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Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?

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Abstract

A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of < 70 years (standard group) and 117 patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p < 0.001), including surgical resection (p < 0.001), Bevacizumab therapy (p < 0.001), and second line chemotherapy other than Temozolomide (p < 0.001). In multivariate analysis, Age ≥70 years was not an independent predictor of overall survival from recurrence (p = 0.602), RTOG-RPA classes 5–6 (p = 0.050) and KPS at recurrence <70 (p < 0.001), available in all cases, were independent significant predictors of shorter overall survival from recurrence. Initial removal of ≥ 90% of enhancing tumor (p = 0.004), initial completion of the standard combined chemoradiotherapy (p = 0.007), oncological treatment from recurrence (p < 0.001), and particularly surgical resection (p < 0.001), Temozolomide (p = 0.046), and Bevacizumab therapy (p = 0.041) were all significant independent predictors of longer overall survival from recurrence. Elderly patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.

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Abbreviations

PFS:

Progression-free survival

EFGR:

Epidermal growth factor receptor

HR:

Hazard ratio

KPS:

Karnofsky performance status

OS:

Overall survival

RTOG-RPA:

Radiation therapy oncology group recursive partitioning analysis

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Acknowledgements

Participating centres (in alphabetical order): Amiens University Hospital – University of Amiens, Angers University Hospital – Angers University, Jean-Minjoz Hospital – University of Besançon, Pellegrin Hospital – University Victor Segalen Bordeaux 2, Avicenne University Hospital – Paris 13 University, Morvan Hospital – University of Brest, Caen University Hospital – University Caen Lower-Normandy, Pasteur Hospital in Colmar, Limoges Hospital – University of Limoges, Pierre Wertheimer Hospital – University of Lyon, La Timone Hospital – University Aix-Marseille, Clairval Clinic in Marseille, Gui de Chauliac Hospital – University of Montpellier, Sainte-Anne Hospital Centre - University Paris Descartes, Beaujon Hospital – University Paris Diderot, Maison Blanche Hospital – University of Reims, Pontchaillou Hospital – University of Rennes, Rouen University Hospital – Rouen University, Paul Strauss Cancer Centre – University of Strasbourg, Sainte-Anne Military Teaching Hospital in Toulon, Gustave Roussy University Hospital, Villejuif. These physicians are greatly acknowledged (in alphabetical order): Georges Abi Lahoud, Felipe Andreiuolo, Alin Borha, Céline Botella, André Busson, Laurent Capelle, Françoise Chapon, Isabelle Catry-Thomas, Karl Champeaux, Françine Chassoux, Anaïs Chivet, Fabrice Chrétien, Philippe Colin, Alain Czorny, Phong Dam-Hieu, Jean-Michel Derlon, Bertrand Devaux, Frédéric Dhermain, Marie-Danièle Diebold, Julien Domont, Hugues Duffau, Sarah Dumont, Julien Duntze, Myriam Edjlali-Goujon, Jan Eskandari, Pascale Fabbro-Peray, Anne Fustier, Clément Gantois, Roberto Gadan, Julien Geffrelot, Edouard Gimbert, Joël Godard, Sylvie Godon-Hardy, Marcel Gueye, Jean-Sébastien Guillamo, N Heil, Dominique Hoffmann, Nicolas Jovenin, Michel Kalamarides, Hassan Katranji, Samih Khouri, Maria Koziak, Elisabeth Landré, V Leon, Dominique Liguoro, Guillaume Louvel, Emmanuel Mandonnet, Michael Mann, Eric Méary, Jean-François Meder, Charles Mellerio, Sophie Michalak, Catherine Miquel, Karima Mokhtari, Philippe Monteil, Edmond Nader, Olivier Naggara, Catherine Oppenheim, Isabelle Quintin-Roue, Philippe Paquis, Vladislav Pavlov, Delphine Pedenon, Philippe Peruzzi, Tanguy Riem, Valérie Rigau, Odile Rigaux-Viodé, Adeline Riondel, Alain Rougier, Céline Salon, Elodie Sorbets, Etienne Théret, Baris Turak, Denis Trystram, Fanny Vandenbos, Pascale Varlet, Gabriel Viennet, Anne Vital, Sonia Zouaoui. We would like to thank the Association des Neuro-Oncologues d’Expression Française (ANOCEF).

