Skip to main content
SpringerLink
Log in

Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0–86) and 8.0 months (mean, 8.5; range, 0–56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03–2.08]; p = 0.032), RTOG–RPA V–VI classes (aHR, 1.38; 95% CI [1.11–1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10–5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44–0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31–0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG–RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG–RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CRF:

Conditional random forest

IQR:

Inter quartile range

KPS:

Karnofsky performance status

OS:

Overall survival

PFS:

Progression-free survival

RPA:

Recursive partitioning analysis

RSF:

Random survival forest

RTOG:

Radiation Therapy Oncology Group

VIMP:

Variable IMPortance

WHO:

World health organization

References

  1. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  2. Weller M, Cloughesy T, Perry JR, Wick W (2013) Standards of care for treatment of recurrent glioblastoma–are we there yet? Neuro-Oncol 15:4–27. https://doi.org/10.1093/neuonc/nos273

    Article  PubMed  Google Scholar 

  3. International Agency for Research on Cancer (2016) WHO classification of tumours of the central nervous system, 4th edn. World Health Organization, Lyon

    Google Scholar 

  4. Lonjon N, Bauchet L, Duffau H et al (2010) Second surgery for glioblastoma. A 4-year retrospective study conducted in both the Montpellier and Nice Departments of Neurosurgery. A literature review. Neurochirurgie 56:36–42. https://doi.org/10.1016/j.neuchi.2009.11.013

    Article  CAS  PubMed  Google Scholar 

  5. De Bonis P, Fiorentino A, Anile C et al (2013) The impact of repeated surgery and adjuvant therapy on survival for patients with recurrent glioblastoma. Clin Neurol Neurosurg 115:883–886. https://doi.org/10.1016/j.clineuro.2012.08.030

    Article  PubMed  Google Scholar 

  6. Hervey-Jumper SL, Berger MS (2014) Reoperation for recurrent high-grade glioma: a current perspective of the literature. Neurosurgery 75:491–499. https://doi.org/10.1227/NEU.0000000000000486 (discussion 498–499)

    Article  PubMed  Google Scholar 

  7. Quick J, Gessler F, Dützmann S et al (2014) Benefit of tumor resection for recurrent glioblastoma. J Neurooncol 117:365–372. https://doi.org/10.1007/s11060-014-1397-2

    Article  CAS  PubMed  Google Scholar 

  8. Clarke JL, Ennis MM, Yung WKA et al (2011) Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? Neuro-Oncol 13:1118–1124. https://doi.org/10.1093/neuonc/nor110

    Article  PubMed  Google Scholar 

  9. Ringel F, Pape H, Sabel M et al (2016) Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection. Neuro-Oncol 18:96–104. https://doi.org/10.1093/neuonc/nov145

    Article  PubMed  Google Scholar 

  10. Woernle CM, Péus D, Hofer S et al (2015) Efficacy of surgery and further treatment of progressive glioblastoma. World Neurosurg 84:301–307. https://doi.org/10.1016/j.wneu.2015.03.018

    Article  PubMed  Google Scholar 

  11. Helseth R, Helseth E, Johannesen TB et al (2010) Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand 122:159–167. https://doi.org/10.1111/j.1600-0404.2010.01350.x

    Article  CAS  PubMed  Google Scholar 

  12. Bloch O, Han SJ, Cha S et al (2012) Impact of extent of resection for recurrent glioblastoma on overall survival: clinical article. J Neurosurg 117:1032–1038. https://doi.org/10.3171/2012.9.JNS12504

    Article  PubMed  Google Scholar 

  13. Barbagallo GMV, Jenkinson MD, Brodbelt AR (2008) “Recurrent” glioblastoma multiforme, when should we reoperate? Br J Neurosurg 22:452–455. https://doi.org/10.1080/02688690802182256

    Article  PubMed  Google Scholar 

  14. Ening G, Osterheld F, Capper D et al (2015) Risk factors for glioblastoma therapy associated complications. Clin Neurol Neurosurg 134:55–59. https://doi.org/10.1016/j.clineuro.2015.01.006

