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Oncological patterns of care and outcomes for 265 elderly patients with newly diagnosed glioblastoma in France

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Abstract

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155–280]; B-CRC n = 21, 318[166–480]; B-RT n = 37, 149[130–214]; RS-CT n = 11, 245[211–na]; RS-CRC n = 18, 372[349–593]; RS-RT n = 39, 269[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.

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Acknowledgements

First, we would like thank the patients and families. We also thank all pathologists, neurosurgeons, neurologists, oncologists, general practitioners, biostatisticians, clinical research technicians, and all those who participated in this important collaborative work.

Funding

This work was conducted with the financial support of grants from the French Institut National du Cancer (INCa), Ligue Nationale Contre le Cancer, Association des Neuro-Oncologues d’Expression Française, Société Française de Neurochirurgie, Associations pour la Recherche sur les Tumeurs Cérébrales (ARTC and ARTC Sud), Schering-Plough Laboratory, Roche Laboratory, Sophysa Laboratory, Archimedes Pharma Laboratory, Département de l’Hérault, Rotary Club (AGLY), and Groupe de Neuro-Oncologie du Languedoc Roussillon.

Conflict of interest

None declared.

Author information

Authors and Affiliations

  1. Department of Neurosurgery and INSERM U1051, Hôpital Saint Eloi—Gui de Chauliac, Centre Hospitalier Universitaire, 80 avenue Augustin Fliche, 34 295, Montpellier cedex 5, France

    Sonia Zouaoui, Hugues Duffau & Luc Bauchet

  2. Department of Medical Oncology and Department of Radiation Oncology, ICM, Montpellier, France

    Amélie Darlix, Michel Fabbro & Christine Kerr

  3. Department of Biostatistics, Institut Universitaire de Recherche Clinique, Montpellier, France and BESPIM, Centre Hospitalier Universitaire, Nîmes, France

    Pascale Fabbro-Peray

  4. Department of Epidemiology, Groupe de Neuro-Oncologie du Languedoc-Roussillon, Registre des Tumeurs de l’Hérault, ICM, Montpellier, France

    Hélène Mathieu-Daudé, Faiza Bessaoud, Fabienne Bauchet & Brigitte Trétarre

  5. Department of Pathology, Centre Hospitalier Universitaire, Hôpital Gui de Chauliac, Montpellier, France

    Valérie Rigau

  6. Department of Medical Oncology and Department of Radiation Oncology, Centre de Lutte Contre le Cancer Val d’Aurelle, Montpellier, France

    Michel Fabbro & Christine Kerr

  7. Neuro Oncology Unit, Department of Neurology, Centre Hospitalier Universitaire, Poitiers, France

    Luc Taillandier

  8. Department of Neuro-Oncology, Hôpital Neurologique, Lyon, France

    François Ducray

  9. Department of Neurosurgery, Centre Hospitalier Universitaire La Milétrie, Poitiers, France

    Michel Wager

  10. Department of Neurosurgery, AP-HP Hôpital Beaujon, Clichy, France

    Thierry Faillot

  11. Department of Neurosurgery, AP-HP Hôpital Pitié-Salpêtrière, Paris, France

    Laurent Capelle

  12. Department of Neurosurgery, Centre Hospitalier Universitaire Pellegrin, Bordeaux, France

    Hugues Loiseau

  13. Department of Neurosurgery, Centre Hospitalier Universitaire, Angers, France

    Philippe Menei

  14. Department of Neuropathology and Inserm U 911, Hôpital de la Timone, Université de la Méditerranée, Marseille, France

    Dominique Figarella-Branger

  15. Department of Neuro-Oncology, Hôpital de la Timone, Université de la Méditerranée, Marseille, France

    Olivier Chinot

Authors
  1. Sonia Zouaoui
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  2. Amélie Darlix
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  3. Pascale Fabbro-Peray
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  4. Hélène Mathieu-Daudé
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  5. Valérie Rigau
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  6. Michel Fabbro
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  7. Faiza Bessaoud
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  8. Luc Taillandier
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  9. François Ducray
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  10. Fabienne Bauchet
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  11. Michel Wager
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  12. Thierry Faillot
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  13. Laurent Capelle
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  14. Hugues Loiseau
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  15. Christine Kerr
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  16. Philippe Menei
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  17. Hugues Duffau
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  18. Dominique Figarella-Branger
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  19. Olivier Chinot
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  20. Brigitte Trétarre
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  21. Luc Bauchet
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Corresponding author

Correspondence to Luc Bauchet.

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Comments

Walter Stummer, Münster, Germany

How old is too old for state-of-the art glioblastoma therapy and what is the consequence for neurosurgeons?

