Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry

Abstract

Background:The choice of chemotherapy in HER2-negative gastric cancer is based on centre’s preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).Methods:We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2–3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of ‘treatment-by-histology’ interaction, was used to estimate treatment effect.Results:Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525–0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054–1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49–0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50–0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46–0.88), P=0.046.Conclusions:As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Trajectories of hospitalization in three groups of patients with incurable gastric cancer identified by hierarchical clustering: A retrospecitve analysis

“…Lauren's histological classi cation classi es gastric cancers into two histological subtypes, intestinal and diffuse, as this variable has been reported to predict survival and responses to chemotherapy [18] [19]. In this study, however, we did not observe a signi cant association of either type with a long OS.…”

<p>Irinotecan Induces Autophagy-Dependent Apoptosis and Positively Regulates ROS-Related JNK- and P38-MAPK Pathways in Gastric Cancer Cells</p>

“…In total, 2 × 10 6 viable SGC7901 cells in 100 μL of PBS were injected subcutaneously into the nude mice. When the resultant tumors reached approximately 100 mm 3 , the animals were injected intraperitoneally with either 1) physiological saline (100 μL) or 2) IRI (20 mg/kg), 3-MA (30 mg/ kg), or their combination once weekly for 15 days. Tumor volume (V) was calculated using the following formula: V = longest diameter × shortest diameter 2 × 0.5.…”

“…2 Despite the advances in diagnosis and treatment, the median 5-year overall survival (OS) rate among patients with advanced gastric cancer after surgical resection is still low. 3 Hence, there is an urgent need to find promising therapeutic techniques for treatment of gastric cancer.…”

Efficacy and safety of chemotherapy in older versus non-older patients with advanced gastric cancer: A real-world data, non-inferiority analysis

“…Patients are from the AGAMENON database, a national registry of consecutive cases of AGC, in which 30 Spanish centers and one Chilean center have participated. The study design, characteristics, method, and data quality criteria have been widely communicated elsewhere (9)(10)(11)(12)(13).AGAMENON is a non-interventionist database sponsored by the investigators themselves. Data are collected by means of a web-based data collection tool (http://www.agamenonstudy.com/).…”