End-to-end testing for stereotactic radiotherapy including the development of a Multi-Modality phantom.

PURPOSE: A new insert for a commercially available end-to-end test phantom was designed and in-house manufactured by 3D printing. Subsequently, the insert was tested for different stereotactic radiation therapy workflows (SRS, SBRT, FSRT, and Multimet) also in comparison to the original insert. MATERIAL AND METHODS: Workflows contained imaging (MR, CT), treatment planning, positioning, and irradiation. Positioning accuracy was evaluated for non-coplanar x-ray, kV- and MV-CBCT systems, as well as surface guided radiation therapy. Dosimetric accuracy of the irradiation was measured with an ionization chamber at four different linear accelerators including dynamic tumor tracking for SBRT. RESULTS: CT parameters of the insert were within the specification. For MR images, the new insert allowed quantitative analysis of the MR distortion. Positioning accuracy of the phantom with the new insert using the imaging systems of the different linacs was < 1 mm/degree also for MV-CBCT and a non-coplanar imaging system which caused > 3 mm deviation with the original insert. Deviation of point dose values was <3% for SRS, FSRT, and SBRT for both inserts. For the Multimet plans deviations exceeded 10% because the ionization chamber was not positioned in each metastasis, but in the center of phantom and treatment plan. CONCLUSION: The in-house manufactured insert performed well in all steps of four stereotactic treatment end-to-end tests. Advantages over the commercially available alternative were seen for quantitative analysis of deformation correction in MR images, applicability for non-coplanar x-ray imaging, and dynamic tumor tracking.

Dosimetry, Optimization and FMEA of Total Skin Electron Irradiation (TSEI).

PURPOSE: Total Skin Electron Irradiation (TSEI) is a method for treating malignant cutaneous T-cell lymphomas. This work aims to implement and optimize the total skin technique established at Strahlenklinik Erlangen, Germany on two new linear accelerators and to quantify the risks using failure mode and effects (FMEA) analysis. MATERIAL AND METHODS: TSEI is performed at a VersaHD accelerator (Elekta, Stockholm) with 6MeV in the "high dose rate mode" HDRE and a nominal field size of 40×40cm2. To reach the entire skin surface, the patients perform 6 different body positions at a distance of 330cm behind an acrylic scatter plate, with two overlapping irradiation fields being radiated at 2 gantry angles per position. The irradiation technique was commissioned according to the recommendation of AAPM report 23. With the help of a reference profile at 270°, 2 gantry angles were calculated, which in total resulted in an optimal dose distribution. This was metrologically verified with ion-chamber measurements in the patient's longitudinal axis. The influence of the shape of the acrylic scatter plate and the distance between the acrylic scatter plate and patient was determined by measurements. The dose homogeneity was verified using an anthropomorphic disc phantom equipped with GafChromic films. The workflows and failure modes of the total skin technique were described in a process map and subsequently quantified with a FMEA analysis. RESULTS: An optimal dose distribution is achieved at a distance of SSD=330cm, using the gantry angles 289° and 251°. The previously used segmented acrylic scatter plate was replaced by a flat plate (200×120×0.5cm3), which is placed at a distance of 50cm in front of the patient. The densitometric evaluation of the GafChromic films in the anthropomorphic disc phantom revealed an expected dose distribution of 3Gy at a depth of up to 1.5cm below the skin surface, with a homogeneity of ±10% over the phantom's longitudinal axis. By FMEA a maximum risk priority number of 30 was determined. CONCLUSION: Based on the calculations and measurements performed on the new accelerators as well as the risk analysis, we concluded that total skin therapy can be implemented clinically.

Low-Dose Radiotherapy Ameliorates Advanced Arthritis in hTNF-α tg Mice by Particularly Positively Impacting on Bone Metabolism.

Inflammation and bone erosion are central in rheumatoid arthritis (RA). Even though effective medications for control and treatment of RA are available, remission is only seen in a subset of patients. Treatment with low-dose radiotherapy (LD-RT) which has been already successfully used for amelioration of symptoms in benign diseases should be a promising approach to reduce pain, inflammation, and particularly bone erosion in patients with RA. Even though anti-inflammatory effects of LD-RT are already described with non-linear dose response relationships, and pain-reducing effects have been clinically observed, the underlying mechanisms are widely unknown. Besides immune cells many other cell types, such as fibroblast-like synoviocytes (FLS), osteoclasts, and osteoblast are present in the affected joint and might be modulated by LD-RT. For this study, these cell types were obtained from human tumor necrosis factor-α transgenic (hTNF-α tg) mice and were consecutively exposed to different doses of ionizing radiation (0.1, 0.5, 1.0, and 2.0 Gy, respectively) in vitro. In order to study the in vivo effects of LD-RT within the arthritic joint, hind paws of arthritic hTNF-α tg mice were locally irradiated with 0.5 Gy, a single dose per fraction that is known for good clinical responses. Starting at a dose of 0.5 Gy, proliferation of FLS was reduced and apoptosis significantly enhanced with no changes in necrosis. Further, expression of RANK-L was slightly reduced following irradiation with particularly 0.5 Gy. Starting from 0.5 Gy, the numbers of differentiated osteoclasts were significantly reduced, and a lower bone resorbing activity of treated osteoclasts was also observed, as monitored via pit formation and Cross Laps presence. LD-RT had further a positive effect on osteoblast-induced mineralization in a discontinuous dose response relationship with 0.5 Gy being most efficient. An increase of the gene expression ratio of OPG/RANK-L at 0.1 and 0.5 Gy and of production of OPG at 0.5 and 1.0 Gy was observed. In vivo, LD-RT resulted in less severe arthritis in arthritic hTNF-α tg mice and in significant reduction of inflammatory and erosive area with reduced osteoclasts and neutrophils. Locally applied LD-RT can, therefore, induce a beneficial micro-environment within arthritic joints by predominantly positively impacting on bone metabolism.