INNV-64. Doubling of survival in glioblastoma with modifications to the Stupp protocol: marked enhancement of survival with elimination of age bias, attention to timing of treatment intervals and dexamethasone dosages, and addition of a stereotactic

Abstract The Stupp protocol is the standard of care for treatment of glioblastoma (GBM). We explore age dependent treatment bias, the impact of a radiosurgical boost during chemoradiotherapy, proper adjustment of dexamethasone dosage, and optimal timing of steps. We examined treatment parameters in 271 patients whose tumors met the 2021 WHO criteria for GBM. In our cohort, patient age had no impact on outcomes should patients receive the same treatment; those ≥65 yrs. or ≥75 yrs. have indistinguishable progression free and overall survivals (PFS and OS) from younger, comparably treated patients. Possible bias prevents older patients from receiving optimal treatment, resulting in worse outcomes. In patients with MGMT-promoter methylation, focal radiation targeting the tumor bed (defined as an area 2 cm from the anatomic boundaries of the first target) while finishing chemoradiation greatly improves methylated patient survival. There is no improvement in PFS or OS in unmethylated patients treated comparably. The intervals between steps in the Stupp protocol greatly impact patient outcomes. A gap between surgery and chemoradiation of ≥32 days greatly improves outcomes, p<0.05. The optimal gap between chemoradiation and initiating adjuvant temozolomide is between 75 and 81 days, p<0.001. This chemoradiation-temozolomide interval is also associated with a 90% improved likelihood of completing the Stupp protocol and linked to lower Dexamethasone usage when starting adjuvant chemotherapy. Dexamethasone dosages below <1.2 mg/m2 result in 12 months increased OS in methylated patients and approximately 8 months in unmethylated patients. Further benefits are found in patients with lower dosages, underscoring its effects on patient outcome. This analysis reveals that the use of a radiosurgical boost, proper intervals between surgery and chemoradiation, optimal timing of the onset of adjuvant therapy, and reducing dexamethasone dosages at critical time periods all eliminate age bias and can double patient OS. The clinician in control of these factors can significantly enhance patient survival by paying careful attention to these parameters.