As we are all getting older we are not necessarily feeling older. The world around us is simply getting younger and at some point we fail to understand why patients of age ranges that we will reach sooner than we would prefer, are not receiving treatments we are discussing at our meetings. In addition, it is an interesting fact that in many trials in malignant gliomas we are simply not treating a representative population. In the Stupp trial (Stupp et al. 2005) the median age was only 56 years, in the Gliadel trial (Westphal et al. 2003) median age was 53 years, yet median age in the general population of glioblastoma patients is 63 years (cbtrus.org). Possibly, we are excluding the true population in these studies because it is our inner belief that older patients will not withstand rigorous standard therapy or have an inherent worse prognosis and will dilute our study results. But careful, this may be a self-fulfilling prophecy!

Nowadays, we are accepting the demographic change and are now more and more focusing on older patients and are conceiving trials looking at these patients. Nevertheless, we have interesting ideas about what is “old”. In the recent “elderly” trials in GBM, elderly have been defined to be >65 years in the Methusalem Study (NOA 08; Wick et al. 2012) and 60 years in the Nordic trial (Malmström et al. 2012). The results of these trials have found their way into several guidelines so far. From a surgical point of view, it is unfortunate that resection status, as derived from early post-operative MRI, was not element of these studies. From a surgical perspective, these were missed opportunities to judge whether resection in the “elderly” matters. Studies looking at surgery in the truly elderly are rare. Vuorinen et al. (2003) presented a randomized study testing biopsy against surgery in glioblastoma patients with a median age of 72 years favoring patients with resection. In a cohort of elderly glioblastoma patients with a median age of 70 years, Ewelt et al. (2012) demonstrated extent of resection to be an independent prognostic factor for survival.

Sonai Zouaoui and co-workers here present a cohort of 256 patients with glioblastomas compiled from The French Brain Tumor Database (FBTDB). To be elderly was defined as having a median age beyond 70 years, with a median age of 75 years.

In this analysis, patients receiving surgery and concomitant radiochemotherapy had the best outcomes. These results suggest that in elderly patients maximal therapy should not be simply withheld because of age. Unfortunately, the present analysis lacks multivariate methodology and offers no analysis of factors that were involved in the initial decision to resect or to biopsy. Thus, only the “good” patients (e.g., with high KPS, small, non-eloquently located tumors) may have received maximal therapy and outcome only depended on non-therapeutic prognostic factors. I do however believe that these results cannot be disregarded.

My group has tackled the question of the value of maximal therapy in older patients in some of our studies. In one study—a safety study of 5-ALA—data were collected during the time of transition from simple radiotherapy to concomitant radiochemotherapy after the seminal Stupp-Trial. Thus, we essentially were studying two cohorts, one with radiotherapy and one with radiochemotherapy (Stummer et al. 2011) with median ages at 68 years. We compared these cohorts and stratified by age. Older patients treated with a combination of fluorescence-guided resections and concomitant radiochemotherapy survived 16.3 months and significantly longer than patients treated “only” by surgery with ALA and radiotherapy (11.2 months). Due to the pseudorandomisation afforded by the change in the paradigms of post-operative therapy, the cohorts defined here were well balanced according to the known prognostic factors.

Given the available and emerging data, my conviction is that we should generally not exclude patients from established therapies just because they are old, as suggested by the work of Zouaoui et al. This includes cytoreductive surgery whenever safely possible using established techniques for intra-operative location of tumor, e.g. with Gliolan® or intra-operative MRI, and mapping/monitoring including awake craniotomies, to make surgery as effective and safe as possible.

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Jürgen Voges, Magdeburg, Germany

The disease glioblastoma multiforme (GBM) has its incidence peak in the sixth through eighth decades of life. With the aging of the population, it is foreseeable that the number of diseased patients will increase in particular in industrial countries. Thus, the here-presented statistical analysis of data of glioblastoma patients ≥ 70 years in age at the time of first diagnosis focused on an important patient subgroup. The tumor data bank utilized by the authors had some shortcomings such as the long delay between data entry and analysis, the lack of biomolecular data, no standardized assessment of the radicality of tumor resection, etc. as mentioned in the manuscript. Nowadays, this analysis demonstrates that already the tenacious sampling of basic data renders possible to characterize the impact of different treatment modalities and prognostic variables on survival. This information will in turn enable researchers to improve the design of prospective clinical studies and to adapt the clinical protocols to relevant problems and questions.

Clearly, more can be expected from “complete” data banks, which to establish and maintain is time consuming and laborious but absolute necessary. In the light of the health economic challenges of the upcoming decades, specific financial support of these activities will be essential. However, the fact that a perfect setting is not realized momentarily should nobody discourage to use already existing tumor networks and or databases intensively.

With the participation of Société Française de Neurochirurgie (SFNC) and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie (CNO-SFNC), Société Française de Neuropathologie (SFNP), and Association des Neuro-Oncologues d’Expression Française (ANOCEF)

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Zouaoui, S., Darlix, A., Fabbro-Peray, P. et al. Oncological patterns of care and outcomes for 265 elderly patients with newly diagnosed glioblastoma in France. Neurosurg Rev 37, 415–424 (2014). https://doi.org/10.1007/s10143-014-0528-8

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  • DOI: https://doi.org/10.1007/s10143-014-0528-8

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