Huber, Peter E;
Timke, Carmen;
Nicolay, Nils H;
Lopez, Ramon
Prognostic and predictive potential of omics studies from blood in pancreatic cancer patients treated with concurrent radiotherapy, gemcitabine, and cetuximab
Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
Prognostic and predictive potential of omics studies from blood in pancreatic cancer patients treated with concurrent radiotherapy, gemcitabine, and cetuximab
Beteiligte:
Huber, Peter E;
Timke, Carmen;
Nicolay, Nils H;
Lopez, Ramon
Erschienen:
American Society of Clinical Oncology (ASCO), 2015
Beschreibung:
<jats:p> 326 </jats:p><jats:p> Background: Pancreatic cancer is a cancer with dismal prognosis. Multimodal therapy approaches integrating targeted drugs into radiochemotherapy regimens may be promising concepts for patients with locally advanced disease. It would be desirable to better understand patterns of therapy response, clinical outcome and side effect spectra by performing gene expression and protein analyses from blood samples before, during and after actual treatments. Methods: At defined time points before, during and after neoadjuvant triple therapy consisting of IMRT +/-gemcitabine chemotherapy +/-cetuximab EGFR antibodies, blood samples were collected from 21 patients with advanced pancreatic cancer. Whole blood transcriptomics was performed using Agilent’s human genome wide microarray platform. Quantitative serum protein analysis was performed using the ‘FastQuant’ (sandwich antibody) system on 20 selected proteins with a focus on cytokines and angiogenesis related proteins. Cluster analyses were performed and array data were correlated to local control, survival, CA19-9 response, and side effects e.g. acne grading and hematotoxicity. Results: Whole blood transcriptomics was feasible and showed statistically significant prognostic and predictive value for therapy specific and patient specific expression signatures. RNA expression signatures obtained before and during treatment course appeared to have significant statistical power to predict CA19-9 response, clinical outcome and side effect parameters. Similarly, the serum proteomic time course correlated with clinical outcome. Moreover, cetuximab increased e.g. PDGF, MCP-1, Rantes, Il-6, Angiopoietin, serum and downregulated TIMP-1, Il-8, and Angiogenin levels while radiochemotherapy had primarily the respective opposite effects. Conclusions: Whole blood analyses provides a promising tool to monitor pancreatic cancer patients undergoing radiotherapy+gemcitabine+cetuximab, and the protein and gene expression “signatures” from blood may be prognostic and predictive for clinical endpoints. </jats:p>