Presentation, management, and outcome of newly diagnosed glioblastoma in elderly patients

Clinical article

View More View Less
  • 1 Departments of Neurosurgery,
  • 3 Neurology, and
  • 4 Radiation Oncology, and
  • 2 Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object

Optimum management for elderly patients with newly diagnosed glioblastoma (GBM) in the temozolomide (TMZ) era is not well defined. The object of this study was to clarify outcomes in this population.

Methods

The authors retrospectively reviewed 105 consecutive cases involving elderly patients (age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008.

Results

The patients' median age was 74 years (range 66–87 years), and the median Karnofsky Performance Status (KPS) score was 80 (range 40–90). Half of the patients underwent biopsy and half underwent resection. Patients with deep-seated lesions (19 patients [18%]) or multifocal lesions (34 patients [32%]) were more likely to have biopsy than resection (p = 0.0001 and 0.0009, respectively). New persistent neurological deficits developed in 7 patients (6.7%). Postoperative hemorrhage occurred in 6 patients (5.7%), all of whom underwent biopsy. Complete follow-up data regarding adjuvant treatment was available in 84 patients. Forty-one (49%) were treated with chemotherapy (mostly TMZ) and radiation therapy (RT), and 23 (27%) with RT alone. Nineteen (23%) received only palliative care after surgery (more common with biopsy, p = 0.03). Chemotherapy complications occurred in 28.6% (Grade 3 or 4 hematological complications in 11.9%). The median values for progression-free survival (PFS) and overall survival (OS) were 3.5 and 5.5 months. In a multivariate analysis, younger age (p = 0.03, risk ratio [RR] 0.34, 95% CI 0.13–0.89), single lesion (p = 0.02, RR 0.51, 95% CI 0.30–0.89), resection (p = 0.04, RR 0.54, 95% CI 0.31–0.94), and adjuvant treatment (p = 0.0001, RR 0.24, 95% CI 0.11–0.49) were associated with better OS. Only adjuvant treatment was significantly associated with prolonged PFS (p = 0.0007, RR 0.27, 95% CI 0.13–0.57). With combined therapy with resection, RT, and chemotherapy, the median PFS and OS were 8 and 12.5 months, respectively.

Conclusions

The prognosis for GBM worsens with increasing age in elderly patients. With important risks, resection and adjuvant treatment are associated with prolonged survival. Although selection bias cannot be excluded in this retrospective study, advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.

Abbreviations used in this paper:GBM = glioblastoma; ICP = intracranial pressure; KPS = Karnofsky Performance Status; OS = overall survival; PFS = progression-free survival; RR = risk ratio; RT = radiation therapy; TMZ = temozolomide.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address correspondence to: Ian F. Parney, M.D., Ph.D., Department of Neurological Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. email: Parney.Ian@mayo.edu.

Please include this information when citing this paper: published online November 23, 2012; DOI: 10.3171/2012.10.JNS112268.

  • 1

    Barnholtz-Sloan JS, , Williams VL, , Maldonado JL, , Shahani D, , Stockwell HG, & Chamberlain M, : Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma. J Neurosurg 108:642648, 2008

    • Search Google Scholar
    • Export Citation
  • 2

    Batchelor TT, , Betensky RA, , Esposito JM, , Pham LD, , Dorfman MV, & Piscatelli N, : Age-dependent prognostic effects of genetic alterations in glioblastoma. Clin Cancer Res 10:228233, 2004

    • Search Google Scholar
    • Export Citation
  • 3

    Bernstein M, & Parrent AG: Complications of CT-guided stereotactic biopsy of intra-axial brain lesions. J Neurosurg 81:165168, 1994

  • 4

    Brandes AA, , Franceschi E, , Tosoni A, , Benevento F, , Scopece L, & Mazzocchi V, : Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115:35123518, 2009

    • Search Google Scholar
    • Export Citation
  • 5

    Brandes AA, & Monfardini S: The treatment of elderly patients with high-grade gliomas. Semin Oncol 30:6 Suppl 19 5862, 2003

  • 6

    Brandes AA, , Vastola F, , Basso U, , Berti F, , Pinna G, & Rotilio A, : A prospective study on glioblastoma in the elderly. Cancer 97:657662, 2003

    • Search Google Scholar
    • Export Citation
  • 7

    Brown PD, , Ballman KV, , Rummans TA, , Maurer MJ, , Sloan JA, & Boeve BF, : Prospective study of quality of life in adults with newly diagnosed high-grade gliomas. J Neurooncol 76:283291, 2006

    • Search Google Scholar
    • Export Citation
  • 8

    Buckner JC: Factors influencing survival in high-grade gliomas. Semin Oncol 30:6 Suppl 19 1014, 2003

  • 9

    Central Brain Tumor Registry of the United States: Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004–2005 (http://www.cbtrus.org/reports/2009-NPCR-04-05/CBTRUSNPCR2004-2005-Report-.pdf) [Accessed October 22, 2012]