    Article  PubMed  Google Scholar 

  15. D’Amico RS, Cloney MB, Sonabend AM et al (2015) The safety of surgery in elderly patients with primary and recurrent glioblastoma. World Neurosurg 84:913–919. https://doi.org/10.1016/j.wneu.2015.05.072

    Article  PubMed  Google Scholar 

  16. Nieder C, Grosu AL, Molls M (2000) A comparison of treatment results for recurrent malignant gliomas. Cancer Treat Rev 26:397–409. https://doi.org/10.1053/ctrv.2000.0191

    Article  CAS  PubMed  Google Scholar 

  17. Preusser M, de Ribaupierre S, Wöhrer A et al (2011) Current concepts and management of glioblastoma. Ann Neurol 70:9–21. https://doi.org/10.1002/ana.22425

    Article  PubMed  Google Scholar 

  18. Archavlis E, Tselis N, Birn G et al (2014) Combined salvage therapies for recurrent glioblastoma multiforme: evaluation of an interdisciplinary treatment algorithm. J Neurooncol 119:387–395. https://doi.org/10.1007/s11060-014-1500-8

    Article  PubMed  Google Scholar 

  19. Archavlis E, Tselis N, Birn G et al (2013) Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme. BMJ Open. https://doi.org/10.1136/bmjopen-2012-002262

    PubMed  PubMed Central  Google Scholar 

  20. Terasaki M, Ogo E, Fukushima S et al (2007) Impact of combination therapy with repeat surgery and temozolomide for recurrent or progressive glioblastoma multiforme: a prospective trial. Surg Neurol 68:250–254. https://doi.org/10.1016/j.surneu.2006.11.042

    Article  PubMed  Google Scholar 

  21. Niyazi M, Siefert A, Schwarz SB et al (2011) Therapeutic options for recurrent malignant glioma. Radiother Oncol J Eur Soc Ther Radiol Oncol 98:1–14. https://doi.org/10.1016/j.radonc.2010.11.006

    Article  Google Scholar 

  22. Franceschi E, Brandes AA (2015) The role of bevacizumab in recurrent glioblastoma: new insights from randomized trials. CNS Oncol 4:117–119. https://doi.org/10.2217/cns.15.7

    Article  CAS  PubMed  Google Scholar 

  23. Gorlia T, Stupp R, Brandes AA et al (2012) New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials. Eur J Cancer 48:1176–1184. https://doi.org/10.1016/j.ejca.2012.02.004

    Article  PubMed  Google Scholar 

  24. Carson KA, Grossman SA, Fisher JD, Shaw EG (2007) Prognostic factors for survival in adult patients with recurrent glioma enrolled onto the new approaches to brain tumor therapy CNS consortium phase I and II clinical trials. J Clin Oncol 25:2601–2606. https://doi.org/10.1200/JCO.2006.08.1661

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kirkpatrick JP, Sampson JH (2014) Recurrent malignant gliomas. Semin Radiat Oncol 24:289–298. https://doi.org/10.1016/j.semradonc.2014.06.006

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tagliamonte SA, Baayen RH (2012) Models, forests, and trees of York English: was/were variation as a case study for statistical practice. Lang Var Change 24:135–178. https://doi.org/10.1017/S0954394512000129

    Article  Google Scholar 

  27. Stupp R, Hegi ME, Mason WP et al. (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide vs radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466. https://doi.org/10.1016/S1470-2045(09)70025-7

    Article  CAS  PubMed  Google Scholar 

  28. Wen PY, Macdonald DR, Reardon DA et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972. https://doi.org/10.1200/JCO.2009.26.3541

    Article  PubMed  Google Scholar 

  29. Macdonald DR, Cascino TL, Schold SC, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280

    Article  CAS  PubMed  Google Scholar 

  30. Mirimanoff R-O, Gorlia T, Mason W et al (2006) Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol 24:2563–2569. https://doi.org/10.1200/JCO.2005.04.5963

