Challenges for the Implementation of Primary Standard Dosimetry in Proton Minibeam Radiation Therapy.

: Spatial fractionation of proton fields as sub-millimeter beamlets to treat cancer has shown better sparing of healthy tissue whilst maintaining the same tumor control. It is critical to ensure primary standard dosimetry is accurate and ready to support the modality's clinical implementation. : This work provided a proof-of-concept, using the National Physical Laboratory's Primary Standard Proton Calorimeter (PSPC) to measure average absorbed dose-to-water in a pMBRT field. A 100 MeV mono-energetic field and a 2 cm wide SOBP were produced with a spot-scanned proton beam incident on a collimator comprising 15 slits of 400 µm width, each 5 cm long and separated by a center-to-center distance of 4 mm. : The results showed the uncertainty on the absorbed dose-to-water in the mono-energetic beam was dominated by contributions of 1.4% and 1.1% (k = 1) for the NPL PSPC and PTW Roos chambers, respectively, originating from the achievable positioning accuracy of the devices. In comparison, the uncertainty due to positioning in the SOBP for both the NPL PSPC and PTW Roos chambers were 0.4%. : These results highlight that it may be more accurate and reliable to perform reference dosimetry measuring the Dose-Area Product or in an SOBP for spatially fractionated fields.