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

摘要

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 cohort Ⅱ and I, respectively. Results. Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort Ⅰ 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 Ⅰ 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 Ⅰ). 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.