Skip to main content
Erschienen in: Journal of Neuro-Oncology 2/2012

01.04.2012 | Clinical Study - Patient Study

Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience

verfasst von: Jeffrey Q. Cao, Barbara J. Fisher, Glenn S. Bauman, Joseph F. Megyesi, Christopher J. Watling, David R. Macdonald

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

Abstract

The landmark Stupp study demonstrated a survival advantage with concomitant and adjuvant temozolomide (TMZ) with standard radiotherapy (RT) in glioblastoma multiforme (GBM) patients but excluded those older than 70 years. The prospective Roa study of older GBM patients treated with hypofractionated 3-week course RT demonstrated equivalence to standard 6-week course RT. Taken together, these trials suggest hypofractionated RT with TMZ may be a reasonable treatment option for elderly GBM patients. We conducted a retrospective review of GBM patients (age ≥60 years) treated with hypofractionated RT and temozolomide at our institution between 2000 and 2010. We identified 112 patients who received hypofractionated RT, with 57 receiving concurrent and adjuvant TMZ and 55 without concurrent chemotherapy. Of the 55 patients who received hypofractionated RT alone initially, 24 subsequently received TMZ as salvage treatment at time of progression. Among the concurrent RT + TMZ patients, mean age was 70 years (range 60–86), median KPS was 80 (range 30–100) and 24/57 (42%) received prior debulking surgery. Median overall survival (OS) among the RT + TMZ patients was 6.9 months (95% CI, 4.5–8.6). Patients without concurrent chemotherapy were similar in demographics (age, sex, corticosteroid use, KPS) except 34/55 (62%) were debulked (P-value 0.045.) Median OS was 9.3 months (95% CI, 5.9–11.8) (P-value 0.351). Sub-group analysis revealed patients treated with initial hypofractionated radiation with salvage TMZ had increased median OS of 13.3 months (95% CI, 9.9–19.3) (P-value 0.012). Our results suggest concurrent and adjuvant TMZ does not confer a survival benefit in elderly GBM patients. A sequential approach may be a more effective and efficient strategy by selecting responding patients who may benefit most from subsequent salvage chemotherapy.
Literatur
1.
Zurück zum Zitat Fine HA et al (2005) Neoplasms of the central nervous system, chapter 39.2. In: DeVita VT, Hellman SA, Rosenburg SA (eds) Cancer: principles and practice of oncology, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1834–1888 Fine HA et al (2005) Neoplasms of the central nervous system, chapter 39.2. In: DeVita VT, Hellman SA, Rosenburg SA (eds) Cancer: principles and practice of oncology, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1834–1888
2.
Zurück zum Zitat Paravati AJ, Heron DE, Landsittel D et al (2010) Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of radiation therapy oncology group-recursive partitioning analysis in the IMRT and temozolomide era. J Neurooncol 104(1):339–349PubMedCrossRef Paravati AJ, Heron DE, Landsittel D et al (2010) Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of radiation therapy oncology group-recursive partitioning analysis in the IMRT and temozolomide era. J Neurooncol 104(1):339–349PubMedCrossRef
3.
Zurück zum Zitat Li J, Wang M, Won M et al (2010) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81(3):623–630PubMedCrossRef Li J, Wang M, Won M et al (2010) Validation and simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81(3):623–630PubMedCrossRef
4.
Zurück zum Zitat 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(suppl. 9):704–710PubMed 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(suppl. 9):704–710PubMed
5.
Zurück zum Zitat CBTRUS (2010). CBTRUS Statistical Report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2006. Source: Central Brain Tumor Registry of the United States, Hinsdale. http://www.cbtrus.org CBTRUS (2010). CBTRUS Statistical Report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2006. Source: Central Brain Tumor Registry of the United States, Hinsdale. http://​www.​cbtrus.​org
6.