    • Search Google Scholar
    • Export Citation
  • 10

    Chaichana KL, , Chaichana KK, , Olivi A, , Weingart JD, , Bennett R, & Brem H, : Surgical outcomes for older patients with glioblastoma multiforme: preoperative factors associated with decreased survival. Clinical article. J Neurosurg 114:587594, 2011

    • Search Google Scholar
    • Export Citation
  • 11

    Chang SM, , Parney IF, , McDermott M, , Barker FG II, , Schmidt MH, & Huang W, : Perioperative complications and neurological outcomes of first and second craniotomies among patients enrolled in the Glioma Outcome Project. J Neurosurg 98:11751181, 2003

    • Search Google Scholar
    • Export Citation
  • 12

    Combs SE, , Wagner J, , Bischof M, , Welzel T, , Wagner F, & Debus J, : Postoperative treatment of primary glioblastoma multiforme with radiation and concomitant temozolomide in elderly patients. Int J Radiat Oncol Biol Phys 70:987992, 2008

    • Search Google Scholar
    • Export Citation
  • 13

    de Robles P, & Cairncross G: Glioblastoma in the elderly: an age-old problem. Ann Neurol 64:597599, 2008

  • 14

    DeAngelis LM, , Burger PC, , Green SB, & Cairncross JG: Malignant glioma: who benefits from adjuvant chemotherapy?. Ann Neurol 44:691695, 1998

    • Search Google Scholar
    • Export Citation
  • 15

    Devaux BC, , O'Fallon JR, & Kelly PJ: Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. J Neurosurg 78:767775, 1993

    • Search Google Scholar
    • Export Citation
  • 16

    Fine HA, , Dear KB, , Loeffler JS, , Black PM, & Canellos GP: Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71:25852597, 1993

    • Search Google Scholar
    • Export Citation
  • 17

    Fiorica F, , Berretta M, , Colosimo C, , Stefanelli A, , Ursino S, & Zanet E, : Glioblastoma in elderly patients: safety and efficacy of adjuvant radiotherapy with concomitant temozolomide. Arch Gerontol Geriatr 51:3135, 2010

    • Search Google Scholar
    • Export Citation
  • 18

    Grossman SA, , Ye X, , Piantadosi S, , Desideri S, , Nabors LB, & Rosenfeld M, : Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res 16:24432449, 2010

    • Search Google Scholar
    • Export Citation
  • 19

    Iwamoto FM, , Cooper AR, , Reiner AS, , Nayak L, & Abrey LE: Glioblastoma in the elderly: the Memorial Sloan-Kettering Cancer Center Experience (1997–2007). Cancer 115:37583766, 2009

    • Search Google Scholar
    • Export Citation
  • 20

    Iwamoto FM, , Reiner AS, , Panageas KS, , Elkin EB, & Abrey LE: Patterns of care in elderly glioblastoma patients. Ann Neurol 64:628634, 2008

    • Search Google Scholar
    • Export Citation
  • 21

    Keime-Guibert F, , Chinot O, , Taillandier L, , Cartalat-Carel S, , Frenay M, & Kantor G, : Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:15271535, 2007

    • Search Google Scholar
    • Export Citation
  • 22

    Kelly PJ, & Hunt C: The limited value of cytoreductive surgery in elderly patients with malignant gliomas. Neurosurgery 34:6267, 1994

  • 23

    Kim JE, , Kim DG, , Paek SH, & Jung HW: Stereotactic biopsy for intracranial lesions: reliability and its impact on the planning of treatment. Acta Neurochir (Wien) 145:547555, 2003

    • Search Google Scholar
    • Export Citation
  • 24

    Kowalczuk A, , Macdonald RL, , Amidei C, , Dohrmann G III, , Erickson RK, & Hekmatpanah J, : Quantitative imaging study of extent of surgical resection and prognosis of malignant astrocytomas. Neurosurgery 41:10281038, 1997

    • Search Google Scholar
    • Export Citation
  • 25

    Kreth FW, , Warnke PC, , Scheremet R, & Ostertag CB: Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme. J Neurosurg 78:762766, 1993

    • Search Google Scholar
    • Export Citation
  • 26

    Lacroix M, , Abi-Said D, , Fourney DR, , Gokaslan ZL, , Shi W, & DeMonte F, : A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190198, 2001

    • Search Google Scholar
    • Export Citation
  • 27

    Lamborn KR, , Chang SM, & Prados MD: Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. Neuro Oncol 6:227235, 2004

    • Search Google Scholar
    • Export Citation
  • 28

    Laperriere N, , Zuraw L, & Cairncross G: Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review. Radiother Oncol 64:259273, 2002

    • Search Google Scholar
    • Export Citation
  • 29

    Laws ER, , Parney IF, , Huang W, , Anderson F, , Morris AM, & Asher A, : Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J Neurosurg 99:467473, 2003

