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Breast cancer patients treated with intrathecal therapy for leptomeningeal metastases in a large real-life database

Authors :
Lionel Uwer
Paule Augereau
Thierry Petit
Matthieu Carton
C. Levy
L. Larrouquere
Luc Cabel
M.-A. Mouret-Reynier
Florence Dalenc
M. Carausu
C. Lefeuvre-Plesse
Michaël Chevrot
Amélie Darlix
M. Campone
Benjamin Verret
A. Gonçalves
Jean-David Fumet
M. Leheurteur
Marc Debled
C. Courtinard
J-M Ferrero
Christelle Jouannaud
David Pasquier
Institut Curie [Paris]
Institut du Cancer de Montpellier (ICM)
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille)
Université Lille Nord de France (COMUE)-UNICANCER
Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)
Institut Bergonié [Bordeaux]
UNICANCER
Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP)
Imagerie Moléculaire et Stratégies Théranostiques (IMoST)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
Institut Paoli-Calmettes
Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)
Institut Claudius Regaud
Institut Gustave Roussy (IGR)
Département de médecine oncologique [Gustave Roussy]
Centre René Gauducheau [Saint-Herblain] (CRLCC Nantes-Atlantique)
Centre Régional de Lutte Contre le Cancer Nantes-Atlantique
Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO)
Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL)
Université Côte d'Azur (UCA)-UNICANCER
Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC)
UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL)
Centre Eugène Marquis (CRLCC)
Centre Paul Strauss
CRLCC Paul Strauss
Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL)
Institut Jean Godinot [Reims]
Centre Léon Bérard [Lyon]
Bordeaux population health (BPH)
Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Université de Lille-UNICANCER
Centre de Recherche en Cancérologie de Marseille (CRCM)
Aix Marseille Université (AMU)-Institut Paoli-Calmettes
Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
UNICANCER-Université Côte d'Azur (UCA)
Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
Admin, Oskar
Source :
ESMO Open, ESMO Open, European Society for Medical Oncology, 2021, 6 (3), pp.100150. ⟨10.1016/j.esmoop.2021.100150⟩, ESMO Open, 2021, 6 (3), pp.100150. ⟨10.1016/j.esmoop.2021.100150⟩
Publication Year :
2021

Abstract

Background Leptomeningeal metastasis (LM) is a rare complication of metastatic breast cancer (MBC), with high morbidity/mortality rates. Our study aimed to describe the largest-to-date real-life population of MBC patients treated with intrathecal (IT) therapy and to evaluate prognostic models. Methods The Epidemiological Strategy and Medical Economics (ESME) MBC database (NCT03275311) includes all consecutive patients who have initiated treatment for MBC since 2008. Overall survival (OS) of patients treated with IT therapy was estimated using the Kaplan–Meier method. Prognostic models were constructed using Cox proportional hazards models. Performance was evaluated using C-index and calibration plots. Results Of the 22 266 patients included in the database between 2008 and 2016, 312 received IT therapy and were selected for our analysis. Compared with non-IT-treated patients, IT-treated patients were younger at MBC relapse (median age: 52 years versus 61 years) and more often had lobular histology (23.4% versus 12.7%) or triple-negative subtype (24.7% versus 13.3%) (all P < 0.001). Median OS was 4.5 months [95% confidence interval (CI) 3.8-5.6] and 1-year survival rate was 25.6%. Significant prognostic factors associated with poorer outcome on multivariable analysis were triple-negative subtype (hazard ratio 1.81, 95% CI 1.32-2.47), treatment line ≥3 (hazard ratio 1.88, 95% CI 1.30-2.73), ≥3 other metastatic sites (hazard ratio 1.33, 95% CI 1.01-1.74) and IT cytarabine or thiotepa versus methotrexate (hazard ratio 1.68, 95% CI 1.28-2.22), while concomitant systemic therapy was associated with better OS (hazard ratio 0.47, 95% CI 0.35-0.62) (all P < 0.001). We validated two previously published prognostic scores, the Curie score and the Breast-graded prognostic assessment, both with C-index of 0.57. Conclusions MBC patients with LM treated with IT therapy have a poor prognosis. We could identify a subgroup of patients with better prognosis, when concomitant systemic therapy and IT methotrexate were used.<br />Highlights • The outcome of BC patients with IT-treated LM is poor, with a median OS of 4.5 months. • Concomitant systemic therapy may improve the outcome in IT-treated patients. • Patients treated with IT methotrexate had better outcome than those treated with IT cytarabine/thiotepa. • The Curie and Breast-graded prognostic assessment scores were prognostic for IT-treated patients.

Details

ISSN :
20597029
Volume :
6
Issue :
3
Database :
OpenAIRE
Journal :
ESMO open
Accession number :
edsair.doi.dedup.....664404b88be174225901ee6670286eb6
Full Text :
https://doi.org/10.1016/j.esmoop.2021.100150⟩