Multi-Institutional Report of Re-Irradiation for Recurrent High-Grade Glioma

• Published in: International journal of radiation oncology, biology, physics Vol. 117; no. 2; pp. S85 - S86
• Main Authors: Zarabi, H., Helis, C.A., Russell, G., Huang, J., Liu, W., Soltys, S.G., Mendoza, M., Braunstein, S.E., Salans, M.A., Wang, T.J.C., Gallitto, M., Shi, W., Cappelli, L., Shen, C., Young, M.D., Mignano, J.E., Halasz, L.M., Barbour, A.B., Masters, A.H., Chan, M.D.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2023
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2023.06.408

Significant heterogeneity exists with regards to prior published reports of re-irradiation (re-RT) in patients with recurrent high grade glioma (HGG). A multi-institutional database of 10 academic centers across the United States was created to analyze prognostic outcomes for re-RT for recurrent HGG, which included WHO Grade III and Grade IV tumors.
Patients with HGG who had initially received standard radiotherapy (RT) and were subsequently treated with a course of re-RT at recurrence were included in the study. Factors assessed to delineate a significant association with overall survival (OS) and toxicity included age, KPS, number of relapses, dose, use of bevacizumab (BEV) or temozolomide (TMZ), time from prior RT, histology, RT target, re-RT target> 5cm and extent of resection, and MGMT methylation status. The Kaplan-Meier Method was used to estimate OS. Cox proportional hazards regression models were used to identify factors associated with OS. Toxicity outcomes were assessed using logistic regression. Significance was assumed if p<0.05. Data management and decision management software were used for all analyses.
Between 2001 and 2022, 280 patients from 10 academic institutions were treated with re-RT for diagnosis of recurrent HGG. 133 patients (71.1%) had a histologic glioblastoma (GBM) at the time of re-RT, with the remainder having Grade 3 gliomas. Median dose delivered at re-RT was 47 Gy BED10 (IQR 47 - 53 Gy BED10), with the most common regimen being 35 Gy in 10 fractions. 83 patients (56%) had GTV greater than 5 cm treated with re-RT. 183 patients (79%) received concurrent systemic therapy, including 95 (41%) who received concurrent TMZ and 86 (45%) who received concurrent BEV. Median OS for the entire cohort was 10 months. Increasing dose at re-RT was associated with improved OS (OR 0.80 95% CI 0.67-0.95, p = 0.10 per 10 Gy BED10), as was dose greater than 47 Gy BED10, which is equivalent to 35 Gy in 10 fractions (OR 0.70, 95% CI 0.54-0.91). Concurrent TMZ was also associated with improved OS (OR 0.68, 95% CI 0.46-0.83, p < 0.01). 32/143 (22%) patients evaluable for toxicity experienced Grade 2 or greater adverse radiation effect (ARE). Use of BEV was associated with decreased toxicity (OR 0.45, 95% CI 0.21-0.98, p = 0.05). Dose at re-RT (OR 1.07 per 10 Gy BED10, p = 0.78), a GTV > 5cm (OR 1.39, p = 0.44), and the use of concurrent TMZ (OR 1.90, p = 0.10) were not associated with Grade 2 or greater ARE.
Higher dose of re-RT and use of concurrent TMZ led to improved OS in recurrent HGG patients without an associated increased rate of ARE. Use of BEV decreased the likelihood of Grade 2 or greater ARE in the re-RT setting for these recurrent HGG patients.