Zurück zum Zitat Iwamoto FM, Reiner AS, Panageas KS, Elkin EB, Abrey LE (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64(suppl. 6):628–634PubMedCrossRef Iwamoto FM, Reiner AS, Panageas KS, Elkin EB, Abrey LE (2008) Patterns of care in elderly glioblastoma patients. Ann Neurol 64(suppl. 6):628–634PubMedCrossRef
7.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(suppl. 10):987–996PubMedCrossRef Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(suppl. 10):987–996PubMedCrossRef
8.
Zurück zum Zitat Mirimanoff RO, 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(suppl. 16):2563–2569PubMedCrossRef Mirimanoff RO, 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(suppl. 16):2563–2569PubMedCrossRef
9.
Zurück zum Zitat Roa W, Brasher PM, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22(suppl. 9):1583–1588PubMedCrossRef Roa W, Brasher PM, Bauman G et al (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22(suppl. 9):1583–1588PubMedCrossRef
10.
Zurück zum Zitat Macdonald DR, Cascino TL, Schold SC, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8(suppl. 7):1277–1280PubMed Macdonald DR, Cascino TL, Schold SC, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8(suppl. 7):1277–1280PubMed
11.
Zurück zum Zitat Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356(suppl. 15):1527–1535PubMedCrossRef Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356(suppl. 15):1527–1535PubMedCrossRef
12.
Zurück zum Zitat Kleinberg L, Slick T, Enger C, Grossman S, Brem H, Wharam MD (1997) Short course radiotherapy is an appropriate option for most malignant glioma patients. Int J Radiat Oncol Biol Phys 38(suppl. 1):31–36PubMed Kleinberg L, Slick T, Enger C, Grossman S, Brem H, Wharam MD (1997) Short course radiotherapy is an appropriate option for most malignant glioma patients. Int J Radiat Oncol Biol Phys 38(suppl. 1):31–36PubMed
13.
Zurück zum Zitat Slotman BJ, Kralendonk JH, van Alphen HA, Kamphorst W, Karim AB (1996) Hypofractionated radiation therapy in patients with glioblastoma multiforme: results of treatment and impact of prognostic factors. Int J Radiat Oncol Biol Phys 34(suppl. 4):895–898PubMed Slotman BJ, Kralendonk JH, van Alphen HA, Kamphorst W, Karim AB (1996) Hypofractionated radiation therapy in patients with glioblastoma multiforme: results of treatment and impact of prognostic factors. Int J Radiat Oncol Biol Phys 34(suppl. 4):895–898PubMed
14.
Zurück zum Zitat Hoegler DB, Davey P (1997) A prospective study of short course radiotherapy in elderly patients with malignant glioma. J Neurooncol 33(suppl. 3):201–204PubMedCrossRef Hoegler DB, Davey P (1997) A prospective study of short course radiotherapy in elderly patients with malignant glioma. J Neurooncol 33(suppl. 3):201–204PubMedCrossRef
15.
Zurück zum Zitat Jeremic B, Shibamoto Y, Grujicic D et al (1999) Short-course radiotherapy in elderly and frail patients with glioblastoma multiforme. A phase II study. J Neurooncol 44(suppl. 1):85–90PubMedCrossRef Jeremic B, Shibamoto Y, Grujicic D et al (1999) Short-course radiotherapy in elderly and frail patients with glioblastoma multiforme. A phase II study. J Neurooncol 44(suppl. 1):85–90PubMedCrossRef
16.
Zurück zum Zitat Chang EL, Yi W, Allen PK, Levin VA, Sawaya RE, Maor MH (2003) Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 56(suppl. 2):519–528PubMedCrossRef Chang EL, Yi W, Allen PK, Levin VA, Sawaya RE, Maor MH (2003) Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 56(suppl. 2):519–528PubMedCrossRef
17.
Zurück zum Zitat Lutterbach J, Ostertag C (2005) What is the appropriate radiotherapy protocol for older patients with newly diagnosed glioblastoma? J Clin Oncol 23(suppl. 12):2869–2870PubMed Lutterbach J, Ostertag C (2005) What is the appropriate radiotherapy protocol for older patients with newly diagnosed glioblastoma? J Clin Oncol 23(suppl. 12):2869–2870PubMed
18.
Zurück zum Zitat Hulshof MC, Schimmel EC, Andries Bosch D, Gonzalez Gonzalez D (2000) Hypofractionation in glioblastoma multiforme. Radiother Oncol 54(suppl. 2):143–148PubMedCrossRef Hulshof MC, Schimmel EC, Andries Bosch D, Gonzalez Gonzalez D (2000) Hypofractionation in glioblastoma multiforme. Radiother Oncol 54(suppl. 2):143–148PubMedCrossRef
