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Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Research

Dexamethasone administration during definitive radiation and temozolomide renders a poor prognosis in a retrospective analysis of newly diagnosed glioblastoma patients

Authors: Lisa B. E. Shields, Brent J. Shelton, Andrew J. Shearer, Li Chen, David A. Sun, Sarah Parsons, T. David Bourne, Renato LaRocca, Aaron C. Spalding

Published in: Radiation Oncology | Issue 1/2015

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Abstract

Background

Dexamethasone (DXM) is commonly used in the management of cerebral edema in patients diagnosed with glioblastoma multiforme (GBM). Bevacizumab (BEV) is FDA-approved for the progression or recurrence of GBM but has not been shown to improve survival when given for newly diagnosed patients concurrently with radiation (RT) and temozolomide (TMZ). Both DXM and BEV reduce cerebral edema, however, DXM has been shown to induce cytokine cascades which could interfere with cytotoxic therapy. We investigated whether DXM would reduce survival of GBM patients in the setting of concurrent TMZ and BEV administration.

Methods

We reviewed the treatment of all 73 patients with GBM who received definitive therapy at our institution from 2005 to 2013 with RT (60 Gy) delivered with concurrent daily TMZ (75 mg/m2). Of these, 34 patients also were treated with concurrent BEV (10 mg/kg every two weeks). Patients received adjuvant therapy (TMZ or TMZ/Bev) until either progression, discontinuation due to toxicity, or 12 months after radiation completion. All patients who had GBM progression with TMZ were offered BEV for salvage therapy, with 19 (56 %) receiving BEV.

Results

With a median follow-up of 15.6 months, 67 (91.8 %) patients were deceased. The OS for the entire cohort was 15.9 months, while the PFS was 7.7 months. The extent of resection was a prognostic indicator for OS (p = .0044). The median survival following gross tumor resection (GTR) was 22.5 months, subtotal resection (STR) was 14.9 months, and biopsy was 12.1 months. The addition of BEV to TMZ with RT was borderline significantly associated with increased PFS (9.4 vs. 5.1 months, p = 0.0574) although was not significantly associated with OS (18.1 vs. 15.3 months respectively, p = 0.3064). In patients receiving TMZ, DXM use concurrent with RT was a poor prognostic indicator of both OS (12.7 vs. 22.6 months, p = 0.003) and PFS (3.6 vs. 8.4 months, p <0.0001). DXM did not reduce OS in patients who received TMZ and BEV concurrently with RT (22.9 vs 22.8 months, p = 0.4818). On multivariable analysis, DXM use predicted an unfavorable OS hazard ratio (HR) = 1.72, p = 0.045).

