BIRN (Biomedical Informatics Research Network) Resources Facilitate the Personalization of Malignant Brain Tumor

Glioblastoma (GBM) is the most common primary malignant neoplasm of the adult brain. Even
after multimodal therapy, treatment outcomes remain poor, with a median survival of
approximately one year. A central challenge facing investigators in the modern era is how to
resolve the heterogeneity inherent in GBM pathology using technology and how to identify
individual genetic or molecular markers that indicate how treatment can be individualized to
improve outcomes with an emphasis on using this heterogeneity to improve patient care. With
advances in imaging and the potential for genetic sequence analysis, increasingly clinicians
and researchers have focused on specific clinical, imaging, and genetic biomarkers to allow
the personalization of brain tumor treatment in an attempt to improve the limitations we have
faced in extending patient survival from this devastating disease. Specific methodologies
have been developed to allow genetic microarray analysis of patient's tumor tissue, and this
type of research is ongoing at one of our participating institutions, Swedish Medical Center.
In addition, centers such as Washington University School of Medicine in St. Louis, Missouri
have extensive experience pursuing advanced imaging biomarkers and their applications to
clinical neuro-oncology research.

Of importance, however, although clinicians and researchers have come to recognize that
in-vivo imaging technologies may have as much if not more relevance than genetic biomarkers
in the personalization of brain tumor treatment, clinical trials attempting to validate these
biomarkers and correlate them with particular outcomes have been limited by a lack of
technology infrastructure that would allow multi-site image acquisition, processing, data
analysis, subsequent correlation with clinical and genetic data, and ultimately sharing of
anonymized data with other researchers from a central archiving site. BIRN infrastructure
will integrate neuroimaging, genetic microarray, and clinical data with a focus on
integrating imaging biomarkers into prospective clinical research in patients with malignant
brain tumors.

In this project, a consortium of neuro-oncology research centers will be federated to obtain
a unified set of clinical, genetic, and imaging data. In the initial phase, 100 patients with
malignant brain tumors at two participating sites will be studied. Our ultimate goal will be
to use the developed protocols and informatics infrastructure to expand the consortium to
include a large number neuro-oncology clinical sites suitable for executing large scale
clinical trials that will facilitate the generation of data to identify which imaging
biomarkers are relevant for the personalization of brain tumor treatment and ultimately
improvement of outcomes for patients with this devastating disease.

Inclusion Criteria:

- Patients will be enrolled in this clinical trial pre-operatively anticipating a
surgical resection with anticipation that the patient carries a likely diagnosis of
malignant glioma.

- Patients will only be enrolled if it is anticipated that the resection will give
significant tissue for subsequent genetic analysis (1 cm of tumor tissue)

- If patients at surgery are found to carry an alternative tissue diagnosis, the
patient's preoperative imaging, clinical, and pathological information will be
uploaded into the database, but the patient will not be counted as one of the
participants

- Ability to undergo serial MR studies

- Enrollment KPS > 70

- Anticipation that surgery will allow subtotal resection or gross total resection,
facilitating removal of tissue specimens for genomic analysis.

Exclusion Criteria:

- Inability to participate in serial MR studies

- KPS < 70

- > 70 years of age