The Effect of Timing of Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma

Seunggu (Jude) Han, W. Caleb Rutledge, Annette M. Molinaro, Susan M. Chang, Jennifer L. Clarke, Michael D. Prados, Jennie W. Taylor, Mitchel S. Berger, Nicholas A. Butowski

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

BACKGROUND: The effect of timing of initiation of concurrent radiation and chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains unclear. OBJECTIVE: To further explore this issue, we analyzed 4 clinical trials for patients newly diagnosed with GBM receiving concurrent and adjuvant temozolomide. METHODS: The cohort study included 198 adult patients with newly diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical trials consisting of radiation plus temozolomide and an experimental agent. The interval to initiation of therapy was determined from the time of surgical resection. The partitioning deletion/substitution/addition algorithm was used to determine the cutoff points for timing of chemoradiation at which there was a significant difference in overall survival (OS) and progression-free survival (PFS). RESULTS: The median wait time between surgery and initiation of concurrent chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]: 0.63, P .03) and prolonged PFS (HR: 0.68, P .06) compared with early initiation of concurrent chemoradiation (<30 days), after adjusting for protocol and baseline prognostic variables including extent of resection by multivariate analysis. A longer delay to chemoradiation beyond 34 days was not associated with improved OS or PFS compared with early initiation (HR: 0.94, P .77 and HR: 0.91, P .63, respectively). CONCLUSION: A short delay in the start of concurrent chemoradiation is beyond the classic paradigm of 4 weeks post-resection and may be associated with prolonged OS and PFS.

Original languageEnglish (US)
Pages (from-to)248-253
Number of pages6
JournalNeurosurgery
Volume77
Issue number2
DOIs
StatePublished - Aug 20 2015
Externally publishedYes

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temozolomide
Glioblastoma
Disease-Free Survival
Survival
Clinical Trials
Radiation
Cohort Studies
Multivariate Analysis
Drug Therapy
Therapeutics

Keywords

  • Chemotherapy
  • Concurrent chemoradiation
  • Delay
  • Glioblastoma
  • Radiation
  • Temozolomide
  • Timing

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Han, S. J., Rutledge, W. C., Molinaro, A. M., Chang, S. M., Clarke, J. L., Prados, M. D., ... Butowski, N. A. (2015). The Effect of Timing of Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma. Neurosurgery, 77(2), 248-253. https://doi.org/10.1227/NEU.0000000000000766

The Effect of Timing of Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma. / Han, Seunggu (Jude); Rutledge, W. Caleb; Molinaro, Annette M.; Chang, Susan M.; Clarke, Jennifer L.; Prados, Michael D.; Taylor, Jennie W.; Berger, Mitchel S.; Butowski, Nicholas A.

In: Neurosurgery, Vol. 77, No. 2, 20.08.2015, p. 248-253.

Research output: Contribution to journalArticle

Han, SJ, Rutledge, WC, Molinaro, AM, Chang, SM, Clarke, JL, Prados, MD, Taylor, JW, Berger, MS & Butowski, NA 2015, 'The Effect of Timing of Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma', Neurosurgery, vol. 77, no. 2, pp. 248-253. https://doi.org/10.1227/NEU.0000000000000766
Han, Seunggu (Jude) ; Rutledge, W. Caleb ; Molinaro, Annette M. ; Chang, Susan M. ; Clarke, Jennifer L. ; Prados, Michael D. ; Taylor, Jennie W. ; Berger, Mitchel S. ; Butowski, Nicholas A. / The Effect of Timing of Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma. In: Neurosurgery. 2015 ; Vol. 77, No. 2. pp. 248-253.
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abstract = "BACKGROUND: The effect of timing of initiation of concurrent radiation and chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains unclear. OBJECTIVE: To further explore this issue, we analyzed 4 clinical trials for patients newly diagnosed with GBM receiving concurrent and adjuvant temozolomide. METHODS: The cohort study included 198 adult patients with newly diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical trials consisting of radiation plus temozolomide and an experimental agent. The interval to initiation of therapy was determined from the time of surgical resection. The partitioning deletion/substitution/addition algorithm was used to determine the cutoff points for timing of chemoradiation at which there was a significant difference in overall survival (OS) and progression-free survival (PFS). RESULTS: The median wait time between surgery and initiation of concurrent chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]: 0.63, P .03) and prolonged PFS (HR: 0.68, P .06) compared with early initiation of concurrent chemoradiation (<30 days), after adjusting for protocol and baseline prognostic variables including extent of resection by multivariate analysis. A longer delay to chemoradiation beyond 34 days was not associated with improved OS or PFS compared with early initiation (HR: 0.94, P .77 and HR: 0.91, P .63, respectively). CONCLUSION: A short delay in the start of concurrent chemoradiation is beyond the classic paradigm of 4 weeks post-resection and may be associated with prolonged OS and PFS.",
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T1 - The Effect of Timing of Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma

