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Detrimental Effects of Tumor Progression on Cognitive Function of Patients With High-Grade Glioma

Paul D. Brown, Ashley W. Jensen, Sara J. Felten, Karla V. Ballman, Paul L. Schaefer, Kurt A. Jaeckle, Jane H. Cerhan, Jan C. Buckner

From the Mayo Clinic, Rochester, MN; Toledo Community Hospital Oncology Program, Toledo, OH; and the Mayo Clinic, Jacksonville, FL

Address reprint requests to Paul D. Brown, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: brown.paul{at}mayo.edu

PURPOSE: There is growing recognition that the primary cause of cognitive deficits in adult patients with primary brain tumors is the tumor itself and more significantly, tumor progression. To assess the cognitive performance of high-grade glioma patients, prospectively collected cognitive performance data were analyzed.

PATIENTS AND METHODS: We studied 1,244 high-grade brain tumor patients entered onto eight consecutive North Central Cancer Treatment Group treatment trials that used radiation and nitrosourea-based chemotherapy. Imaging studies and Folstein Mini-Mental State Examination (MMSE) scores recorded at baseline, 6, 12, 18, and 24 months were analyzed to assess tumor status and cognitive function over time.

RESULTS: The proportion of patients without tumor progression who experienced clinically significant cognitive deterioration compared with baseline was stable at 6, 12, 18, and 24 months (18%, 16%, 14%, and 13%, respectively). In patients without radiographic evidence of progression, clinically significant deterioration in MMSE scores was a strong predictor of a more rapid time to tumor progression and death. At evaluations preceding interval radiographic evidence of progression, there was significant deterioration in MMSE scores for patients who were to experience progression, whereas the scores remained stable for the patients who did not have tumor progression.

CONCLUSION: The proportion of high-grade glioma patients with cognitive deterioration over time is stable, most consistent with the constant pressure of tumor progression over time. Although other factors may contribute to cognitive decline, the predominant cause of cognitive decline seems to be subclinical tumor progression that precedes radiographic changes.

Supported in part by Public Health Service Grants No. CA-25224, CA-37404, CA-15083, CA-35415, and the Linse Bock Foundation, and conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.