Research Article| Volume 378, P3-8, July 15, 2017

Pattern of care and outcome in elderly patients with glioblastoma: Data in 151 patients from 3 Lombardia Hospitals

Published:April 18, 2017DOI:


      • We report a retrospective analysis of 151 elderly glioblastoma (GBM) patients.
      • Higher KPS, macroscopical total resection, radiotherapy and chemotherapy positively influence overall survival (OS).
      • Advanced age, seizure at onset, antiepileptic treatment and additional surgical resection did not influence OS.
      • In elderly fit patients extensive surgery and adjuvant treatment should be proposed.
      • Randomized controlled study is needed to develop treatment guidelines for elderly GBM patients.


      The appropriate treatment approach for elderly patients with glioblastoma multiforme (GBM) is unclear, although different studies suggest survival benefit in fit patients treated with radiotherapy and chemiotherapy after surgery. We performed a retrospective analysis of 151 patients older than 65 years with GBM treated in 3 Lombardia Hospitals. In univariate regression analysis higher KPS (p = 0.02), macroscopical total resection (p < 0.003), radiotherapy (p < 0.0001), chemotherapy (p < 0.0001) and second line chemotheraphy (p = 0.02) were of positive prognostic value. On the contrary older age (>70 years), presence of seizure at onset and additional resection after tumor recurrence did not influence OS. Multivariate analysis revealed radiotherapy (HR 0.2 p < 0.0001) and extent of surgery (HR 0.3, p = 0,0063) as positive independent prognostic factors. Patients receiving radio-chemiotherapy displayed more treatment-related toxicities with a slightly prolonged OS versus those receiving hypofractionated radiotherapy. With the limits of a retrospective study, our data suggest that in elderly fit patients extensive surgery should be considered, moreover adjuvant treatments led to an increase in OS. Randomized controlled study are needed to develop treatment guidelines for elderly GBM patients and to assess whether the combination of post-surgical radio and chemiotherapy may be superior to hypofractionated radiotherapy and chemiotherapy in fit patients.


