A Clinical Dose Prescription System for Proton Radiotherapy Based on the Mayo Clinic Florida Microdosimetric Kinetic...

Clinical proton dose prescription uses a fixed relative biological effectiveness (RBE) factor of 1.1 despite preclinical and clinical evidence that RBE varies with dose, radiation quality, and tissue radiosensitivity, particularly near the distal edge of treatments. We present a proton clinical dose-prescription system which: (1) is consistent with the clinical RBE of 1.1 for target dose definition, (2) uses full microdosimetric spectral distributions including primary and secondary ions, and (3) accounts for RBE variations in a framework analogous to that clinically used in carbon ion radiotherapy.

Monte Carlo simulations were performed using OpenTOPAS. The clinical dose was defined as the product of the absorbed dose, the biological RBE calculated with the Mayo Clinic Florida microdosimetric kinetic model (MCF MKM) relative to the mid of a reference 2 Gy (RBE) spread-out Bragg peak, and a clinical scaling factor. The clinical dose system was evaluated across various dose levels, target depths, and spread-out Bragg peak widths. The results were compared with calculations using the fixed RBE factor and two approaches based on dose-averaged linear energy transfer of protons only (Beltran and McNamara models).

Across the investigated scenarios, the target-averaged MCF MKM-based RBE ranged from 1.08 to 1.18. The corresponding target-averaged RBE values obtained with the McNamara and the Beltran model were typically 1% lower (range, 86%-105%) and 9% higher (range, 103%-122%), respectively. For all models, substantially higher RBE values were observed at the distal edge and out-of-field.

This work establishes a clinical dose system for proton radiotherapy inspired by corresponding Japanese system for carbon ions. The proposed approach maintains consistency with historical proton practice based on a fixed RBE of 1.1 and accounts for the spatial variations of the radiation quality using microdosimetric distributions that include all primary and secondary ions.