Survival effect of first- and second-line treatments for patients with primary glioblastoma: A cohort study from a prospective registry, 1997-2010

Francesca Nava, Irene Tramacere, Andrea Fittipaldo, Maria Grazia Bruzzone, Francesco Dimeco, Laura Fariselli, Gaetano Finocchiaro, Bianca Pollo, Andrea Salmaggi, Antonio Silvani, Mariangela Farinotti, Graziella Filippini

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Abstract

BackgroundProspective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010.MethodsSurvival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively.ResultsSurvival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II).ConclusionsWe found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.

Original languageEnglish
Pages (from-to)719-727
Number of pages9
JournalNeuro-Oncology
Volume16
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Glioblastoma
Registries
Cohort Studies
Disease-Free Survival
Survival
Recurrence
Radiosurgery
temozolomide
fotemustine
Reoperation
Drug Therapy
Therapeutics
Mitoxantrone
Clinical Protocols
Brain Neoplasms
Italy
Neoplasms

Keywords

  • Glioblastoma
  • Surgery
  • Survival analysis
  • Treatment effectiveness
  • Treatments

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology
  • Medicine(all)

Cite this

@article{e70b6ba6bba84b8fa56e4fd37173ab84,
title = "Survival effect of first- and second-line treatments for patients with primary glioblastoma: A cohort study from a prospective registry, 1997-2010",
abstract = "BackgroundProspective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010.MethodsSurvival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively.ResultsSurvival probabilities were 54{\%} at 1 year, 21{\%} at 2 years, and 11{\%} at 3 years, respectively, in cohort II compared with 47{\%}, 11{\%}, and 5{\%}, respectively, in cohort I. PFS was 22{\%} and 12{\%} at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22{\%} relative decrease in the risk of death and a 27{\%} relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II).ConclusionsWe found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.",
keywords = "Glioblastoma, Surgery, Survival analysis, Treatment effectiveness, Treatments",
author = "Francesca Nava and Irene Tramacere and Andrea Fittipaldo and Bruzzone, {Maria Grazia} and Francesco Dimeco and Laura Fariselli and Gaetano Finocchiaro and Bianca Pollo and Andrea Salmaggi and Antonio Silvani and Mariangela Farinotti and Graziella Filippini",
year = "2014",
doi = "10.1093/neuonc/not316",
language = "English",
volume = "16",
pages = "719--727",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Survival effect of first- and second-line treatments for patients with primary glioblastoma

T2 - A cohort study from a prospective registry, 1997-2010

AU - Nava, Francesca

AU - Tramacere, Irene

AU - Fittipaldo, Andrea

AU - Bruzzone, Maria Grazia

AU - Dimeco, Francesco

AU - Fariselli, Laura

AU - Finocchiaro, Gaetano

AU - Pollo, Bianca

AU - Salmaggi, Andrea

AU - Silvani, Antonio

AU - Farinotti, Mariangela

AU - Filippini, Graziella

PY - 2014

Y1 - 2014

N2 - BackgroundProspective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010.MethodsSurvival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively.ResultsSurvival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II).ConclusionsWe found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.

AB - BackgroundProspective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010.MethodsSurvival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively.ResultsSurvival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II).ConclusionsWe found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.

KW - Glioblastoma

KW - Surgery

KW - Survival analysis

KW - Treatment effectiveness

KW - Treatments

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U2 - 10.1093/neuonc/not316

DO - 10.1093/neuonc/not316

M3 - Article

C2 - 24463354

AN - SCOPUS:84899450186

VL - 16

SP - 719

EP - 727

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 5

ER -