To validate that altering radiotherapy dose rate through either changing pulse repetition frequency or instantaneous dose rate does not have an effect on cell survival, two human carcinoma and a hamster lung cell line were irradiated with various beam settings. Varian TrueBeam linac with a flattening filter free mode of operation was used for all experiments. The results obtained indicate that either method of changing dose rate has no effect on cell survival in the three cell lines studied. Filtered and filter free modes were also compared in treatments with protracted dose delivery which significantly increases overall treatment time. Cell survival indicated no difference between filter and filter free beam delivery in any of the protraction schemes. An increase in survival was seen in both modes upon protracting dose delivery to 15, 30 or 60 min rather than delivering acutely. Further, analysis of induced DNA double-strand breaks via the γH2AX assay showed no difference between filtered and unfiltered beams. The following study suggests that increasing dose rate is an acceptable manner of decreasing radiotherapy treatment time that does not have any detrimental effects on in vitro cell eradication.

Purpose: To assess dosimetric properties and identify required updates to commonly used protocols (including use of film and ionization chamber) pertaining to a clinical linac configured into FLASH (ultra-high dose rate) electron mode.Methods: An 18MV photon beam of a Varian iX linac was converted to FLASH electron beam by replacing the target and the flattening filter with an electron scattering foil. The dose was prescribed by entering the MUs through the console. Fundamental beam properties, including energy, dose rate, dose reproducibility, field size, and dose rate dependence on the SAD, were examined in preparation for radiobiological experiments. Gafchromic EBT-XD film was evaluated for usability in measurements at ultra-high dose rates by comparing the measured dose to the inverse square model. Selected previously reported models of chamber efficiencies were fitted to measurements in a broad range of dose rates. Results:The performance of the modified linac was found adequate for FLASH radiobiological experiments. With exception of the increase in the dose per MU on increase in the repetition rate, all fundamental beam properties proved to be in line with expectations developed with conventional linacs. The field size followed the theorem of similar triangles. The highest average dose rate (2 × 10 4 Gy/s) was found next to the internal monitor chamber, with the field size of FWHM = 1.5 cm.Independence of the dose readings on the dose rate (up to 2 × 10 4 Gy/s) was demonstrated for the EBT-XD film. A model of recombination in an ionization chamber was identified that provided good agreement with the measured chamber efficiencies for the average dose rates up to at least 2 × 10 3 Gy/s. Conclusion: Dosimetric measurements were performed to characterize a linac converted to FLASH dose rates. Gafchromic EBT-XD film and dose rate-corrected cc13 ionization chamber were demonstrated usable at FLASH dose rates.

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Dose rate and presence of a flattening filter showed no effect on cell survival, however, survival was significantly affected when dose delivery time was protracted to that typical of conformal field therapy. Volumetric arc based gated SBRT may be beneficial for tumor cell kill, though the gating window and duty cycle have to be balanced against the effect of dose delivery protraction. Research Support (Varian Medical Systems).

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