INNV-63. Temporal optimization of the Stupp Protocol- Proper Use of Salvage Therapy including Bevacizumab significantly enhances survival and quality of life

Abstract We examined therapies that extend life after use of the Stupp protocol and their patient selection biases. There is a focus on the use of Bevacizumab to aid completion of the Stupp protocol, and the optimization of salvage strategies, re-resection, re-irradiation and use of B/CCNU chemotherapeutics. The cohort of 269 was selected from patients harvested by our data support team, winnowed down to those who met the WHO’s 2021 glioblastoma definition and a full patient record. Physical condition, not patient age, should dictate aggressiveness of treatment. Even if patients fail and cannot complete Stupp, there is a clear benefit to pursuing these salvage therapies. Salvage normally occurs after MRI scans indicate progression. However, when clinicians deem radiological abnormalities as pseudoprogression and continue the Stupp protocol, we observe a statistically significant improvement in patient outcome, with doubling of survival in a number of patient subgroups. Dexamethasone levels greatly impact patient outcomes including when used with salvage therapies, and must be lowered in critical time periods. Bevacizumab infusion drops dexamethasone-dependency from 2.2 mg/m2 to <0.6 mg/m2, p<0.0001. Bevacizumab has its greatest impact on patient outcome when used during treatment with temozolomide, both during chemoradiation and/or adjuvant temozolomide cycles. Patients who progress prior to completing chemoradiation or 6-cycles of adjuvant chemotherapy, or the appearance of a new, satellite lesion, are best treated with a second resection or reirradiation, p<0.02 unmethylated. We find no clear temporal signature for the use of B/CCNU or reradiation. There is an exquisite impact of patient dexamethasone levels prior to treatment with B/CCNU or reradiation and outcomes. Before the initiation of B/CCNU or irradiation, dexamethasone levels need to be below a critical threshold of 1.2 mg/m².