Originally published as JCO Early Release 10.1200/JCO.2008.19.1098 on January 12 2009

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Association Between Hyperglycemia and Survival in Patients With Newly Diagnosed Glioblastoma

From the Division of Endocrinology and Metabolism; and the Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD.

Corresponding author: Rachel L. Derr, MD, PhD, c/o The NABTT CNS Consortium, Cancer Research Building #2, Suite 1M-16, 1550 Orleans St, Baltimore, MD 21231; e-mail: rderr{at}jhmi.edu.

Purpose Hyperglycemia has been associated with poor outcomes in many disease states. This retrospective study assessed the association between hyperglycemia and survival in patients with newly diagnosed glioblastoma multiforme (GBM).

Patients and Methods Between 1999 and 2004, before the standard use of temozolomide, 191 patients were accrued onto New Approaches to Brain Tumor Therapy CNS Consortium trials with similar eligibility criteria. Time-weighted mean glucose and mean glucocorticoid dose were calculated for each patient using all values collected regularly in follow-up. The primary outcome was survival.

Results Mean glucose levels ranged between 65 and 459 mg/dL. These were divided into quartiles: quartile one (< 94 mg/dL), quartile two (94 to 109 mg/dL), quartile three (110 to 137 mg/dL), and quartile four (> 137 mg/dL). Median survival times for patients in quartiles one, two, three, and four were 14.5, 11.6, 11.6, and 9.1 months, respectively. The association between higher mean glucose and shorter survival persisted after adjustment for mean daily glucocorticoid dose, age, and baseline Karnofsky performance score (KPS). Compared with patients in the lowest mean glucose quartile, those in quartile two (adjusted hazard ratio [HR], 1.29; 95% CI, 0.85 to 1.96), quartile three (adjusted HR, 1.35; 95% CI, 0.89 to 2.06), and quartile four (adjusted HR, 1.57; 95% CI, 1.02 to 2.40) were at progressively higher risk of dying (P = .041 for trend).

Conclusion In these patients with newly diagnosed GBM and good baseline KPS, hyperglycemia was associated with shorter survival, after controlling for glucocorticoid dose and other confounders. The effect of intensive management of glucocorticoid-related hyperglycemia on survival deserves additional study in patients with GBM.

Supported by Grant No. CA062475 from the National Institutes of Health. R.L.D. was supported by an institutional research training grant (T32 DK062707-03) for clinical diabetes research.

Presented at the 44th Annual Meeting of the American Society of Clinical Oncology, June 2, 2008, Chicago, IL.

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

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