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How low it must be, and how tall the peaks may be, is not pinned down.","posed_since":"2000","precise":"Determine the tolerance surface in the plane of valley dose and peak-to-valley dose ratio, for beam widths of 25 to 1000 micron and spacing of 200 to 4000 micron, in central nervous system, skin and lung. State which of peak dose, valley dose or their ratio controls toxicity for each tissue. An answer is a tolerance criterion with measured thresholds in rad.","problem_ref":null,"references":"","settled_by":"Animal dose-response series in which valley dose and peak-to-valley ratio are varied independently at fixed beam geometry.","status_note":"A 2025 proton-minibeam study (Prezado et al., Radiotherapy and Oncology) argues peak dose also drives toxicity, against the common view that valley dose alone governs it.","title":"Valley-dose and peak-to-valley thresholds for tissue 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