    Article  CAS  PubMed  Google Scholar 

  31. Hothorn T, Hornik K, Zeileis A (2004) Unbiased Recursive Partitioning: A Conditional Inference Framework. http://epub.wu.ac.at/676/. Accessed 25 Sep 2017

  32. Ishwaran H, Kogalur UB, Blackstone EH, Lauer MS (2008) Random survival forests. Ann Appl Stat 2:841–860. https://doi.org/10.1214/08-AOAS169

    Article  Google Scholar 

  33. Breiman L (2001) Random forests. Mach Learn 45:5–32. https://doi.org/10.1023/A:1010933404324

    Article  Google Scholar 

  34. Harrell F (2016) Regression modeling strategies: with applications to linear models, logistic and ordinal regression, and survival analysis. Springer S.l., New York

    Google Scholar 

  35. Hothorn T, Zeileis A (2015) Partykit: a modular toolkit for recursive partytioning in R. J Mach Learn Res 16:3905–3909

    Google Scholar 

  36. Hervey-Jumper SL, Li J, Lau D et al (2015) Awake craniotomy to maximize glioma resection: methods and technical nuances over a 27-year period. J Neurosurg 123:325–339. https://doi.org/10.3171/2014.10.JNS141520

    Article  PubMed  Google Scholar 

  37. Chaichana KL, Zadnik P, Weingart JD et al (2013) Multiple resections for patients with glioblastoma: prolonging survival. J Neurosurg 118:812–820. https://doi.org/10.3171/2012.9.JNS1277

    Article  PubMed  Google Scholar 

  38. Goldman DA, Panageas KS (2016) Letter to the editor: biases in estimation of overall survival in patients who underwent repeat resection of glioblastoma. J Neurosurg 125:519–522. https://doi.org/10.3171/2015.11.JNS152515

    Article  PubMed  Google Scholar 

Download references

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, Morvan Hospital—University of Brest, Assistance Publique-Hôpitaux de Paris Avicenne Hospital—University Paris 13, 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, Guy 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, Caroline Apra, Alin Borha, Céline Botella, André Busson, Laurent Capelle, Karl Champeaux, Françoise Chapon, Françine Chassoux, Isabelle Catry-Thomas, Fabrice Chrétien, Philippe Colin, Alain Czorny, Jean-Michel Derlon, Bertrand Devaux, Frédéric Dhermain, Marie-Danièle Diebold, Julien Domont, Hugues Duffau, Sarah Dumont, Myriam Edjlali-Goujon, Jan Eskandari, 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, François Nataf, Catherine Oppenheim, Isabelle Quintin-Roue, Philippe Page, Philippe Paquis, Delphine Pedenon, Philippe Peruzzi, Tanguy Riem, Valérie Rigau, Odile Rigaux-Viodé, Alain Rougier, François-Xavier Roux, Céline Salon, Etienne Théret, Baris Turak, Denis Trystram, Fanny Vandenbos, Pascale Varlet, Gabriel Viennet, Anne Vital. We would like to thank the Association des Neuro-Oncologues d’Expression Française (ANOCEF).

Author information

Author notes

  1. Etienne Audureau and Anaïs Chivet have contributed equally to this work.

Authors and Affiliations

  1. Public Health Department, Henri Mondor Teaching Hospital, Créteil, France

    Etienne Audureau, Edouard Dezamis, Marc Zanello & Alexandre Roux

  2. Laboratoire d’Investigation Clinique, EA 4393, Université Paris Est Créteil, Créteil, France

    Etienne Audureau, Edouard Dezamis, Marc Zanello & Alexandre Roux

  3. Department of Neurosurgery, Sainte-Anne Hospital, Paris, France

    Anaïs Chivet & Johan Pallud

  4. Paris Descartes University, Paris, France

    Anaïs Chivet & Johan Pallud

  5. Department of Neurology, Avicenne Hospital, AP-HP, Bobigny, France

    Renata Ursu & Antoine Carpentier

  6. Department of Neurosurgery, Leeds General Infirmary, Leeds, UK

    Robert Corns & Jean-Luc Barat

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

    Philippe Metellus

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

    Philippe Metellus

  9. Department of Radiotherapy, Centre de Lutte Contre le Cancer Paul Strauss, Strasbourg, France

    Georges Noel

  10. Radiobiology laboratory, EA 3440, Federation of Translational Medicine de Strasbourg (FMTS), Strasbourg University, Strasbourg, France

