Intracranial dose constraints in IDH-wildtype glioblastoma: a framework for context-specific application

Intracranial dose constraints are often treated as fixed properties of neural tissue, yet their meaning depends on the metric, volume definition, source population and clinical time horizon in which they were derived. In IDH-wildtype glioblastoma, these conditions may differ from current planning practice. We identify three potential discontinuities: non-equivalent dose metrics may be treated as interchangeable; volume- or subregion-specific recommendations may be collapsed into single organ-level limits; and thresholds derived in longer-surviving populations may be transferred to a disease in which competing mortality may precede several late endpoints. The brainstem illustrates the metrological problem particularly clearly, whereas the hippocampus and subventricular/periventricular regions illustrate the problem of disease-specific validation. We propose a structure-specific framework with three operations: evaluation of each constraint in its source metric and anatomical definition; classification of each objective by predefined criteria of evidentiary status, endpoint severity and latency, which separates established limits from optimisation objectives; and explicit documentation of any target-coverage trade-off. No new numerical thresholds are proposed, and prognosis never justifies exceeding an established limit. Constraints protecting against severe irreversible injury, including those for the optic nerves and chiasm, are not reassessed.