    • Search Google Scholar
    • Export Citation
  • 30

    Lutterbach J, , Sauerbrei W, & Guttenberger R: Multivariate analysis of prognostic factors in patients with glioblastoma. Strahlenther Onkol 179:815, 2003

    • Search Google Scholar
    • Export Citation
  • 31

    Mangiola A, , Maira G, , De Bonis P, , Porso M, , Pettorini B, & Sabatino G, : Glioblastoma multiforme in the elderly: a therapeutic challenge. J Neurooncol 76:159163, 2006

    • Search Google Scholar
    • Export Citation
  • 32

    McGirt MJ, , Mukherjee D, , Chaichana KL, , Than KD, , Weingart JD, & Quinones-Hinojosa A: Association of surgically acquired motor and language deficits on overall survival after resection of glioblastoma multiforme. Neurosurgery 65:463470, 2009

    • Search Google Scholar
    • Export Citation
  • 33

    Minniti G, , De Sanctis V, , Muni R, , Filippone F, , Bozzao A, & Valeriani M, : Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88:97103, 2008

    • Search Google Scholar
    • Export Citation
  • 34

    Mirimanoff RO, , Gorlia T, , Mason W, , Van den Bent MJ, , Kortmann RD, & Fisher B, : Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol 24:25632569, 2006

    • Search Google Scholar
    • Export Citation
  • 35

    Mohan DS, , Suh JH, , Phan JL, , Kupelian PA, , Cohen BH, & Barnett GH: 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 42:981987, 1998

    • Search Google Scholar
    • Export Citation
  • 36

    Nitta T, & Sato K: Prognostic implications of the extent of surgical resection in patients with intracranial malignant gliomas. Cancer 75:27272731, 1995

    • Search Google Scholar
    • Export Citation
  • 37

    Oszvald A, , Güresir E, , Setzer M, , Vatter H, , Senft C, & Seifert V, : Glioblastoma therapy in the elderly and the importance of the extent of resection regardless of age. Clinical article. J Neurosurg 116:357364, 2012

    • Search Google Scholar
    • Export Citation
  • 38

    Roa W, , Brasher PM, , Bauman G, , Anthes M, , Bruera E, & Chan A, : Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22:15831588, 2004

    • Search Google Scholar
    • Export Citation
  • 39

    Rosenblum ML, , Gerosa M, , Dougherty DV, , Reese C, , Barger GR, & Davis RL, : Age-related chemosensitivity of stem cells from human malignant brain tumours. Lancet 1:885887, 1982

    • Search Google Scholar
    • Export Citation
  • 40

    Sanai N, & Berger MS: Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753764, 2008

  • 41

    Sawaya R, , Hammoud M, , Schoppa D, , Hess KR, , Wu SZ, & Shi WM, : Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors. Neurosurgery 42:10441056, 1998

    • Search Google Scholar
    • Export Citation
  • 42

    Scott JG, , Suh JH, , Elson P, , Barnett GH, , Vogelbaum MA, & Peereboom DM, : Aggressive treatment is appropriate for glioblastoma multiforme patients 70 years old or older: a retrospective review of 206 cases. Neuro Oncol 13:428436, 2011

    • Search Google Scholar
    • Export Citation
  • 43

    Sijben AE, , McIntyre JB, , Roldán GB, , Easaw JC, , Yan E, & Forsyth PA, : Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89:97103, 2008

    • Search Google Scholar
    • Export Citation
  • 44

    Simpson JR, , Horton J, , Scott C, , Curran WJ, , Rubin P, & Fischbach J, : Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials. Int J Radiat Oncol Biol Phys 26:239244, 1993

    • Search Google Scholar
    • Export Citation
  • 45

    Stewart LA: Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:10111018, 2002

    • Search Google Scholar
    • Export Citation
  • 46

    Stummer W, , Pichlmeier U, , Meinel T, , Wiestler OD, , Zanella F, & Reulen HJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392401, 2006

    • Search Google Scholar
    • Export Citation
  • 47

    Stupp R, , Mason WP, , van den Bent MJ, , Weller M, , Fisher B, & Taphoorn MJ, : Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987996, 2005

    • Search Google Scholar
    • Export Citation
  • 48

    Tait MJ, , Petrik V, , Loosemore A, , Bell BA, & Papadopoulos MC: Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases. Br J Neurosurg 21:496500, 2007

    • Search Google Scholar
    • Export Citation
  • 49

    Tilgner J, , Herr M, , Ostertag C, & Volk B: Validation of intraoperative diagnoses using smear preparations from stereotactic brain biopsies: intraoperative versus final diagnosis—influence of clinical factors. Neurosurgery 56:257265, 2005

    • Search Google Scholar
    • Export Citation
  • 50

    Wrensch M, , Minn Y, , Chew T, , Bondy M, & Berger MS: Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol 4:278299, 2002

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 682 169 13
Full Text Views 290 25 0
PDF Downloads 147 13 0
EPUB Downloads 0 0 0