Overall Survival In Gastric Cancer Research Articles

Low Maruyama Index Surgery for Gastric Cancer

Japanese definitions and treatment guidelines have dominated extent-of-surgery concepts in gastric cancer for over 4 decades, despite the fact that such definitions/guidelines have changed considerably over time, and the fact they have largely failed to improve survival in prospective, randomized clinical trials. To briefly review lessons from previous surgical trials in gastric cancer, and, more specifically, to review data validating the concept of "low Maruyama Index surgery" as a data-driven guide to surgical treatment. Review of results from blinded multivariate analyses of two separate, prospective, randomized clinical trials: (a) the Macdonald Trial of adjuvant postoperative chemo-radiation, Intergroup 0116, conducted in North America; and (b) the Dutch D1-D2 Trial. Blinded univariate and multivariate analysis of both trials establish "Maruyama Index of Unresected Disease" (MI) <5 as a strong independent predictor of better disease-free and overall survival in gastric cancer. Moreover, a strong "dose response" effect for MI versus survival is apparent. In contrast to surgery focused on achievement of a particular Japanese-defined D-level, "low Maruyama Index surgery" is associated with increased disease-free and overall survival. Further, the dose-response effect suggests MI can be used to quantify the adequacy of lymphadenectomy for a given patient. Low MI surgery can be prospectively planned by using the Maruyama Computer Program pre-operatively or intraoperatively.

Surgical outcomes of patients with gastric carcinoma: the importance of primary tumor location and microvessel invasion

Background This study was done to identify clinicopathologic predictors of disease-free survival (DFS) and overall survival (OS) among patients undergoing potentially curative resections for gastric carcinoma. Methods We reviewed 110 patients surgically treated between 1987 and 2001. There were 74 men and 36 women with a mean age of 65.2 years (range 27 to 87 years). Log-rank tests and Kaplan-Meier survival curves were generated to determine clinicopathologic factors influencing DFS and OS. Significant factors were then determined with Cox multivariate analysis. Results Median survival for all patients was 38.2 months and the estimated 5-year OS was 42.3%. There were no significant differences in DFS or OS for female sex, black race, or age>65. Symptoms associated with lower DFS were weight loss and palpable abdominal mass (P<.05), although none were predictive for OS. Median survival was markedly worse in patients undergoing esophagogastrectomy versus gastrectomy (26.8 vs 52.3 months; P<.05), although there were no significant differences between patients undergoing total gastrectomy versus subtotal gastrectomy. As expected, OS was inversely proportional to the American Joint Committee on Cancer's tumor stage. When compared with patients with partial-thickness tumors (T 1-2), full-thickness (T 3-4) tumors had a decreased median survival (63.8 vs 27.9 months; P<.01). Although N 2 stage was associated with decreased survival (20.6 months), patient outcomes were similar for N 0 and N 1 stages (52.5 and 48.8 months). Lymphatic and capillary invasion (21.4 vs 45.3 months; P<.02) and proximal location of primary tumors (28.5 vs 58.6 months; P<.02) were the only other factors adversely affecting survival. Lauren classification and histologic grade were not significant predictors of patient outcomes. Conclusions In addition to the American Joint Committee on Cancer stage, microvessel involvement and tumor location are important predictors of DFS and OS in gastric cancer and should be included in risk stratification and selection criteria for patients entering novel adjuvant or neoadjuvant clinical trials.

C-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems.

The c-erbB-2 gene (encoding the protein p185) is overexpressed in diverse human cancers and has been implicated to be of prognostic value in gastric cancer. Recent studies suggest a role of p185 in tumor progression by specifically promoting the invasive capacity of tumor cells. Therefore, the present study was conducted with the following three objectives: (1) to support the prognostic value of c-erbB-2 in gastric cancer in a large prospective series using a monoclonal antibody and a highly sensitive immunohistochemical method; (2) to determine the association of c-erbB-2 expression with the expression of invasion-related genes; and (3) to perform the first overall multivariate analysis including c-erbB-2 and the invasion-related tumor-associated protease systems. In a consecutive prospective series of 203 gastric cancer patients (median follow-up, 42 months), expression of c-erbB-2 and a panel of tumor-associated proteases and inhibitors by tumor cells were evaluated semiquantitatively (score 0 to 3) and analyzed for correlation (chi(2) test, Bonferroni-corrected). Kaplan-Meier survival analysis and multivariate Cox analysis were performed to determine the relative prognostic impact of c-erbB-2 and the invasion-related parameters. Kaplan-Meier analysis (log-rank statistics) revealed a significant association of increasing expression of c-erbB-2 with shorter disease-free (P =. 0023) and overall survival (P =.0160). High amounts of p185 were significantly associated with a high expression of urokinase-type plasminogen activator (uPA) (P <.010), uPA-receptor (P =.030), type-1 plasminogen activator inhibitor (PAI) (P <.010), type-2 PAI (P =.021), cathepsin D (P =.036), matrix metalloproteinase-2 (P =. 024), alpha-1-antichymotrypsin (P =.025), and alpha-2-macroglobulin (P =.017). Multivariate analysis considering these proteases/protease inhibitors, in addition to alpha-1-antitrypsin, tissue plasminogen activator, plasminogen, alpha-2-antiplasmin, and antithrombin III, and established prognostic parameters revealed that, in addition to surgical curability, pT stage, pN stage, and PAI-1, c-erbB-2 is an independent prognostic factor for overall survival of curatively resected patients (n = 139; P =.049; relative risk, 1.54; 95% confidence interval, 1.08 to 1.67) and all patients (P =.028; relative risk 1.33; 95% CI, 1.28 to 1.38). c-erbB-2 is confirmed as a new independent, functional prognostic parameter for overall survival in gastric cancer, even when a panel of invasion-related factors, including the strong prognostic parameter PAI-1, are considered. The significant correlation of p185 with several tumor-associated proteases supports the hypothesis that c-erbB-2 is a promoter of invasion and metastasis. This strongly suggests that c-erbB-2 may be a promising target for anti-invasive therapy in gastric cancer.