Trimodality Therapy is Associated with Improved Overall Survival in Gliosarcoma: A Multi-Site Experience

Abstract

Gliosarcoma (GS) is a rare pathologic variant of glioblastoma with a lack of guidance for optimal management. We present our analysis of treatment outcomes and prognostic factors for patients with GS. One-hundred and eighteen (118) consecutive patients with GS underwent treatment from 1997 to 2019 at our multi-site institution. Patient, tumor, and treatment characteristics were analyzed with chi-squared testing. Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method and compared with the log-rank test. Prognostic factors were assessed using univariate and multivariate cox regressions for the final models. Data at time of first recurrence was analyzed. Median follow-up of surviving patients was 12.1 (range, 0.4-131.6) months. Sixty-four percent of patients were male, and 87.3% of patients had an ECOG performance status of 0-1. The temporal lobe was the most common site of disease (46.6%). Of 40 patients tested for MGMT methylation status, 20% were methylated. Seventy-seven (65.3%) patients underwent gross total resection; 38 (32.2%) patients underwent subtotal resection, and 3 (2.5%) patients underwent biopsy. Nighty-five (80.5%) patients received trimodality therapy (any degree of resection other than biopsy and adjuvant chemoradiation); 103 (87.3%) patients received chemotherapy; 8 (6.8%) patients received tumor-treating fields. In those who received adjuvant radiotherapy (RT) (99%), RT was delivered with a median of 60 (range, 40-76) Gy in 30 (range, 15-42) fractions. For the entire cohort, median OS, CSS, and PFS was 16.8 (95% CI, 14.4-18), 16.8 (95% CI, 15.6-19.2), and 8.4 (95% CI, 7.2-8.4) months, respectively. On multivariate analysis, trimodality therapy was associated with improved OS (HR 0.29; 95% CI 0.15-0.54; P<0.01), CSS (HR 0.30; 95% CI 0.15-0.62; P<0.01), and PFS (HR 0.27, 95% CI 0.15-0.50; P<0.01). ECOG status of 0 or 1 was associated with improved OS (HR 0.21, 95% CI 0.09-0.45; P<0.01). On subgroup analysis, patients with gross total resection trended towards improved OS compared to subtotal resection, but this difference was not statistically significant (HR 0.70, 95% CI 0.44-1.13; P = 0.16). Treatment at time of first recurrence was associated with improved OS (HR 0.06, 95% CI 0.02-0.14; P<0.01). No other factors were associated with OS including age, MGMT methylation status, RT total dose, and RT dose fractionation. Our clinical outcomes of gliosarcoma are comparable to glioblastoma. Trimodality therapy is associated with improved overall survival in patients with gliosarcoma. While acknowledging potential selection bias, our study supports trimodality therapy as well as treatment at time of first recurrence for this rare malignancy especially in patients with good performance status.