19.
Zurück zum Zitat Phillips C, Guiney M, Smith J, Hughes P, Narayan K, Quong G (2003) A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma. Radiother Oncol 68(suppl. 1):23–26PubMedCrossRef Phillips C, Guiney M, Smith J, Hughes P, Narayan K, Quong G (2003) A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma. Radiother Oncol 68(suppl. 1):23–26PubMedCrossRef
20.
Zurück zum Zitat Fiorica F, Berretta M, Colosimo C et al (2010) Glioblastoma in elderly patients: safety and efficacy of adjuvant radiotherapy with concomitant temozolomide. Arch Gerontol Geriatr 51(suppl. 1):31–35PubMedCrossRef Fiorica F, Berretta M, Colosimo C et al (2010) Glioblastoma in elderly patients: safety and efficacy of adjuvant radiotherapy with concomitant temozolomide. Arch Gerontol Geriatr 51(suppl. 1):31–35PubMedCrossRef
21.
Zurück zum Zitat Gerstein J, Franz K, Steinbach JP et al (2010) Postoperative radiotherapy and concomitant temozolomide for elderly patients with glioblastoma. Radiother Oncol 97(suppl. 3):382–386PubMedCrossRef Gerstein J, Franz K, Steinbach JP et al (2010) Postoperative radiotherapy and concomitant temozolomide for elderly patients with glioblastoma. Radiother Oncol 97(suppl. 3):382–386PubMedCrossRef
22.
Zurück zum Zitat Kimple RJ, Grabowski S, Papez M, Collichio F, Ewend MG, Morris DE (2010) Concurrent temozolomide and radiation, a reasonable option for elderly patients with glioblastoma multiforme? Am J Clin Oncol 33(suppl. 3):265–270PubMed Kimple RJ, Grabowski S, Papez M, Collichio F, Ewend MG, Morris DE (2010) Concurrent temozolomide and radiation, a reasonable option for elderly patients with glioblastoma multiforme? Am J Clin Oncol 33(suppl. 3):265–270PubMed
23.
Zurück zum Zitat Minniti G, Salvati M, Arcella A et al (2011) Correlation between O(6)-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol 102(suppl. 2):311–316PubMedCrossRef Minniti G, Salvati M, Arcella A et al (2011) Correlation between O(6)-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurooncol 102(suppl. 2):311–316PubMedCrossRef
24.
Zurück zum Zitat 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 Biol Phys 70(suppl. 4):987–992PubMedCrossRef 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 Biol Phys 70(suppl. 4):987–992PubMedCrossRef
25.
Zurück zum Zitat Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88(suppl. 1):97–103PubMedCrossRef Minniti G, De Sanctis V, Muni R et al (2008) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in elderly patients. J Neurooncol 88(suppl. 1):97–103PubMedCrossRef
26.
Zurück zum Zitat Glantz M, Chamberlain M, Liu Q, Litofsky NS, Recht LD (2003) Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Cancer 97(suppl. 9):2262–2266PubMedCrossRef Glantz M, Chamberlain M, Liu Q, Litofsky NS, Recht LD (2003) Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Cancer 97(suppl. 9):2262–2266PubMedCrossRef
27.
Zurück zum Zitat Chinot OL, Barrie M, Frauger E et al (2004) Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations. Cancer 100(suppl. 10):2208–2214PubMedCrossRef Chinot OL, Barrie M, Frauger E et al (2004) Phase II study of temozolomide without radiotherapy in newly diagnosed glioblastoma multiforme in an elderly populations. Cancer 100(suppl. 10):2208–2214PubMedCrossRef
28.
Zurück zum Zitat Chamberlain MC, Chalmers L (2007) A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. J Neurooncol 82(suppl. 2):207–209PubMedCrossRef Chamberlain MC, Chalmers L (2007) A pilot study of primary temozolomide chemotherapy and deferred radiotherapy in elderly patients with glioblastoma. J Neurooncol 82(suppl. 2):207–209PubMedCrossRef
29.
Zurück zum Zitat Laigle-Donadey F, Figarella-Branger D, Chinot O et al (2010) Up-front temozolomide in elderly patients with glioblastoma. J Neurooncol 99(suppl. 1):89–94PubMedCrossRef Laigle-Donadey F, Figarella-Branger D, Chinot O et al (2010) Up-front temozolomide in elderly patients with glioblastoma. J Neurooncol 99(suppl. 1):89–94PubMedCrossRef
30.
