title: Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.
abstract: In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index = 0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values.
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France. mjary@chu-besancon.fr.|INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France. mjary@chu-besancon.fr.|Clinical Investigation Center 1431, EFS Bourgogne-Franche Comté, Besançon, France. mjary@chu-besancon.fr.
authors.forename: Marine
authors.identifier: 0000-0001-7502-7708
authors.initials: M
authors.lastname: Jary
authors.affiliation: CNRS, Unit 7292, University François-Rabelais, Tours, France.|Department of HepatoGastroenterology and Digestive Oncology, University Hospital, Tours, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lecomte
authors.affiliation: Department of HepatoGastroenterology and Digestive Oncology, University Hospital Robert Debré, Reims, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France.|Clinical Investigation Center 1431, EFS Bourgogne-Franche Comté, Besançon, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France.
authors.forename: Erion
authors.initials: E
authors.lastname: Dobi
authors.affiliation: INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Queiroz
authors.affiliation: Department of Medical Oncology, Leclerc Anticancer Center, Dijon, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France.|Department of Gastroenterology, University Hospital, Besançon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Etienne
authors.affiliation: INSERM, Clinical Investigational Center CIC 1415, Tours, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Léger
authors.affiliation: INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Godet
authors.affiliation: INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Balland
authors.affiliation: Department of Digestive Surgery and Liver Transplantation, University Hospital, Besançon, France.
authors.forename: Zaher
authors.initials: Z
authors.lastname: Lakkis
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France.|INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Adotevi
authors.affiliation: INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France.|Clinical Investigation Center 1431, EFS Bourgogne-Franche Comté, Besançon, France.|Methodological and Quality of Life in Oncology Unit, EA 3181, University Hospital, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Medical Oncology, University Hospital, Besançon, France.|INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France.|Clinical Investigation Center 1431, EFS Bourgogne-Franche Comté, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: INSERM, Unit 1098, University of Bourgogne- Franche Comté, Besançon, France.|Clinical Investigation Center 1431, EFS Bourgogne-Franche Comté, Besançon, France.|Methodological and Quality of Life in Oncology Unit, EA 3181, University Hospital, Besançon, France.
authors.forename: Dewi
authors.initials: D
authors.lastname: Vernerey
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D053668:Syndecan-1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; C508241:SDC1 protein, human; D053668:Syndecan-1
keywords: CD138; Syndecan-1; biomarker; colorectal cancer; prognostic score