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Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study

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Abstract

Introduction

To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain.

Methods

Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals.

Results

Median age was 64 years (range: 19–84; 33% ≥ 70 years), 54% were men, and 59% had a performance status (PS) ≥ 2 at diagnosis. Median delay to diagnosis was 47 days (IQR 24–81). Diagnostic delay > 47 days was associated with PS ≥ 2 (OR 1.99; 95% CI 1.13–3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14–5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40 days, p = 0.04). Median overall survival (OS) was 8.9 months [95% CI 5.9–11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1 months (95%CI 7.7–20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients ≥ 70 years (4.1 vs. 13.4 months; p < 0.0001). Multivariate analysis identified age ≥ 65 years, PS ≥ 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival.

Conclusions

Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients ≥ 70 years.

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Acknowledgements

We thank all the institutions that made possible the review of the medical records. We thank CERCA Programme/Generalitat de Catalunya for institutional support.

GELTAMO (Grupo para el Estudio de Linfomas y Trasplante Autólogo de Médula Ósea): Department of Hematology. Catalan Institute of Oncologia-Hospital Duran i Reynals. IDIBELL Universitat de Barcelona. L’Hospitalet de Llobregat, Barcelona (Eva González-Barca), Department of Pathology, Hospital Universitari de Bellvitge, IDIBELL, L´Hospitalet, Barcelona (Fina Climent), Department of Oncology, Hospital Universitario y Politécnico La Fe, Valencia, Spain (Gemma Bruixola), Department of Hematology. Hospital Universitari Vall d’Hebron. Barcelona (Pau Abrisqueta), Department of Hematology. Hospital Universitario de Salamanca, Salamanca, Spain (Alejandro Martin García-Sancho; Míriam Lopez Parra), Department of Hematology. ICO-Hospital Universitari de Tarragona Joan XXIII. Universitat Rovira I Virgili, Tarragona, Spain. (Lourdes Escoda), Department of Hematology. ICO-Hospital Germans Trias i Pujol. Badalona (Marc Sorigué). GENOSEN (Grupo de Estudio de Neurooncología de la Sociedad Española de Neurología): Department of Neurology, Hospital Universitario La Fe, Valencia (Luis Bataller), Department of Neurology, Fundación Jimenez Diaz, Madrid (Raúl Córdoba), Department of Neurology, Hospital Universitario Miguel Servet, Zaragoza (Miguel González Sánchez), Department of Neurosurgery, Hospital Universitario Marqués de Valdecilla, Santander (Juan Martino), Department of Neurology, Hospital Rey Juan Carlos, Madrid (Javier Pardo-Moreno)

Funding

This work was partially supported by Grant PI1501303 from ISCIII and Fondo Europeo de Desarrollo Regional (FEDER).

Author information

Author notes

  1. R. Velasco and S. Mercadal contributed equally to the development of this article.

  2. R. Velasco and F. Graus should be considered co-senior authors.

Authors and Affiliations

  1. Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO Duran i Reynals, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain

    R. Velasco, N. Vidal & J. Bruna

  2. Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain

    R. Velasco & J. Bruna

  3. Department of Hematology, Catalan Institute of Oncology-Hospital Duran i Reynals, IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain

    S. Mercadal & M. Encuentra

  4. Department of Pathology, Unit of Neuro-Oncology. Hospital Universitari de Bellvitge-ICO Duran i Reynals, IDIBELL, L’Hospitalet del Llobregat, Barcelona, Spain

