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


METHODS
Survival 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.


RESULTS
Survival 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).


CONCLUSIONS
We 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.
Unit of Neuroepidemiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (F.N., I.T., A.F., M.F., G.F.); Unit of Neuroradiology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (M.G.B., L.F.); Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Department of Neurological Surgery, Johns Hopkins Medical School, Baltimore, Maryland (F.D.); Unit of Molecular Neuro-oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (G.F.); Unit of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (B.P.); Department of Neurology, Ospedale Alessandro Manzoni, Lecco, Italy (A.S.); Unit of Clinical Neuro-oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (A.S.).
Francesca
F
Nava
Irene
I
Tramacere
Andrea
A
Fittipaldo
Maria Grazia
MG
Bruzzone
Francesco
F
Dimeco
Laura
L
Fariselli
Gaetano
G
Finocchiaro
Bianca
B
Pollo
Andrea
A
Salmaggi
Antonio
A
Silvani
Mariangela
M
Farinotti
Graziella
G
Filippini
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D016019:Survival Analysis
D000970:Antineoplastic Agents
glioblastoma; surgery; survival analysis; treatment effectiveness; treatments