Uncertainties in the steps of external beam radiotherapy (EBRT) affect patient outcomes. However, few studies have investigated major contributors to these uncertainties. This study investigated factors contributing to reducing uncertainty in delivering a dose to a target volume. The EBRT process was classified into four steps: reference dosimetry, relative dosimetry [percentage depth doses (PDDs) and off-center ratios (OCRs)], dose calculations (PDDs and OCRs in a virtual water phantom), and patient setup using an image-guided radiation therapy system. We evaluated the uncertainties for these steps in conventionally fractionated EBRT for intracranial disease using 4-, 6-, and 10-MV flattened photon beams generated from clinical linear accelerators following the Guide to the Expression of Uncertainty in Measurement and an uncertainty evaluation method with uncorrected deflection. The following were the major contributors to these uncertainties: beam quality conversion factors for reference dosimetry
charge measurements, chamber depth, source-to-surface distance, water evaporation, and field size for relative dosimetry
dose calculation accuracy for the dose calculations
image registration, radiation-imaging isocenter coincidence, variation in radiation isocenter due to gantry and couch rotation, and intrafractional motion for the patient setup. Among the four steps, the relative dosimetry and dose calculation (namely, both penumbral OCRs) steps involved an uncertainty of more than 5% with a coverage factor of 1. In the EBRT process evaluated herein, the uncertainties in the relative dosimetry and dose calculations must be reduced.