Optimizing the Stupp protocol for treatment of glioblastoma: eliminating age bias, enhancing treatment timing, use of stereotactically-guided sequential boost, and dexamethasone dosing

BACKGROUND: The Stupp protocol is the standard of care for glioblastoma, yet implementation remains inconsistent, particularly regarding age selection, treatment timing, dexamethasone dosing, and usage of stereotactically-guided sequential boost (SGS-Boost). This study evaluated how treatment intervals, dexamethasone exposure, and sequential fractionated radiotherapy boost affect survival, with emphasis on eliminating age bias.

METHODS: We retrospectively analyzed 269 patients meeting the 2021 World Health Organization criteria for glioblastoma treated at our institution. Of these, 173 patients underwent maximal safe resection followed by chemoradiotherapy, and adjuvant temozolomide was planned. Following stratification by O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, we examined treatment timing, SGS-Boost, dexamethasone exposure, and adjuvant temozolomide cycles. Cox multivariable analysis was performed on key parameters to elucidate relationships between these factors.

RESULTS: Stupp protocol completion significantly improved OS in both methylated and unmethylated populations (p < 0.0001). In methylated patients, both initiating chemoradiotherapy 32-49-days post-surgery and adding SGS-Boost independently improves outcome (p < 0.0001). Poor outcomes were found when dexamethasone was given at ≥ 1.2 mg/m 2 at critical treatment points. Cox multivariable analysis confirms the importance of timing of steps and dexamethasone dosages during chemoradiation, adjuvant temozolomide, and pre-palliatively. Importantly, patients ≥ 70-years-of-age who undergo maximal safe resection and chemoradiation have identical outcomes to equivalently-treated younger patients.

CONCLUSIONS: Optimizing treatment intervals including timing of onset of chemoradiation, incorporating a SGS-Boost in methylated patients, minimizing dexamethasone, and eliminating age bias significantly improves survival. Refinements of the Stupp protocol maximize therapeutic benefit.