Top Line: There’s no benefit to dose escalation beyond 60 Gy for glioblastoma, right?
The Studies: Numerous trials have failed to definitively show a benefit to dose escalation. Here are two recent studies that revisit that question by using advanced imaging to better define a dose-escalated boost volume. The first was a phase 2 study of 75 patients that used F18-DOPA PET/CT, an amino acid tracer with higher uptake in GBM than normal brain, to identify biologically-aggressive GBM. Using both MRI and F18-DOPA intensities, three simultaneous dose levels were treated: 51 Gy, 60 Gy, and 76 Gy in the same 30 fractions with concurrent TMZ. The 76 Gy volume was mainly defined using PET/CT and included no CTV margin. Grade 3 necrosis occurred in 13.3% of patients, and most received treatment with bevacizumab. PFS and OS were favorable compared to historical controls. In the second, smaller phase 2 study, 23 patients received 60 Gy in 30 fractions using a single-volume approach with a dose-escalated SIB to 75 Gy. This volume (median 11 cc) was defined using high b-value DWI and DCE-MRI sequences, which are more widely available than many molecular tracers. Most tumor failures (69%) occurred outside the high dose volume. Acute grade 3 CNS toxicity occurred in 17% (4 patients) and was reversible with steroids +/- bev while late grade 3 CNS toxicity occurred in 9% (2 patients).
TBL: Newer imaging techniques may help delineate GBM target volumes amenable to dose escalation, however it remains to be seen if this generation of dose-escalation will improve treatment outcomes. | Laack and Kim, Int J Radiat Oncol Biol Phys 2021