Conclusions

Our results with TMZ, BEV, and RT are similar to previous studies in terms of PFS and OS. DXM use during RT with concurrent TMZ correlated with reduced OS and PFS unless BEV was administered.
Literature
1.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMed
2.
go back to reference Albert FK, Forsting M, Sartor K, Adams HP, Kunze S. Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis. Neurosurgery. 1994;34(1):45–60.CrossRefPubMed Albert FK, Forsting M, Sartor K, Adams HP, Kunze S. Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis. Neurosurgery. 1994;34(1):45–60.CrossRefPubMed
3.
go back to reference 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. 1993;71(8):2585–97.CrossRefPubMed 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. 1993;71(8):2585–97.CrossRefPubMed
4.
go back to reference Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190–8.CrossRefPubMed Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001;95(2):190–8.CrossRefPubMed
5.
go back to reference Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol. 1999;17(8):2572–8.PubMed Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol. 1999;17(8):2572–8.PubMed
6.
go back to reference Ronning PA, Helseth E, Meling TR, Johannesen TB. A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. Neuro Oncol. 2012;14(9):1178–84.PubMedCentralCrossRefPubMed Ronning PA, Helseth E, Meling TR, Johannesen TB. A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. Neuro Oncol. 2012;14(9):1178–84.PubMedCentralCrossRefPubMed
7.
go back to reference Stupp R, Dietrich PY, Ostermann KS, Pica A, Maillard I, Maeder P, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol. 2002;20(5):1375–82.CrossRefPubMed Stupp R, Dietrich PY, Ostermann KS, Pica A, Maillard I, Maeder P, et al. Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol. 2002;20(5):1375–82.CrossRefPubMed
8.
go back to reference Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, 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(5):459–66.CrossRefPubMed Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, 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(5):459–66.CrossRefPubMed
9.
go back to reference Szczepanek D, Marchel A, Moskala M, Krupa M, Kunert P, Trojanowski T. Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study. Neurol Neurochir Pol. 2013;47(2):101–8.PubMed Szczepanek D, Marchel A, Moskala M, Krupa M, Kunert P, Trojanowski T. Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study. Neurol Neurochir Pol. 2013;47(2):101–8.PubMed
10.
go back to reference Knizhnik AV, Roos WP, Nikolova T, Quiros S, Tomaszowski KH, Christmann M, et al. Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS ONE. 2013;8(1):e55665.PubMedCentralCrossRefPubMed Knizhnik AV, Roos WP, Nikolova T, Quiros S, Tomaszowski KH, Christmann M, et al. Survival and death strategies in glioma cells: autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS ONE. 2013;8(1):e55665.PubMedCentralCrossRefPubMed
11.
go back to reference Sur P, Sribnick EA, Patel SJ, Ray SK, Banik NL. Dexamethasone decreases temozolomide-induced apoptosis in human gliobastoma T98G cells. Glia. 2005;50(2):160–7.CrossRefPubMed Sur P, Sribnick EA, Patel SJ, Ray SK, Banik NL. Dexamethasone decreases temozolomide-induced apoptosis in human gliobastoma T98G cells. Glia. 2005;50(2):160–7.CrossRefPubMed
12.
go back to reference Vredenburgh JJ, Cloughesy T, Samant M, Prados M, Wen PY, Mikkelsen T, et al. Corticosteroid use in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study. Oncologist. 2010;15(12):1329–34.PubMedCentralCrossRefPubMed Vredenburgh JJ, Cloughesy T, Samant M, Prados M, Wen PY, Mikkelsen T, et al. Corticosteroid use in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study. Oncologist. 2010;15(12):1329–34.PubMedCentralCrossRefPubMed
13.
go back to reference Deutsch MB, Panageas KS, Lassman AB, DeAngelis LM. Steroid management in newly diagnosed glioblastoma. J Neurooncol. 2013;113(1):111–6.CrossRefPubMed Deutsch MB, Panageas KS, Lassman AB, DeAngelis LM. Steroid management in newly diagnosed glioblastoma. J Neurooncol. 2013;113(1):111–6.CrossRefPubMed
14.
go back to reference Chinot O, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Phase III trial of bevacizumab added to standard radiotherapy and temozolomide for newly-diagnosed glioblastoma: mature progression-free survival and preliminary overall survival results in Avaglio [Abstract]. Neuro-Oncology. 2012;14(6):101. Chinot O, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Phase III trial of bevacizumab added to standard radiotherapy and temozolomide for newly-diagnosed glioblastoma: mature progression-free survival and preliminary overall survival results in Avaglio [Abstract]. Neuro-Oncology. 2012;14(6):101.
15.
go back to reference Chinot OL, de La Motte RT, Moore N, Zeaiter A, Das A, Phillips H, et al. AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Ther. 2011;28(4):334–40.CrossRefPubMed Chinot OL, de La Motte RT, Moore N, Zeaiter A, Das A, Phillips H, et al. AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Ther. 2011;28(4):334–40.CrossRefPubMed
16.
go back to reference Gilbert MR, Dignam J, Won M. RTOG: 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). J Clin Oncol 2013, 31(Suppl(abstr 1)). Gilbert MR, Dignam J, Won M. RTOG: 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). J Clin Oncol 2013, 31(Suppl(abstr 1)).
17.
go back to reference Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–72.CrossRefPubMed Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–72.CrossRefPubMed
18.
go back to reference Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.CrossRef
19.
go back to reference Cox DR. Regression models and life-tables. J R Statist Soc B. 1972;34(2):187–220. Cox DR. Regression models and life-tables. J R Statist Soc B. 1972;34(2):187–220.
20.
