EFFECTIVENESS OF BEVACIZUMAB TO MANAGE SYMPTOMATIC STEROID REFRACTORY PSEUDOPROGRESSION OCCURRING DURING OR EARLY FOLLOWING RADIATION THERAPY FOR GLIOBLASTOMA
Michael Back, Benjamin Challis, Marina Kastelan, Jackie Yim, Victoria Tung, James Drummond, Helen WheelerAbstract
AIMS
Approximately 15% of patients with glioblastoma (GBM) managed with Stupp Protocol(Stupp60Gy), experience symptomatic steroid-refractory mass effects from pseudoprogression resulting in significant morbidity. Beva- cizumab (BEV) potentially produces a clinical response allowing corticosteroid minimisation and completion of definitive therapy.
This study examines the clinical and radiological volumetric outcomes following early BEV (earlyBEV), defined as commencement during or within 3 months of IMRT completion.
METHODS
Consecutive patients managed with earlyBEV for Glioblastoma(IDHwt) with Stupp60Gy between 2016-2023 were identified from a prospective database. The preBEV and postBEV (month+2/3) scans were used for vol- umetric response. Calculation of midline shift at 3rd/lateral ventricle was performed.
Baseline patient/tumour characteristics were assessed. Pattern of relapse, specifically distant failure outside of initial GTV was assessed. The primary endpoint was volumetric reduction of T1gd/T2 volumes at month+2/3 post BEV. Secondary endpoints were survival outcomes compared with overall cohort.
RESULTS
284 patients were managed, of which forty (14%) received early BEV. Compared to remaining 244 patient cohort, earlyBEV had worse initial ECOG0,1 (50%vs76%); less near-total resection (5%vs42%) and less MGMT methyla- tion (35%vs46%).
Median time to earlyBEV was 1.4months postIMRT, including seven patients before IMRT completion. Median T1gd/T2 volumes before earlyBEV were 36cm3(q1-3:22-62cm3) and 114cm3(q1-3:89-147cm3). All patients re- sponded to BEV, though one patient had stable T1gd, and one died before reassessment. The median volumes postBEV were 16cm3(q1-3:7-23cm3) and 40cm3(28-53cm3); with median volume reduction of 65% and 67%.
The overall survival (mOS) post BEV commencement was 8.1months (95%CI:7.5-8.6). The mOS post diagnosis was 11.9months (95%CI:8.9-14.0) vs 19.9months (95%CI:18.1-21.6) for the whole cohort (p<0.001). A component of distant relapse was evident in 40% of earlyBEV vs 34% in total cohort.
Only one serious adverse event occurred with fatal intracranial haemorrhage at day10 after initial BEV dose.
CONCLUSION
This study data demonstrates efficacy of earlyBEV for steroid-refractory pseudoprogression, but also confirms the poor prognosis of this high-risk cohort.