Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
04 2019
Historique:
received: 23 10 2018
revised: 02 01 2019
accepted: 13 01 2019
pubmed: 4 3 2019
medline: 27 5 2020
entrez: 4 3 2019
Statut: ppublish

Résumé

The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design.

Sections du résumé

BACKGROUND
The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting.
METHODS
We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model.
RESULTS
The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392).
CONCLUSION
We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design.

Identifiants

pubmed: 30826661
pii: S0959-8049(19)30040-1
doi: 10.1016/j.ejca.2019.01.019
pii:
doi:

Substances chimiques

CA-19-9 Antigen 0

Types de publication

Journal Article Multicenter Study Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

94-106

Investigateurs

Ludovic Evesque (L)
Alexandra Heurgué (A)
Jérôme Desramé (J)
Thierry Lecomte (T)
Wulfran Cacheux (W)
Jean-Baptiste Bachet (JB)
Jean-Marc Phelip (JM)
Vincent Hautefeuille (V)
Nassim Hammoudi (N)
Florence Mary (F)
Christophe Locher (C)
Anne Bidault-Thirot (A)
Lysiane Marthey (L)
Yann Touchefeu (Y)
Valérie Moulin (V)
Aziz Zaanan (A)
Julien Taïeb (J)
Mariaelena Casagrande (M)
Sabina Murgioni (S)
Daniele Santini (D)
Lorenzo Fornaro (L)
Francesco Montagnani (F)
Francesco Leone (F)
Luca Faloppi (L)
Elisa Giommoni (E)
Stefania Eufemia Lutrino (SE)
Andrea Palloni (A)
Oronzo Brunetti (O)
Francesca Bergamo (F)
Enrico Vasile (E)
David Malka (D)
David Propper (D)

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Cindy Neuzillet (C)

Medical Oncology, Curie Institute, Versailles Saint-Quentin University, Saint-Cloud, France; Medical Oncology, Henri Mondor University Hospital, AP-HP, Créteil, France. Electronic address: cindy.neuzillet@curie.fr.

Andrea Casadei Gardini (A)

Division of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, Italy.

Bertrand Brieau (B)

Gastroenterology, Cochin University Hospital, AP-HP, Paris, France.

Caterina Vivaldi (C)

Oncology, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.

Cristina Smolenschi (C)

GI Oncology, Gustave Roussy Institute, Villejuif, France.

Giovanni Brandi (G)

Oncology, Policlinico S. Orsola-Malpighi, Bologna, Italy.

David Tougeron (D)

Hepato-Gastroenterology, Poitiers University Hospital, Jean Bernard Hôpital, Poitiers, France.

Roberto Filippi (R)

Medical Oncology, Candiolo Cancer Institute, FPO, IRCCS, Candiolo, Italy; Department of Oncology, University of Turin, Italy.

Angélique Vienot (A)

Oncology, Besançon University Hospital, Besançon, France.

Nicola Silvestris (N)

Medical Oncology Unit and Scientific Directorate, Cancer Institute "Giovanni Paolo II", Bari, Italy.

Anne-Laure Pointet (AL)

Gastroenterology and GI Oncology, George Pompidou European University Hospital, AP-HP, Paris, France.

Sara Lonardi (S)

Medical Oncology 1 Unit, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy.

Benoît Rousseau (B)

Medical Oncology, Henri Mondor University Hospital, AP-HP, Créteil, France.

Mario Scartozzi (M)

Medical Oncology Unit, University of Cagliari, Cagliari, Italy.

Laetitia Dahan (L)

Pôle "DACCORD" (Digestif, Anatomie Pathologique, Chirurgie, CISIH, Oncologie, Radiothérapie, Dermatologie), Service d'Oncologie Digestive, CHU Timone, Marseille, France.

Giuseppe Aprile (G)

Department of Oncology, Ospedale San Bortolo, Azienda ULSS8 Berica, Distretto Est, Vicenza, Italy; Department of Oncology, University Hospital of Udine, Udine, Italy.

Tarek Boussaha (T)

Oncology, Centre Multidisciplinaire d'Oncologie-CePo, Lausanne, Switzerland.

David Malka (D)

GI Oncology, Gustave Roussy Institute, Villejuif, France.

Shantini M Crusz (SM)

Oncology, Barts Cancer Institute-Queen Mary University of London, London, United Kingdom.

Samuel Le Sourd (S)

Gastroenterology and Hepatology, Centre Eugène Marquis, Rennes, France.

Aurélia Meurisse (A)

Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France; Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France.

Astrid Lièvre (A)

Gastroenterology, Pontchaillou University Hospital, Rennes, France; Rennes 1 University, Rennes, France.

Dewi Vernerey (D)

Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France; Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, F-25000, Besançon, France. Electronic address: dvernerey@chu-besancon.fr.

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