Versa hdtm

For clonogenic X‐ray irradiations, five dose points were investigated in triplicate, 0, 1.5, 3, 4.5, and 6 Gy, chosen to decrease the survival fraction by approximately two orders of magnitude to give a sufficient cell survival curve fitting for each cell line and nanoparticle combination, whereas the DNA damage samples were irradiated with 1 Gy. Before irradiating with X‐rays, the dishes were filled with medium, providing adequate scattering conditions. The dishes were then sealed using Parafilm M (Sigma‐Aldrich, UK) immediately before irradiation. Irradiations were carried out at the National Physical Laboratory, Teddington, UK, with a 6 MV linac (Elekta Versa HDTM), with a dose rate of 6.5 Gy min⁻¹. Dishes were placed in the center of a 10 × 10 cm² field (Figure9), where dose calculations were based on reference conditions using depth dose data from ionization chamber measurements for this field size. The dose output was also confirmed with ionization chamber measurements traceable to the UK primary standard. The beam uniformity was assessed using Gafchromic EBT3 film (Ashland ISP Advanced Materials, NJ, USA), where the dose variation across the sample was less than 2%.

VMAT or HT was planned with the aim of accomplishing better homogeneity and conformity of target coverage while sparing adjacent normal organs to minimize exposure to the heart and other organs at risk. A dose-volume histogram was used to evaluate the dose constraints of the target volumes and other organs at risk. The criteria were at least 100% of the CTV was to receive 100% of the prescribed dose, at least 95% of the PTV was to receive 95–100% of the prescribed dose, and the maximal dose to the PTV region should be less than 110% of the prescribed dose. The constraints to the heart were a mean heart dose < 20 Gy, and V25 < 10%. A Pinnacle3 planning system (version 9.8.1, Philips Medical Systems, Madison, WI, USA) was used to plan VMAT, which was delivered by using a linear accelerator machine (Versa HDTM, Elekta, Crawley, West Sussex, UK). A tomotherapy Hi Art Planning system (version 5.1.3, Tomotherapy, Inc., Madison, WI, USA) was used to plan HT, which was delivered by using a Tomotherapy^® Hi-Art or HD system (Tomotherapy^®; Accuray Inc., Madison, WI, USA).

The 6FFF beam modality on Elekta’s VersaHD^TM linear accelerator (linac) with Integrity 4.0.4 control software, was fully commissioned and the corresponding beam model validated in Elekta’s Monaco® TPS, version 5.11.02.⁸ Beam tuning, MLC calibration, and MLC beam modeling in Monaco® were performed according to Elekta’s recommended procedure, taking into account most recent findings.⁹ Performance of these procedures was well within required specifications. MLC parameters in Monaco® were fine‐tuned to achieve optimal agreement for point dose measurement and dose distribution for a range of VMAT and dynamic conformal arc therapy (DCAT) plans.¹⁰ However, clinical VMAT plans still showed unacceptably low pass rates on the VersaHD^TM linac, especially for highly modulated fields and small targets. SunNuclear’s ArcCheck^TM was used for these measurements.