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Authors and Affiliations

  1. Department of Neurosurgery, Sainte-Anne Hospital, 1, rue Cabanis, 75674, Paris Cedex 14, France

    Marc Zanello, Alexandre Roux, Sophie Peeters, Edouard Dezamis & Johan Pallud

  2. Paris Descartes University, Sorbonne Paris Cité, Paris, France

    Marc Zanello, Alexandre Roux, Sophie Peeters, Edouard Dezamis & Johan Pallud

  3. Service de Neurologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Bobigny, France

    Renata Ursu & Antoine Carpentier

  4. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Sophie Peeters

  5. Department of Neurosurgery, University Hospital of Montpellier, Montpellier, France

    Luc Bauchet

  6. Inserm, U1051, Montpellier, France

    Luc Bauchet

  7. University Radiotherapy Department, Comprehensive Cancer Center Paul Strauss, Unicancer, Strasbourg, France

    Georges Noel

  8. Radiobiology Laboratory, EA 3440, Federation of Translationnal Medicine de Strasbourg (FMTS), Strasbourg University, Strasbourg, France

    Georges Noel

  9. Service of Neurosurgery D, Lyon Civil Hospitals, Pierre Wertheimer Neurological and Neurosurgical Hospital, Lyon, France

    Jacques Guyotat

  10. Department of Neurosurgery, University Hospital Pontchaillou, Rennes, France

    Pierre-Jean Le Reste

  11. Department of Neurosurgery, APHP Beaujon Hospital, Clichy, France

    Thierry Faillot

  12. Department of Neurosurgery, Maison Blanche Hospital, Reims University Hospital, Reims, France

    Fabien Litre

  13. Department of Neurosurgery, Sainte Anne Military Teaching Hospital, Toulon, France

    Nicolas Desse

  14. Departement of Neurosurgery, University Hospital of Caen, University of Lower Normandy, Caen, France

    Evelyne Emery

  15. Department of Neurosurgery, University Hospital Jean Minjoz, Besancon, France

    Antoine Petit

  16. Department of Neurosurgery, Amiens University Hospital, Amiens, France

    Johann Peltier

  17. Department of Neurosurgery, Pasteur Hospital, Colmar, France

    Jimmy Voirin

  18. Service de Neurochirurgie, CHU de Limoges, Limoges, France

    François Caire

  19. Department of Neurosurgery, Clairval Private Hospital, Marseille, France

    Jean-Luc Barat & Philippe Metellus

  20. Service de Neurochirurgie A, CHU Pellegrin, Bordeaux Cedex, France

    Jean-Rodolphe Vignes

  21. Department of Neurosurgery, CHU d’Angers, Angers, France

    Philippe Menei

  22. Department of Neurosurgery, Rouen University Hospital, Rouen, France

    Olivier Langlois

  23. Centre Psychiatrie et Neurosciences, Inserm, U894, Paris, France

    Edouard Dezamis & Johan Pallud

  24. Department of Neurosurgery, University Medical Centre, Faculty of Medicine, University of Brest, Brest, France

    Phong Dam Hieu

  25. UMR911, CRO2, Aix-Marseille Université, Marseille, France

    Philippe Metellus

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  1. Marc Zanello
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On the Behalf of the Club de Neuro-Oncologie of the Société Française de Neurochirurgie

Corresponding author

Correspondence to Johan Pallud.

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Conflict of interest

Johan Pallud has received honoraria for consultancy from Kyowa Hakko Kirin Co. Johan Pallud and Alexandre Roux have received honoraria for speaking engagements (including travel and accommodation) from Kyowa Hakko Kirin Co.

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11060_2017_2573_MOESM2_ESM.docx

Supplementary Table 1 Progression-free survival. Unadjusted and adjusted prognostic factors by Cox proportional hazards model. Supplementary Table 2 Overall survival after treated recurrence. Unadjusted and adjusted prognostic factors by Cox proportional hazards model (DOCX 74 KB)

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Zanello, M., Roux, A., Ursu, R. et al. Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?. J Neurooncol 135, 285–297 (2017). https://doi.org/10.1007/s11060-017-2573-y

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