Top

Published in:

01-11-2017 | Clinical Study

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

Authors: Marc Zanello, Alexandre Roux, Renata Ursu, Sophie Peeters, Luc Bauchet, Georges Noel, Jacques Guyotat, Pierre-Jean Le Reste, Thierry Faillot, Fabien Litre, Nicolas Desse, Evelyne Emery, Antoine Petit, Johann Peltier, Jimmy Voirin, François Caire, Jean-Luc Barat, Jean-Rodolphe Vignes, Philippe Menei, Olivier Langlois, Edouard Dezamis, Antoine Carpentier, Phong Dam Hieu, Philippe Metellus, Johan Pallud, On the Behalf of the Club de Neuro-Oncologie of the Société Française de Neurochirurgie

Published in: Journal of Neuro-Oncology | Issue 2/2017

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.

Available only for authorised users

Ostrom QT, Gittleman H, Fulop J et al (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-Oncol 17 Suppl 4:iv1–iv62. doi:10.1093/neuonc/nov189 CrossRefPubMedPubMedCentral

Colby SL, Ortman JM et al (2015) Projections of the size and composition of the US population: 2014 to 2060. Curr Popul Rep 9:1–13

Rigau V, Zouaoui S, Mathieu-Daudé H et al (2011) French brain tumor DataBase: 5-year histological results on 25 756 cases. Brain Pathol 21:633–644. doi:10.1111/j.1750-3639.2011.00491.x CrossRefPubMed

Curran WJ, Scott CB, Horton J et al (1993) Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 85:704–710CrossRefPubMed

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. doi:10.1200/JCO.2005.04.5963 CrossRefPubMed

Michaelsen SR, Christensen IJ, Grunnet K et al (2013) Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution. BMC Cancer 13:402. doi:10.1186/1471-2407-13-402 CrossRefPubMedPubMedCentral

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

Vuorinen V, Hinkka S, Färkkilä M, Jääskeläinen J (2003) Debulking or biopsy of malignant glioma in elderly people—a randomised study. Acta Neurochir (Wien) 145:5–10. doi:10.1007/s00701-002-1030-6 CrossRef

Chaichana KL, Garzon-Muvdi T, Parker S et al (2011) Supratentorial glioblastoma multiforme: the role of surgical resection versus biopsy among older patients. Ann Surg Oncol 18:239–245. doi:10.1245/s10434-010-1242-6 CrossRefPubMed

10.

Scott JG, Suh JH, Elson P et al (2011) Aggressive treatment is appropriate for glioblastoma multiforme patients 70 years old or older: a retrospective review of 206 cases. Neuro-Oncol 13:428–436. doi:10.1093/neuonc/nor005 CrossRefPubMedPubMedCentral

11.

Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535. doi:10.1056/NEJMoa065901 CrossRefPubMed

12.

Gállego Pérez-Larraya J, Ducray F, Chinot O et al (2011) Temozolomide in elderly patients with newly diagnosed glioblastoma and poor performance status: an ANOCEF phase II trial. J Clin Oncol 29:3050–3055. doi:10.1200/JCO.2011.34.8086 CrossRefPubMed

13.

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. doi:10.1056/NEJMoa043330 CrossRefPubMed

14.

Perry JR, Laperriere N, O’Callaghan CJ et al (2016) A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (CCTG CE.6, EORTC 26062–22061, TROG 08.02, NCT00482677). J Clin Oncol. doi:10.1093/neuonc/nou209.16 PubMedCentral

15.

Iwamoto FM, Reiner AS, Panageas KS et al (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64:628–634. doi:10.1002/ana.21521 CrossRefPubMed

16.

Bauchet L, Zouaoui S, Darlix A et al (2014) Assessment and treatment relevance in elderly glioblastoma patients. Neuro-Oncol 16:1459–1468. doi:10.1093/neuonc/nou063 CrossRefPubMedPubMedCentral

17.

Morgan ER, Norman A, Laing K, Seal MD (2017) Treatment and outcomes for glioblastoma in elderly compared with non-elderly patients: a population-based study. Curr Oncol Tor Ont 24:e92–e98. doi:10.3747/co.24.3424 CrossRef

18.

Combs SE, Wagner J, Bischof M et al (2008) Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant Temozolomide in elderly patients. Int J Radiat Oncol 70:987–992. doi:10.1016/j.ijrobp.2007.07.2368 CrossRef

19.

Ewelt C, Goeppert M, Rapp M et al (2011) Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival. J Neurooncol 103:611–618. doi:10.1007/s11060-010-0429-9 CrossRefPubMed

20.