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        • Ostrom Q.T.
        • Gittleman H.
        • Liao P.
        • et al.
        CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011.
        Neuro-Oncology. 2014; 16: iv1-i63
        • Iwamoto F.M.
        • Reiner A.S.
        • Panageas K.S.
        • Elkin E.B.
        • Abrey L.E.
        Patterns of care in elderly glioblastoma patients.
        Ann. Neurol. 2008; 64: 628-634
        • Kita D.
        • Ciernik I.F.
        • Vaccarella S.
        • et al.
        Age as a predictive factor in glioblastomas: population-based study.
        Neuroepidemiology. 2009; 33: 17-22
        • Paszat L.
        • Laperriere N.
        • Groome P.
        • Schulze K.
        • Mackillop W.
        • Holowaty E.
        A population-based study of glioblastoma multiforme.
        Int. J. Radiat. Oncol. Biol. Phys. 2001; 51: 100-107
        • Barnholtz-Sloan J.S.
        • Williams V.L.
        • Maldonado J.L.
        • et al.
        Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma.
        J. Neurosurg. 2008; 108: 642-648
        • Keime-Guibert F.
        • Chinot O.
        • Taillandier L.
        • et al.
        Radiotherapy for glioblastoma in the elderly.
        N. Engl. J. Med. 2007; 356: 1527-1535
        • Wick W.
        • Platten M.
        • Meisner C.
        • et al.
        Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial.
        Lancet Oncol. 2012; 13: 707-715
        • Malmström A.
        • Grønberg B.H.
        • Marosi C.
        • et al.
        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. 2012; 13: 916-926
        • Roa W.
        • Brasher P.M.
        • Bauman G.
        • et al.
        Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.
        J. Clin. Oncol. 2004; 22: 1583-1588
        • Minniti G.
        • De Sanctis V.
        • Muni R.
        • et al.
        Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients.
        J. Neuro-Oncol. 2008; 88: 97-103
        • Brandes A.A.
        • Bartolotti M.
        Neuro-oncology: treatment decisions in elderly patients with glioblastoma.
        Nat. Rev. Neurol. 2012; 8: 664-665
        • Hoffermann M.
        • Bruckmann L.
        • Kariem Mahdy A.
        • Asslaber M.
        • Payer F.
        • von Campe G.
        Treatment results and outcome in elderly patients with glioblastoma multiforme – a retrospective single institution analysis.
        Clin. Neurol. Neurosurg. 2015; 128: 60-69
        • Lombardi G.
        • Pace A.
        • Pasqualetti F.
        • et al.
        Predictors of survival and effect of short (40 Gy) or standard course (60 Gy) irradiation plus concomitant temozolomide on elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-oncology).
        J. Neuro-Oncol. 2015; 125: 359-367
        • Stupp R.
        • Hegi M.E.
        • Mason W.P.
        • et al.
        Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.
        Lancet Oncol. 2009; 10: 459-466
        • Perry J.R.
        • Laperriere N.
        • O'Callaghan C.J.
        • et al.
        Short course radiation plus temozolomide in elderly patients with glioblastoma.
        N. Engl. J. Med. 2017; 376: 1027-1037
        • Scott J.G.
        • Bauchet L.
        • Fraum T.J.
        • et al.
        Recursive partitioning analysis of prognostic factors for glioblastoma patients aged 70 years or older.
        Cancer. 2012; 118: 5595-5600
        • Jaeckle K.A.
        • Ballman K.
        • Furthh A.
        • Buckner J.C.
        Correlation of enzyme-inducing anticonvulsant use with outcome of patients with glioblastoma.
        Neurology. 2009; 73: 1207-1213
        • Weller M.
        • Gorlia T.
        • Cairncross J.G.
        • et al.
        Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.
        Neurology. 2011; 77: 1156-1164
        • Kerkhof M.
        • Dielemans J.C.
        • van Breemen M.S.
        • et al.
        Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme.
        Neuro-Oncology. 2013; 15: 961-967
        • Guthrie G.D.
        • Eljamel S.
        Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme.
        J. Neurosurg. 2013; 118: 859-865
        • Kim Y.H.
        • Kim T.
        • Joo J.D.
        • et al.
        Survival benefit of levetiracetam in patients treated with concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma multiforme.
        Cancer. 2015; 121: 2926-2932
        • Bobustuc G.C.
        • Baker C.H.
        • Limaye A.
        • et al.
        Levetiracetam enhances p53-mediated MGMT inhibition and sensitizes glioblastoma cells to temozolomide.
        Neuro-Oncology. 2010; 12: 917-927
        • Chaichana K.L.
        • Chaichana K.K.
        • Olivi A.
        • et al.
        Surgical outcomes for older patients with glioblastoma multiforme: preoperative factors associated with decreased survival. Clinical article.
        J. Neurosurg. 2011; 114: 587-594
        • Oszvald A.
        • Güresir E.
        • Setzer M.
        • et al.
        Glioblastoma therapy in the elderly and the importance of the extent of resection regardless of age.
        J. Neurosurg. 2012; 116: 357-366
        • Martinez R.
        • Janka M.
        • Soldner F.
        • Behr R.
        Gross-total resection of malignant gliomas in elderly patients: implications in survival.
        Zentralbl. Neurochir. 2007; 68: 176-181
        • Barker C.A.
        • Chang M.
        • Chou J.F.
        • et al.
        Radiotherapy and concomitant temozolomide may improve survival of elderly patients with glioblastoma.
        J. Neuro-Oncol. 2012; 109: 391-397
        • Ewelt C.
        • Goeppert M.
        • Rapp M.
        • Steiger H.J.
        • Stummer W.
        • Sabel M.
        Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival.
        J. Neuro-Oncol. 2011; 103: 611-618
        • Iwamoto F.M.
        • Cooper A.R.
        • Reiner A.S.
        • Nayak L.
        • Abrey L.E.
        Glioblastoma in the elderly: the Memorial Sloan-Kettering Cancer Center Experience (1997–2007).
        Cancer. 2009; 115: 3758-3766
        • Uzuka T.
        • Aoki H.
        • Natsumeda M.
        • Takahashi H.
        • Fujii Y.
        Effectiveness of maximal safe resection for glioblastoma including elderly and low Karnofsky performance status patients: retrospective review at a single institute.
        Neurol. Med. Chir. (Tokyo). 2012; 52: 570-576
        • Zachenhofer I.
        • Maier R.
        • Eiter H.
        • et al.
        Overall survival and extent of surgery in adult versus elderly glioblastoma patients: a population based retrospective study.
        Wien. Klin. Wochenschr. 2011; 123: 364-368
        • Minniti G.
        • Scaringi C.
        • Lanzetta G.
        • et al.
        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. Biol. Phys. 2015; 91: 109-115
        • Behm T.
        • Horowski A.
        • Schneider S.
        • et al.
        Concomitant and adjuvant temozolomide of newly diagnosed glioblastoma in elderly patients.
        Clin. Neurol. Neurosurg. 2013; 115: 2142-2146
        • Cao J.Q.
        • Fisher B.J.
        • Bauman G.S.
        • Megyesi J.F.
        • Watling C.J.
        • Mac-Donald D.R.
        Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience.
        J. Neuro-Oncol. 2012; 107: 395-405
        • Reifenberger G.
        • Hentschel B.
        • Felsberg J.
        • et al.
        Predictive impact of MGMT promoter methylation in glioblastoma of the elderly.
        Int. J. Cancer. 2012; 131: 1342-1350
        • Minniti G.
        • De Sanctis V.
        • Muni R.
        • et al.
        Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma.
        J. Neuro-Oncol. 2009; 91: 95-100
        • Yin A.A.
        • Zhang L.H.
        • Cheng J.X.
        • et al.
        Radiotherapy plus concurrent or sequential temozolomide for glioblastoma in the elderly: a meta-analysis.
        PLoS One. 2013; 8: e74242
        • Gerstner E.R.
        • Yip S.
        • Wang D.L.
        • Louis D.N.
        • Iafrate A.J.
        • Batchelor T.T.
        MGMT methylation is a prognostic biomarker in elderly patients with newly diagnosed glioblastoma.
        Neurology. 2009; 73: 1509-1510
        • Brandes A.A.
        • Franceschi E.
        • Tosoni A.
        • et al.
        Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status.
        Cancer. 2009; 115: 3512-3518
        • Minniti G.
        • Salvati M.
        • Arcella A.
        • et al.
        Correlation between O6-methylguanine- DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide.
        J. Neuro-Oncol. 2011; 102: 311-316
        • Yin A.A.
        • Cai S.
        • Dong Y.
        • et al.
        A meta-analysis of temozolomide versus radiotherapy in elderly glioblastoma patients.
        J. Neuro-Oncol. 2014; 116: 315-324
        • Weller M.
        • Wick W.
        Are we ready to demystify age in glioblastoma? Or does older age matter in glioblastoma?.
        Neuro-Oncology. 2011; 13: 365-366