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How much it rises in patients is unknown.","posed_since":"1990","precise":"Determine the proton relative biological effectiveness as a function of dose-averaged linear energy transfer $\\mathrm{LET}_{d}$ from $1 \\text{ to } 15\\,\\mathrm{keV}/\\mathrm{micron}$, dose per fraction from $100 \\text{ to } 1000\\,\\mathrm{rad}$, and tissue $\\alpha/\\beta$ from $200 \\text{ to } 1000\\,\\mathrm{rad}$, for clinically relevant normal-tissue endpoints. The clinical standard $\\mathrm{RBE} = 1.1$ is constant. An answer is a validated RBE model with uncertainty bands usable in treatment planning.","problem_ref":null,"references":"","settled_by":"Clinical outcome data correlating observed normal-tissue changes with planned $\\mathrm{LET}_{d}$ distributions, combined with in vivo endpoint measurements along a spread-out Bragg peak.","status_note":"Imaging-based evidence of elevated effect at the distal edge in brain accumulated through 2024, but no variable-RBE model had been clinically adopted.","title":"Variable biological effectiveness of proton 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