Zurück zum Zitat Wick W, Engel C, Combs SE et al (2010) NOA-08 randomized phase III trial of 1-week-on/1-week-off temozolomide versus involved-field radiotherapy in elderly (older than age 65) patients with newly diagnosed anaplastic astrocytoma or glioblastoma (methusalem). ASCO Meeting Abstracts 28(suppl. 18_suppl):LBA2001 Wick W, Engel C, Combs SE et al (2010) NOA-08 randomized phase III trial of 1-week-on/1-week-off temozolomide versus involved-field radiotherapy in elderly (older than age 65) patients with newly diagnosed anaplastic astrocytoma or glioblastoma (methusalem). ASCO Meeting Abstracts 28(suppl. 18_suppl):LBA2001
31.
Zurück zum Zitat Malmstrom A, Gronberg BH, Stupp R et al (2010) Glioblastoma (GBM) in elderly patients: a randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ). ASCO Meeting Abstracts 28(suppl. 18_suppl):LBA2002 Malmstrom A, Gronberg BH, Stupp R et al (2010) Glioblastoma (GBM) in elderly patients: a randomized phase III trial comparing survival in patients treated with 6-week radiotherapy (RT) versus hypofractionated RT over 2 weeks versus temozolomide single-agent chemotherapy (TMZ). ASCO Meeting Abstracts 28(suppl. 18_suppl):LBA2002
32.
Zurück zum Zitat Ewelt C, Goeppert M, Rapp M, Steiger HJ, Stummer W, Sabel M (2010) Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival. J Neurooncol 103(3):611–618PubMedCrossRef Ewelt C, Goeppert M, Rapp M, Steiger HJ, Stummer W, Sabel M (2010) Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival. J Neurooncol 103(3):611–618PubMedCrossRef
33.
Zurück zum Zitat Muni R, Minniti G, Lanzetta G et al (2010) Short-term radiotherapy followed by adjuvant chemotherapy in poor-prognosis patients with glioblastoma. Tumori 96(suppl. 1):60–64PubMed Muni R, Minniti G, Lanzetta G et al (2010) Short-term radiotherapy followed by adjuvant chemotherapy in poor-prognosis patients with glioblastoma. Tumori 96(suppl. 1):60–64PubMed
34.
Zurück zum Zitat Brandes AA, Franceschi E, Tosoni A et al (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115(suppl. 15):3512–3518PubMedCrossRef Brandes AA, Franceschi E, Tosoni A et al (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115(suppl. 15):3512–3518PubMedCrossRef
35.
Zurück zum Zitat Minniti G, De Sanctis V, Muni R et al (2009) Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 91(suppl. 1):95–100PubMedCrossRef Minniti G, De Sanctis V, Muni R et al (2009) Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma. J Neurooncol 91(suppl. 1):95–100PubMedCrossRef
36.
Zurück zum Zitat Sijben AE, McIntyre JB, Roldan GB et al (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89(suppl. 1):97–103PubMedCrossRef Sijben AE, McIntyre JB, Roldan GB et al (2008) Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme. J Neurooncol 89(suppl. 1):97–103PubMedCrossRef
37.
Zurück zum Zitat Brandes AA, Vastola F, Basso U et al (2003) A prospective study on glioblastoma in the elderly. Cancer 97(suppl. 3):657–662PubMedCrossRef Brandes AA, Vastola F, Basso U et al (2003) A prospective study on glioblastoma in the elderly. Cancer 97(suppl. 3):657–662PubMedCrossRef
38.
Zurück zum Zitat Bauman GS, Gaspar LE, Fisher BJ, Halperin EC, Macdonald DR, Cairncross JG (1994) A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys 29(suppl. 4):835–839PubMed Bauman GS, Gaspar LE, Fisher BJ, Halperin EC, Macdonald DR, Cairncross JG (1994) A prospective study of short-course radiotherapy in poor prognosis glioblastoma multiforme. Int J Radiat Oncol Biol Phys 29(suppl. 4):835–839PubMed
39.
Zurück zum Zitat Luciani A, Ascione G, Bertuzzi C et al (2010) Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13. J Clin Oncol 28(suppl. 12):2046–2050PubMedCrossRef Luciani A, Ascione G, Bertuzzi C et al (2010) Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13. J Clin Oncol 28(suppl. 12):2046–2050PubMedCrossRef
Metadaten
Titel
Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience
verfasst von
Jeffrey Q. Cao
Barbara J. Fisher
Glenn S. Bauman
Joseph F. Megyesi
Christopher J. Watling
David R. Macdonald
Publikationsdatum
01.04.2012
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2012
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-011-0766-3

Weitere Artikel der Ausgabe 2/2012

Journal of Neuro-Oncology 2/2012 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.