go back to reference SAS Institute Inc. SAS/STAT 9.2 User’s Guide. 2008. SAS Institute Inc. SAS/STAT 9.2 User’s Guide. 2008.
21.
go back to reference Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 2010;16(8):2443–9.PubMedCentralCrossRefPubMed Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 2010;16(8):2443–9.PubMedCentralCrossRefPubMed
22.
go back to reference Lai A, Filka E, McGibbon B, Nghiemphu PL, Graham C, Yong WH, et al. Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. Int J Radiat Oncol Biol Phys. 2008;71(5):1372–80.CrossRefPubMed Lai A, Filka E, McGibbon B, Nghiemphu PL, Graham C, Yong WH, et al. Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. Int J Radiat Oncol Biol Phys. 2008;71(5):1372–80.CrossRefPubMed
23.
go back to reference Lai A, Tran A, Nghiemphu PL, Pope WB, Solis OE, Selch M, et al. Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol. 2011;29(2):142–8.PubMedCentralCrossRefPubMed Lai A, Tran A, Nghiemphu PL, Pope WB, Solis OE, Selch M, et al. Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol. 2011;29(2):142–8.PubMedCentralCrossRefPubMed
24.
go back to reference Narayana A, Gruber D, Kunnakkat S, Golfinos JG, Parker E, Raza S, et al. A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma. J Neurosurg. 2012;116(2):341–5.CrossRefPubMed Narayana A, Gruber D, Kunnakkat S, Golfinos JG, Parker E, Raza S, et al. A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma. J Neurosurg. 2012;116(2):341–5.CrossRefPubMed
25.
go back to reference Vredenburgh JJ, Desjardins A, Kirkpatrick JP, Reardon DA, Peters KB, Herndon JE et al. Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Bio Phys 2012;82(1):58-66. Vredenburgh JJ, Desjardins A, Kirkpatrick JP, Reardon DA, Peters KB, Herndon JE et al. Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Bio Phys 2012;82(1):58-66.
26.
go back to reference Vredenburgh JJ, Desjardins A, Reardon DA, Peters KB, Herndon JE, Marcello J, et al. The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma. Clin Cancer Res. 2011;17(12):4119–24.PubMedCentralCrossRefPubMed Vredenburgh JJ, Desjardins A, Reardon DA, Peters KB, Herndon JE, Marcello J, et al. The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma. Clin Cancer Res. 2011;17(12):4119–24.PubMedCentralCrossRefPubMed
27.
go back to reference Vredenburgh JJ, Desjardins A, Kirkpatrick JP, Reardon DA, Peters KB, Herndon JE, et al. Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2012;82(1):58–66.CrossRefPubMed Vredenburgh JJ, Desjardins A, Kirkpatrick JP, Reardon DA, Peters KB, Herndon JE, et al. Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 2012;82(1):58–66.CrossRefPubMed
28.
go back to reference Kreth FW, Thon N, Simon M, Westphal M, Schackert G, Nikkhah G, et al. Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol. 2013;24(12):3117–23.CrossRefPubMed Kreth FW, Thon N, Simon M, Westphal M, Schackert G, Nikkhah G, et al. Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol. 2013;24(12):3117–23.CrossRefPubMed
29.
go back to reference Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709–22.CrossRefPubMed Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709–22.CrossRefPubMed
30.
go back to reference Haines IE, Gabor Miklos GL. Bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(21):2048.CrossRefPubMed Haines IE, Gabor Miklos GL. Bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(21):2048.CrossRefPubMed
32.
go back to reference Hohwieler SM, Freidberg SR, Heatley GJ, Lo TC. Glucocorticoid dependency as a prognostic factor in radiotherapy for cerebral gliomas. Acta Oncol. 1989;28(1):51–5.CrossRef Hohwieler SM, Freidberg SR, Heatley GJ, Lo TC. Glucocorticoid dependency as a prognostic factor in radiotherapy for cerebral gliomas. Acta Oncol. 1989;28(1):51–5.CrossRef
33.
go back to reference Mayer A, Vaupel P, Struss HG, Giese A, Stockinger M, Schmidberger H. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme. Strahlenther Onkol. 2014;190(10):933–8.CrossRefPubMed Mayer A, Vaupel P, Struss HG, Giese A, Stockinger M, Schmidberger H. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme. Strahlenther Onkol. 2014;190(10):933–8.CrossRefPubMed
34.
go back to reference Michaelsen SR, Christensen IJ, Grunnet K, Stockhausen MT, Broholm H, Kosteljanetz M, et al. 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. 2013;13:402.PubMedCentralCrossRefPubMed Michaelsen SR, Christensen IJ, Grunnet K, Stockhausen MT, Broholm H, Kosteljanetz M, et al. 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. 2013;13:402.PubMedCentralCrossRefPubMed
35.
go back to reference Watne K, Hannisdal E, Nome O, Hager B, Hirschberg H. Prognostic factors in malignant gliomas with special reference to intra-arterial chemotherapy. Acta Oncol. 1993;32(3):307–10.CrossRefPubMed Watne K, Hannisdal E, Nome O, Hager B, Hirschberg H. Prognostic factors in malignant gliomas with special reference to intra-arterial chemotherapy. Acta Oncol. 1993;32(3):307–10.CrossRefPubMed
36.
go back to reference Gorlia T, Stupp R, Brandes AA, Rampling RR, Fumoleau P, Dittrich C, et al. New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials. Eur J Cancer. 2012;48(8):1176–84.CrossRefPubMed Gorlia T, Stupp R, Brandes AA, Rampling RR, Fumoleau P, Dittrich C, et al. New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: a pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials. Eur J Cancer. 2012;48(8):1176–84.CrossRefPubMed
Metadata
Title
Dexamethasone administration during definitive radiation and temozolomide renders a poor prognosis in a retrospective analysis of newly diagnosed glioblastoma patients
Authors
Lisa B. E. Shields
Brent J. Shelton
Andrew J. Shearer
Li Chen
David A. Sun
Sarah Parsons
T. David Bourne
Renato LaRocca
Aaron C. Spalding
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0527-0

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