Cellular Damage in the Target and Out-of-Field Peripheral Organs during VMAT SBRT Prostate Radiotherapy: An In Vitro Phantom-Based Study

New developments show that patients with prostate cancer can benefit from radiotherapy deliv-ered with a hypo-fractionated regimen. The aim of our study was to investigate the effect of hy-po-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer on out-of-field organs. We used a humanoid phantom to irradiate prostate cells in conditions similar to patient therapy, using SBRT planning. Our results show that radiation doses in the location of the intes-tine and lung resulted in significantly higher radiation doses than the further locations. We observed a high radiotoxic effect in the cells irradiated in the prostate, and a small increase in DNA damage and cell killing in the intestine location. Gene expression analysis revealed significant enrichment of the biological processes related to the radiation response in the prostate. In the lung and thyroid, the enrichment of several gene groups was revealed, however the processes were not clearly related to the response to radiation. Our study provides extensive data on out-of-field safety of prostate SBRT. The PNT1A cells were placed and irradiated in a quasi-humanoid phantom under conditions similar to those of real-life radiotherapy. The phantom was made with water-equivalent poly(methyl methacrylate) (PMMA) slices in the coronal plane to simulate the torso, head, and neck. The slices included natural cork and gypsum inhomogeneities in the lung and head locations to simulate lung tissue and bones, respectively. The layer for cell irradiation was equipped with a water container to allow for the placement of five flasks with the cells. A radiation treatment plan was created for the T-25 culture flask containing PNT1A cells in the prostate location, which was delineated as the gross tumour volume (GTV). The flask was considered the clinical target volume (CTV). To create the planning target volume (PTV), a margin of 3 mm was added around the CTV, following the usual clinical practice to ensure that the PTV received the prescribed dose. The other four flasks were placed in the water containers in the following locations at various distances from the axial plane: intestine (transverse colon) (15 cm from the axial plane; lung (35 cm); thyroid (52 cm); and brain (74 cm). Figure 1 shows the VMAT plan for these organs at risk. We used a 6 MV photon beam with a flattening filter to deliver the total dose of 70 Gy to the cells in the prostate, delivered in seven consecutive fractions of 10 Gy each (the highest fraction dose delivered for prostate SBRT). This approach is known as dose scaling (see AAPM Report 158). The 10 Gy SBRT fraction was used for planning (instead of 2 Gy, which is used for conventional fractionations, to a total dose of 70 Gy) because we wanted to assure the same scheme of collimator leaves’ movement (a different scheme is used for different doses per fraction during arc therapies). Treatment plans were prepared for the RapidArc VMAT technique using three co-planar arcs, with the first, second, and third arcs delivered, respectively, counterclockwise (gantry angles from 140° to 220°), clockwise (181° to 179°), and counterclockwise (179° to 181°), and with a 0.5 cm multi-leaf collimator