The GOLD ReGISTry: a Global, Prospective, Observational Registry Collecting Longitudinal Data on Patients with Advanced and Localised Gastrointestinal Stromal Tumours

Barrios, Carlos H.; Blackstein, Martin E.; Blay, Jean‐Yves; Casali, Paolo G.; Chacón, Matías; Gu, Jin; Kang, Yoon Koo; Nishida, Toshirou; Purkayastha, Das; Woodman, Richard C.; Reichardt, Peter

doi:10.1016/j.ejca.2015.07.010

Cited by 33 publications

(27 citation statements)

References 31 publications

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“…Because of the presence of KIT or PDGFRA mutations in the majority of patients with GIST, imatinib mesylate, a selective tyrosine kinase inhibitor (TKI), has been written into consensus at home and abroad as the first-line treatment for patients with GIST (7)(8)(9). Consummate pathologic examination and genetic testing can predict the efficacy of imatinib mesylate for patients with GIST, especially with the KIT and PDGFRA mutations (10)(11)(12)(13). The response rate to imatinib in patients with GIST with KIT exon 9 mutations is 48%, approximately as half as that of patients with exon 11 mutations (83.5%).…”

Section: Introductionmentioning

confidence: 99%

Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors

Zhang

Qian

et al. 2018

Molecular Cancer Therapeutics

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Gastrointestinal stromal tumors (GIST) are the most prevalent mesenchymal tumors of the digestive tract. To investigate the association of imatinib mesylate plasma concentration with adverse drug reactions (ADRs) and influences of genetic polymorphisms on ADRs in GIST patients taking imatinib, a cohort of GIST patients consecutively treated with imatinib were included in the observational study. Clinical, pathologic and genotype information was recorded at enrollment and blood samples were collected at time as design. The plasma concentration of the imatinib was detected by LC-MS/MS. A questionnaire was used to evaluate the ADRs at each visit. SNPs in 13 genes were analyzed for a possible association with ADRs. The mean plasma trough concentration of 129 patients taking imatinib was 1.45 AE 0.79 mg/ml, average peak concentration was 2.63 AE 1.07 mg/ml. The imatinib concentration in patients treated with 600 mg/day was significantly higher than other dosage groups (P < 0.05). The ADRs were mostly mild. Edema, vomiting, and fatigue were significantly correlated with imatinib concentration (P < 0.05). Mutations of IL13 rs1800925 and CXCL14 rs7716492 were related with the incidence of leukopenia and rash in our research, separately (P < 0.05). We confirmed that with the increase of imatinib concentration, the incidence of edema, vomiting, and fatigue rises as well. Mutations of IL13 rs1800925 and CXCL14 rs7716492 may be the promising biomarkers to predict the ADRs of imatinib. The results of the study are of guiding significance for the use of imatinib in patients with GIST.

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Section: Introductionmentioning

confidence: 99%

Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors

Zhang

Qian

et al. 2018

Molecular Cancer Therapeutics

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“…These rare malignancies represent around 5% of all the gastric neoplasms, and most commonly include GISTs, NENs of the stomach, and/or primary gastric lymphomas. [3][4][5] From the molecular standpoint, the pathogenesis of gastric tumors is diverse, and even though several risk factors for stomach cancer have been identified recently, the exact biochemical and cellular mechanisms underlying the formation of gastric tumors remain only partially known.…”

Section: Introductionmentioning

confidence: 99%

Peripheral trafficking of bone-marrow-derived stem cells in patients with different types of gastric neoplasms

et al. 2016

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Recently, there has been a growing interest in the importance of stem cells (SCs) in the development/progression of gastric neoplasms. In this study, we performed a comprehensive analysis of different populations of bone-marrow-derived stem cells (BMSCs) in patients with various types of gastric malignancies, including gastric cancer, gastrointestinal stromal tumors (GISTs), neuroendocrine neoplasms (NENs), and lymphomas. We found significantly lower numbers of circulating Lin-/CD45 +/ CD133 + hematopoietic stem/progenitor cells (HSPCs), and intensified peripheral trafficking of both Lin-/CD45-/CXCR4+/CD34+/CD133+ very small embryonic/epiblast-like stem cells (VSELs) and CD105 + /STRO-1 +/ CD45- mesenchymal SCs (MSCs) in patients with gastric cancer, but not in those with other types of gastric neoplasms. No significant differences in the absolute numbers of circulating CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were observed between the groups. This abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was neither associated with clinical stage of the disease nor with systemic levels of stromal-derived factor-1 (SDF-1), as these were comparable to the values observed in control individuals. Interestingly, the absolute numbers of circulating BMSCs correlated with the concentrations of complement cascade-derived anaphylatoxins/molecules (mainly C5b-9/membrane attack complex-MAC) and sphingosine-1-phosphate (S1P). In summary, our translational study revealed that abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Further, our findings indicate that highlighted complement cascade-derived molecules and S1P, but not SDF-1, are significant players associated with this phenomenon.

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“…Other less frequently occurring types of neoplasms, which may have milder and less debilitating clinical outcomes, may also develop within the gastric tissue. These include gastrointestinal stromal tumors (GISTs), neuroendocrine neoplasms (NENs), and/or diverse types of gastric lymphomas456789. However, even though significant effort has been directed toward elucidating the pathogenesis of various types of gastric neoplasms, the exact mechanisms and factors responsible for the development and/or progression of these tumors in humans remain unknown.…”

mentioning

confidence: 99%

Interleukins 17 and 23 in patients with gastric neoplasms

Błogowski

Madej-Michniewicz

Marczuk

et al. 2016

Sci Rep

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Recently there has been heightened interest in the potential significance of interleukin (IL)-17 and IL-23 in the development/progression of human malignancies. Here, we analyzed the systemic levels of these cytokines in 75 patients with different types of gastric neoplasms (carcinoma, gastrointestinal stromal tumors, neuroendocrine neoplasms, and lymphomas) and 42 healthy volunteers. We found that patients with all types of gastric neoplasms have significantly lower IL-23 levels. However, in comparison to the levels in healthy individuals, IL-17 concentrations were lower only in patients with types of gastric neoplasms other than carcinoma. Interestingly, IL-17 levels significantly differed between patients with early and advanced gastric carcinoma. No significant associations were detected between the systemic levels of examined interleukins and TNM staging. However, peripheral levels of IL-23 were correlated with the absolute numbers of circulating populations of bone marrow-derived mesenchymal and very small embryonic/epiblast-like stem cells in patients with gastric carcinoma. ROC curve analyses demonstrated that systemic levels of IL-17 seem to meet basic criteria for consideration as a helpful diagnostic marker in the detection of gastric carcinoma. In conclusion, our study provides translational evidence confirming the clinical significance of IL-17 and IL-23 in the pathogenesis of different types of gastric neoplasms in humans.

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The GOLD ReGISTry: a Global, Prospective, Observational Registry Collecting Longitudinal Data on Patients with Advanced and Localised Gastrointestinal Stromal Tumours

Abstract: In this real-world GIST registry, patients with advanced GIST were treated with imatinib and patients with localised GIST received surgical resection, in accordance with prevailing clinical recommendations.

Cited by 33 publications

References 31 publications

Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors

Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors

Peripheral trafficking of bone-marrow-derived stem cells in patients with different types of gastric neoplasms

Interleukins 17 and 23 in patients with gastric neoplasms

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