    Georges Noel

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

    Sonia Zouaoui & Luc Bauchet

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

    Jacques Guyotat

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

    Pierre-Jean Le Reste

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

    Thierry Faillot

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

    Fabien Litre & Julien Duntze

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

    Nicolas Desse

  17. Department of Neurosurgery, University Hospital Jean Minjoz, Besançon, France

    Antoine Petit

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

    Evelyne Emery

  19. Department of Pathology, Caen University Hospital, Caen, France

    Emmanuelle Lechapt-Zalcman

  20. CNRS, UMR 6232 CERVOxy Group, Caen, France

    Emmanuelle Lechapt-Zalcman

  21. University of Caen Basse-Normandie, UMR 6232 CERVOxy Group, Caen, France

    Emmanuelle Lechapt-Zalcman

  22. CEA, UMR 6232 CERVOxy Group, Caen, France

    Emmanuelle Lechapt-Zalcman

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

    Johann Peltier

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

    Jimmy Voirin

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

    Philippe Menei

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

    François Caire

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

    Phong Dam Hieu

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

    Olivier Langlois

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

    Jean-Rodolphe Vignes

  30. Department of Biostatistique, Epidémiologie clinique, Santé Publique, Informations Médicales, University Hospital of Nîmes, Nîmes, France

    Pascale Fabbro-Peray, Adeline Riondel & Elodie Sorbets

  31. Inserm, U894, IMABRAIN, Centre Psychiatrie et Neurosciences, Paris, France

    Alexandre Roux & Johan Pallud

  32. Inserm, U1051, Montpellier, France

    Luc Bauchet

Authors
  1. Etienne Audureau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anaïs Chivet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renata Ursu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Corns
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Philippe Metellus
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Georges Noel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sonia Zouaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jacques Guyotat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pierre-Jean Le Reste
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Thierry Faillot
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Fabien Litre
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Nicolas Desse
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Antoine Petit
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Evelyne Emery
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Emmanuelle Lechapt-Zalcman
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Johann Peltier
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Julien Duntze
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Edouard Dezamis
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Jimmy Voirin
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Philippe Menei
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. François Caire
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Phong Dam Hieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Jean-Luc Barat
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Olivier Langlois
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Jean-Rodolphe Vignes
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Pascale Fabbro-Peray
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Adeline Riondel
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Elodie Sorbets
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Marc Zanello
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Alexandre Roux
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Antoine Carpentier
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Luc Bauchet
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Johan Pallud
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the Club de Neuro-Oncologie of the Société Française de Neurochirurgie

Corresponding author

Correspondence to Johan Pallud.

Ethics declarations

Financial disclosures

Johan Pallud, Philippe Menei, Julien Duntze, Antoine Petit, and Philippe Metellus have received honoraria for consultancy from Kyowa Kirin Pharma. Johan Pallud, Johann Peltier, Thierry Faillot, Nicolas Desse, Evelyne Emery, Antoine Petit, Philippe Metellus, Vladislav Pavlov, Olivier Langlois, Alexandre Roux, and Marc Zanello have done speaking engagements (including travel and accommodation) from Kyowa Kirin Pharma.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Audureau, E., Chivet, A., Ursu, R. et al. Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model. J Neurooncol 136, 565–576 (2018). https://doi.org/10.1007/s11060-017-2685-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-017-2685-4

Keywords

Search

Navigation