P11.13.B Long-term outcome of patients with WHO grade 3 glioma treated with radiotherapy and temozolomide or radiotherapy alone
Authors: Kiese D , Caliebe A , Haag J , Röcken C , Synowitz M , Ahmeti H 
Published: September 2022

Abstract

Background
For a long time, for patients with WHO grade 3 glioma the gold-standard after surgical treatment has been radiotherapy (RT). Since the combined radio-chemotherapy became the standard as a postoperative therapy for patients with glioblastoma in 2005, the role of radio-chemotherapy with temozolomide (RT/TMZ) for patients with WHO grade 3 glioma has long been controversial. Evidence is growing that RT/TMZ provides advantages in progression-free survival (PFS) and overall survival (OS) in WHO grade 3 gliomas as well. The aim of this study was to compare RT/TMZ (after 2005) and RT alone (before or after 2005) for patients with WHO grade 3 glioma in the long term.

Material and Methods
167 adult patients with first diagnosis of a WHO grade 3 glioma between 1994 and 2019 and treatment with surgery and either RT/TMZ (after 2005) or RT (before or after 2005) were included. Clinical and sociodemographic parameters as well as IDH1/2-mutation-, MGMT-promotor methylation- and 1p/19q-codeletion-status of the patient’s FFPE-tumor-tissue have been retrospectively investigated. Primary outcome was PFS and OS depending on postoperative treatment with RT before 2005 (n = 75) vs. RT after 2005 (n = 33) vs. RT/TMZ after 2005 (n = 48). Therefore, Kaplan-Meier analysis has been performed.

Results
RT before 2005 showed a significant advantage over RT/TMZ after 2005 and RT after 2005 regarding the PFS (p &lt; 0.05) and OS (p &lt; 0.001). Median PFS was 3.34 years (95%-CI = 1.08 - 5.59) for RT before 2005 vs. 1.96 years (95%-CI = 0.89 - 3.02) for RT/TMZ after 2005 and 1.22 years (95%-CI = 0.00 - 2.50) for RT after 2005. RT/TMZ after 2005 showed a significant advantage over RT after 2005 regarding the OS (p &lt; 0.05). Median OS was not reached for RT before 2005 vs. 4.90 years (95%-CI = 2.14 - 7.66) for RT/TMZ after 2005 and 1.60 years (95%CI = 0.43 - 2.78) for RT after 2005. To measure the variability of the therapy groups, a stratified risk analysis of risk factors including IDH1/2-mutation-, MGMT-promotor-methylation- and 1p/19q-codeletion-status, extent of resection, initial Karnofsky Performance Score, Ki67-score, age, gender, tumor entity and dose in gray has been performed by using the Kruskal-Wallis test and Fisher-Freeman-Halton test. There has been a significant difference in IDH1/2-mutation- and MGMT-promotor-methylation-status and dose in gray. Single risk analysis of that parameters resulted in superiority of the RT before 2005 over RT/TMZ after 2005 and RT after 2005 regarding the OS.

Conclusion
There have been several limitations in this study, for example the retrospective setting or the missing randomization of the patients. RT before 2005 resulted in the best long-term outcome, what has to be further investigated. However, RT/TMZ after 2005 showed a significant benefit for the OS in the long term vs. RT after 2005, supporting recent findings regarding the role of RT/TMZ in the therapy of WHO grade 3 gliomas.