Park H-K, Koh Y-C, Song SW (2014) The clinico-oncologic outcomes of elderly patients with glioblastoma after surgical resection followed by concomitant chemo-radiotherapy. Brain Tumor Res Treat 2:69. doi:10.14791/btrt.2014.2.2.69 CrossRefPubMedPubMedCentral

21.

Babu R, Komisarow JM, Agarwal VJ et al (2016) Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival. J Neurosurg 124:998–1007. doi:10.3171/2015.4.JNS142200 CrossRefPubMed

22.

Rusthoven CG, Koshy M, Sher DJ et al (2016) Combined-modality therapy with radiation and chemotherapy for elderly patients with glioblastoma in the temozolomide era: a national cancer database analysis. JAMA Neurol. doi:10.1001/jamaneurol.2016.0839 PubMed

23.

Huang J, Samson PP, Perkins SM et al (2016) Trends in utilization and impact of concurrent chemotherapy with radiation therapy for elderly patients with newly diagnosed glioblastoma: a review of the national cancer data base. J Clin Oncol 34:2034

24.

Martinez-Garcia M, Pineda E, Barco SD et al (2016) Feasibility and efficacy of concomitant chemoradiation (Ch-RT) in the management of newly diagnosed elderly glioblastoma (GB) patients: results from the GLIOCAT study. J Clin Oncol 34:2045

25.

Amsbaugh MJ, Yusuf MB, Gaskins J et al (2017) Patterns of care and predictors of adjuvant therapies in elderly patients with glioblastoma: an analysis of the National Cancer Database. Cancer. doi:10.1002/cncr.30730 PubMed

26.

Flanigan PM, Jahangiri A, Kuang R et al (2017) Developing an algorithm for optimizing care of elderly patients with glioblastoma. Neurosurgery. doi:10.1093/neuros/nyx148

27.

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. doi:10.1093/neuonc/nos273 CrossRefPubMed

28.

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

29.

Li J, Wang M, Won M et al (2011) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol 81:623–630. doi:10.1016/j.ijrobp.2010.06.012 CrossRef

30.

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. doi:10.1200/JCO.2009.26.3541 CrossRefPubMed

31.

Marko NF, Weil RJ, Schroeder JL et al (2014) Extent of resection of glioblastoma revisited: personalized survival modeling facilitates more accurate survival prediction and supports a maximum-safe-resection approach to surgery. J Clin Oncol Off J Am Soc Clin Oncol 32:774–782. doi:10.1200/JCO.2013.51.8886 CrossRef

32.

Stupp R, Brada M, van den Bent MJ et al (2014) High-grade glioma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii93–i101. doi:10.1093/annonc/mdu050 CrossRefPubMed

33.

Mason WP, Maestro RD, Eisenstat D et al (2007) Canadian recommendations for the treatment of glioblastoma multiforme. Curr Oncol Tor Ont 14:110–117CrossRef

34.

Chargari C, Feuvret L, Bauduceau O et al (2012) Treatment of elderly patients with glioblastoma: from clinical evidence to molecular highlights. Cancer Treat Rev 38:988–995. doi:10.1016/j.ctrv.2011.12.010 CrossRefPubMed

35.

Hartmann C, Hentschel B, Wick W et al (2010) Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol (Berl) 120:707–718. doi:10.1007/s00401-010-0781-z CrossRef

36.

Yin A, Zhang L, Cheng J et al (2014) The predictive but not prognostic value of MGMT promoter methylation status in elderly glioblastoma patients: a meta-analysis. PLoS ONE 9:e85102. doi:10.1371/journal.pone.0085102 CrossRefPubMedPubMedCentral

37.

Weller M, Wick W (2011) Are we ready to demystify age in glioblastoma? Or does older age matter in glioblastoma? Neuro-Oncol 13:365–366. doi:10.1093/neuonc/nor019 CrossRefPubMedPubMedCentral

38.

Wick W, Platten M, Meisner C et al (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715. doi:10.1016/S1470-2045(12)70164-X CrossRefPubMed

39.

Mohan DS, Suh JH, Phan JL et al (1998) Outcome in elderly patients undergoing definitive surgery and radiation therapy for supratentorial glioblastoma multiforme at a tertiary care institution. Int J Radiat Oncol Biol Phys 42:981–987CrossRefPubMed

40.

Muacevic A, Kreth FW (2003) Quality-adjusted survival after tumor resection and/or radiation therapy for elderly patients with glioblastoma multiforme. J Neurol 250:561–568. doi:10.1007/s00415-003-1036-x CrossRefPubMed

41.

