We thank Dr. Caldarella and colleagues for their interest in our article, “Changing prognosis of glioblastoma in the 21st century: Who has benefited most?”1 Our study, based on the Surveillance, Epidemiology and End Results (SEER) Database, showed an incremental improvement in overall survival (OS) for the entire population of glioblastoma (GBM) patients, but no improvement in OS for patients aged ≥70 years.

Caldarella and colleagues hypothesize that our major findings may be the result of various biases, including tumor misclassification. Although we agree with Dr. Caldarella and colleagues that there are many limitations with the SEER database, we do not agree that these fully account for the poor OS for elderly patients seen in our study. Although we did include subjects with “no surgery performed,” when we analyzed the subset of elderly patients' status after gross total resection and radiation therapy (and thus with a histologically confirmed diagnosis), we again found no significant change in median survival time between 2001 and 2007 (9 vs 8 months, P = .2). Some of the forms of bias that were suggested (increasing use of magnetic resonance imaging, increasing ability to biopsy small lesions) would artificially improve prognosis, the converse of our findings. Our study concerned the period from 2001 to 2007, hence, changes to the World Health Organization pathological classification in the 1990s are of limited relevance.

The results of our study are consistent with previous findings that GBM in the elderly is a more aggressive disease than that seen in younger patients. One explanation of this discrepancy is the recent reports that the favorable “proneural” molecular subtype is more predominant among younger patients.2 Given the rising incidence of GBM in elderly patients,3 future research efforts should aim to further define optimal treatment regimens for this patient population.


  1. Top of page
  • 1
    Lawrence YR, Mishra MV, Werner-Wasik M, et al. Improving prognosis of glioblastoma in the 21st century: Who has benefited most? Cancer. 2011; doi: 10.1002/cncr.26685.
  • 2
    Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17: 98-110.
  • 3
    Werner MH, Phuphanich S, Lyman GH. The increasing incidence of malignant gliomas and primary central nervous system lymphoma in the elderly. Cancer. 1995; 76: 1634-1642.

Mark V. Mishra MD*, Yaacov Richard Lawrence MBBS, MRCP* †, * Thomas Jefferson University, Department of Radiation Oncology, Philadelphia, Pennsylvania, † Sheba Medical Center, Department of Radiation Oncology, Ramat Gan, Israel.