AU - Han, Seunggu (Jude)

AU - Rutledge, W. Caleb

AU - Molinaro, Annette M.

AU - Chang, Susan M.

AU - Clarke, Jennifer L.

AU - Prados, Michael D.

AU - Taylor, Jennie W.

AU - Berger, Mitchel S.

AU - Butowski, Nicholas A.

PY - 2015/8/20

Y1 - 2015/8/20

N2 - BACKGROUND: The effect of timing of initiation of concurrent radiation and chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains unclear. OBJECTIVE: To further explore this issue, we analyzed 4 clinical trials for patients newly diagnosed with GBM receiving concurrent and adjuvant temozolomide. METHODS: The cohort study included 198 adult patients with newly diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical trials consisting of radiation plus temozolomide and an experimental agent. The interval to initiation of therapy was determined from the time of surgical resection. The partitioning deletion/substitution/addition algorithm was used to determine the cutoff points for timing of chemoradiation at which there was a significant difference in overall survival (OS) and progression-free survival (PFS). RESULTS: The median wait time between surgery and initiation of concurrent chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]: 0.63, P .03) and prolonged PFS (HR: 0.68, P .06) compared with early initiation of concurrent chemoradiation (<30 days), after adjusting for protocol and baseline prognostic variables including extent of resection by multivariate analysis. A longer delay to chemoradiation beyond 34 days was not associated with improved OS or PFS compared with early initiation (HR: 0.94, P .77 and HR: 0.91, P .63, respectively). CONCLUSION: A short delay in the start of concurrent chemoradiation is beyond the classic paradigm of 4 weeks post-resection and may be associated with prolonged OS and PFS.

AB - BACKGROUND: The effect of timing of initiation of concurrent radiation and chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains unclear. OBJECTIVE: To further explore this issue, we analyzed 4 clinical trials for patients newly diagnosed with GBM receiving concurrent and adjuvant temozolomide. METHODS: The cohort study included 198 adult patients with newly diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical trials consisting of radiation plus temozolomide and an experimental agent. The interval to initiation of therapy was determined from the time of surgical resection. The partitioning deletion/substitution/addition algorithm was used to determine the cutoff points for timing of chemoradiation at which there was a significant difference in overall survival (OS) and progression-free survival (PFS). RESULTS: The median wait time between surgery and initiation of concurrent chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]: 0.63, P .03) and prolonged PFS (HR: 0.68, P .06) compared with early initiation of concurrent chemoradiation (<30 days), after adjusting for protocol and baseline prognostic variables including extent of resection by multivariate analysis. A longer delay to chemoradiation beyond 34 days was not associated with improved OS or PFS compared with early initiation (HR: 0.94, P .77 and HR: 0.91, P .63, respectively). CONCLUSION: A short delay in the start of concurrent chemoradiation is beyond the classic paradigm of 4 weeks post-resection and may be associated with prolonged OS and PFS.

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KW - Glioblastoma

KW - Radiation

KW - Temozolomide

KW - Timing

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