Prognostic Factors and Survival of Gliomatosis Cerebri: A Systematic Review and Meta-Analysis

Background Gliomatosis cerebri (GC) is a fatal diffusely infiltrating glioma. Because of its rarity, only scarce evidence is available regarding outcome predictors and the proper management of GC. Methods Reported studies of patients with histologically confirmed GC were systematically reviewed and individual patient-level data ( n  = 523) extracted. Multivariable Cox proportional hazard models were fit for overall survival (OS) and progression-free survival (PFS). Results The median OS and PFS were 13 and 10 months, with 5-year rates of 18% and 13%, respectively. Age ≥65 years at diagnosis (hazard ratio for OS [HR OS ], 2.32; 95% confidence interval [CI], 1.62–3.31), high-grade tumor (HR PFS for grade III, 1.57; 95% CI, 1.02–2.40; HR PFS for grade IV, 1.74; 95% CI, [0.98–3.10), GC type II (HR OS , 1.49; 95% CI, 1.12–1.98; HR PFS , 1.56; 95% CI, 1.04–2.34), more central nervous system (CNS) regions involved (HR OS , 1.09; 95% CI, 1.01–1.18), focal neurological deficits (HR OS , 1.41; 95% CI, 1.07–1.86), cerebellar symptoms (HR PFS , 2.20; 95% CI, 1.42–3.39), more symptoms at presentation (HR OS , 1.21; 95% CI, 1.05–1.40), Karnofsky performance scale score OS , 3.58; 95% CI, 1.73–7.39; HR PFS , 4.48; 95% CI, 1.39–14.4), magnetic resonance imaging contrast enhancement (HR OS , 1.48; 95% CI, 1.12–1.96; HR PFS , 1.74; 95% CI, 1.18–2.55), symmetric bilateral CNS invasion (HR OS , 1.42; 95% CI, 1.03–1.96), and high proliferation index (Ki-67 >5%; HR OS , 2.32; 95% CI, 1.11–4.86) were independent predictors of poor outcomes. In contrast, seizure occurrence (HR OS , 0.77; 95% CI, 0.60–1.00; HR PFS , 0.68; 95% CI, 0.47–0.95), isocitrate dehydrogenase 1 mutation (HR OS , 0.16; 95% CI, 0.05–0.49), and O6-methylguanine-DNA-methyltransferase promoter methylation (HR OS , 0.23; 95% CI, 0.09–0.59) were associated with prolonged survival. Chemotherapy and surgical resection were associated with improved outcomes, but radiotherapy, whether monotherapy or combined with chemotherapy, was not superior to chemotherapy alone. Conclusions In the largest study to date on GC, we have identified clinical, imaging, and molecular outcome predictors that are similar to other gliomas and highlight the beneficial effect of chemotherapy and surgical resection, when feasible, on outcomes.