The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma

Sani Kizilbash, Caterina Giannini, Jesse S. Voss, Paul A. Decker, Robert Brian Jenkins, John Hardie, Nadia N Laack, Ian F Parney, Joon H. Uhm, Jan Craig Buckner

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Abstract

This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3 %, p = 0.02) and IDH mutation (78.9 vs. 22.0 %, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.

Original languageEnglish (US)
Pages (from-to)85-93
Number of pages9
JournalJournal of Neuro-Oncology
Volume120
Issue number1
DOIs
StatePublished - Sep 27 2014

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temozolomide
Isocitrate Dehydrogenase
Astrocytoma
Radiation
Mutation
Survival
Proportional Hazards Models

Keywords

  • Anaplastic astrocytoma
  • Isocitrate dehydrogenase mutation
  • Malignant glioma
  • Temozolomide

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Cite this

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title = "The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma",
abstract = "This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3 {\%}, p = 0.02) and IDH mutation (78.9 vs. 22.0 {\%}, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.",
keywords = "Anaplastic astrocytoma, Isocitrate dehydrogenase mutation, Malignant glioma, Temozolomide",
author = "Sani Kizilbash and Caterina Giannini and Voss, {Jesse S.} and Decker, {Paul A.} and Jenkins, {Robert Brian} and John Hardie and Laack, {Nadia N} and Parney, {Ian F} and Uhm, {Joon H.} and Buckner, {Jan Craig}",
year = "2014",
month = "9",
day = "27",
doi = "10.1007/s11060-014-1520-4",
language = "English (US)",
volume = "120",
pages = "85--93",
journal = "Journal of Neuro-Oncology",
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T1 - The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma

AU - Kizilbash, Sani

AU - Giannini, Caterina

AU - Voss, Jesse S.

AU - Decker, Paul A.

AU - Jenkins, Robert Brian

AU - Hardie, John

AU - Laack, Nadia N

AU - Parney, Ian F

AU - Uhm, Joon H.

AU - Buckner, Jan Craig

PY - 2014/9/27

Y1 - 2014/9/27

N2 - This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3 %, p = 0.02) and IDH mutation (78.9 vs. 22.0 %, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.

AB - This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3 %, p = 0.02) and IDH mutation (78.9 vs. 22.0 %, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.

KW - Anaplastic astrocytoma

KW - Isocitrate dehydrogenase mutation

KW - Malignant glioma

KW - Temozolomide

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U2 - 10.1007/s11060-014-1520-4

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