Grant Number:	5R03CA150048-02 Interpret this number
Primary Investigator:	Dubrow, Robert
Organization:	Yale University
Project Title:	Patterns of Care and Outcomes for Glioblastoma Patients
Fiscal Year:	2011

DESCRIPTION (provided by applicant): Glioblastoma (GBM), the most malignant form of brain cancer, has a dismal prognosis. Temozolomide (TMZ), an alkylating agent that penetrates the blood-brain barrier, was approved by the FDA in 1999 for treatment of recurrent anaplastic astrocytoma (grade 3 glioma); off-label use of TMZ for GBM (grade 4 glioma) began shortly thereafter. In 2005, a landmark phase 3 clinical trial demonstrated that surgery, followed by radiotherapy plus concomitant TMZ, followed by adjuvant TMZ, resulted in a clinically meaningful and statistically significant survival benefit compared to the standard therapy of surgery followed by radiotherapy, with minimal added toxicity. This regimen has become the new standard of care. However, the level of benefit found in the landmark trial, which was restricted to patients with certain favorable prognostic characteristics, may not translate into the same level of benefit in an unselected general population of GBM patients. Furthermore, delivery of the standard treatment to a general population of GBM patients may be less optimal than delivery in the clinical trial setting. Thus, even after a phase 3 trial has established treatment efficacy, it is essential to use observational databases to determine which patients are actually receiving the new standard of care and whether the new standard of care has meaningfully improved survival in the "real world" setting. Furthermore, the landmark trial did not include patients over age 70, for whom there is no generally-accepted standard of care. In this situation, in which a standard of care has not been established, it is critical to utilize observational databases to understand patterns of care and outcomes. For these reasons, a study of patterns of care and outcomes for GBM patients will be timely and informative. Utilizing a population-based, records- based, retrospective cohort study design, we propose to compare the effectiveness of first-line TMZ treatment versus non-TMZ-based treatments in a general population of GBM patients newly diagnosed during 1995-2007 and reported to the Veterans Administration (VA) Central Cancer Registry, which aims to register all cancer cases diagnosed and/or treated at VA medical centers. Cancer registry data will be linked with pharmacy, clinical, and demographic data from other VA national automated databases. Patients will be followed to the end of 2009. The study will have the following specific aims: 1) to describe usage of the new standard TMZ treatment and to identify predictors (e.g., age, race, ethnicity, marital status, co-morbidity) of this treatment among newly-diagnosed GBM patients, overall and by age at diagnosis (<70 years and >70 years); and 2) to determine whether the new standard TMZ treatment has meaningfully improved survival of GBM patients, with an acceptable level of toxicity, overall and by age at diagnosis. The proposed study will be the first to assess usage and outcomes for the current standard of care in a general population and will lay the groundwork for continuing surveillance of patterns of care and outcomes for GBM. It also will establish a prototype for studying patterns of care and outcomes for other forms of cancer utilizing the strengths of the VA national databases. PUBLIC HEALTH RELEVANCE: In 2005, a landmark randomized clinical trial of the drug temozolomide established a new standard of care for treatment of glioblastoma, the most malignant form of brain cancer. However, the benefit found in the landmark trial may not translate into the same benefit for the general population of glioblastoma patients because patients in the clinical trial had different characteristics than general population patients and because treatment delivery may be less optimal to the general population than in the clinical trial setting. The proposed study aims to determine which glioblastoma patients are actually receiving the new standard of care and whether the new standard of care has meaningfully improved survival in a "real world" setting.





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