Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide

Shahed N. Badiyan, Stephanie Markovina, Joseph R. Simpson, Clifford G. Robinson, Todd DeWees, David D. Tran, Gerry Linette, Rohan Jalalizadeh, Ralph Dacey, Keith M. Rich, Michael R. Chicoine, Joshua L. Dowling, Eric C. Leuthardt, Gregory J. Zipfel, Albert H. Kim, Jiayi Huang

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)877-885
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume90
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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temozolomide
Glioblastoma
radiation therapy
Radiotherapy
dosage
Disease-Free Survival
progressions
Survival
Karnofsky Performance Status

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide. / Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd; Tran, David D.; Linette, Gerry; Jalalizadeh, Rohan; Dacey, Ralph; Rich, Keith M.; Chicoine, Michael R.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H.; Huang, Jiayi.

In: International Journal of Radiation Oncology Biology Physics, Vol. 90, No. 4, 01.01.2014, p. 877-885.

Research output: Contribution to journalArticle

Badiyan, SN, Markovina, S, Simpson, JR, Robinson, CG, DeWees, T, Tran, DD, Linette, G, Jalalizadeh, R, Dacey, R, Rich, KM, Chicoine, MR, Dowling, JL, Leuthardt, EC, Zipfel, GJ, Kim, AH & Huang, J 2014, 'Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide', International Journal of Radiation Oncology Biology Physics, vol. 90, no. 4, pp. 877-885. https://doi.org/10.1016/j.ijrobp.2014.07.014
Badiyan, Shahed N. ; Markovina, Stephanie ; Simpson, Joseph R. ; Robinson, Clifford G. ; DeWees, Todd ; Tran, David D. ; Linette, Gerry ; Jalalizadeh, Rohan ; Dacey, Ralph ; Rich, Keith M. ; Chicoine, Michael R. ; Dowling, Joshua L. ; Leuthardt, Eric C. ; Zipfel, Gregory J. ; Kim, Albert H. ; Huang, Jiayi. / Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide. In: International Journal of Radiation Oncology Biology Physics. 2014 ; Vol. 90, No. 4. pp. 877-885.
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abstract = "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.",
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T1 - Radiation therapy dose escalation for glioblastoma multiforme in the era of temozolomide

AU - Badiyan, Shahed N.

AU - Markovina, Stephanie

AU - Simpson, Joseph R.

AU - Robinson, Clifford G.

AU - DeWees, Todd

AU - Tran, David D.

AU - Linette, Gerry

AU - Jalalizadeh, Rohan

AU - Dacey, Ralph

AU - Rich, Keith M.

AU - Chicoine, Michael R.

AU - Dowling, Joshua L.

AU - Leuthardt, Eric C.

AU - Zipfel, Gregory J.

AU - Kim, Albert H.

AU - Huang, Jiayi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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