Are there any volumetric constraints associated with toxicity in the dose range that is moderately above prescription (i.e. 30-35 Gy range), when planning hippocampal-sparing whole brain radiation?

This is an important question worth some discussion. As the question mentions, clinical trials of HA-WBRT have permitted a hot spot of 133% of the prescription dose of 30 Gy (or 40 Gy) to D2% of the whole-brain parenchyma as an acceptable protocol variation. Importantly, none of these trials have demonstrated any difference in treatment-related toxicity between conventional WBRT and HA-WBRT (Brown et al., PMID 32058845).

Whereas conventional WBRT plans (using lateral opposed fields) create dose-per-fraction hot spots along the midline cerebral convexity (this can be reduced with field-in-field planning), HA-WBRT IMRT plans to create dose-per-fraction hot spots in the axial plane of the hippocampal avoidance regions (this can be reduced with...