Stark AM, Hedderich J, Held-Feindt J, Mehdorn HM (2007) Glioblastoma–the consequences of advanced patient age on treatment and survival. Neurosurg Rev 30:56–61. doi:10.1007/s10143-006-0051-7 CrossRefPubMed

42.

Filippini G, Falcone C, Boiardi A et al (2008) Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma. Neuro-Oncol 10:79–87. doi:10.1215/15228517-2007-038 CrossRefPubMedPubMedCentral

43.

Iwamoto FM, Cooper AR, Reiner AS et al (2009) Glioblastoma in the elderly: the Memorial Sloan-Kettering Cancer Center experience (1997–2007). Cancer 115:3758–3766. doi:10.1002/cncr.24413 CrossRefPubMed

44.

Roa W, Kepka L, Kumar N et al (2015) International atomic energy agency randomized phase III study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 33:4145–4150. doi:10.1200/JCO.2015.62.6606 CrossRefPubMed

45.

Minniti G, Scaringi C, Lanzetta G et al (2015) Standard (60 Gy) or short-course (40 Gy) irradiation plus concomitant and adjuvant temozolomide for elderly patients with glioblastoma: a propensity-matched analysis. Int J Radiat Oncol 91:109–115. doi:10.1016/j.ijrobp.2014.09.013 CrossRef

46.

Malmström A, Grønberg BH, Marosi C et al (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13:916–926. doi:10.1016/S1470-2045(12)70265-6 CrossRefPubMed

47.

Kim HR, Kim KH, Kong D-S et al (2015) Outcome of salvage treatment for recurrent glioblastoma. J Clin Neurosci 22:468–473. doi:10.1016/j.jocn.2014.09.018 CrossRefPubMed

48.

Socha J, Kepka L, Ghosh S et al (2016) Outcome of treatment of recurrent glioblastoma multiforme in elderly and/or frail patients. J Neurooncol 126:493–498. doi:10.1007/s11060-015-1987-7 CrossRefPubMed

49.

Scott JG, Bauchet L, Fraum TJ et al (2012) Recursive partitioning analysis of prognostic factors for glioblastoma patients aged 70 years or older. Cancer 118:5595–5600. doi:10.1002/cncr.27570 CrossRefPubMedPubMedCentral

50.

Nguyen LT, Touch S, Nehme-Schuster H et al (2013) Outcomes in newly diagnosed elderly glioblastoma patients after concomitant temozolomide administration and hypofractionated radiotherapy. Cancers 5:1177–1198. doi:10.3390/cancers5031177 CrossRefPubMedPubMedCentral

51.

Wildiers H, Heeren P, Puts M et al (2014) International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 32:2595–2603. doi:10.1200/JCO.2013.54.8347 CrossRefPubMedPubMedCentral

52.

Pallis AG, Ring A, Fortpied C et al (2011) EORTC workshop on clinical trial methodology in older individuals with a diagnosis of solid tumors. Ann Oncol 22:1922–1926. doi:10.1093/annonc/mdq687 CrossRefPubMed

53.

Hurria A, Dale W, Mooney M et al (2014) Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol 32:2587–2594. doi:10.1200/JCO.2013.55.0418 CrossRefPubMedPubMedCentral

54.

Park JK, Hodges T, Arko L et al (2010) Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol 28:3838–3843. doi:10.1200/JCO.2010.30.0582 CrossRefPubMedPubMedCentral

Title: Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?
Authors: Marc Zanello
Alexandre Roux
Renata Ursu
Sophie Peeters
Luc Bauchet
Georges Noel
Jacques Guyotat
Pierre-Jean Le Reste
Thierry Faillot
Fabien Litre
Nicolas Desse
Evelyne Emery
Antoine Petit
Johann Peltier
Jimmy Voirin
François Caire
Jean-Luc Barat
Jean-Rodolphe Vignes
Philippe Menei
Olivier Langlois
Edouard Dezamis
Antoine Carpentier
Phong Dam Hieu
Philippe Metellus
Johan Pallud
On the Behalf of the Club de Neuro-Oncologie of the Société Française de Neurochirurgie
Publication date: 01-11-2017
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-017-2573-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2017

SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway

Walking ability in patients with glioblastoma: prognostic value of the Berg Balance Scale and the 10 meter walk test

IDH mutation status trumps the Pignatti risk score as a prognostic marker in low-grade gliomas

Extraneuraxial metastases in medulloblastoma: is histology and molecular biology important?

Radiomic features predict Ki-67 expression level and survival in lower grade gliomas

Volumetric quantification of glioblastoma: experiences with different measurement techniques and impact on survival