencing in SGC7901 cells.
    No preview · Article · Nov 2013 · Molecular and Cellular Biochemistry
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