Prognostic factors for survival in adult patients with recurrent glioma enrolled onto the new approaches to brain tumor therapy CNS consortium phase I and II clinical trials

Purpose Prognostic factor analyses have proven useful in predicting outcome in patients with newly diagnosed malignant glioma. Similar analyses in patients with recurrent glioma could affect the design and conduct of clinical trials substantially. Patients and Methods Between 1995 and 2002, 333 adults with recurrent gliomas were enrolled onto 10 phase I or II trials of systemic or local therapy. The studies had similar inclusion criteria and were conducted within the New Approaches to Brain Tumor Therapy CNS Consortium. Ninety-three percent of the patients have died. Cox proportional hazards (PH) regression and recursive partitioning analysis (RPA) were performed to identify prognostic factors. Results Factors associated with an increased risk of death were increased age, lower Karnofsky performance score (KPS), initial and on-study histologies of glioblastoma multiforme (GBM), corticosteroid use, shorter time from original diagnosis to recurrence, and tumor outside frontal lobe. The final PH model included initial histology of GBM (relative risk [RR] = 2.01), 10-year increase in age (RR = 1.23), KPS less than 80 (RR = 1.54), and corticosteroid use (RR = 1.49). RPA resulted in seven classes. Median survival time was poorest in non-GBM patients with KPS less than 80 or GBM patients, age >= 50 years, corticosteroid use (4.4 months; 95% CI, 3.6 to 5.4 months); median survival was best in patients with initial histology other than GBM with KPS >= 80 and tumor confined to the frontal lobe (25.7 months; 95% CI, 18.7 to 52.5), and was 7.0 months (95% CI, 6.2 to 8.0 months) for all patients. Conclusion Initial histology, age, KPS, and corticosteroid use are prognostic for survival in recurrent glioma patients. To allow comparisons across phase II trials, enrollment criteria may need to be restricted.