    N. Vidal

  5. Department of Neurology, Complejo Asistencial Universitario, Salamanca, Spain

    M. Alañá

  6. Department of Neurology, Hospital Universitario Son Espases, Palma de Mallorca, Spain

    M. I. Barceló

  7. Department of Neurology, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    M. J. Ibáñez-Juliá

  8. Department of Hematology, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron, Barcelona, Spain

    S. Bobillo

  9. Department of Neurology, Hospital Universitario Miguel Servet, Zaragoza, Spain

    R. Caldú Agud

  10. Department of Neurology, Virgen de la Arrixaca University Hospital, Murcia, Spain

    E. García Molina

  11. Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain

    P. Martínez

  12. Department of Neurology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain

    P. Cacabelos

  13. Department of Hematology, Hospital Universitario Mutua de Terrassa, Terrassa, Spain

    A. Muntañola

  14. Department of Neurosurgery, Hospital Universitario Marqués de Valdecilla, Santander, Spain

    G. García-Catalán

  15. Department of Hematology, ICO-IJC-Hospital Germans Trias i Pujol, Badalona, Spain

    J. M. Sancho

  16. Department of Neurology, Hospital Universitario Cruces, Barakaldo, Vizcaya, Spain

    I. Camro

  17. Department of Hematology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

    T. Lado

  18. Neurology Department, Complejo Hospitalario de Navarra, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain

    M. E. Erro

  19. Department of Neurology, Hospital Universitario Quirónsalud Madrid, Pozuelo de Alarcón, Madrid, Spain

    L. Gómez-Vicente

  20. Department of Hematology, Hospital del Mar, Barcelona, Spain

    A. Salar

  21. Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    A. C. Caballero

  22. Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla, Spain

    M. Solé-Rodríguez

  23. Departament of Neurology, Clínica Universidad de Navarra, IdiSNA, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain

    J. Gállego Pérez-Larraya

  24. Department of Neurology, Hospital Universitario Severo Ochoa, Leganés, Madrid, Spain

    N. Huertas

  25. Department of Neurology, Hospital Parc Taulí, Sabadell, Spain

    J. Estela

  26. Unit of Neurology, Hospital Universitario Fundación Alcorcón, Madrid, Spain

    M. Barón

  27. Department of Neurology, Hospital Universitario Rey Juan Carlos, HURJC-HUIE-HCV, Madrid, Spain

    N. Barbero-Bordallo

  28. Department of Hematology and Neurology, Hospital Clínic de Barcelona, Barcelona, Spain

    I. Dlouhy & F. Graus

  29. Department of Neurology, Neuro-Oncology Unit, Hospital Universitari de Bellvitge and ICO L’Hospitalet, C/Feixa Llarga S/N, L’Hospitalet de Llobregat, 08907, Barcelona, Spain

    R. Velasco

Authors
  1. R. Velasco
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  2. S. Mercadal
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  3. N. Vidal
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Consortia

GELTAMO and GENOSEN group

  • Eva González-Barca
  • , Fina Climent
  • , Gemma Bruixola
  • , Pau Abrisqueta
  • , Alejandro Martin García-Sancho
  • , Míriam Lopez Parra
  • , Lourdes Escoda
  • , Marc Sorigué
  • , Luis Bataller
  • , Raúl Córdoba
  • , Miguel González Sánchez
  • , Juan Martino
  •  & Javier Pardo-Moreno

Contributions

RV, SM, NV, JB conceived and designed the analysis. RV,SM, NV, FG, MA, AM, IB, MJIJ, LB, SB, PA, RC, EG, PM, PC, AM, JM, JMS, IC, TLL, EE, LG, AS, AC, MS, JG, NH, JE, MB, NB, JP, RC, LE, ED, EGB, ID collected the data. RV, SM, JB, and ME performed the analysis. RV, SM, and FG wrote the paper.

Corresponding author

Correspondence to R. Velasco.

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Conflict of interest

R.V. discloses membership on speaker bureau for Gilead and Novartis. A.S. discloses research funding and membership on advisory committees or speakers bureau for Roche, Celgene, Gilead or Janssen. F.G. holds a patent licensed to Euroimmun for the use of IgLON5 in an autoantibody test, for which he receives royalties, and receives honoraria from MedLink Neurology. The other authors declare no conflict of interest.

Ethical approval

The study was approved by the Institutional Ethical Committee of the coordinating center and, subsequently, by each participating center.

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The members of the study GELTAMO and GENOSEN group are listed in acknowledgement section.

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Velasco, R., Mercadal, S., Vidal, N. et al. Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study. J Neurooncol 148, 545–554 (2020). https://doi.org/10.1007/s11060-020-03547-z

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