Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide
To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Adult patients aged <70 years with...
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| Published in | International journal of radiation oncology, biology, physics Vol. 90; no. 4; pp. 877 - 885 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
15.11.2014
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0360-3016 1879-355X 1879-355X |
| DOI | 10.1016/j.ijrobp.2014.07.014 |
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| Abstract | To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT).
Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM.
Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR.
Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM. |
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| AbstractList | Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM. To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT).PURPOSETo review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT).Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM.METHODS AND MATERIALSAdult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM.Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR.RESULTSEighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR.Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.CONCLUSIONModerate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM. To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM. To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM. Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an alpha / beta ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status greater than or equal to 80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM. |
| Author | Simpson, Joseph R. Leuthardt, Eric C. Zipfel, Gregory J. Robinson, Clifford G. Tran, David D. Dowling, Joshua L. Dacey, Ralph Jalalizadeh, Rohan DeWees, Todd Markovina, Stephanie Rich, Keith M. Huang, Jiayi Badiyan, Shahed N. Chicoine, Michael R. Linette, Gerry Kim, Albert H. |
| Author_xml | – sequence: 1 givenname: Shahed N. orcidid: 0000-0001-6243-526X surname: Badiyan fullname: Badiyan, Shahed N. organization: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri – sequence: 2 givenname: Stephanie orcidid: 0000-0002-1139-5533 surname: Markovina fullname: Markovina, Stephanie organization: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri – sequence: 3 givenname: Joseph R. surname: Simpson fullname: Simpson, Joseph R. organization: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri – sequence: 4 givenname: Clifford G. orcidid: 0000-0002-1399-9904 surname: Robinson fullname: Robinson, Clifford G. organization: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri – sequence: 5 givenname: Todd surname: DeWees fullname: DeWees, Todd organization: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri – sequence: 6 givenname: David D. surname: Tran fullname: Tran, David D. organization: Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri – sequence: 7 givenname: Gerry surname: Linette fullname: Linette, Gerry organization: Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri – sequence: 8 givenname: Rohan surname: Jalalizadeh fullname: Jalalizadeh, Rohan organization: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri – sequence: 9 givenname: Ralph surname: Dacey fullname: Dacey, Ralph organization: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri – sequence: 10 givenname: Keith M. surname: Rich fullname: Rich, Keith M. organization: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri – sequence: 11 givenname: Michael R. surname: Chicoine fullname: Chicoine, Michael R. organization: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri – sequence: 12 givenname: Joshua L. surname: Dowling fullname: Dowling, Joshua L. organization: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri – sequence: 13 givenname: Eric C. surname: Leuthardt fullname: Leuthardt, Eric C. organization: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri – sequence: 14 givenname: Gregory J. surname: Zipfel fullname: Zipfel, Gregory J. organization: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri – sequence: 15 givenname: Albert H. surname: Kim fullname: Kim, Albert H. organization: Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri – sequence: 16 givenname: Jiayi surname: Huang fullname: Huang, Jiayi email: jhuang@radonc.wustl.edu organization: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri |
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| Snippet | To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients... Purpose To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in... Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in... |
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| Title | Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide |
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