Hybrid ultra-high and conventional dose rate treatments with electrons and photons for the clinical transfer of FLASH-RT to deep-seated targets: A treatment planning study

•HUC RT combines UHDR electrons (20–250 MeV) with CDR IMRT for deep-seated tumours.•HUC plans matched clinical quality, with similar PTV coverage and OAR sparing.•“HUC boost” treatments may deliver large fraction doses to optimize FLASH sparing.•HUC treatments are dosimetrically feasible for delivering conformal FLASH-RT.•HUC RT may improve accessibility to FLASH-RT by reducing technical burdens. This study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT. HUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20–250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses. For all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V95% within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (Dmedian of 50–69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D2%,PTV) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D2%,PTV, 31 % for D2%,Brain). From a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT.