Gastric cancer†: ESMO–ESSO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Waddell, Tom; Verheij, Marcel; Allum, William; Cunningham, David; Cervantes, Andrés; Arnold, Dirk

doi:10.1016/j.radonc.2013.09.015

Cited by 111 publications

(139 citation statements)

References 45 publications

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“…In 88 patients, two blocks obtained from the same resection specimen were retrieved, and for 76 of them, a third additional block was also available. Per patient, the median number of biopsy fragments retrieved was five (range [1][2][3][4][5][6][7][8].…”

Section: Her2 Status In Paired Samples and Correlation With Clinicopamentioning

confidence: 99%

“…Additionally, despite the lack of a global standard [3], use of anthracyclines is supported by a meta-analysis highlighting significant survival advantages with anthracycline-containing triplets in a palliative setting [4]. As a result, regimens such as ECF (or ECF modifications) are recommended by current European and North American guidelines for both resectable and first-line settings [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

et al. 2016

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Background HER2 and topoisomerase 2 alpha (TOP2A) genomic status was previously reported to predict benefit from anthracyclines in breast cancer. We sought to define the prognostic impact and possible pitfalls related to these biomarkers in resectable gastroesophageal adenocarcinoma. Methods HER2 and TOP2A gene amplification by fluorescent in situ hybridization and HER2 protein expression by immunohistochemistry (IHC) were assessed on whole tissue sections from 101 patients receiving peri-or postoperative epirubicin-based chemotherapy. In a subgroup of patients, at least two matched tumor blocks, originating either from surgical procedures (n = 88) or diagnostic biopsies (n = 32), were available for HER2 analyses by IHC. Results Eighteen of 101 patients (17.8 %) were HER2 positive, whereas TOP2A was amplified in 4 of 84 patients (4.7 %). HER2 positivity was significantly associated with improved disease-free survival [HR = 0.47 (95 % CI 0.22-0.99), P = 0.046] and overall survival [HR = 0.33 (95 % CI 0.13-0.83), P \ 0.018], independent of clinicalpathologic features. HER2 expression in matched tumor blocks from the same resection specimen was discordant in up to 11.8 % of pairs, while this rate increased up to 27.2 % when diagnostic biopsies and paired surgical samples were compared. Conclusions HER2 status is an independent prognostic biomarker in gastroesophageal adenocarcinomas receiving epirubicin-based chemotherapy. Compared to diagnostic biopsies, HER2 assessment in multiple resection specimens might lower the risk of sampling errors. These findings have several implications with respect to the optimal choice of the sample to be submitted to IHC testing of HER2.

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Section: Her2 Status In Paired Samples and Correlation With Clinicopamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

et al. 2016

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“…While a number of different first-line chemotherapy regimens have been validated for use in this setting, there is as yet no consensus recommendation for the most effective combination of agents for this patient group [2]. Most commonly, eligible patients with advanced esophagogastric cancer will receive combination chemotherapy regimens based on a platinumfluoropyrimidine doublet [3]. The addition of an anthracycline or docetaxel to such doublets has been shown to improve overall survival, albeit at the cost of increased toxicity [2,[4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer

et al. 2016

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Background This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). Methods Patients aged C18 years with advanced or metastatic solid tumors were enrolled in a 3 ? 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m 2 followed by oxaliplatin 130 mg/m 2 (maximum 8 cycles) and then S-1 [20 mg/m 2 (cohort 1) or 25 mg/m 2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapynaïve advanced or metastatic esophagogastric cancer. Results DLT was reported for two of the five patients in cohort 2, defining 20 mg/m 2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m 2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. Conclusions The promising activity of EOS (S-1 dose level, 25 mg/m 2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.

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“…The risk factors for gastric cancer include male gender, cigarette smoking, Helicobacter pyroli infection, atrophic gastritis and partial gastrectomy. A small number of patients may have a genetic propensity syndrome [2]. The focus is not only on the well-established targeted treatments for GC, like anti-epidermal growth factor receptor therapies, Anti-HER2 (ERBB2) therapy, angiogenesis pathways, hepatocyte growth factor/c-MET signalling pathway and programmed cell death-1 receptor and its ligands but also on the determination of predictive markers and co-development of drugs with these markers [3].…”

Section: Introductionmentioning

confidence: 99%

Structure Prediction and in Silico Designing of Drugs Against Kallikrein Protein 12

Devgan¹

2017

Int J Curr Pharm Sci

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Objective: Human Kallikrein protein 12 (hK12) might serve as a novel diagnostic and prognostic biomarker, as well as a potential therapeutic target, in gastric cancer. Methods:In this work, a theoretical model of hK12 receptor protein was generated using the concepts of homology modeling and loop modeling. The resulting model was validated with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against hK12 receptor protein using AutoDock Vina in PyRx 0.8. The structure of ligand DB04786 (Suramin), with least binding energy, was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 16 new ligands. Results:The results indicated that the ligand10 bears the minimum binding energy (-12.3 Kcal/mol) with the target protein and thus the prospects of binding are high. The results also clearly demonstrated that the in silico molecular docking studies of selected ligands, i.e., suramin, ligands 5, 6, 10 and 16 with hK12 protein exhibited favourable binding interactions and warranted. Conclusion:Further studies needed for the development of potent inhibitors for the overexpression of hK12 protein making the management of gastric cancer more efficient.

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Gastric cancer†: ESMO–ESSO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Cited by 111 publications

References 45 publications

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

Assessment of HER2 status in patients with gastroesophageal adenocarcinoma treated with epirubicin-based chemotherapy: heterogeneity-related issues and prognostic implications

Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer

Structure Prediction and in Silico Designing of Drugs Against Kallikrein Protein 12

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